Fulminant hepatic failure as the presenting form of type 1 autoimmune hepatitis in the elderly

AJG – May, 2002

Letters to the Editor

Department of Tropical Medicine National Liver Institute Menoufeya, Egypt

REFERENCES 1. Pession F, Ramond MJ, Njapoum C, et al. Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology 2001;34:121–5. 2. Yu MW, Hsu FC, Sheen I-S, et al. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carrier. Am J Epidemiol 1997;145: 1039 – 47. 3. Klatisky AL, Armstrong MA. Alcohol, smoking, coffee and cirrhosis. Am J Epidemiol 1992;136:1248 –57. 4. Mori M, Hara M, Wada I, et al. Prospective study of hepatitis B and C viral infection, cigarette smoking, alcohol consumption and other factors associated with hepatocellular carcinoma risk in Japan. Am J Epidemiol 2000;151:131–9. 5. Ayanian JZ, Cleary PD. Perceived risks of heart disease and cancer among cigarette smokers. JAMA 1999;281:1019 –21. 6. McAloon EJ, Streiff RR, Kitchens CS. Erythrocytosis associated with carboxyhemoglobinemia in smokers. South Med J 1980;73:137–9. 7. Murray JF. Classification of polycythemic disorders with comments on the diagnostic value of arterial oxygen analysis. Ann Intern Med 1966;64:892. 8. Balcerzek SP, Bromberg PA. Secondary polycythemia. Semin Hematol 1975;12:339 –51. 9. Finch CA, Lenfant C. Oxygen transport in man. N Engl J Med 1972;286:407. 10. Smith JR, Landaw SA. Smokers’ polycythemia. N Engl J Med 1978;298:6 –10. 11. Sagon AL Jr, Balcerzak SP. Absolute erythrocytosis as a result of smoking. Clin Res 1973;21:566. 12. Bacon BR, Britton RS. The pathology of hepatic iron overload: A free radical-mediated process? Hepatology 1990; 11:127. 13. Nakanishi N, Youshida H, Nakamura K, et al. Predictors for development of hyperuricemia: An 8-years longitudinal study in middle aged Japanese men. Metabolism 2001;50:621– 6. 14. Yildiz D, Ercal N, Armstrong DW. Nicotine enantiomers and oxidative stress. Toxicology 1998;130:155– 65. 15. Weitberg A, Corvese D. Oxygen radicals potentiate the genetic toxicity of tobacco-specific nitrosamines. Clin Genet 1993;43:88 –91. 16. St Clair DK, Jordan JA, Wan XS, Gairola CG. Protective role of manganese superoxide dismutase against cigarette smokeinduced cytotoxiocity. J Toxicol Environ Health 1994;43: 239 – 49. 17. Miro O, Alonso JR, Jarreta D, et al. Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes. Carcinogenesis 1999;20:1331– 6. 18. Liu CS, Wei Y-H. Age-associated alteration of blood thiolgroup-related antioxidants in smokers. Environ Res 1999;80: 18 –24. 19. Heitzer T, Just H, Mu¨ nzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 1996; 94:6 –9. 20. Lee H-C, Lim MLR, Lu C-Y, et al. Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging—smoking enhances oxidative stress on the aged tissues. Arch Biochem Biophys 1999;362:309 –16.

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21. Balansky R, Izzoti A, Scatolini L, et al. Induction by carcinogens and chemoprevention by N-acetylcysteine of adducts to mitochondrial DNA in rat organs. Cancer Res 1996;56: 1642–7. Reprint requests and correspondence: Abdel-Rahman ElZayadi, M.D., Cairo Liver Center, 5, El Gergawy Street, DokkiGiza, Cairo, Egypt. Received Nov. 21, 2001; accepted Dec. 3, 2001.

Fulminant Hepatic Failure as the Presenting Form of Type 1 Autoimmune Hepatitis in the Elderly TO THE EDITOR: Autoimmune hepatitis (AIH) type 1 usually progresses insidiously, and in many cases, cirrhosis is already established when diagnosis is made, at the first presentation of symptoms. There are three different subtypes of AIH, with type 1 characterized by the presence of smooth muscle antibodies and antinuclear antibodies (1). We report a case of acute liver failure in an 80-yr-old woman due to AIH type 1—to our knowledge, the first described case of this condition in such an advanced age. Fulminant hepatic failure has been previously described in postpubertal female patients as an unusual form of presentation of AIH type 1. It has been related to estrogen, and the patients reported on seldom responded to immunosuppressive therapy (1–3). An 80-yr-old white female, with a history of hypertension treated with atenolol and appendectomy and typhoid fever 40 yr before, was referred to our hospital for vomiting, jaundice, asthenia, and anorexia that developed 2 wk before. She did not refer to any blood transfusions, previous episodes of jaundice, alcohol or drug consumption, or risky sexual habits. She had a blood test extracted 1 yr before that showed no significant abnormalities in liver enzymes or coagulation figures. A physical examination found her deeply jaundiced, and neurologically she was normal, without flapping tremor. Hepatomegaly of 3 cm of the left lobe was evident, and an abdominal exam did not reveal ascites, splenomegaly, or masses. She did not say she was in abdominal pain, and no peritoneal signs were found. The results of the blood test were as follows: Hb, 12.6; white blood cell count, 6,810/mm3; platelets, 210,000/mm3; total bilirubin, 17.1 mg/dl; direct bilirubin, 8.5 mg/dl; prothrombin activity, 41%; international normalized ratio, 2.3; factor V, 37%; AST, 1215 U/L; ALT, 890 U/L; ALP, 81 U/L; ␥-glutamyltransferase, 110 U/L; total protein, 5.9 g/dl; albumin, 2.3 g/dl; and ␥-globulin, 2.08 g/dl. Abdominal Doppler ultrasound study showed a discrete hepatomegaly with a normal liver ecogenicity, a minimal quantity of ascitic fluid, and a cholelitiasis; there were no signs of portal hypertension or chronic liver disease. With the clinical diagnosis of acute liver failure the patient was admitted to our unit. The clinical course led quickly into a multiorganic

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failure, and our patient developed encephalopathy and a progressive impairment of coagulation, dying after 72 h. At admission blood samples were obtained to determine viral serologies for hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, and toxoplasma (all of which were negative) and autoantibodies and iron metabolism (normal). We found a positive antinuclear antibody (titers ⬎ 1/320) and smooth muscle antibody (titers ⬎ 1/320). Unfortunately those results were received immediately after her death. Necropsy was proposed to the family, but they denied it for religious reasons. Fulminant failure is defined broadly as the development of severe hepatic dysfunction within 8 wk of the onset of symptoms, in the absence of a preexisting liver disease. Nevertheless, for some authors, the presence of preexisting liver disease does not rule out a diagnosis of acute liver failure, as conditions such as Wilson’s disease or hepatitis B reactivation may present with it (4, 5). AIH type 1 is the most frequent form of AIH, with a higher incidence than that of AIH type 2. The clinical picture of this entity usually consists of an insidious and, often, asymptomatic course with a severe impairment in liver function and a wide degree of histological damage (1). The patient did not have clinical or biochemical signs of previous liver disease, and abdominal ultrasound showed no portal hypertension data. Yet, the lack of viral etiology, the presence of typical autoantibodies, and hypergammaglobulinemia, in the absence of any other recognized cause of hepatic disease, makes AIH type 1 the most probable diagnosis. Cases of this condition previously described in the literature were found in postpubertal females, in which it is considered an additional form of presentation for AIH type 1, probably related to increasing estradiol levels (1–3), but this condition is not described along with the usual causes of acute liver failure (6). Nevertheless, to our knowledge, this is the first case of acute liver failure in an old woman being the first symptom of AIH type 1. Eduardo Redondo-Cerezo, M.D. Flor Nogueras-Lo´ pez, M.D. Rafael Martı´n-Vivaldi, M.D. Esperanza Egea Simo´ n, M.D. Unidad de Hepatologı´a Servicio de Aparato Digestivo Hospital Universitario Virgen de las Nieves Granada, Spain

REFERENCES 1. Herzog D, Rasquin-Weber AM, Debray D, Alvarez F. Subfulminant hepatic failure in autoimmune hepatitis type 1: An unusual form of presentation. J Hepatol 1997;27:578 – 82. 2. Gregorio GV, Portmann B, Vergani D, et al. Autoimmune hepatitis in childhood: A 20 year review. Hepatology 1993;18: 175A. 3. Tan KL, Mondragon RS, Vougas V, et al. Liver transplantation

AJG – Vol. 97, No. 5, 2002

for fulminant hepatic failure and late onset of hepatic failure in children. Br J Surg 1992;79:1192– 4. 4. Smithson JE, Neuberger JM. Acute liver failure. Overview. Eur J Gastroenterol Hepatol 1999;11:943– 8. 5. O’Grady J, Schalm S, Williams R. Acute liver failure; redefining the syndromes. Lancet 1993;342:273–5. 6. Bernal W, Wendom J. Acute liver failure; clinical features and management. Eur J Gastroenterol Hepatol 1999;11:977– 84. Reprint requests and correspondence: Eduardo Redondo-Cerezo, M.D., Servicio de Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Avenida Fuerzas Armadas No. 2, Granada— 18014, Spain. Received Nov. 27, 2001; accepted Dec. 3, 2001.

Recombinant Activated Factor VII Prevents Bleeding During a Surgical Procedure in a Patient With Uncontrollable Rectal Hemorrhage TO THE EDITOR: Prophylactic treatment in connection with minor and major invasive procedures is used as standard practice in approximately 74% of all risk patients with severe prolonged PT (1). Around 50% of these patients are treated with fresh frozen plasma and/or vitamin K. Unfortunately, results of treatment and prevention of bleeding using these treatment modalities remain unsatisfactory (2). Initiation of hemostasis involves the formation of a complex between tissue factor and activated factor VII after injury. It has recently been shown that the administration of recombinant activated factor VII (rFVIIa) in high doses can induce hemostasis in hemophilia patients with inhibitors who cannot benefit from conventional therapies (3). Several clinical trials have clearly demonstrated that rFVIIa is a safe and effective therapy for home treatment of mild to moderate bleeding episodes, and recommended doses range from 60 to 120 ␮g/kg body weight (3). Indications for the use of rFVIIa have been extended, and preliminary reports suggest that rFVIIa could be useful in patients with platelet disorders and with liver disease and prolonged PT to prevent the increased risk of severe bleeding episodes with minor invasive procedures, because these patients are known to have low levels of factor VII (4). In this sense, a pilot study was performed in nonbleeding volunteer cirrhotic patients with prolonged PT. They were given three successive dosages of rFVIIa (5, 20, and 80 ␮g/kg) during a 3-wk period, and the mean PT transiently corrected to normal in all three dosages groups (5). Here we report the case of a patient with liver cirrhosis due to hepatitis C virus and portal hypertension. This patient was 65 yr old and for 3 yr had had impaired coagulation induced by his liver disease, suffered repeated epistaxis episodes treated with tamponade measures, and had gingivorrhagias, otorrhagias, and frequent hematomas. He was admitted to the hospital for massive rectal hemorrhage sec-