Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis

Atorvastatin and other members of the statin family are widely used for the treatment of hypercholesterolaemia in order to reduce the risk of atherosclerosis and cardiovascular disease. Atorvastatin-induced adverse events are mostly mild and only a few cases of lupus-like syndrome or severe acute hepatitis have been documented. In this case report we describe a patient who developed an atorvastatin-induced severe autoimmune hepatitis. In addition, this patient presented with a concomitant systemic lupus-like syndrome which has been already described for statins but not in association with severe liver disease. Although the drug was immediately withdrawn the disease persisted and even deteriorated to a fulminant disease with evidence of acute hepatic failure. The patient failed to respond to conventional immunosuppression with corticosteroids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery of the patient. Interestingly, the patient was HLA DR3- and HLA DR4-positive, which are well-known genetic factors associated with autoimmune diseases. This case is the first report of a drug-induced lupus-likesyndrome concomitant with a severe autoimmune hepatitis in a genetically predisposed patient.     

Celiac disease associated with antiphospholipid syndrome

INTRODUCTION: celiac disease may be associated with pathologies of immune etiology. We present its association with antiphospholipid syndrome. CASE 1: a 26-year-old female was diagnosed with celiac disease. Six months later she became pregnant, and experienced fetal death. The following year she became pregnant again. IgG anticardiolipin antibodies: 20 GPL U/ml (normal value < 11), and IgM anticardiolipin antibodies: 9 MPL U/ml (n. v. < 10). Hematological tests were otherwise uneventful. Medicated with acetylsalicylic acid she had a normal pregnancy. CASE 2: a 48-year-old female diagnosed with celiac disease presented with thrombosis in her left lower limb and renal infarction. Hematological tests showed no prothrombotic alterations (antiphospholipid antibodies were not measured). A year and a half later she had thrombosis in a finger of her hand. IgG anticardiolipin antibodies: 10 GPL (n. v. < 13), and IgM anticardiolipin antibodies: 35 MPL (n. v. < 12). CASE 3: a 38-year-old female was diagnosed with celiac disease. Some time later she experienced two spontaneous abortions and a transient ischemic cerebral attack. Nowadays, she is in her sixth month of pregnancy. IgM anticardiolipin antibodies: 75 MPL/ml (n. v. up to 20), and IgG anticardiolipin antibodies within normal values. Hematological tests revealed no other prothrombotic alterations. DISCUSSION: antiphospholipid syndrome is characterized by arterial and venous thrombosis, and spontaneous fetal death. Its association with celiac disease has been described in few cases. Celiac disease is associated with spontaneous fetal death; consequently, we hypothesize that antiphospholipid syndrome may be one of the causes for this event.     

Severe autoimmune neutropenia associated with acute autoimmune hepatitis

A 49-year-old previously healthy female presented with acute hepatitis and severe neutropenia. A diagnosis of type 1 autoimmune hepatitis was made based on the histological appearance of a liver core biopsy, positive anti-smooth muscle antibodies, and positive anti-neutrophil cytoplasmic antibody (atypical ANCA). Hemogram revealed mild leukopenia with severe neutropenia (absolute neutrophil count 256/mm³), normal hemoglobin and mild thrombocytopenia (115000/mm³). A bone marrow biopsy and aspirate had a normal karyotype, increase in granulopoiesis, prominence of promyelocytes (31%) and absence of mature granulocytes. Anti-neutrophil antibodies were detected in the patient’s blood. Therapy was directed at the underlying hepatitis with resolution of neutropenia without the use of colony-stimulating factors.     

Hepatocellular carcinoma associated with autoimmune hepatitis

Autoimmune hepatitis (AIH) is a disorder of unknown etiology, which often progresses to cirrhosis and carries a high mortality, even though its treatment with corticosteroids has become common. Hepatocellular carcinoma (HCC) has been reported as a rare complication of AIH. We describe herein a patient with HCC associated with AIH, in whom microwave coagulation therapy provided a means of definitive management, and we also review the literature. Male sex and longstanding cirrhosis seem to be the risk factors for hepatocarcinogenesis in AIH. The prognosis of this disease is extremely poor because of the low resectability caused by poor hepatic reserve. It is important to pay attention to hepatic disorders and the possible development of HCC at the time of diagnosis of AIH. Surgeons should select suitable treatment, without undue surgical stress, whenever the diagnosis of HCC has been established. Microwave coagulation therapy is a preferred option for the treatment of high-risk patients with poor hepatic reserve or unresectable multiple HCCs.     

Sjögren's syndrome associated with autoimmune hepatitis. A case report

Summary Liver involvement in patients with primary Sjögren's syndrome is rare, usually without clinical significance and histologically characterized by a feature like stage 1 primary biliary cirrhosis. We describe herein a case of acute and severe autoimmune hepatitis in a patient suffering from primary Sjögren's syndrome. The diagnosis of Sjögren's syndrome was performed in 1989.In June 1995 the patient presented severe weakness, jaundice and elevation of transaminases; moreover IgG raised to 5560 mg/dl and ANA titre increased to 1:20480. The patient denied alcohol and drug use and a viral hepatitis was excluded. Antimitochondrial antibodies, anti-smooth muscle antibodies and antibodies against liver kidney microsomes were negative. An abdomen ultrasound examination revealed hepatomegaly, with irregular echogenic structure and lymphoadenomegaly near the celiac tripod. Liver biopsy demonstrated a picture of autoimmune hepatitis.The patient was treated with prednisone 50 mg/day and azathioprine 50 mg/day, with improvement in clinical and liver function indices. At present, the patient is given only 10 mg/day of prednisone.The association of Sjögren's syndrome with autoimmune hepatitis is very rare: in the literature only one other similar case has been reported.     

Chronic hepatitis C virus infection associated with primary warm-type autoimmune hemolytic anemia

Autoimmune hematologic abnormalities are not well recognized in chronic hepatitis C virus infection. We demonstrate an unusual association between primary autoimmune hemolytic anemia and chronic hepatitis C virus infection. A 69-year-old woman who had a history of hepatitis C virus-related liver cirrhosis was found to have deteriorating anemia with reticulocytosis when admitted to the hospital. Laboratory work revealed both positive direct and indirect Coombs' tests, and warm-type immunoglobulin G against surface antigens of red blood cells. After prednisolone therapy, her anemia improved dramatically. To our knowledge, this is the first reported case of chronic hepatitis C virus infection linked with autoimmune hemolytic anemia in its natural course, not related to prior interferon treatment. Our report suggests that isolated autoimmune hemolytic anemia may be one of the unusual hematologic manifestations of chronic hepatitis C virus infection.     

Chronic hepatitis C and celiac sprue: an infrequent association

Celiac sprue (CS) has been described in association with hepatitis C virus (HCV) as another immunologic manifestation of this infectious disease. We report 2 patients, a 42-year-old woman and a 59-year-old man, with chronic HCV hepatitis. Upper digestive endoscopy and duodenal biopsy were performed to investigate diverse symptoms. The results of histological analysis and serological study were compatible with CS. The association between both diseases, including immunological aspects and the implications of anti-HCV treatment, is discussed.     

Severe autoimmune neutropenia and thrombopenia associated with chronic C hepatitis: effect of antiviral therapy

We report the case of a 45-year-old man admitted for severe autoimmune thrombopenia and neutropenia associated with chronic viral C hepatitis. After failed, intravenous gammaglobulin and corticosteroid therapy antiviral treatment with interferon and ribavirin was given for one year. Thrombopenia improved progressively during antiviral therapy and worsened after the end of treatment. Neutropenia improved during antiviral therapy. Two years after the end of treatment, serum RNA-HCV was positive, white cell count was normal and platelet count was 77 G/L. In conclusion, these results suggest that antiviral therapy may be useful in patients with auto-immune cytopenia associated with viral hepatitis C infection.     

Hepatitis A vaccine associated with autoimmune hepatitis

To describe a case of probable relapsing autoimmune hepatitis associated with vaccination against hepatitis A virus （HAV）. A case report and review of literature were written concerning autoimmune hepatitis in association with hepatitis A and other hepatotropic viruses. Soon a~er the administration of formalin-inactivated hepatitis A vaccine, a man who had recently recovered from an uncharacterized but self-limiting hepatitic illness, experienced a severe deterioration （AST 1687 U/L, INR 1.4）. Anti-nuclear antibodies were detectable, and liver biopsy was compatible with autoimmune hepatitis. The observation supports the role of HAV as a trigger of autoimmune hepatitis. Studies in helper T-cell activity and antibody expression against hepatic proteins in the context of hepatitis A infection are summarized, and the concept of molecular mimicry with regard to other forms of viral hepatitis and autoimmunity is briefly explored.