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Hepatobiliary Disease
SECTION III: PRACTICE: APPROACH TO THE PATIENT IN THE TROPICS
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CHAPTER 133 Hepatobiliary Disease Mohammad S. Khuroo • Mehnaaz S. Khuroo
INTRODUCTION
DISEASES CAUSED BY HEPATITIS VIRUSES
A broad group of infections affect hepatobiliary organs in the tropical countries. These include infections prevalent in nontropical zones and those restricted to tropical zones of the world (Table 133.1). Amongst the hepatitis viruses, hepatitis E virus (HEV) has the most significant palpable impact.1 A number of nonviral infectious agents predominantly prevalent in tropical countries affect the liver and biliary tract as primary targets.2 Commonest amongst these are amebiasis, echinococcosis, schistosomiasis and hepatobiliary and pancreatic ascariasis (HBPA). Tuberculosis and the acquired immunodeficiency syndrome (AIDS) are endemic in tropics and can involve both the liver and/or biliary tree.3,4 Several viral and nonviral tropical infections such as malaria, typhoid, dengue fever, and leptospirosis may affect the heptobiliary system as a part of multiorgan involvement.5 Hepatobiliary infections prevalent in tropical countries have a special predilection and distinct pattern for expatriate Western travelers to such countries.6,7
Acute Sporadic Viral Hepatitis
DIAGNOSTIC CONSIDERATIONS Methodology to be followed for proper evaluation of hepatobiliary diseases in tropics is no different than that employed in nontropical countries.8 This includes a proper history, thorough physical examination, routine blood counts and serum chemistries including bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Abnormal liver tests can be classified into definite patterns: (1) hepatocellular (elevated bilirubin; elevated ALT/AST >500 IU; ALT>AST; normal to <3 times normal elevation of ALP); (2) cholestatic (elevated bilirubin, normal to <300 IU ALT/AST; >4 times normal elevation of ALP); (3) haemolytic/Gilbert’s syndrome (isolated elevation of unconjugated bilirubin rarely above 5 mg/dL); (4) synthetic liver failure (elevated bilirubin, modestly elevated ALT, AST, and ALP; low albumin, high globulins, and high prothrombin time); and (5) infiltrative (isolated >4 times normal elevation of ALP). Each pattern has different clinical connotations and defines corresponding further workup. Hepatobiliary ultrasound with Doppler is a valued complement to clinical examination for hepatobiliary diseases and is strongly recommended as a part of primary evaluation. Ultrasound with Doppler is useful for detecting gallstones, thickened gallbladder, dilated bile ducts, cysts and masses within the liver, periportal fibrosis, hepatosplenomegaly, and evidence of portal hypertension.9 Based on findings, further cost-effective, evidencebased laboratory tests, imaging tools such as computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or other invasive tests such as liver biopsy or guided fine needle aspiration biopsies may need to be employed.
Viral hepatitis (see Chapters 64–66) is highly endemic in tropical countries and is a cause of significant morbidity and mortality. Etiology of acute sporadic hepatitis in these countries is different than in the West. Around half of sporadic viral hepatitis in the tropics is related to HEV. Hepatitis B virus (HBV), hepatitis C virus (HCV), and non-A-E hepatitis constitute around 22%, 9%, and 25% of patients, respectively. Hepatitis A virus (HAV), a dominant cause of acute hepatitis in the West, is an uncommon (<4%) cause of hepatitis in adults in the tropics and is mostly encountered in children below 10 years of age.10–14 Acute viral hepatitis affects adults predominantly in the age group of 25–45 years. Male : female ratio is 1.4 : 1. Pregnant women especially in the third trimester are often infected with HEV and constitute around one-fourth of the females infected.15 The clinical profiles and serum chemistries are typical of acute viral hepatitis as seen in the West. However, around 20% of patients with HEV infection present with prolonged cholestasis. Abdominal ultrasound is usually unremarkable. However, it may show a hypoechoic liver with focal bright spots (starry sky appearance). The gallbladder often shows wall edema and pericholecystic fluid resembling features of acalculous cholecystitis.16 Recovery takes 4–6 weeks. Acute liver failure develops in around 8–10% of hospitalized patients. However, over 50% of pregnant women with HEV infections develop acute liver failure with high maternal and perinatal mortality.15 Patients with sporadic hepatitis need to be evaluated for acute markers of hepatitis viruses (IgM anti-HAV; HBsAg and IgM anti-HBc; anti-HCV; IgM anti-HEV), cytomegalovirus (CMV) and Epstein–Barr virus.17 Dengue fever, typhoid fever, malaria, and leptospirosis may cause abnormal liver tests of hepatocellular damage; however, these infections cause systemic manifestations and these should be carefully evaluated.4
Epidemic Hepatitis Epidemic hepatitis in tropical countries is exclusively caused by HEV.18–21 Epidemiological features of HEV infection have several peculiar characteristics, which remain unexplained. HEV presents as repeated large-scale waterborne epidemics of jaundice in highly endemic areas occurring every 10–20 years. HEV is a disease of adult populations, and during epidemics attack rates in adults are higher than in children. HEV has an increased incidence and severity in pregnant women, and the major cause of mortality in epidemics is the high rate of fulminant hepatitis in pregnant women.22–25 The clinical and biochemical presentations of HEV are similar to those of infection with other hepatitis viruses and encompass a wide variety of
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Disease
Agents
Endemic Areas
Manifestations
Diagnosis
Treatment
Acute markers (IgM anti-HEV; HBsAg and anti-HBc IgM; anti-HCV; IgM anti-HEV); Monospot test (CMV). Ultrasound to exclude EHBO IgM anti-HEV
Supportive care
Acute markers of HV; lab data to assess severity of liver failure and prognostic factors
Intensive care management; early consideration for liver transplant
Acute markers of HV
Supportive treatment
Serological markers and NAT for HBV and HCV
Consider antiviral therapy; supportive treatment for established cirrhosis
Evaluate serologic markers of HV; lab tests to assess severity of liver failure
Supportive treatment; antiviral therapy if indicated
Hepatic Disease Caused by Hepatitis Viruses Acute sporadic hepatitis
HEV (40%), HBV (22%), HCV (9%), non-A-E (25%), HAV (4%). Children often infected with HAV
Endemic in all developing countries
Adults involved; prolonged cholestasis in 20%; mortality 8–10% (high in pregnant women with HEV)
Epidemic hepatitis
HEV
All developing countries with unsafe water supplies and poor sanitation
Acute liver failure
HEV (37%), HBV (18%), HCV (5%), non-A-E (37%), HAV (3%). Antitubercular drugs small percentage
Endemic in all developing countries
Subacute hepatic failure
HEV, HBV
Indian subcontinent
Chronic hepatitis/ cirrhosis
HBV, HCV
All developing countries
Acute on chronic liver failure (AOCLF)
HEV superinfection on established HBV/HCV cirrhosis, reactivation HBV and HCV
Indian subcontinent
Repeated large-scale epidemics; adult disease; high incidence in pregnant women; mortality in pregnant women 20%; no chronic liver disease; vertical transmission with severe neonatal HEV Encephalopathy; cerebral edema; coagulopathy; multiorgan failure; GI bleed; death. ALF related to HEV in pregnant women – explosive disease with DIC; may represent a severe manifestation of a Schwartzman-like phenomenon Progressive jaundice, ascites, renal failure and SBP, terminal encephalopathy Asymptomatic; incidental abnormal liver tests; recurrent jaundice; established cirrhosis presents as signs of liver failure and portal hypertension Rapid decompensation of stable liver disease; presents as jaundice, ascites, renal failure, and GI bleed
PRACTICE: APPROACH TO THE PATIENT IN THE TROPICS
Table 133.1 Hepatobiliary Diseases Caused by Infectious Agents in Tropical Countries
Safe water and sewage disposal to control epidemics
Hepatobiliary Disorders Caused by Nonviral Infections Prevalent in the Tropics Escherichia coli, Klebsiella pneumoniae, enterococci, anaerobes Entamoeba histolytica Echinococcus granulosus
Worldwide
Insidious onset, fever, RUQ pain and tenderness
Ultrasound or CECT and aspiration
IV antibiotic plus image-guided drainage; surgery in select cases
Tropical and subtropical areas Sheep and cattle raising areas
Alveolar hepatic hydatid disease
Echinococcus multilocularis
Ultrasound or CECT plus serology Ultrasound or CECT plus serology; ERCP to define biliary disease Ultrasound or CECT plus serology; ERCP to define biliary disease
Metronidazole plus diloxanide furoate Surgery or PAIR and albendazole; therapeutic ERCP for biliary disease Long-term albendazole, resection, therapeutic ERCP
Polycystic hepatic hydatid disease
Echinococcus vogeli, E. oligarthrus
Germany, Austria, Switzerland, France, Turkey, Iran, Afghanistan, India (Kashmir), Canada, Japan Panama, Ecuador, Colombia, Venezuela, French Guiana
Acute onset, fever, RUQ pain and tenderness Incidental, mass lesion, infection, rupture into bile duct causes cholangitis and cholestasis Expanding hepatic mass, portal hypertension, liver failure, cholestasis due to bile duct disease
Expanding hepatic mass, portal hypertension, liver failure, cholestasis due to bile duct disease
Ultrasound or CECT plus serology; ERCP to define biliary disease
Long-term albendazole, resection, therapeutic ERCP
Pyogenic liver abscess
Amebic liver abscess Cystic hepatobiliary hydatid disease
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Agents
Endemic Areas
Manifestations
Diagnosis
Treatment
Hepatobiliary and pancreatic ascariasis
Ascaris lumbricoides
Developing countries
Biliary colic, cholangitis, cholecystitis, pancreatitis, liver abscess
Ultrasound and ERCP
Hepatic schistosomiasis
Schistosoma mansoni, S. japonicum, S. intercalatum, S. mekongi Fasciola hepatica
Asia, Africa, South America, Caribbean
Portal hypertension and variceal bleeding
Serology, hepatic imaging, ova in stool/rectal or liver biopsy
Anthelminthic therapy and worm extraction at ERCP Praziquantel therapy and treat portal hypertension
Cattle and sheep raising areas
Cholangitis, cholestasis
Eggs in feces/bile ERCP
Clonorchis sinensis, Opisthorcis viverrini, O. felineus Mycobacterium spp.
Southeast Asia
Cholangitis, cholestasis, cholangiocarcinoma
Ova in stool, ERCP
Developing countries
Fever, weight loss, hepatomegaly and elevated liver tests RUQ pain, fever, jaundice
Tuberculin skin test; serology for TB; liver biopsy Elevated ALP; ERCP papillitis and bile duct stricture; duodenal biopsy shows typical organisms
Antitubercular drugs
Look for parasites in blood film; lab tests to evaluate severity of liver disease
Antimalarial therapy; supportive treatment
Antimalarial antibodies; high IgM levels; liver biopsy: hepatic sinusoidal lymphocytosis (B cells) Blood, urine and stool culture; serology; lab tests to evaluate severity of liver disease Isolation of organism from blood or CSF; serologic tests (MAT or ELISA)
Long-term antimalarial therapy
Fascioliasis
Clonorchiasis/ opisthorchiasis
Hepatobiliary tuberculosis HIV cholangiopathy (in AIDS with CD4+ <200/ mm3)
Cryptosporidium parvum, Microsporidia, Cyclospora cayetanensis, Isospora belli; CMV
Worldwide
Triclabendazole/ bithionol, therapeutic ERCP Praziquantel therapy and therapeutic ERCP
Hepatobiliary Disease Chapter 133
Table 133.1 Hepatobiliary Diseases Caused by Infectious Agents in Tropical Countries—cont’d
Antibiotics; therapeutic ERCP
Hepatobiliary Involvement Caused by Tropical Diseases as a Manifestation of Multiorgan Disease Malarial hepatitis
Plasmodium spp.
Asia, Africa, South America
Tropical splenomegaly syndrome
Plasmodium spp.
Asia, Africa, South America
Typhoid hepatitis
Salmonella spp.
Indian subcontinent, South/Central America
Leptospirosis hepatitis
Leptospira spp.
Tropical countries (sewage workers)
Hyperinfection syndrome
Strongyloides stercoralis
Tropical and subtropical countries (high-risk AIDS and renal transplant)
Invasive candidiasis
Candida spp.
Worldwide (acute leukemia on immunosuppression)
Hepatitis occurs in 11–25% of infections; presents as jaundice, tender hepatomegaly, elevated liver tests, hepatic failure in severe P. falciparum Massive splenomegaly
Occurs in 1–26%; presents as jaundice, RUQ pain, elevated liver tests, rarely liver failure occurs, typhoid abscess may occur Hepatic involvement in second week; presents as RUQ pain, severe jaundice, elevated liver tests, rarely liver failure Jaundice and elevated liver tests
Chronic debilitating illness, RUQ pain, high fever, weight loss, hepatomegaly, elevated ALP
Stool for S. stercoralis larvae; liver biopsy shows eosinophilic granulomatous hepatitis with larvae in canaliculi Ultrasound/CECT hypoechoic hepatic masses; guided needle aspiration biopsy of lesions
Antibiotic therapy; supportive treatment
Antibiotic (penicillin, ampicillin, or erythromycin) therapy Ivermectin
Amphotericin or fluconazole
ALF, acute liver failure; ALP, alkaline phosphatase; CECT, contrast-enhanced computed tomography; CMV, cytomegalovirus; DIC, disseminated intravascular coagulation; EHBO, extrahepatic biliary obstruction; ERCP, endoscopic retrograde cholangiopancreatography; GI, gastrointestinal; HV, hepatitis virus; MAT, microscopic agglutination test; NAT, nucleic acid amplification testing; PAIR, puncture, aspiration or injection of a scolicidal agent and reaspiration; RUQ, right upper quadrant; SBP, spontaneous bacterial peritonitis.
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symptoms. Prolonged intrahepatic cholestasis lasting from 3 to 6 months occurs in about 20% of patients and simulates large bile duct obstruction. A small percentage of patients show a biphasic enzyme elevation; however, no chronic liver disease or chronic hepatitis is known to develop after HEV in immunocompetent hosts.
Acute Liver Failure Acute liver failure (ALF), a dramatic and challenging syndrome in clinical medicine,26,27 is characterized by rapid and progressive deterioration of liver function from massive hepatocellular necrosis or infiltration leading to encephalopathy and multiorgan failure. There is little information on the epidemiology of ALF in various regions of the world. Crude estimates suggest that ALF affects approximately 2000 individuals annually in the United States. In contrast, ALF caused by HEV infection is a substantial health problem in developing countries. Most ALF in the tropics is caused by hepatitis viruses.25,28,29 Amongst these, HEV is the cause of ALF in over 40% of patients. HBV and non-A-E constitute 17% and 33% of patients, respectively. HAV is an uncommon (<4%) cause of ALF in tropical countries. In comparison, HAV, HBV, and non-A-E cause 14%, 33%, and 53% of viral ALF in the United Kingdom. HEV is an uncommon cause of ALF in developed countries and is either seen in Western travelers to the Indian subcontinent or as a result of recently recognized zoonotic foodborne autochthonous HEV infections. Drugs, especially antitubercular drugs, cause <4% of ALF in developing countries, in contrast to developed countries where drugs, namely acetaminophen and anti-inflammatory drugs, constitute more substantial etiologies of ALF. A number of transplant centers from the West have defined prognostic criteria in ALF and these criteria can be applied to estimate the probability of spontaneous recovery in a given patient. While one model of prognostic indicators has been developed at King’s College Hospital, London,30 data from India have shown that these prognostic indicators may not be valid for other geographical regions, in view of differences in the etiologic causes, behavior, and clinical profiles of ALF.25,29 Early predictors of a poor outcome are non-HEV etiology, prothrombin time >30 seconds, grade of coma >2, and age >40 years.
Subacute Hepatic Failure Subacute hepatic failure is an entity reported from the Indian subcontinent.31,32 The hepatic failure shows a more protracted illness and is characterized by development of progressive jaundice, ascites, coagulopathy and renal failure during the course of acute hepatitis. Patients often develop spontaneous bacterial peritonitis and gastrointestinal bleeding. Encephalopathy is usually a preterminal event. Liver biopsy reveals extensive bridging, submassive necrosis, and cholestasis. HBV and HEV are the causes in most patients.
Acute on Chronic Liver Failure Acute on chronic liver failure (AOCLF) is a recently recognized entity wherein there is rapid hepatic decompensation once acute hepatic insult is superimposed on established stable chronic liver disease.36–38 Alcoholic cirrhosis constitutes 50–70% of the underlying liver diseases in AOCLF in Western countries, whereas in most of tropical countries HBV constitutes 70% and alcohol only about 15% of the etiologies of AOCLF. Autoimmune liver disease, Wilson’s disease, metabolic liver disease, and chronic cholestatic liver disease constitute only a minority of patients. Among the precipitating causes of AOCLF, HEV superinfection has remained a very important acute insult in the Indian subcontinent and is an important cause of mortality in patients with cirrhosis.38–40 Reactivation of HBV and HCV infections leading to hepatitis “flares” are the other major causes of AOCLF in the Asian region.41 In contrast to this, sepsis and variceal bleeding play important roles in the sudden decompensation of established chronic liver disease in the West.
DISEASES CAUSED BY TROPICAL NONVIRAL INFECTIOUS AGENTS Pyogenic Liver Abscess Pyogenic liver abscess is responsible for 8–20 cases per 100 000 hospital admissions. Pyogenic abscesses most often occur in patients over 40 years of age, with a peak incidence in the sixth decade. No significant gender, ethnic, or geographic differences exist for the development of pyogenic liver abscesses. About one-half of patients have a solitary abscess. Abscesses involve the right lobe in 75%, left lobe in 20%, and caudate lobe in 5% of cases. Suppurative cholangitis as a result of bile duct stones, benign and malignant biliary strictures, and endoscopic, radiologic, and operative biliary interventions are the major identifiable causes of pyogenic liver abscess in the West.42–47 In endemic areas, Ascaris lumbricoides (see Chapter 115) and Clonorchis sinensis (see Chapter 123) can invade the biliary tree, cause cholangitis, and commonly predispose to liver abscesses.2,45 Liver abscesses can be caused by Salmonella enterica serovar Typhi, Mycobacterium tuberculosis and Brucella spp. (Fig. 133.1). Most pyogenic liver abscesses are polymicrobial. The frequently isolated organisms include Escherichia coli, Klebsiella pneumoniae, Streptococcus viridans, Staphylococcus aureus, Enterococcus faecalis, Bacteroides spp., Fusobacterium spp., anaerobic streptococci, Actinomyces spp., and rarely Clostridia spp. In the past, patients typically presented with acute-onset abdominal pain (89%), high fever with rigors and chills (67%), and right upper
Chronic Hepatitis and Cirrhosis
978
Chronic active hepatitis in the tropics is caused most commonly by HBV and HCV (see Chapters 65 and 66).33,34 Coinfection with hepatitis delta virus (HDV) may accelerate the course of chronic HBV infection.35 While failure to resolve infection with these agents may lead to cirrhosis or hepatoma, persons with chronic hepatitis may remain asymptomatic for years, despite persistently elevated hepatic enzymes. Serologic testing and liver biopsy confirm the diagnosis. Macronodular or “postnecrotic” cirrhosis develops in up to 25% of chronic hepatitis B surface antigen carriers and in over 20% of persons infected with HCV for over 20 years. The process may be clinically silent for several years before the appearance of symptoms and signs of hepatocellular dysfunction and portal hypertension such as jaundice, encephalopathy, ascites, and bleeding from esophageal varices. The liver is firm, nodular, and shrunken.
Figure 133.1 Liver abscess caused by brucellosis in a 30-year-old woman who presented with fever, arthralgia, hepatomegaly, and elevated serum alkaline phosphatase. Contrast-enhanced CT scan image of liver shows hypodense mass in the left lobe with thick ring enhancement of the margins. (From Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, eds. Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press; 2004:158, Fig. 1B.)
Table 133.2 Differentiating Features of Pyogenic and Amebic Liver Abscesses Feature Distribution of disease Age of occurrence Sex distribution
Worldwide
Number Location
Often multiple (50%) Either lobe
Duration of illness Symptoms
Usually 1 month Low-grade fever, RUQ pain and tenderness Mild unless associated with biliary disease Positive (50–90%) Mass lesion with fluid component Negative Intravenous antibiotics plus drainage 16% Jaundice, low albumin, comorbid disease
Amebic Liver Abscess Amebic liver abscess is the most common extraintestinal manifestation of Entamoeba histolytica infection (see Chapter 92) and occurs in approximately 8.5% of such patients. The disease is endemic in many tropical regions namely Mexico, Central America, northern South America, West and South Africa, and India.48–53 Amebic liver abscess most often occurs in the age group 20–45 years. Most patients present with an acute illness, and duration of symptoms is usually <2 weeks. Clinical symptoms and signs include low-grade fever and chills, RUQ pain and tenderness, and hepatomegaly. Left lobe abscesses can present with toxemia; epigastric pain, tenderness, and guarding; and a large epigastric mass. Multiple liver abscesses usually present with high fever, toxemia, jaundice, and encephalopathy. Complications of amebic liver abscess include secondary bacterial infection, rupture, and compression of the bile ducts. Diagnosis is made on hepatic imaging and amebic serology. Ultrasound and CECT are useful in delineating and localizing the abscess as well as to monitor the response to treatment. Amebic serologic tests, (e.g., enzyme immunoassay) can have sensitivities of 99% and specificities >90% in patients with amebic liver abscess. Amebic liver abscess needs to be differentiated from pyogenic liver abscess in endemic areas, especially in view of the different treatment regimens employed in the two entities and different responses to therapy (Table 133.2). Metronidazole, 800 mg three times per day orally for 10 days, is curative in over 90% of patients with amebic liver abscess. Clinical improvement is usually seen within 3–5 days. After clinical cure, the abscess cavity disappears in 6–9 months. Alternative agents include secnidazole 500 mg orally three times per day, and tinidazole 600 mg orally twice per day for 7 days. A luminal amebicide, diloxanide furoate 500 mg three times per day for 10 days, is often used to eradicate intestinal carriage of the organism. Unlike pyogenic liver abscess, needle aspiration or abscess drainage offers no additional therapeutic benefit. Aspiration is indicated in patients with persistent symptoms after 5 days of medical therapy and in those with: (1) very large abscess, (2) abscess involving the left lobe, (3) abscess which shows signs of imminent rupture, and (4) abscess with secondary bacterial infection. Open surgical drainage is indicated when an abscess has ruptured into the peritoneum or adjacent viscera.
Hepatic Hydatid Disease Hydatid disease, echinococcosis, (see Chapter 120), is a zoonotic infection caused by larval forms (metacestodes) of the tapeworms of the genus Echinococcus and is characterized by development of expanding cysts in the liver and other body organs (Fig. 133.2).54–59 Within the genus Echinococcus, four principal causes of human disease are recognized. E. granulosus causes cystic hydatid disease, E. multilocularis causes alveolar hydatid disease, and E. vogeli and E. oligarthrus cause polycystic hydatid disease. The most clinically relevant form is cystic echinococcosis caused by E. granulosus. Uncomplicated liver cysts usually present with dull ache in the RUQ or a feeling of abdominal swelling or distension. A large cyst
Pyogenic Liver Abscess
Jaundice
Blood culture Hepatic imaging Amebic serology Treatment
Mortality High-risk groups
Above 40 years Equal
Amebic Liver Abscess Tropical and subtropical regions 20–45 years 3–10 times more in males than females Often single (80%) Often right lobe under dome of diaphragm Often 2 weeks Low-grade fever, RUQ pain and tenderness
Hepatobiliary Disease Chapter 133
quadrant (RUQ) tenderness (70%). Since the introduction of antibiotics, the presentation of pyogenic liver abscess has become less acute, often insidious and characterized by malaise, low-grade fever, and dull abdominal pain. Diagnostic imaging studies are essential in making the diagnosis of pyogenic liver abscess. Sonography is highly sensitive (94%) and is the imaging method of choice in patients with suspected biliary disease. Contrast-enhanced computed tomography (CECT) has high sensitivity (100%), and visualizes abscesses better because contrast enhancement highlights the unaffected liver. Treatment of pyogenic liver abscess requires antibiotic therapy and image-guided percutaneous drainage of the abscess. Such treatments are successful in 85–90% of patients. Surgical drainage is reserved in the following situations: (1) percutaneous drainage is unsuccessful, (2) there is coexisting intra-abdominal disease requiring surgery, and (3) abscess is complicated by rupture or extension into adjacent structures.
Moderate in large and multiple abscesses Negative Mass lesion with fluid component Positive Metronidazole plus diloxanide furoate 2–18% Multiple abscesses, left lobe abscess, high bilirubin, encephalopathy, low albumin
RUQ, right upper quadrant. (Reproduced with permission from Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, eds. Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press; 2004:161.)
Figure 133.2 Cystic hepatic echinococcosis. A 50-year-old man complained of RUQ discomfort of 6 months’ duration. An axial T1-weighted MR image shows a large rounded lesion occupying the whole right lobe of the liver. The lesion reveals multiple rounded low signal lesions (daughter cysts). The remainder of the contents reveal high intensity signal (matrix). (From Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, eds. Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press, 2004:163, Fig. 2.)
in the hilar region can compress the common hepatic duct causing cholestasis. Cyst rupture into the biliary tree causes obstruction of the ducts by daughter cysts and laminated membranes and presents as biliary colic, cholangitis, and progressive cholestasis. Serology and imaging tools can help establish the diagnosis (see Chapter 120). Serology detects specific serum antibodies or circulating
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antigen by a variety of immunodiagnostic methods. Positive test results need confirmation by the arc-5 immunoelectrophoretic (IEP) test, which detects antibodies against immunodominant and specific antigen (antigen 5) of the cestode. Liver cysts are well visualized by ultrasound. Cysts may appear univesicular, rounded with well-defined margins containing pure fluid or multivesicular (daughter cysts) with pure fluid collection in each vesicle. Cysts may have a hyperechoic solid pattern (pseudotumor appearance) or may have reflective walls suggestive of calcification. Rupture of liver cysts into the bile ducts can be suspected on ultrasound. Ultrasound appearances in such cases include dilated bile ducts, non-shadowing echogenic structures within the ducts, and loss of continuity of the cyst wall adjacent to the bile duct representing the site of communication. However, ERCP is the recommended tool and reveals filling defects of varying shape and size in the dilated bile ducts and leakage of contrast medium into the cyst cavity. Treatment options for cystic hydatid disease are surgery, drug therapy, and percutaneous drainage (see Chapter 120). Surgery has the potential to remove cysts and lead to complete cure. The surgical procedure of choice is cystectomy with removal of the germinal and laminated layers and preservation of pericyst. Operative mortality varies from 0.5% to 4.0% in centers with adequate medical and surgical facilities. Albendazole and praziquantel can be effective in small cysts (<4 cm diameter), in cysts with thin walls, and in younger patients. Alternatively, percutaneous treatment of hepatic hydatid cysts, known as PAIR (puncture, aspiration, installation of scolicidal agent, and respiration) has been efficacious. The procedure is minimally invasive, cost-effective, involves reduced hospital stay, and has less morbidity and mortality than surgery.
Hepatobiliary and Pancreatic Ascariasis Ascariasis is caused by the nematode Ascaris lumbricoides (see Chapter 115). Hepatobiliary and pancreatic ascariasis (HPA) is one of the most common complications caused by intestinal Ascaris infections. Ascarides in the duodenum can enter the ampullary orifice and block it; they can advance further to the bile duct and hepatic ducts (Fig. 133.3). While in the common duct, the cystic duct can be blocked by worms entering its orifice. Less often, worms can reach the gallbladder or enter the pancreatic duct.60–63 HPA is more common in women than men (female : male ratio of 3 : 1) with a mean age of occurrence being 35 years (range 4–70 years). HPA is more frequent in pregnant women and in patients with previous
Figure 133.3 Hepatobiliary and pancreatic ascariasis. A 30-yearwoman presented to the emergency room with intractable pain RUQ. Duodenoscopy shows a large ascaride entering the ampullary orifice. A cholangiogram (not shown) showed the remaining part of the ascaride in the bile duct. Endoscopic extraction of the worm from the papilla caused immediate relief of biliary pain. (From Khuroo et al. Gastrointest Endosc. 1993;39, 680–685, Fig. 1.)
cholecystectomy, choledocholithotomy, sphincteroplasty, and endoscopic sphincterotomy in whom the widened ampullary orifice facilitates passage of worms into the bile ducts. HPA can cause five distinct clinical presentations, namely intractable biliary colic, acalculous cholecystitis, acute cholangitis, acute pancreatitis, and liver abscesses. Diagnosis of HPA can be made by ultrasonography and ERCP. Ultrasonography is a highly sensitive and specific method for detection of worms in the biliary tree. This noninvasive investigation can be used in patients with symptoms and repeated frequently to monitor movement of worms in the ducts. ERCP has an advantage as a diagnostic tool in that it permits identification of the worms in the duodenum and those across the papilla and also allows removal of worms from the ducts or the duodenum.
Hepatic Schistosomiasis Hepatic schistosomiasis is caused by Schistosoma mansoni, S. japonicum, S. intercalatum, and S. mekongi (see Chapter 122). Hepatic schistosomiasis is characterized by granuloma formation in the liver with hepatic fibrosis leading to portal hypertension and manifests as splenomegaly, esophageal varices, and portosystemic collateral shunts at other sites (Fig. 133.4). Variceal bleeding in hepatic schistosomiasis is better tolerated than variceal bleeding in posthepatitic or alcoholic cirrhosis and encephalopathy is not usually precipitated following bleed. Patients with hepatic schistosomiasis may be coinfected with HBV or HCV that may cause rapid deterioration of liver functions in such patients.64–66 Ultrasonography with Doppler is noninvasive, inexpensive, and a sensitive tool to stage the severity of disease and monitor the response to therapy. Liver biopsy is helpful in excluding other causes of liver disease. The presence of schistosome eggs in the biopsy is seen as often as positive findings on stool examination or rectal biopsy. Hepatic schistosomiasis is managed by antischistosomal chemotherapy and measures to treat portal hypertension and its complications and hepatic failure following standard guidelines. Drug therapy eradicates the infection, prevents progression of disease, and interrupts egg excretion and disease dissemination.
Liver Flukes: Fascioliasis Fascioliasis is caused by the liver fluke Fasciola hepatica (see Chapter 123). Mature flukes reside in the biliary tree and cause chronic obstructive biliary symptoms. Fascioliasis is endemic in parts of Europe and Latin America, North Africa, Asia, the Western Pacific, and some parts of the United States.67–71
Figure 133.4 Schistosomiasis. Microscopic examination of a mesenteric mass in a 40-year-old male who had a laparotomy for intestinal obstruction. A mesenteric mass with adhesions to the bowel loops was seen at surgery. Histology of the mass shows an adult worm of Schistosoma mansoni curled up in the mesenteric vein. Two eggs, oval in shape and with lateral spines (S. mansoni eggs), are nearby. (From Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, (eds). Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press; 2004:169, Fig. 4.)
Liver Flukes: Clonorchiasis and Opisthorchiasis The liver flukes include Clonorchis sinensis, Opisthorchis viverrini, and O. felineus (see Chapter 123). C. sinensis and O. viverrini are prevalent in East and Southeast Asia, and O. felineus is prevalent in eastern Europe.72–75 Clinical manifestations are caused by the presence of adult flukes in the bile duct, which release eggs that cause severe inflammation and fibrosis. Fever, RUQ pain, tender hepatomegaly, and eosinophilia are initial manifestations. Later chronic biliary obstruction can occur. Patients develop cholelithiasis, cholecystitis, and recurrent pyogenic cholangitis. Long-term infection leads to exuberant inflammation, marked biliary epithelial hyperplasia, and dysplasia, and a substantially increased risk of cholangiocarcinoma. Diagnosis is made by detection of characteristic fluke eggs in the stool except late in the disease. Cholangiography, percutaneously or at ERCP, reveals slender, uniform filling defects within intrahepatic ducts. Bile ducts reveal strictures, dilatation, and sacculation mimicking sclerosing cholangitis.
Hepatobiliary Tuberculosis Tuberculosis (see Chapter 35) is a disease of developing countries; however, its incidence is increasing in developed countries, mainly in immigrant populations and in patients with AIDS.3,76 Hepatobiliary tuberculosis is seen in a number of situations: 1. Incidental. Liver involvement is seen at autopsy in 25–50% of patients dying from active pulmonary tuberculosis. 2. Miliary tuberculosis, due to hematogenous spread of tubercle bacilli, causes multiple granulomas within the liver. 3. Granulomatous hepatitis. Patients present with unexplained fever, jaundice, hepatomegaly, elevated ALP, and abnormalities of other liver function tests. Imaging of the liver may be normal or reveal nonspecific abnormalities. Laparoscopy is useful and shows cheesy white irregular nodules on the liver surface. Biopsy from such lesions reveals caseating granulomas. Granulomatous hepatitis with multiple granulomas in the liver may also be seen following
vaccination with bacillus Calmette–Guérin, especially in persons with impaired immune response. 4. Nodular disease. In this entity single or multiple focal masses develop in the liver and are seen as low-density non-enhancing lesions with or without peripheral rim enhancement. Such appearances need to be differentiated from lymphoma, fungal infection, and metastasis. Diagnosis is confirmed by image-guided fine needle aspiration biopsy of the lesion. 5. Tuberculous liver abscess. Tuberculous abscesses in the liver are extremely rare. Clinical picture and imaging resembles pyogenic or amebic liver abscess. Culture of the aspirated material clinches the diagnosis by growth of tubercle bacilli. 6. Tubular disease. These patients present with obstructive jaundice due to involvement of bile ducts. Bile ducts may be involved by an enlarged tuberculous lymph node compressing the bile duct or diffuse involvement of the intrahepatic ducts by tubercle bacilli. ERCP reveals multiple intrahepatic biliary strictures, areas of dilatation, beading and ectasia, resembling sclerosing cholangitis or cholangiocarcinoma. Biliary stricture may occur at the hilar region or distal common bile duct with dilatation of the intrahepatic ducts.
Hepatobiliary Disease Chapter 133
Three clinical syndromes are recognized: acute or invasive, chronic latent, and chronic obstructive. The acute phase corresponds to migration of young flukes through the liver and is marked by fever, RUQ pain, urticaria, hepatomegaly, and eosinophilia. The latent phase corresponds to the settling of the flukes into the bile ducts and can last for months to years. The chronic obstructive phase is a consequence of intrahepatic and extrahepatic bile duct inflammation and hyperplasia evoked by the flukes. Recurrent biliary colic, cholangitis, cholelithiasis, and cholestasis may result. Liver tests reveal features of biliary obstruction. Long-term infection can lead to biliary cirrhosis and secondary sclerosing cholangitis. Diagnosis of acute infection can be done by serologic detection of antibodies. Chronic infection can be diagnosed by detection of eggs in feces, duodenal aspirate, or bile. Hepatic imaging by ultrasonography or CECT is useful to define biliary dilatation and secondary hepatic changes due to cholestasis. ERCP will demonstrate adult flukes in the biliary tree and can be used to extract the parasites from the ducts.
HIV Cholangiopathy A number of parasites can involve the biliary tree in patients with HIV infection and lead to a spectrum of clinical manifestations including HIV cholangiopathy and acute cholecystitis (see Chapter 139). Among these are included Cryptosporidium parvum (see Chapter 94), Microsporidia (see Chapter 102), Cyclospora cayetanensis (see Chapter 95), and Isospora belli (see Chapter 95). Most patients with cholangiopathy have severe immunosuppression, with CD4+ counts of <200/mm3. HIV cholangiopathy can also be caused by infection with cytomegalovirus (CMV) (see Chapter 56), Mycobacterium avium-intracellulare complex infection (see Chapter 35), and Candida albicans (see Chapter 88).4,77 Typical symptoms are RUQ pain, fever, and elevated serum ALP. Jaundice is uncommon. Diarrhea is common because many of the pathogens infect the small bowel as well. On physical examination RUQ or epigastric tenderness is characteristic. ERCP shows intrahepatic or extrahepatic changes of sclerosing cholangitis. Papillary stenosis is also common. Diagnosis and treatment of the etiologic infections are considered in the pathogen specific chapters. In addition, endoscopic management of biliary disease may be required. Endoscopic sphincterotomy is adequate in patients with papillary stenosis, while bile duct strictures may need dilation or stenting.
HEPATOBILIARY DISEASE CAUSED BY TROPICAL INFECTIONS AS A PART OF MULTIORGAN INVOLVEMENT Other systemic tropical diseases that can involve the hepatobiliary tree as a part of multiorgan involvement include malaria, typhoid, leptospirosis, strongyloidiasis, and invasive candidiasis.5,78,79 Table 133.1 briefly delineates the hepatobiliary disease caused by these agents.
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CHAPTER 133 Hepatobiliary Disease Mohammad S. Khuroo • Mehnaaz S. Khuroo
INTRODUCTION
DISEASES CAUSED BY HEPATITIS VIRUSES
A broad group of infections affect hepatobiliary organs in the tropical countries. These include infections prevalent in nontropical zones and those restricted to tropical zones of the world (Table 133.1). Amongst the hepatitis viruses, hepatitis E virus (HEV) has the most significant palpable impact.1 A number of nonviral infectious agents predominantly prevalent in tropical countries affect the liver and biliary tract as primary targets.2 Commonest amongst these are amebiasis, echinococcosis, schistosomiasis and hepatobiliary and pancreatic ascariasis (HBPA). Tuberculosis and the acquired immunodeficiency syndrome (AIDS) are endemic in tropics and can involve both the liver and/or biliary tree.3,4 Several viral and nonviral tropical infections such as malaria, typhoid, dengue fever, and leptospirosis may affect the heptobiliary system as a part of multiorgan involvement.5 Hepatobiliary infections prevalent in tropical countries have a special predilection and distinct pattern for expatriate Western travelers to such countries.6,7
Acute Sporadic Viral Hepatitis
DIAGNOSTIC CONSIDERATIONS Methodology to be followed for proper evaluation of hepatobiliary diseases in tropics is no different than that employed in nontropical countries.8 This includes a proper history, thorough physical examination, routine blood counts and serum chemistries including bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Abnormal liver tests can be classified into definite patterns: (1) hepatocellular (elevated bilirubin; elevated ALT/AST >500 IU; ALT>AST; normal to <3 times normal elevation of ALP); (2) cholestatic (elevated bilirubin, normal to <300 IU ALT/AST; >4 times normal elevation of ALP); (3) haemolytic/Gilbert’s syndrome (isolated elevation of unconjugated bilirubin rarely above 5 mg/dL); (4) synthetic liver failure (elevated bilirubin, modestly elevated ALT, AST, and ALP; low albumin, high globulins, and high prothrombin time); and (5) infiltrative (isolated >4 times normal elevation of ALP). Each pattern has different clinical connotations and defines corresponding further workup. Hepatobiliary ultrasound with Doppler is a valued complement to clinical examination for hepatobiliary diseases and is strongly recommended as a part of primary evaluation. Ultrasound with Doppler is useful for detecting gallstones, thickened gallbladder, dilated bile ducts, cysts and masses within the liver, periportal fibrosis, hepatosplenomegaly, and evidence of portal hypertension.9 Based on findings, further cost-effective, evidencebased laboratory tests, imaging tools such as computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or other invasive tests such as liver biopsy or guided fine needle aspiration biopsies may need to be employed.
Viral hepatitis (see Chapters 64–66) is highly endemic in tropical countries and is a cause of significant morbidity and mortality. Etiology of acute sporadic hepatitis in these countries is different than in the West. Around half of sporadic viral hepatitis in the tropics is related to HEV. Hepatitis B virus (HBV), hepatitis C virus (HCV), and non-A-E hepatitis constitute around 22%, 9%, and 25% of patients, respectively. Hepatitis A virus (HAV), a dominant cause of acute hepatitis in the West, is an uncommon (<4%) cause of hepatitis in adults in the tropics and is mostly encountered in children below 10 years of age.10–14 Acute viral hepatitis affects adults predominantly in the age group of 25–45 years. Male : female ratio is 1.4 : 1. Pregnant women especially in the third trimester are often infected with HEV and constitute around one-fourth of the females infected.15 The clinical profiles and serum chemistries are typical of acute viral hepatitis as seen in the West. However, around 20% of patients with HEV infection present with prolonged cholestasis. Abdominal ultrasound is usually unremarkable. However, it may show a hypoechoic liver with focal bright spots (starry sky appearance). The gallbladder often shows wall edema and pericholecystic fluid resembling features of acalculous cholecystitis.16 Recovery takes 4–6 weeks. Acute liver failure develops in around 8–10% of hospitalized patients. However, over 50% of pregnant women with HEV infections develop acute liver failure with high maternal and perinatal mortality.15 Patients with sporadic hepatitis need to be evaluated for acute markers of hepatitis viruses (IgM anti-HAV; HBsAg and IgM anti-HBc; anti-HCV; IgM anti-HEV), cytomegalovirus (CMV) and Epstein–Barr virus.17 Dengue fever, typhoid fever, malaria, and leptospirosis may cause abnormal liver tests of hepatocellular damage; however, these infections cause systemic manifestations and these should be carefully evaluated.4
Epidemic Hepatitis Epidemic hepatitis in tropical countries is exclusively caused by HEV.18–21 Epidemiological features of HEV infection have several peculiar characteristics, which remain unexplained. HEV presents as repeated large-scale waterborne epidemics of jaundice in highly endemic areas occurring every 10–20 years. HEV is a disease of adult populations, and during epidemics attack rates in adults are higher than in children. HEV has an increased incidence and severity in pregnant women, and the major cause of mortality in epidemics is the high rate of fulminant hepatitis in pregnant women.22–25 The clinical and biochemical presentations of HEV are similar to those of infection with other hepatitis viruses and encompass a wide variety of
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Disease
Agents
Endemic Areas
Manifestations
Diagnosis
Treatment
Acute markers (IgM anti-HEV; HBsAg and anti-HBc IgM; anti-HCV; IgM anti-HEV); Monospot test (CMV). Ultrasound to exclude EHBO IgM anti-HEV
Supportive care
Acute markers of HV; lab data to assess severity of liver failure and prognostic factors
Intensive care management; early consideration for liver transplant
Acute markers of HV
Supportive treatment
Serological markers and NAT for HBV and HCV
Consider antiviral therapy; supportive treatment for established cirrhosis
Evaluate serologic markers of HV; lab tests to assess severity of liver failure
Supportive treatment; antiviral therapy if indicated
Hepatic Disease Caused by Hepatitis Viruses Acute sporadic hepatitis
HEV (40%), HBV (22%), HCV (9%), non-A-E (25%), HAV (4%). Children often infected with HAV
Endemic in all developing countries
Adults involved; prolonged cholestasis in 20%; mortality 8–10% (high in pregnant women with HEV)
Epidemic hepatitis
HEV
All developing countries with unsafe water supplies and poor sanitation
Acute liver failure
HEV (37%), HBV (18%), HCV (5%), non-A-E (37%), HAV (3%). Antitubercular drugs small percentage
Endemic in all developing countries
Subacute hepatic failure
HEV, HBV
Indian subcontinent
Chronic hepatitis/ cirrhosis
HBV, HCV
All developing countries
Acute on chronic liver failure (AOCLF)
HEV superinfection on established HBV/HCV cirrhosis, reactivation HBV and HCV
Indian subcontinent
Repeated large-scale epidemics; adult disease; high incidence in pregnant women; mortality in pregnant women 20%; no chronic liver disease; vertical transmission with severe neonatal HEV Encephalopathy; cerebral edema; coagulopathy; multiorgan failure; GI bleed; death. ALF related to HEV in pregnant women – explosive disease with DIC; may represent a severe manifestation of a Schwartzman-like phenomenon Progressive jaundice, ascites, renal failure and SBP, terminal encephalopathy Asymptomatic; incidental abnormal liver tests; recurrent jaundice; established cirrhosis presents as signs of liver failure and portal hypertension Rapid decompensation of stable liver disease; presents as jaundice, ascites, renal failure, and GI bleed
PRACTICE: APPROACH TO THE PATIENT IN THE TROPICS
Table 133.1 Hepatobiliary Diseases Caused by Infectious Agents in Tropical Countries
Safe water and sewage disposal to control epidemics
Hepatobiliary Disorders Caused by Nonviral Infections Prevalent in the Tropics Escherichia coli, Klebsiella pneumoniae, enterococci, anaerobes Entamoeba histolytica Echinococcus granulosus
Worldwide
Insidious onset, fever, RUQ pain and tenderness
Ultrasound or CECT and aspiration
IV antibiotic plus image-guided drainage; surgery in select cases
Tropical and subtropical areas Sheep and cattle raising areas
Alveolar hepatic hydatid disease
Echinococcus multilocularis
Ultrasound or CECT plus serology Ultrasound or CECT plus serology; ERCP to define biliary disease Ultrasound or CECT plus serology; ERCP to define biliary disease
Metronidazole plus diloxanide furoate Surgery or PAIR and albendazole; therapeutic ERCP for biliary disease Long-term albendazole, resection, therapeutic ERCP
Polycystic hepatic hydatid disease
Echinococcus vogeli, E. oligarthrus
Germany, Austria, Switzerland, France, Turkey, Iran, Afghanistan, India (Kashmir), Canada, Japan Panama, Ecuador, Colombia, Venezuela, French Guiana
Acute onset, fever, RUQ pain and tenderness Incidental, mass lesion, infection, rupture into bile duct causes cholangitis and cholestasis Expanding hepatic mass, portal hypertension, liver failure, cholestasis due to bile duct disease
Expanding hepatic mass, portal hypertension, liver failure, cholestasis due to bile duct disease
Ultrasound or CECT plus serology; ERCP to define biliary disease
Long-term albendazole, resection, therapeutic ERCP
Pyogenic liver abscess
Amebic liver abscess Cystic hepatobiliary hydatid disease
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Agents
Endemic Areas
Manifestations
Diagnosis
Treatment
Hepatobiliary and pancreatic ascariasis
Ascaris lumbricoides
Developing countries
Biliary colic, cholangitis, cholecystitis, pancreatitis, liver abscess
Ultrasound and ERCP
Hepatic schistosomiasis
Schistosoma mansoni, S. japonicum, S. intercalatum, S. mekongi Fasciola hepatica
Asia, Africa, South America, Caribbean
Portal hypertension and variceal bleeding
Serology, hepatic imaging, ova in stool/rectal or liver biopsy
Anthelminthic therapy and worm extraction at ERCP Praziquantel therapy and treat portal hypertension
Cattle and sheep raising areas
Cholangitis, cholestasis
Eggs in feces/bile ERCP
Clonorchis sinensis, Opisthorcis viverrini, O. felineus Mycobacterium spp.
Southeast Asia
Cholangitis, cholestasis, cholangiocarcinoma
Ova in stool, ERCP
Developing countries
Fever, weight loss, hepatomegaly and elevated liver tests RUQ pain, fever, jaundice
Tuberculin skin test; serology for TB; liver biopsy Elevated ALP; ERCP papillitis and bile duct stricture; duodenal biopsy shows typical organisms
Antitubercular drugs
Look for parasites in blood film; lab tests to evaluate severity of liver disease
Antimalarial therapy; supportive treatment
Antimalarial antibodies; high IgM levels; liver biopsy: hepatic sinusoidal lymphocytosis (B cells) Blood, urine and stool culture; serology; lab tests to evaluate severity of liver disease Isolation of organism from blood or CSF; serologic tests (MAT or ELISA)
Long-term antimalarial therapy
Fascioliasis
Clonorchiasis/ opisthorchiasis
Hepatobiliary tuberculosis HIV cholangiopathy (in AIDS with CD4+ <200/ mm3)
Cryptosporidium parvum, Microsporidia, Cyclospora cayetanensis, Isospora belli; CMV
Worldwide
Triclabendazole/ bithionol, therapeutic ERCP Praziquantel therapy and therapeutic ERCP
Hepatobiliary Disease Chapter 133
Table 133.1 Hepatobiliary Diseases Caused by Infectious Agents in Tropical Countries—cont’d
Antibiotics; therapeutic ERCP
Hepatobiliary Involvement Caused by Tropical Diseases as a Manifestation of Multiorgan Disease Malarial hepatitis
Plasmodium spp.
Asia, Africa, South America
Tropical splenomegaly syndrome
Plasmodium spp.
Asia, Africa, South America
Typhoid hepatitis
Salmonella spp.
Indian subcontinent, South/Central America
Leptospirosis hepatitis
Leptospira spp.
Tropical countries (sewage workers)
Hyperinfection syndrome
Strongyloides stercoralis
Tropical and subtropical countries (high-risk AIDS and renal transplant)
Invasive candidiasis
Candida spp.
Worldwide (acute leukemia on immunosuppression)
Hepatitis occurs in 11–25% of infections; presents as jaundice, tender hepatomegaly, elevated liver tests, hepatic failure in severe P. falciparum Massive splenomegaly
Occurs in 1–26%; presents as jaundice, RUQ pain, elevated liver tests, rarely liver failure occurs, typhoid abscess may occur Hepatic involvement in second week; presents as RUQ pain, severe jaundice, elevated liver tests, rarely liver failure Jaundice and elevated liver tests
Chronic debilitating illness, RUQ pain, high fever, weight loss, hepatomegaly, elevated ALP
Stool for S. stercoralis larvae; liver biopsy shows eosinophilic granulomatous hepatitis with larvae in canaliculi Ultrasound/CECT hypoechoic hepatic masses; guided needle aspiration biopsy of lesions
Antibiotic therapy; supportive treatment
Antibiotic (penicillin, ampicillin, or erythromycin) therapy Ivermectin
Amphotericin or fluconazole
ALF, acute liver failure; ALP, alkaline phosphatase; CECT, contrast-enhanced computed tomography; CMV, cytomegalovirus; DIC, disseminated intravascular coagulation; EHBO, extrahepatic biliary obstruction; ERCP, endoscopic retrograde cholangiopancreatography; GI, gastrointestinal; HV, hepatitis virus; MAT, microscopic agglutination test; NAT, nucleic acid amplification testing; PAIR, puncture, aspiration or injection of a scolicidal agent and reaspiration; RUQ, right upper quadrant; SBP, spontaneous bacterial peritonitis.
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symptoms. Prolonged intrahepatic cholestasis lasting from 3 to 6 months occurs in about 20% of patients and simulates large bile duct obstruction. A small percentage of patients show a biphasic enzyme elevation; however, no chronic liver disease or chronic hepatitis is known to develop after HEV in immunocompetent hosts.
Acute Liver Failure Acute liver failure (ALF), a dramatic and challenging syndrome in clinical medicine,26,27 is characterized by rapid and progressive deterioration of liver function from massive hepatocellular necrosis or infiltration leading to encephalopathy and multiorgan failure. There is little information on the epidemiology of ALF in various regions of the world. Crude estimates suggest that ALF affects approximately 2000 individuals annually in the United States. In contrast, ALF caused by HEV infection is a substantial health problem in developing countries. Most ALF in the tropics is caused by hepatitis viruses.25,28,29 Amongst these, HEV is the cause of ALF in over 40% of patients. HBV and non-A-E constitute 17% and 33% of patients, respectively. HAV is an uncommon (<4%) cause of ALF in tropical countries. In comparison, HAV, HBV, and non-A-E cause 14%, 33%, and 53% of viral ALF in the United Kingdom. HEV is an uncommon cause of ALF in developed countries and is either seen in Western travelers to the Indian subcontinent or as a result of recently recognized zoonotic foodborne autochthonous HEV infections. Drugs, especially antitubercular drugs, cause <4% of ALF in developing countries, in contrast to developed countries where drugs, namely acetaminophen and anti-inflammatory drugs, constitute more substantial etiologies of ALF. A number of transplant centers from the West have defined prognostic criteria in ALF and these criteria can be applied to estimate the probability of spontaneous recovery in a given patient. While one model of prognostic indicators has been developed at King’s College Hospital, London,30 data from India have shown that these prognostic indicators may not be valid for other geographical regions, in view of differences in the etiologic causes, behavior, and clinical profiles of ALF.25,29 Early predictors of a poor outcome are non-HEV etiology, prothrombin time >30 seconds, grade of coma >2, and age >40 years.
Subacute Hepatic Failure Subacute hepatic failure is an entity reported from the Indian subcontinent.31,32 The hepatic failure shows a more protracted illness and is characterized by development of progressive jaundice, ascites, coagulopathy and renal failure during the course of acute hepatitis. Patients often develop spontaneous bacterial peritonitis and gastrointestinal bleeding. Encephalopathy is usually a preterminal event. Liver biopsy reveals extensive bridging, submassive necrosis, and cholestasis. HBV and HEV are the causes in most patients.
Acute on Chronic Liver Failure Acute on chronic liver failure (AOCLF) is a recently recognized entity wherein there is rapid hepatic decompensation once acute hepatic insult is superimposed on established stable chronic liver disease.36–38 Alcoholic cirrhosis constitutes 50–70% of the underlying liver diseases in AOCLF in Western countries, whereas in most of tropical countries HBV constitutes 70% and alcohol only about 15% of the etiologies of AOCLF. Autoimmune liver disease, Wilson’s disease, metabolic liver disease, and chronic cholestatic liver disease constitute only a minority of patients. Among the precipitating causes of AOCLF, HEV superinfection has remained a very important acute insult in the Indian subcontinent and is an important cause of mortality in patients with cirrhosis.38–40 Reactivation of HBV and HCV infections leading to hepatitis “flares” are the other major causes of AOCLF in the Asian region.41 In contrast to this, sepsis and variceal bleeding play important roles in the sudden decompensation of established chronic liver disease in the West.
DISEASES CAUSED BY TROPICAL NONVIRAL INFECTIOUS AGENTS Pyogenic Liver Abscess Pyogenic liver abscess is responsible for 8–20 cases per 100 000 hospital admissions. Pyogenic abscesses most often occur in patients over 40 years of age, with a peak incidence in the sixth decade. No significant gender, ethnic, or geographic differences exist for the development of pyogenic liver abscesses. About one-half of patients have a solitary abscess. Abscesses involve the right lobe in 75%, left lobe in 20%, and caudate lobe in 5% of cases. Suppurative cholangitis as a result of bile duct stones, benign and malignant biliary strictures, and endoscopic, radiologic, and operative biliary interventions are the major identifiable causes of pyogenic liver abscess in the West.42–47 In endemic areas, Ascaris lumbricoides (see Chapter 115) and Clonorchis sinensis (see Chapter 123) can invade the biliary tree, cause cholangitis, and commonly predispose to liver abscesses.2,45 Liver abscesses can be caused by Salmonella enterica serovar Typhi, Mycobacterium tuberculosis and Brucella spp. (Fig. 133.1). Most pyogenic liver abscesses are polymicrobial. The frequently isolated organisms include Escherichia coli, Klebsiella pneumoniae, Streptococcus viridans, Staphylococcus aureus, Enterococcus faecalis, Bacteroides spp., Fusobacterium spp., anaerobic streptococci, Actinomyces spp., and rarely Clostridia spp. In the past, patients typically presented with acute-onset abdominal pain (89%), high fever with rigors and chills (67%), and right upper
Chronic Hepatitis and Cirrhosis
978
Chronic active hepatitis in the tropics is caused most commonly by HBV and HCV (see Chapters 65 and 66).33,34 Coinfection with hepatitis delta virus (HDV) may accelerate the course of chronic HBV infection.35 While failure to resolve infection with these agents may lead to cirrhosis or hepatoma, persons with chronic hepatitis may remain asymptomatic for years, despite persistently elevated hepatic enzymes. Serologic testing and liver biopsy confirm the diagnosis. Macronodular or “postnecrotic” cirrhosis develops in up to 25% of chronic hepatitis B surface antigen carriers and in over 20% of persons infected with HCV for over 20 years. The process may be clinically silent for several years before the appearance of symptoms and signs of hepatocellular dysfunction and portal hypertension such as jaundice, encephalopathy, ascites, and bleeding from esophageal varices. The liver is firm, nodular, and shrunken.
Figure 133.1 Liver abscess caused by brucellosis in a 30-year-old woman who presented with fever, arthralgia, hepatomegaly, and elevated serum alkaline phosphatase. Contrast-enhanced CT scan image of liver shows hypodense mass in the left lobe with thick ring enhancement of the margins. (From Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, eds. Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press; 2004:158, Fig. 1B.)
Table 133.2 Differentiating Features of Pyogenic and Amebic Liver Abscesses Feature Distribution of disease Age of occurrence Sex distribution
Worldwide
Number Location
Often multiple (50%) Either lobe
Duration of illness Symptoms
Usually 1 month Low-grade fever, RUQ pain and tenderness Mild unless associated with biliary disease Positive (50–90%) Mass lesion with fluid component Negative Intravenous antibiotics plus drainage 16% Jaundice, low albumin, comorbid disease
Amebic Liver Abscess Amebic liver abscess is the most common extraintestinal manifestation of Entamoeba histolytica infection (see Chapter 92) and occurs in approximately 8.5% of such patients. The disease is endemic in many tropical regions namely Mexico, Central America, northern South America, West and South Africa, and India.48–53 Amebic liver abscess most often occurs in the age group 20–45 years. Most patients present with an acute illness, and duration of symptoms is usually <2 weeks. Clinical symptoms and signs include low-grade fever and chills, RUQ pain and tenderness, and hepatomegaly. Left lobe abscesses can present with toxemia; epigastric pain, tenderness, and guarding; and a large epigastric mass. Multiple liver abscesses usually present with high fever, toxemia, jaundice, and encephalopathy. Complications of amebic liver abscess include secondary bacterial infection, rupture, and compression of the bile ducts. Diagnosis is made on hepatic imaging and amebic serology. Ultrasound and CECT are useful in delineating and localizing the abscess as well as to monitor the response to treatment. Amebic serologic tests, (e.g., enzyme immunoassay) can have sensitivities of 99% and specificities >90% in patients with amebic liver abscess. Amebic liver abscess needs to be differentiated from pyogenic liver abscess in endemic areas, especially in view of the different treatment regimens employed in the two entities and different responses to therapy (Table 133.2). Metronidazole, 800 mg three times per day orally for 10 days, is curative in over 90% of patients with amebic liver abscess. Clinical improvement is usually seen within 3–5 days. After clinical cure, the abscess cavity disappears in 6–9 months. Alternative agents include secnidazole 500 mg orally three times per day, and tinidazole 600 mg orally twice per day for 7 days. A luminal amebicide, diloxanide furoate 500 mg three times per day for 10 days, is often used to eradicate intestinal carriage of the organism. Unlike pyogenic liver abscess, needle aspiration or abscess drainage offers no additional therapeutic benefit. Aspiration is indicated in patients with persistent symptoms after 5 days of medical therapy and in those with: (1) very large abscess, (2) abscess involving the left lobe, (3) abscess which shows signs of imminent rupture, and (4) abscess with secondary bacterial infection. Open surgical drainage is indicated when an abscess has ruptured into the peritoneum or adjacent viscera.
Hepatic Hydatid Disease Hydatid disease, echinococcosis, (see Chapter 120), is a zoonotic infection caused by larval forms (metacestodes) of the tapeworms of the genus Echinococcus and is characterized by development of expanding cysts in the liver and other body organs (Fig. 133.2).54–59 Within the genus Echinococcus, four principal causes of human disease are recognized. E. granulosus causes cystic hydatid disease, E. multilocularis causes alveolar hydatid disease, and E. vogeli and E. oligarthrus cause polycystic hydatid disease. The most clinically relevant form is cystic echinococcosis caused by E. granulosus. Uncomplicated liver cysts usually present with dull ache in the RUQ or a feeling of abdominal swelling or distension. A large cyst
Pyogenic Liver Abscess
Jaundice
Blood culture Hepatic imaging Amebic serology Treatment
Mortality High-risk groups
Above 40 years Equal
Amebic Liver Abscess Tropical and subtropical regions 20–45 years 3–10 times more in males than females Often single (80%) Often right lobe under dome of diaphragm Often 2 weeks Low-grade fever, RUQ pain and tenderness
Hepatobiliary Disease Chapter 133
quadrant (RUQ) tenderness (70%). Since the introduction of antibiotics, the presentation of pyogenic liver abscess has become less acute, often insidious and characterized by malaise, low-grade fever, and dull abdominal pain. Diagnostic imaging studies are essential in making the diagnosis of pyogenic liver abscess. Sonography is highly sensitive (94%) and is the imaging method of choice in patients with suspected biliary disease. Contrast-enhanced computed tomography (CECT) has high sensitivity (100%), and visualizes abscesses better because contrast enhancement highlights the unaffected liver. Treatment of pyogenic liver abscess requires antibiotic therapy and image-guided percutaneous drainage of the abscess. Such treatments are successful in 85–90% of patients. Surgical drainage is reserved in the following situations: (1) percutaneous drainage is unsuccessful, (2) there is coexisting intra-abdominal disease requiring surgery, and (3) abscess is complicated by rupture or extension into adjacent structures.
Moderate in large and multiple abscesses Negative Mass lesion with fluid component Positive Metronidazole plus diloxanide furoate 2–18% Multiple abscesses, left lobe abscess, high bilirubin, encephalopathy, low albumin
RUQ, right upper quadrant. (Reproduced with permission from Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, eds. Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press; 2004:161.)
Figure 133.2 Cystic hepatic echinococcosis. A 50-year-old man complained of RUQ discomfort of 6 months’ duration. An axial T1-weighted MR image shows a large rounded lesion occupying the whole right lobe of the liver. The lesion reveals multiple rounded low signal lesions (daughter cysts). The remainder of the contents reveal high intensity signal (matrix). (From Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, eds. Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press, 2004:163, Fig. 2.)
in the hilar region can compress the common hepatic duct causing cholestasis. Cyst rupture into the biliary tree causes obstruction of the ducts by daughter cysts and laminated membranes and presents as biliary colic, cholangitis, and progressive cholestasis. Serology and imaging tools can help establish the diagnosis (see Chapter 120). Serology detects specific serum antibodies or circulating
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antigen by a variety of immunodiagnostic methods. Positive test results need confirmation by the arc-5 immunoelectrophoretic (IEP) test, which detects antibodies against immunodominant and specific antigen (antigen 5) of the cestode. Liver cysts are well visualized by ultrasound. Cysts may appear univesicular, rounded with well-defined margins containing pure fluid or multivesicular (daughter cysts) with pure fluid collection in each vesicle. Cysts may have a hyperechoic solid pattern (pseudotumor appearance) or may have reflective walls suggestive of calcification. Rupture of liver cysts into the bile ducts can be suspected on ultrasound. Ultrasound appearances in such cases include dilated bile ducts, non-shadowing echogenic structures within the ducts, and loss of continuity of the cyst wall adjacent to the bile duct representing the site of communication. However, ERCP is the recommended tool and reveals filling defects of varying shape and size in the dilated bile ducts and leakage of contrast medium into the cyst cavity. Treatment options for cystic hydatid disease are surgery, drug therapy, and percutaneous drainage (see Chapter 120). Surgery has the potential to remove cysts and lead to complete cure. The surgical procedure of choice is cystectomy with removal of the germinal and laminated layers and preservation of pericyst. Operative mortality varies from 0.5% to 4.0% in centers with adequate medical and surgical facilities. Albendazole and praziquantel can be effective in small cysts (<4 cm diameter), in cysts with thin walls, and in younger patients. Alternatively, percutaneous treatment of hepatic hydatid cysts, known as PAIR (puncture, aspiration, installation of scolicidal agent, and respiration) has been efficacious. The procedure is minimally invasive, cost-effective, involves reduced hospital stay, and has less morbidity and mortality than surgery.
Hepatobiliary and Pancreatic Ascariasis Ascariasis is caused by the nematode Ascaris lumbricoides (see Chapter 115). Hepatobiliary and pancreatic ascariasis (HPA) is one of the most common complications caused by intestinal Ascaris infections. Ascarides in the duodenum can enter the ampullary orifice and block it; they can advance further to the bile duct and hepatic ducts (Fig. 133.3). While in the common duct, the cystic duct can be blocked by worms entering its orifice. Less often, worms can reach the gallbladder or enter the pancreatic duct.60–63 HPA is more common in women than men (female : male ratio of 3 : 1) with a mean age of occurrence being 35 years (range 4–70 years). HPA is more frequent in pregnant women and in patients with previous
Figure 133.3 Hepatobiliary and pancreatic ascariasis. A 30-yearwoman presented to the emergency room with intractable pain RUQ. Duodenoscopy shows a large ascaride entering the ampullary orifice. A cholangiogram (not shown) showed the remaining part of the ascaride in the bile duct. Endoscopic extraction of the worm from the papilla caused immediate relief of biliary pain. (From Khuroo et al. Gastrointest Endosc. 1993;39, 680–685, Fig. 1.)
cholecystectomy, choledocholithotomy, sphincteroplasty, and endoscopic sphincterotomy in whom the widened ampullary orifice facilitates passage of worms into the bile ducts. HPA can cause five distinct clinical presentations, namely intractable biliary colic, acalculous cholecystitis, acute cholangitis, acute pancreatitis, and liver abscesses. Diagnosis of HPA can be made by ultrasonography and ERCP. Ultrasonography is a highly sensitive and specific method for detection of worms in the biliary tree. This noninvasive investigation can be used in patients with symptoms and repeated frequently to monitor movement of worms in the ducts. ERCP has an advantage as a diagnostic tool in that it permits identification of the worms in the duodenum and those across the papilla and also allows removal of worms from the ducts or the duodenum.
Hepatic Schistosomiasis Hepatic schistosomiasis is caused by Schistosoma mansoni, S. japonicum, S. intercalatum, and S. mekongi (see Chapter 122). Hepatic schistosomiasis is characterized by granuloma formation in the liver with hepatic fibrosis leading to portal hypertension and manifests as splenomegaly, esophageal varices, and portosystemic collateral shunts at other sites (Fig. 133.4). Variceal bleeding in hepatic schistosomiasis is better tolerated than variceal bleeding in posthepatitic or alcoholic cirrhosis and encephalopathy is not usually precipitated following bleed. Patients with hepatic schistosomiasis may be coinfected with HBV or HCV that may cause rapid deterioration of liver functions in such patients.64–66 Ultrasonography with Doppler is noninvasive, inexpensive, and a sensitive tool to stage the severity of disease and monitor the response to therapy. Liver biopsy is helpful in excluding other causes of liver disease. The presence of schistosome eggs in the biopsy is seen as often as positive findings on stool examination or rectal biopsy. Hepatic schistosomiasis is managed by antischistosomal chemotherapy and measures to treat portal hypertension and its complications and hepatic failure following standard guidelines. Drug therapy eradicates the infection, prevents progression of disease, and interrupts egg excretion and disease dissemination.
Liver Flukes: Fascioliasis Fascioliasis is caused by the liver fluke Fasciola hepatica (see Chapter 123). Mature flukes reside in the biliary tree and cause chronic obstructive biliary symptoms. Fascioliasis is endemic in parts of Europe and Latin America, North Africa, Asia, the Western Pacific, and some parts of the United States.67–71
Figure 133.4 Schistosomiasis. Microscopic examination of a mesenteric mass in a 40-year-old male who had a laparotomy for intestinal obstruction. A mesenteric mass with adhesions to the bowel loops was seen at surgery. Histology of the mass shows an adult worm of Schistosoma mansoni curled up in the mesenteric vein. Two eggs, oval in shape and with lateral spines (S. mansoni eggs), are nearby. (From Khuroo MS, Khuroo NS. Non-viral infections of the liver. In: Al Knawy B, Schiffman ML, Wiesner RH, (eds). Hepatology: A Practical Approach. Amsterdam: Elsevier BV Academic Press; 2004:169, Fig. 4.)
Liver Flukes: Clonorchiasis and Opisthorchiasis The liver flukes include Clonorchis sinensis, Opisthorchis viverrini, and O. felineus (see Chapter 123). C. sinensis and O. viverrini are prevalent in East and Southeast Asia, and O. felineus is prevalent in eastern Europe.72–75 Clinical manifestations are caused by the presence of adult flukes in the bile duct, which release eggs that cause severe inflammation and fibrosis. Fever, RUQ pain, tender hepatomegaly, and eosinophilia are initial manifestations. Later chronic biliary obstruction can occur. Patients develop cholelithiasis, cholecystitis, and recurrent pyogenic cholangitis. Long-term infection leads to exuberant inflammation, marked biliary epithelial hyperplasia, and dysplasia, and a substantially increased risk of cholangiocarcinoma. Diagnosis is made by detection of characteristic fluke eggs in the stool except late in the disease. Cholangiography, percutaneously or at ERCP, reveals slender, uniform filling defects within intrahepatic ducts. Bile ducts reveal strictures, dilatation, and sacculation mimicking sclerosing cholangitis.
Hepatobiliary Tuberculosis Tuberculosis (see Chapter 35) is a disease of developing countries; however, its incidence is increasing in developed countries, mainly in immigrant populations and in patients with AIDS.3,76 Hepatobiliary tuberculosis is seen in a number of situations: 1. Incidental. Liver involvement is seen at autopsy in 25–50% of patients dying from active pulmonary tuberculosis. 2. Miliary tuberculosis, due to hematogenous spread of tubercle bacilli, causes multiple granulomas within the liver. 3. Granulomatous hepatitis. Patients present with unexplained fever, jaundice, hepatomegaly, elevated ALP, and abnormalities of other liver function tests. Imaging of the liver may be normal or reveal nonspecific abnormalities. Laparoscopy is useful and shows cheesy white irregular nodules on the liver surface. Biopsy from such lesions reveals caseating granulomas. Granulomatous hepatitis with multiple granulomas in the liver may also be seen following
vaccination with bacillus Calmette–Guérin, especially in persons with impaired immune response. 4. Nodular disease. In this entity single or multiple focal masses develop in the liver and are seen as low-density non-enhancing lesions with or without peripheral rim enhancement. Such appearances need to be differentiated from lymphoma, fungal infection, and metastasis. Diagnosis is confirmed by image-guided fine needle aspiration biopsy of the lesion. 5. Tuberculous liver abscess. Tuberculous abscesses in the liver are extremely rare. Clinical picture and imaging resembles pyogenic or amebic liver abscess. Culture of the aspirated material clinches the diagnosis by growth of tubercle bacilli. 6. Tubular disease. These patients present with obstructive jaundice due to involvement of bile ducts. Bile ducts may be involved by an enlarged tuberculous lymph node compressing the bile duct or diffuse involvement of the intrahepatic ducts by tubercle bacilli. ERCP reveals multiple intrahepatic biliary strictures, areas of dilatation, beading and ectasia, resembling sclerosing cholangitis or cholangiocarcinoma. Biliary stricture may occur at the hilar region or distal common bile duct with dilatation of the intrahepatic ducts.
Hepatobiliary Disease Chapter 133
Three clinical syndromes are recognized: acute or invasive, chronic latent, and chronic obstructive. The acute phase corresponds to migration of young flukes through the liver and is marked by fever, RUQ pain, urticaria, hepatomegaly, and eosinophilia. The latent phase corresponds to the settling of the flukes into the bile ducts and can last for months to years. The chronic obstructive phase is a consequence of intrahepatic and extrahepatic bile duct inflammation and hyperplasia evoked by the flukes. Recurrent biliary colic, cholangitis, cholelithiasis, and cholestasis may result. Liver tests reveal features of biliary obstruction. Long-term infection can lead to biliary cirrhosis and secondary sclerosing cholangitis. Diagnosis of acute infection can be done by serologic detection of antibodies. Chronic infection can be diagnosed by detection of eggs in feces, duodenal aspirate, or bile. Hepatic imaging by ultrasonography or CECT is useful to define biliary dilatation and secondary hepatic changes due to cholestasis. ERCP will demonstrate adult flukes in the biliary tree and can be used to extract the parasites from the ducts.
HIV Cholangiopathy A number of parasites can involve the biliary tree in patients with HIV infection and lead to a spectrum of clinical manifestations including HIV cholangiopathy and acute cholecystitis (see Chapter 139). Among these are included Cryptosporidium parvum (see Chapter 94), Microsporidia (see Chapter 102), Cyclospora cayetanensis (see Chapter 95), and Isospora belli (see Chapter 95). Most patients with cholangiopathy have severe immunosuppression, with CD4+ counts of <200/mm3. HIV cholangiopathy can also be caused by infection with cytomegalovirus (CMV) (see Chapter 56), Mycobacterium avium-intracellulare complex infection (see Chapter 35), and Candida albicans (see Chapter 88).4,77 Typical symptoms are RUQ pain, fever, and elevated serum ALP. Jaundice is uncommon. Diarrhea is common because many of the pathogens infect the small bowel as well. On physical examination RUQ or epigastric tenderness is characteristic. ERCP shows intrahepatic or extrahepatic changes of sclerosing cholangitis. Papillary stenosis is also common. Diagnosis and treatment of the etiologic infections are considered in the pathogen specific chapters. In addition, endoscopic management of biliary disease may be required. Endoscopic sphincterotomy is adequate in patients with papillary stenosis, while bile duct strictures may need dilation or stenting.
HEPATOBILIARY DISEASE CAUSED BY TROPICAL INFECTIONS AS A PART OF MULTIORGAN INVOLVEMENT Other systemic tropical diseases that can involve the hepatobiliary tree as a part of multiorgan involvement include malaria, typhoid, leptospirosis, strongyloidiasis, and invasive candidiasis.5,78,79 Table 133.1 briefly delineates the hepatobiliary disease caused by these agents.
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