Case reports Autoimmune liver disease in a Nigerian woman *Otegbayo JA, Akere A, Ola SO, Soyemi OM, Akande KO Gastrointestinal and Liver Unit, Department of Medicine, University College Hospital & University of Ibadan, PMB 5116, Ibadan, Nigeria.
Abstract Autoimmune liver diseases are chronic liver disease with similar clinical features to viral and non-autoimmune liver disorders but with distinct sero-autoimmunologic features. In developed countries, it accounts for about 20% of all liver transplantations in the USA. Most studies on liver disease in Nigeria centred on viral or alcohol aetiology with complete absence of data on autoimmune liver disease. We here report a case of a young woman with autoimmune hepatitis for the first time in Nigeria. The patient presented with features of chronic liver disease of neither viral nor alcoholic aetiology. The diagnosis was based on the presence of hypergammaglobulinaemia and auto-antibodies in the serum. We concluded that physicians should always bear in mind the possibility of autoimmune hepatitis in patients with features of chronic liver disease, especially when the viral markers are negative and there is no history of significant alcohol consumption. Keywords: Liver, Autoimmune, Nigeria. African Health Sciences 2010; 10(2): 208 - 210
Introduction Diseases of the liver are ranked as the 8th most common cause of death1 and were the third most common on Medical Wards at the University College Hospital, Ibadan, Nigeria. They also accounted for 12.1% of all admitted patients on the medical ward by Onadeko et al, in 1977 2. Autoimmune liver diseases are chronic liver diseases with similar clinical features to viral and non-autoimmune liver disorders but with distinct seroautoimmunologic features. In developed countries autoimmune liver diseases are a significant cause of end stage liver disease (ESLD) and account for approximately 20 % of all liver transplantations in the USA, 2.6% in Europe (European Liver Transplant Registry), and 5.9% of the National Institutes of Health (NIDDK). The major types of autoimmune liver diseases are autoimmune hepatitis, primary biliary cirrhosis and primar y sclerosing cholangitis. In the USA, autoimmune hepatitis (AIH) affects 100,000-200,000 individuals, but there is no data on autoimmune liver diseases in Nigeria as most studies on liver centered *Correspondence author: Jesse A Otegbayo Gastrointestinal and Liver Unit Department of Medicine University College Hospital & University of Ibadan PMB 5116, Ibadan, Nigeria E-mail:
[email protected] 208
on viral or alcohol aetiology even though there are reports on autoimmune disorders3, 4, 5. We hereby report a case of a young woman with autoimmune liver disease for the first time in Nigeria, to sensitize clinicians to its presence in Nigeria. Case report A 33 year old businesswoman with a six week history of fever, four week history of jaundice and two days of irrational talk was referred from a private hospital to our health facility. Fever was high grade and associated with chills and rigors. She also had dark-coloured urine but no pale stools or pruritus. Irrational talk was preceded by days of insomnia but no headache or neck pain. No history of alcohol or tobacco use was reported. She had antimalarial therapy in the private hospital without improvement. She had had two episodes of jaundice at ages 26 and 30 years. The first episode disappeared spontaneously while the second episode resolved with the use of herbal concoction. Three years before presentation she had received a plasma transfusion for unclear reasons and also had appendectomy at age 23. Clinical examination at entry revealed a conscious but deeply icteric woman who was neither pale nor febrile. There were no peripheral stigmata of chronic liver disease. Ascites and flapping tremor were noted as well as circumoral and periorbital African Health Sciences Vol 10 No 2 June 2010
depigmented macules that were seen suggestive of vitiligo. The clinical impression was that of chronic hepatitis probably viral in grade II hepatic encephalopathy. Autoimmune hepatitis was also considered because of her gender and the vitiligo. She was placed on intravenous fluids and anti-hepatic failure regimen, while awaiting results of laboratory investigations.
Ascitic fluid became massive and paracentesis was done with administration of fresh frozen plasma. Results of laboratory investigations are shown in Table 1. Samples were also tested for lupus anticoagulant and serum immunoglobulin. The patient was then started on oral prednisolone. She developed haematemesis as her prothrombin time got prolonged in spite of blood transfusion. She died four weeks after admission. Post-mortem examination was refused by family members.
Table 1: Results of laboratory tests in a Nigerian female patient with autoimmune hepatitis Tests At presentation 2nd Week 3rd Week 4th Week PCV 34% Serum bilirubin 28.2mg/dl 24.1mg/dl Direct bilirubin 12.5 15mg/dl Alkaline phosphatase 351 I.U/L 407 I.U/L Aspartate Transaminases 425 I.U/L 121 I.U/L Alanine Transaminases 185 I.U/L 70 I.U/L Total protein 6.8mg/dl 6.7mg/dl Serum Albumin 1.3mg/l 3.7mg/dl Prothrombin Time 51s control 15s 120s control 14s Total Anti-HBc Positive HBsAg Negative Anti HCV Negative Serum IgG 1308mg/dl Serum IgA 143mg/dl Serum IgM 276mg/dl Urine bilirubin +++ Serum Potassium 2 ANA + AMA + pANCA + LKM-1 SLA/LP HBV-DNA Abdominal Ultrasonography Shrunken liver with no intra hepatic mass or nodule. Gallbladder is markedly enlarged with thickened irregular hypoechoic wall and contains sludge. Significant ascites was present. Impression was chronic chlolecystitis, to keep in view infilterative gallbladder disease.
Discussion The cause of autoimmune hepatitis is not known, but factors believed to be responsible include, genetic mimicry, autoantigens and viral agents among others. The characteristic features are interface hepatitis on histology, hypergammaglobulinaemia and autoanti bodies in serum6. Diagnosis requires exclusion of other forms of liver disease with similar features, like those caused by viruses for example (ref 7). Although autoimmune liver disease may be chronic, it may also present acutely and sometimes fulminating. African Health Sciences Vol 10 No 2 June 2010
The immunologic tests essential for diagnosis are Antinuclear antibodies (ANA), Smooth muscle antibodies (SMA) and antibodies to liver/kidney microsome type 1 (anti-LKM1)8. The case being presented had features of chronic hepatocellular inflammation as evidenced by the moderate rise of transaminases and low serum albumin. The absence of pruritus and the presence of vitiligo in our patient are in support of autoimmune hepatitis, while intense pruritus would argue against this diagnosis. 209
Although, features like ascites and hepatic encephalopathy which our patient presented with are uncommon findings at the initial medical consultation9, it is most likely that this is a progression of a disease that started some years back, since this patient had two episodes of jaundice in the past. The findings of a shrunken liver on hepatic ultrasonography further support the development of cirrhosis in this patient. Also in support of an autoimmune phenomenon in our patient is the absence of the major viral markers associated with liver diseases in our environment, as she was negative for both hepatitis B and C and had no history of alcohol ingestion. The significance of enlarged gallbladder filled with sludge with no stones in this patient on abdominal ultrasound, cannot be ascertained. This might be an incidental finding. The finding of hypergammaglobulinaemia, ANA, SMA and pANCA all support the diagnosis of autoimmune hepatitis and more precisely type 1. Although, histologic features of interface hepatitis7 are desirable, the shrunken liver, massive ascites and coagulopathy stood as contraindication for a liver biopsy in the patient. The usefulness of the procedure in this patient is also in doubt as it may not yield the known features of autoimmune liver disease as a result of development of cirrhosis. Notwithstanding, the presence of conventional autoantibodies like ANA, SMA, pANCA in the serum of this patient makes autoimmune hepatitis a likely cause of disease. The patient’s poor response to treatment might be due to her late presentation, as she was already in hepatic encephalopathy with coagulopathy. A liver transplantation would probably have helped but is currently not possible in Nigeria.
References 1. Adetuyibi A, Akisanya JB, Onadeko BO. Analysis of the causes of death on the medical wards of the University College Hospital, Ibadan over a 14-year period (1960-1973). Trans R Soc Trop Med Hyg. 1977;70:466-473. 2. Talabi OA, Owolabi MO, Osotimehin BO. Autoimmune diseases in a Nigerian woman- a case report. West Afr J Med. 2003. 22-361-363. 3. Talabi OA, Abjah UM, Ocheni S, Akinyemi OA, Aken’ova YA, Ogunniyi A. Benefit of modified plasmapheresis in the management of myasthenia gravis: a case report. Niger J Med. 2006,15:162-164. 4. Ogunbiyi AO, George AO, Brown O, Okafor BO. Diagnostic and treatment difficulties in systemic lupus erythematosus coexisting with sickle cell disease. West Afr J Med. 2007, 26:152155 PubMed . 5. Adelowo OO, Salimonu LS, Arinola OG. Autoantibodies to DNA in the sera of Nigerians attending a rheumatic diseases clinic. Afr J Med Med Sci. 1998; 27:173-176. 6. Czaja A. Autoimmune hepatitis: Evolving concepts and treatment strategies. Dig Dis Sci. 1995, 40:435. 7. Alvarez F, Berg P, Bianchi F, et al. International Autoimmune Hepatitis Group report: Review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999, 31:929. 8. Czaja A, Homburger H. Antibodies in liver disease. Gastroenterology 2001, 120:239 9. Roberts S, Therneau T, Czaja A. Prognosis of histologic cirrhosis in type 1 autoimmune hepatitis. Gastroenterology 1996, 110:848.
Acknowledgement We acknowledge Prof. Claude P. Muller of the Institute of Immunology, Luxembourg for facilitating the HBV-DNA and serum autoantibodies analyses.
Conclusion In conclusion, physicians should always bear in mind the possibility of autoimmune hepatitis in patients who present with features of chronic liver disease in whom viral studies are negative, no history of alcohol intake and no obvious aetiology is known. Screening for autoantibodies should be part of the general workup of such patients. 210
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