Intrahepatic Obstructive Jaundice Due to Amyloidosis of the Liver

Intrahepatic Obstructive Jaundice Due to Amyloidosis of the Liver

Vol. 61, No.2 GASTROENTEROLOGY Printed in U.S.A. Copyright@ 1971 by The Williams & Wilkins Co. CASE REPORTS INTRAHEPATIC OBSTRUCTIVE JAUNDICE DUE...

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Vol. 61, No.2

GASTROENTEROLOGY

Printed in U.S.A.

Copyright@ 1971 by The Williams & Wilkins Co.

CASE REPORTS

INTRAHEPATIC OBSTRUCTIVE JAUNDICE DUE TO AMYLOIDOSIS OF THE LIVER A case report and review of the literature M. LEvY, M.D., C. H.

F'RYD,

M.D.,

AND

M.

ELIAKIM,

M .D.

Department of Medicine A, Hadassah University Hospital, Jerusalem, and the Department of Medicine B, Donolo Hospital, Tel Aviv, Israel

The prevalence of jaundice in amyloidosis of the liver is about 5%. When present, it is usually mild. The occurrence of severe intrahepatic obstructive jaundice in a 57-year-old patient with primary amyloidosis is reported. Pruritus, loss of weight, acholic stool, abdominal pain, hepatomegaly, ascites, and gastrointestinal bleeding were the main clinical manifestations. Serum bilirubin reached 40.0 mg per 100 ml, the alkaline phosphatase and cholesterol levels were elevated, while serum glutamic pyruvic transaminase and the flocculation tests were normal. Cardiac and renal involvement were also present. A review of the literature indicates that, although rarely, amyloidosis of the liver may cause intrahepatic biliary obstruction and thereby present a difficult diagnostic problem. Hepatic involvement is common in all forms of amyloidosis. 1- 5 Jaundice is nevertheless rare, and when present, is usually mild. 2 • 3 • 5 - 8 The prevalence of jaundice in a total of 490 cases of amyloidosis of the liver was 4. 7%. In most jaundiced patients the serum bilirubin level did not exceed 5.0 mg per 100 ml. We have recently observed a patient with primary amyloidosis complicated by severe obstructive jaundice. A review of the literature revealed 4 additional patients

who exhibited distinct features of intrahepatic biliary obstruction. 9 - 12 Some of these cases presented difficult differential diagnostic problems. This report gives an account of our case and a review of the other reported cases.

Case Report S. Y., a Sephardic Jew, aged 57, born in Jerusalem. He was deaf-mute from childhood but was otherwise healthy until 8 months before death. The family history was irrelevant. Two of his sisters and 2 of his sons were examined; none had abnormal physical findings and all had normal liver function tests. Mild lymphadenopathy in the cervical and axillary regions was detected in the patient in March 1969. Two months later the glands decreased in size without treatment. In May 1969, he began to suffer from pain in the epigastrium and right hypochondrium, anorexia, nausea, and occasional vomiting of bloody gastric contents. By August 1969, when the patient was hospitalized in the Donolo Hospital, he had

Received October 30, 1970. Accepted March 4, 1971.

Address requests for reprints to: Dr. M. Levy, Department of Medicine A, Hadassah University Hospital, P. 0 . Box 499, Jerusalem, Israel. The advice of Dr. N. Rosen from the Pathological Institute of the Donolo Hospital, Professor I. Levji and Professor H. Ungar from the Department of Pathology at the Hadassah University Hospital in the interpretation of the biopsy and postmortem findings is gratefully acknowledged. 234

August 1971

CASE REPORTS

lost 15 kg in body weight and his liver was palpable 6 em below the costal margin. The spleen was not palpable. Urinalysis revealed a few red blood cells per high power field but no protein. The erythrocyte sedimentation rate was 68/108 mm (Westergren). Hemoglobin was 12 g per 100 ml and white blood count 12,000 per mm a. The serum bilirubin level, normal on admission, rose gradually to 12.0 mg per 100 ml (8.2 mg per 100 ml conjugated) within 3 weeks. The alkaline phosphatase level was 18 (BessyLawry units, total cholesterol 300 to 395 mg per 100 ml, serum glutamic oxaloacetic transaminase (SGOT) 60 to 135 U, prothrombin time 28 to 65 % of normal. Thymol turbidity and cephalin flocculation were normal. Complement fixation for echinococcosis was negative. The electrocardiogram showed inverted T waves in L 3 and aVF. An oral cholangiogram showed poor visualization of the biliary passages. A liver scan showed diffusely scattered filling defects. The appearance of jaundice was accompanied by severe itching. With a presumptive diagnosis of cholangiolitic hepatitis, the patient received a short course of prednisone and cholestyramine as well as one injection of chlorpromazine, 25 mg intramuscularly. Within the next 3 weeks, the itching decreased and the serum bilirubin fell to 4.8 mg per 100 mi. A

235

percutaneous liver biopsy performed at this stage revealed extensive amyloidosis. Swelling of the legs, ascites, and severe itching appeared again in September 1969. In October 1969, proteinuria was detected and the blood urea was 68 mg per 100 mi. The serum bilirubin was 15.0 mg per 100 ml (8.9 mg per 100 ml conjugated) , the alkaline phosphatase 8.8 Bessy-Lowry units, cholesterol 480 mg per 100 ml, and SGOT 105 units. The pain in the upper abdominal region increased and "coffee ground" vomiting and melena appeared on several occasions. The patient was then hospitalized in the Hadassah Hospital. He was deeply jaundiced, the liver was palpable 6 em below the costal margin and was very firm. The spleen was not palpable but ascites was present. The urine contained 1 to 2 g of protein in 24 hr and numerous red blood cells. Hemoglobin was 14.5 g per 100 ml (following blood transfusions), white blood count 15,000 to 23,000 per mm a. Blood urea was 125 mg per 100 ml, total protein 6.7 g per 100 mi. Electrophoresis revealed 37.2% albumin, 3.9% a 1-globulin, 16.6% a 2-globulin, 13.4% ,8-globulin, and 28.8 % ')'-globulin. A paraprotein identified on immunoelectrophoresis as IgG was present in the 'Y region. Serum bilirubin rose from 15.8 to 40.0 mg per 100 ml within 3 weeks. More !han 50% of the bilirubin

FIG. 1. Liver section showing extensive amyloid deposits between liver cells causing pressure atrophy of the cell trabeculae. Note marked fibrosis in large portal space and absence of large bile duct. Two small ducts are seen on the right side of the portal space (H & E, X 60) .

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CASE REPORTS

Vol . 61, No.2

,

.'.:\.':. r\ ·;; ' .

~':

---.,:'.,' .\t

FIG. 2. Liver section showing large masses of amyloid between liver cells and sinusoids as well as a large bile thrombus in canaliculi of atrophic liver cords.

was conjugated. The alkaline phosphatase was 22.4 Bessy-Lowry units, and the total serum cholesterol 377 mg per 100 ml. Serum glutamic pyruvic transaminase was 27 U, prothrombin time 43 % of normal, and the flocculation tests were normal. A gastrointestinal X-ray series revealed no abnormal findings. During this hospitalization the stool was acholic with occasional melena. The ascitic fluid contained 1.5 g per 100 ml of protein and no cancer cells. Signs of pleural effusion appeared and the jaundice deepened steadily. The blood urea rose to 242 mg per 100 ml and the patient died on the 21st day of hospitalization. Postmortem examination revealed amyloidosis of the liver, spleen, gastrointestinal tract, pancreas, adrenal glands, kidneys, heart, and abdominal lymph nodes. The liver weighed 3100 g and bile stasis was obvious on macroscopic examination. The gallbladder, the bile ducts, and the portal vein were normal. Microscopically, heavy amyloid deposits causing pressure atrophy of the cell trabeculae, bile stasis, and liver cell necrosis were seen (fig. 1). There were no inflammatory changes. The portal spaces showed extensive fibrosis and a remarkable paucity of bile ducts which were not seen at all in many spaces and were conspicuously small in others (fig. 2). The spleen weighed

405 g and was virtually replaced by amyloid. The pancreas weighed 580 g but no neoplastic process was found . The kidneys were greenish and showed glomerular and arteriolar amyloidosis. Areas of chronic pyelonephritis were also found. Amyloid was present in some of the abdominal blood vessels and small mucosal hemorrhages were seen throughout the whole gastrointestinal tract. Bilateral basal atelectasis, emphysema of the left pleural cavity, and an abscess in the left lower lung lobe (caused by Nocardia asteroides) were additional findings.

Discussion The appearance in this patient of severe jaundice accompanied by pruritus, acholic stool, elevated alkaline phosphatase and cholesterol levels, normal or slightly elevated transaminase activity, and negative flocculation tests raised the possibility of extrahepatic biliary obstruction by a stone in the common duct or by a pancreatic tumor. This suspicion was further substantiated by the alleged rarity of jaundice in amyloidosis of the liver and by the fact that amyloidosis may be secondary to malig-

August 1971

237

CASE REPORTS

nancy. 13 Postmortem examination revealed that the sole cause of the jaundice was amyloid deposition in the liver which strangled the hepatic cells, encased the bile ducts, and caused severe bile stasis. The pancreas, although enlarged, did not compress the common duct. A search in the literature revealed 4 additional cases with intrahepatic biliary obstruction due to amyloidosis of the liver. 9- 12 A summary of the clinical and laboratory features of these cases is given in table 1. All patients had primary amyloidosis and were male. They suffered characteristically from weight loss and abdominal pain. Hepatosplenomegaly was found in all cases. The frequent finding of splenomegaly in jaundiced patients is remarkable in view of the fact that it is relatively rare (13.6%) in unselected patients with primary amyloidosis. 5 Renal and/or cardiac involvement was present in all cases. Ascites and gastrointestinal bleeding were found in at least 4 of the 5

cases, although the prevalence of ascites has been reported as 20% in primary amyloidosis 14 and that of gastrointestinal bleeding as 3% 5 and 45% 15 in two large series. It is worth noting that stigmata of chronic liver disease like spider angiomata, clubbing, gynecomastia, etc., were absent. All 5 cases exhibited clinical and laboratory features of biliary obstruction such as pruritus, acholic stools (sometimes masked by gastrointestinal bleeding), high serum bilirubin, alkaline phosphatase and cholesterol levels, and normal flocculation tests. It must be noted, however, that changes in serum cholesterol and protein levels may be partly due to the nephrotic syndrome present in almost all cases. Three of these 5 cases underwent surgery and our own patient was, at one stage, hospitalized in the surgical department because of suspected extrahepatic biliary obstruction. The pathogenesis of the jaundice in amyloidosis is not clear since many cases

1. Clinical and laboratory features of 5 cases of primary amyloidosis with marked jaundice

TABLE

Cas en 1'

.. . . . ... . ... . . . .. Age . . . . . . . . .. . . . . . . . .. ... Sex ... . . . . . . . . . . . . . . . . Weight loss Abdominal pain . . . . . . . . . . . . . . .. .. . . . .. . Hepatomegaly . . . . . . . . . . . .. . ... .. . . . . . . . . . . . . .. .. Splenomegaly . . . . . . . . . .. . . Heart involvement . Kidney involvement . . . . . ... . . . . . . . Duration of jaundice . . . . .. Pruritus . . . .... . . . . ... . . ... . Acholic stool ... . . . . . . . . Ascites Gastrointestinal bleeding . . . . . . . . . . . . . . . Operated . . . . . ... . . Bilirubin (mg per 100 ml) . . . . . . . . . . . . . . . Alkaline phosphatase (units)" ....... Total cholesterol (m g per 100 ml) . . . . . .. . . ... . . Thymol turbidity Cephalin fl occulation . . . . . . . . . . . . . . . . . . . . ... .... .. . . . . . . SGPT (units) Liver size (g) ... .... ... . . . . •













0







••••



















0





••



44 Male + + + + + 1 week + + +· + 9.4

2"

44 Male + + + + + + 1 year + + + + 16. 3 36.6 (B) 512

3"

46 Male + + + + + + 2 years + +

4"

62 Male + + + + 3 months + +

+ 33< 220 (KA) 417

+ 15.6 414 (KA) 847 Norm al

Normal 2200

5900

3190

2200

a The superior figures are references. +. present; -,absent; blank spaces, not mentioned. • Intestinal vessels involved. c Icterus index. " B, Bodansky units; KA, King-Armstron g units; BL, Bessy-Lowry units.

Present case

57 Male + + + + + + 3 months + + + + 40 .0 22.4 (BL) 480 Normal Normal 27 3100

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CASE REPORTS

with heavy amyloid deposits have normal bilirubin levels. However, biliary obstruction is indicated by the finding of elevated alkaline phosphatase levels in about 60% of the cases, even in the absence of jaundice.'· 6 • 16 Several authors 8 • 10 have suggested a numerical insufficiency of liver cells and blockage of bile canaliculi as causes of jaundice. Obliteration of bile ducts in the portal areas, a striking feature in our case, may be a important factor in the pathogenesis of intrahepatic biliary obstruction. A rapid downhill course with deepening of the jaundice ensued in our patient following the onset of gastrointestinal bleeding. As seen from table 1 bleeding was present in at least 3 of the 5 jaundiced cases. It is probable that ischemia of the liver secondary to blood loss is an additional factor in the genesis of the jaundice. The possible role of extrahepatic factors in the pathogenesis of jaundice is further indicated by the fact that in 3 of the cases included in table 1, jaundice first appeared, or deepened, after an exploratory laparotomy. REFERENCES 1. Levine RA: Amyloid disease of the liver. Amer J Med 33:349-357, 1962 2. Briggs GW: Amyloidosis. Ann Intern Med 55: 943-957, 1961 3. Dahling DC: Secondary amyloidosis. Ann Intern Med 31:105-119, 1949 4. Kleckner MS Jr, Magidson J: Amyloidosis of the liver. Correlation of clinical and pathologic features. Gastroenterology 29:56-63, 1955

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5. Rukavina JC, Block, WD, Jackson CE, et a!: Primary systemic amyloidosis: a review and an experimental, genetic, and clinical study of 29 cases with particular emphasis on the familial form. Medicine (Bait) 35:239-334, 1956 6. Stauffer MH, Gross JB, Foulk WT, et a!: Amyloidosis: Diagnosis with needle biopsy of liver in 18 patients. Gastroenterology 41:92-96, 1961 7. Tiber AM, Perlman AW, Cohen SE: Hepatic function in patients with amyloidosis. Arch Intern Med (Chicago) 68:309-324, 1941 8. Spain DM, Riley RL: Jaundice in amyloidosis of the liver. Amer J Clin Path 14:284-288, 1944 9. Bannick EG, Berkman JM, Beaver DC: Diffuse amyloidosis: three unusual cases: a clinical and pathologic study. Arch Intern Med (Chicago) 51 : 978-990, 1933 10. Orloff J, Felder L : Primary systemic amyloidosis: Jaundice as a rare accompaniment. Amer J Med Sci 212:275-279, 1946 11. Atkinson AJ : Clinical pathological conference. Gastroenterology 7:477-482, 1946 12. Barth WF, Willerson JT, Waldmann TA, et a!: Primary amyloidosis. Amer J Med 47:259-273, 1969 13. Kimball KG: Amyloidosis in association with neoplastic diseases. Ann Intern Med 55:958-974, 1961 14. Gregg JA, Herskovic T, Bartholomew LG: Ascites in systemic amyloidosis. Arch Intern Med (Chicago) 116:605-610, 1965 15. Brandt K, Cathcart ES, Cohen AS : A clinical analysis of the course and prognosis of forty-two patients with amyloidosis. Amer J Med 44:955969, 1968 16. Bero GL: Amyloidosis: Its clinical and pathologic manifestations with a report of 12 cases. Ann Intern Med 46:931-955, 1957