Acute-onset autoimmune hepatitis treated with living donor-liver transplantation

A 50-year-old woman was diagnosed with acute-onset autoimmune hepatitis. She did not respond to steroid therapy including pulse therapy, and was subsequently treated with living donor-liver transplantation 36 days after the beginning of steroid therapy. Except for a period of transient mild acute rejection, her liver function tests remained within a normal range for 2.5 years after the operation. The courses of autoimmune hepatitis patients treated with living-donor liver transplantation have not been previously documented to our knowledge. Living donor-liver transplantation is thought to be one of the therapy options for severe autoimmune hepatitis.     

Recurrence of autoimmune hepatitis after liver transplantation without elevation of alanine aminotransferase

It is controversial whether steroid therapy should be continued to prevent the recurrence of autoimmune hepatitis(AIH)in patients who have undergone liver transplantation(LTx)due to AIH.We report a case of recurrent autoimmune hepatitis after LTx despite a persistently normal range of alanine aminotransferase(ALT).A 50-year-old woman was admitted to our hospital because of jaundice and severe liver dysfunction,where she was diagnosed with liver failure due to AIH.Steroid therapy was not effective enough and the patient received living-donor LTx in 1999.Following the operation,the level of ALT was maintained within a normal range and anti-nuclear antibody(ANA)became negative,however,the serum level of IgG gradually elevated and ANA became positive,while platelets decreased.A liver biopsy performed 6 years after LTx showed histological findings of AIH and she was diagnosed with recurrent AIH.A recurrence of AIH may occur after LTx even if the level of ALT remains within a normal range.We consider that a protocol liver biopsy should be performed in patients who undergo LTx due to AIH to decide the indication for steroid therapy.     

Autoimmune hepatitis triggered by acute hepatitis A

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (x320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.     

Acute-onset autoimmune hepatitis resembling acute hepatitis: a case report and review of reported cases

We report a 54-year-old Japanese man, whose ALT level was 1689 IU/L, without increased gamma-globulin level or autoantibodies. He could not be diagnosed as autoimmune hepatitis (AIH) using scoring systems, and his liver function became normalized after steroid treatment. Recently, AIH with acute presentation of disease and acute-onset AIH without bridging fibrosis have been increasingly reported but cases without the character of increasing gamma-globulin level or autoantibodies before immunosuppressive treatment are extremely rare. This is the third such case report in the literature.     

Prolonged intrahepatic cholestasis in acute-onset, severe autoimmune hepatitis

A 72-year-old woman was admitted because of jaundice and hepatocellular dysfunction. She was diagnosed with autoimmune hepatitis from laboratory test results showing high titers of antinuclear antibodies and negativity for hepatitis viral markers. Steroid i.v. pulse therapy and oral administration of prednisolone were effective in improving the liver function test results, except for hyperbilirubinemia. Elevated serum bilirubin levels, of approximately 20mg/dl persisted for more than 6 months, despite the administration of ursodeoxycholic acid. Insulin-glucagon therapy was given for normalization of transaminases and then withdrawn 3 weeks after admission, but it was resumed at 3 months, resulting in a dramatic decrease in serum bilirubin levels, which then normalized in 2.5 months. Liver biopsy 6 months after onset showed chronic active hepatitis with bile plugs. Insulin-glucagon therapy, because of its choleretic effect, may be worth continuing even after recovery of acute hepatic failure.     

Prolonged hepatitis after acute infection with genotype H hepatitis B virus

We present a case report of a Japanese patient who showed prolonged infection after acute hepatitis B with genotype H. The patient was a 60-year-old man who underwent an annual health care check every year for several years and was never pointed out to have any liver damage, and markers for hepatitis B and C were negative. He was found to be positive for hepatitis B surface antigen (HBsAg) at his health care check in December 2005. After one month, he had an elevated aminotransferase level with hepatitis B e antigen and a high level of serum HBV DNA. He was diagnosed as having acute hepatitis B. On HBV genotype, he had genotype H by the direct sequence method, and he was given a 100 mg of lamivudine daily. However, his acute hepatitis tended to go toward prolonged infection. After two months, he was treated with interferon daily for 28 days. He had negative HBsAg in August 2006. Genotype H, the newest type of hepatitis B, could be the type which shows a poor response to lamivudine. The present paper is the first report, describing the clinical course of acute hepatitis B with genotype H from onset to remission.     

Autoimmune hepatitis associated with Graves' disease

A 31-year-old woman with Graves' disease with a 12-month-history of propylthiouracil intake and autoantibodies in the sera was admitted to our hospital. The differential diagnosis between autoimmune hepatitis and propylthiouracil-induced hepatitis was intractable. Steroid therapy was started and she showed a complete response to the treatment. Liver biopsy demonstrated acute hepatitis and plasma cell infiltration. A second liver biopsy, which was performed 10 months after starting steroid therapy, showed some inflammatory cells in the portal tracts. These findings suggest that she had been suffering from autoimmune hepatitis.     

A case of pneumatosis cystoides intestinalis induced by steroid pulse therapy for severe acute hepatitis B

A 26-year-old Japanese woman was admitted to the hospital because of fever and general fatigue. A diagnosis of acute hepatitis B was given because of high levels of transaminase and positivity for HBs-Ag, HBe-Ag and HBc-IgM. On the 2nd day progression to fulminant hepatitis was suspected, and steroid pulse therapy, cyclosporin, entecavir, and interferon-β were started. Her laboratory data improved until transaminase showed an increase on 18th day, and steroid was once again administered. Abdominal CT scan and plain abdominal X-ray showed pneumatosis cystoides intestinalis (PCI) mainly along the ascending colon without any symptoms. After discontinuation of steroid therapy, abnormal gas gradually disappeared. This is a very rare case of PCI, which may have been caused by short-term steroid pulse therapy.     

A 40-year-old female patient with seronegative autoimmune hepatitis following a newly acquired hepatitis B infection

We report the case of a 40-year-old female patient admitted at our clinic because of recent onset jaundice and elevated transaminases. Two months before admission the patient had unprotected sexual contact with a potential hepatitis B-infected man. Virological screening performed in our clinic revealed IgM antibodies against hepatitis B virus core protein (anti-HBc-IgM) and elevated HBV-DNA. Our first diagnosis was an acute hepatitis B virus infection. During her stay at our clinic the patient achieved HBe seroconversion and a loss of HBV-DNA. Nevertheless the transaminases remained high and jaundice persisted. The histological examination of the liver biopsy showed interface hepatitis with plasma cells as the characteristic signs of autoimmune hepatitis. On that basis we started an immunosuppressive therapy with prednisolone in parallel with a prophylactic lamivudine therapy and after two weeks there was a complete resolution of jaundice and a normalisation of transaminases. In conclusion, we present a rare case report of an autoimmune hepatitis as a result a newly acquired hepatitis B infection. This case report highlights the relationship between viral infection and autoimmunity within the liver.     

Horizontal transmission of de novo hepatitis B between spouses: A case report

We report a female patient with acute hepatitis B due to horizontal transmission of hepatitis B virus from her husband, who suffered from de novo hepatitis B. A 48‐year‐old man underwent peripheral blood stem cell transplantation (PBSCT) for adult T‐cell leukemia/lymphoma. Nine months after the initial treatment, he was referred to our hospital because of jaundice. Laboratory data showed elevated serum aminotransferase levels and hepatitis B surface antigen (HBsAg) positivity. We diagnosed de novo hepatitis B because a pre‐PBSCT serum sample was negative for HBsAg and positive for anti‐hepatitis B core antibody (HBcAb). His liver function improved with entecavir therapy. Two months after his diagnosis of hepatitis B, his 31‐year‐old wife was admitted with fever and appetite loss. She was diagnosed with acute hepatitis B because of increased serum aminotransferase levels and HBsAg and immunoglobulin M HBcAb positivity. Sequencing of HBV DNA in the serum obtained from both patients showed 99.9% homology. Therefore, we diagnosed her acute hepatitis B as due to horizontal transmission of de novo hepatitis B from her husband. HBV derived from de novo hepatitis B should be considered a potential source of infection, although intrafamilial transmission of de novo hepatitis B is rare.     

Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents: A Case Report

The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents.A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient''s liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient''s liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient''s high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence.This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule out organic solvent-induced hepatitis.     

Steroid treatment for severe acute cryptogenic hepatitis

OBJECTIVE: Acute cryptogenic hepatitis may represent both a self-limited disease as well as the onset of chronic hepatitis. The aim of this analysis was to evaluate the effect of steroid treatment in patients with acute cryptogenic hepatitis. METHODS: We retrospectively analyzed four patients with acute cryptogenic hepatitis. Histories were negative for alcohol and hepatotoxic drug intake. Markers of metabolic liver disease, liver-related autoantibodies, and viral markers were negative in all patients. Gamma globulins were in the normal range. ALT rose above 1000 U/L in all patients and bilirubin levels were elevated to more than 400 micromol/L. Histopathological assessment revealed minimal infiltration with plasma cells, eosinophils and bile duct lesions. Using the international scoring system for the diagnosis of autoimmune hepatitis, all patients were classified as 'probable disease' in the absence of specific markers. RESULTS: We started immunosuppressive treatment with prednisolone because of persisting high aminotransferases and impaired liver function. All patients responded to steroids with normalization of liver function and a rapid decrease of aminotransferases. In one patient, additional treatment with azathioprine was necessary due to rebounding aminotransferases during steroid tapering. CONCLUSION: Steroids have to be taken into account in the therapy for severe acute cryptogenic hepatitis. The response to steroid treatment could be indicative for an autoimmune genesis of the disease.     

Fulminant hepatic failure in a case of autoimmune hepatitis in hepatitis C during peg-interferon-alpha 2b plus ribavirin treatment

A 27-year-old Caucasian female with hepatitis C virus (HCV) infection treated with interferon (IFN) who developed severe autoimmune hepatitis (AIH) is described. The infecting viral strain was of genotype Ib and the pre-treatment HCV viral load was at a high level. The patient was treated with pegylated IFN-alpha 2b and ribavirin,and her HCV-RNA became negative at wk 12,but after that she developed fulminant hepatic failure. The patient recovered after steroid pulse therapy consisting of methylprednisolone 1000 mg/d for three days which was administered twice. A needle liver biopsy revealed the typical pathological findings of AIH.     

A case of fulminant liver failure associated with hepatitis C virus

Fulminant hepatitis due to acute hepatitis C virus (HCV) infection is rarely observed. We present a case study of a 21-year-old male patient who developed HCV-associated fulminant hepatitis after receiving steroid pulse therapy for optic neuritis. Despite daily plasmapheresis, the disease progressed to irreversible liver failure with grade 3 hepatic encephalopathy by the 6th day after symptom onset. The patient received a liver transplant on the 8th day. Serum anti-HCV antibody was negative at that time, but became positive on the 12th day. Positive HCV RNA in the serum at admission was reported after transplantation. Positive changes in anti-HCV antibodies and acute hepatitis with massive necrosis in the histology of the explanted liver indicated fulminant hepatitis due to acute HCV infection. Because of severe hepatitis recurrence, he started 12 months of interferon therapy on the 48th day, and obtained sustained virological response. His anti-HCV antibodies became negative again by 1.5 years after cessation of therapy. HCV genomes recovered from the patient’s serum on the 7th and 48th days revealed 2 different clones out of 20 clones with 30 % amino acid difference in hypervariable region 1 of HCV second envelope glycoprotein. One of the 2 clones expanded further after liver transplantation. We conclude that early diagnosis of HCV-associated fulminant hepatitis requires the detection of HCV RNA in the serum. Severe hepatitis recurrence after liver transplantation might occur in patients with fulminant hepatitis due to HCV because of its monoclonal expansion.     

Autoimmune hepatitis and overlap syndromes

Autoimmune hepatitis is a well-established chronic liver disease. It primarily affects women, is characterized by circulating autoantibodies and elevated gammaglobulins and is associated with extrahepatic immune-mediated syndromes. Treatment regimens have remained unchanged for a number of years because of the high efficacy of steroid monotherapy, or combination therapy of azathioprine and steroids. In approximately 90% of patients remission of the disease is reached by medical therapy, which is usually administered lifelong because long-term remission after drug withdrawal is achieved in only 17% of patients. In 10% of patients treatment failure is observed. The challenge of remission induction involves the use of transplant immunosuppressants such as cyclosporine, mycophenolate moffetil, and tacrolimus. The challenge of maintenance therapy minimizing steroid side-effects involves the evaluation of topical steroids and the use of azathioprine monotherapy. Overlap syndromes occur in approximately 20% of autoimmune liver diseases. The diagnosis is broadly based on serological, biochemical, clinical and histological parameters. Most common are the overlap of autoimmune hepatitis and primary biliary cirrhosis, as well as autoimmune hepatitis with primary sclerosing cholangitis. These yet incompletely defined syndromes are an important differential diagnosis in the difficult-to-treat patient with autoimmune hepatitis.     

Acute exacerbation of autoimmune hepatitis induced by Twinrix

We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix? In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid, and led to complete normalization of the pathological liver function tests. We believe that Twinrix led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.     

A case of severe skin eruption caused by Lamivudine in a patient with chronic hepatitis B]

Lamivudine is widely used for the treatment of chronic hepatitis B infection because of it's remarkable antiviral efficacy and safety. We report a case of severe skin eruption caused by lamivudine. A 47-year-old female was admitted because of jaundice and itching sensation. She was diagnosed as chronic hepatitis B infection a few years ago but did not receive any specific treatment. Laboratory data showed acute deterioration of chronic hepatitis B infection. We prescribed lamivudine as a rescue therapy. Her general condition improved and lab data showed improvement in liver function test thereafter. However, she complained of severe skin eruption and itching sensation a few days after the discharge. We stopped lamivudine because the symptoms did not improve despite the use of anti-histamine. Skin biopsy showed interface dermatitis. After stopping lamivudine, her symptoms improved. However, the skin eruption developed again after lamivudine was restarted. Adefovir was used instead, and the patient did not experience any further skin problems since then.     

Hepatitis-associated aplastic anemia and transfusion-transmitted virus infection

A 17-year-old man was admitted to our hospital because of severe acute hepatitis. Serologic studies were negative for A, B, C and G hepatitis viruses. Later, he was found to be positive for transfusion-transmitted virus (TTV) DNA. He was discharged after normalization of liver function tests. Four months after the onset of hepatitis, he was re-admitted because of pancytopenia. Bone marrow findings were consistent with aplastic anemia. The anemia responded to steroid therapy. In this case, TTV was probably involved in the development of aplastic anemia.     

Autoimmune hepatitis: the present status in Japan

A nationwide survey using questionnaires was carried out concerning lupoid hepatitis and related diseases (518 cases) during the 8-year period from January, 1975 to December, 1982. The following results were obtained. A total of 253 cases of autoimmune hepatitis, consisting of 97 lupoid hepatitis and 156 lupoid type CAH, were reported. Autoimmune hepatitis was overwhelmingly predominant in females, while male cases of B type CAH with a gamma-globulin level of more than 2 g/dl significantly outnumbered female CAH cases of the same type. The liver function tests at the first examination demonstrated that transaminases, total bilirubin, ICG (R15) and gamma-globulin were increased, and ChE was decreased in lupoid hepatitis. Lupoid type CAH showed a close similarity with lupoid hepatitis rather than to the nLnB type or B type with regard to liver function. Of the 289 patients who could be followed up, 280 cases (97%) received steroid hormones, and 247 (85%) received no another drug. Immunosuppressive treatment was also performed in 40% of the HBs antigen-positive cases of B type CAH. The efficacy was about 90% in the lupoid hepatitis group as well as in the lupoid type CAH group. It was no greater than approximately 70% in any other group. Analysis of survival revealed the following: 1) The cumulative survival rates of autoimmune hepatitis was lowest among the different types of CAH. 2) Patients who had a high serum level of total bilirubin tended to die sooner than those who had a low level. There was no correlation between the cumulative survival rate and serum gamma-globulin concentration or antinuclear antibody titer. 3) The duration of steroid hormone therapy and the total dosage of immunosuppressants were thought to be important factors affecting the prognosis of autoimmune hepatitis.     

Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves' ophthalmopathy treated successfully with glucocorticoids themselves

We report a case of acute hepatitis of autoimmune origin which occurred in a 43-yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves' ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no previous history of liver disorders or conditions predisposing to GC-associated liver damage. After the administration of a 4.7-g cumulative dose of methylprednisolone acetate, there was a marked increase of liver enzymes, prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes increased further, reaching a peak 45 days later, with values 30- to 50-fold greater than those prior to therapy, associated with evidence of impaired liver function. Liver biopsy showed a marked lymphocytic infiltration, likely indicating an autoimmune hepatitis. Based on the assumption that following GC-induced immune suppression, autoimmune hepatitis might have been precipitated by sudden re-activation of the immune system during interpulse periods, we treated the patient with im and then oral GC, in order to re-induce immune suppression. Within three days from re-institution of GC therapy, there was a marked reduction of liver enzymes and amelioration of liver function. Complete normalization was achieved two months later, while the patient was still receiving a low maintenance dose of oral prednisone.