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.     

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 autoimmune hepatitis diagnosed after acute hepatitis B

We describe a case of autoimmune hepatitis diagnosed after acute hepatitis B. The patient was a 65-year-old man admitted because of markedly elevated transaminase level. Laboratory tests showed positive IgM-HBc antibody and a short prothorombin time. He was diagnosed as severe acute hepatitis B due to sexual transmission. He received lamivudine and steroid pulse therapy. Transaminase level increased again after steroid pulse therapy and liver atrophy progressed, so cyclosporine was induced. Liver biopsy was done because of prolonged liver function disorder. Biopsy specimens showed not only centrizonal inflammation but also interface hepatitis and bridging fibrosis, which were characteristic of autoimmune hepatitis. We diagnosed autoimmune hepatitis which became clinically evident after acute hepatitis B. Lamivudine was discontinued 7 months after diagnosis and he is now receiving 3mg prednisolone.     

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.     

自身免疫性肝炎与系统性红斑狼疮性肝损伤临床特征对比

目的比较自身免疫性肝炎（AIH）与系统性红斑狼疮（SLE）性肝损伤在临床表现、血清学检查及病理学上的异同点。方法回顾性分析44例自身免疫性肝炎与26例狼疮性肝损伤的临床资料、血清学检查及病理学特点。结果AIH以女性多发,发病高峰为（47.32±13.61）岁,临床表现以消化系统为主,以ALT、AST升高,高球蛋白血症及IgG升高为主要特征,存在多种自身抗体,伴发其他自身免疫性疾病比率高,病理有特征性改变,对激素及免疫抑制剂有效,病情呈波动性变化。SLE以女性多发,发病高峰（33.46±14.32）岁,临床表现多样化,肝损伤为初发患者一过性ALT、AST升高,有明显低补体血症,存在多种自身抗体,并发其他自身免疫性疾病比率低,病理无特征性改变,激素治疗有效。结论AIH、SLE均以女性多发,有过敏史的比率高于正常人群,激素治疗有效;AIH肝损伤重,呈波动性变化,易伴发其他自身免疫性疾病,SLE肝损伤轻,多为一过性,可累及全身多个系统,二者为相互独立的疾病。     

自身免疫性肝炎的临床和病理

目的 研究自身免疫性肝炎（ａｕｔｏｉｍｍｕｎｅ ｈｅｐａｔｉｔｉｓ,ＡＩＨ）的临床表现,肝活检病理学特征。方法 回顾性总结１４例ＡＩＨ肝脏损害患者的临床表现及肝病理活检结果。结果 ＡＩＨ主要影响女性,女：男为１３：１,年龄２８－６６岁,伴有迁延性丙氨酸转氨酶（ａｌａｎｉｎｅ ｔｒａｓａｍｉｎａｓｅ,ＡＬＴ）和天冬氨酸转氨酶（ａｓｐａｒｔａｔｅ ｔｒａｎｓａｍｉｎａｓｅ,ＡＳＴ）异常,高球蛋白,高γ     

肝移植术治疗自身免疫性肝炎(附1例报告)

目的探讨肝移植术在自身免疫性肝炎(AIH)中的治疗价值。方法对1例AIH肝硬化患者行肝移植手术。结果患者术后恢复顺利,随访1年未出现排斥反应及复发,抗核抗体(ANA)转阴,肝功能正常。结论肝移植术可作为终末期AIH的有效治疗手段。     

Autoimmune hepatitis in pediatric patients]

BACKGROUND: Autoimmune hepatitis (AIH) is an inflammatory disease of unknown origin that is responsible for progressive liver necrosis and ultimately cirrhosis. OBJECTIVE: Our aim was to evaluate the characteristics of autoimmune hepatitis presenting in the pediatric age. MATERIAL AND METHODS: We conducted a retrospective study of all patients diagnosed with AIH in our hospital department during the last 10 years. Variables analyzed included age, sex, clinical presentation, hepatic function, immunoglobulins, autoimmunity markers, histology, treatment, need for transplant, and clinical evolution. According to the positive level of auto-antibodies, AIH patients were classified as type I AIH (ANA and/or smooth-muscle antibodies) and type II (anti-LKM-1). RESULTS: Seven patients were diagnosed in this period -5 girls (71.5%) and 2 boys (28.5%). Five patients presented with type-I serological markers, and two with type-II markers. Age range at diagnosis was from 21 months to 12 years. In the type-I group, 3 patients presented with acute hepatitis while 2 other patients were diagnosed from laboratory findings while asymptomatic. Elevated aminotransferase (10 times the normal level) was observed in 71.5%, and 85% had elevated immunoglobulins. Treatment with azathioprine and prednisone was started after diagnosis with an average time to remission of 14 months. Two patients relapsed following steroid withdrawal. CONCLUSION: AIH can have different forms of clinical presentation, and is sometimes indistinguishable from viral hepatitis. AIH must be ruled out in patients presenting with concomitant elevation of aminotransferases and immunoglobulins. The commonly accepted treatment is a combination of azathioprine and corticosteroids. A high percentage of patients experience a relapse of disease after steroids are withdrawn. Therefore, some patients will need to stay on combined therapy with minimal doses of steroids.     

A case of autoimmune hepatitis exacerbated by the administration of etanercept in the patient with rheumatoid arthritis

A 50-year-old woman was admitted for active rheumatoid arthritis (RA). She was found to have RA 1 year prior to this admission. Past history was unremarkable and she had no family history for rheumatic diseases. As nonsteroidal anti-inflammatory drug (NSAID) and methotrexate were not effective, etanercept was started (25 mg, twice a week). Mild elevation of alanine transaminase (ALT) and aspartate transaminase (AST) was found as an outpatient, and it was considered to be NSAID-induced liver injury. Two weeks after the first dose of etanercept, she developed progressive elevation of AST and ALT with right upper quadrant tenderness and hepatomegaly. Etanercept was discontinued and liver biopsy was performed, which demonstrated portal-area-dominant lymphoplasmacytic inflammatory cell infiltration. She was diagnosed as autoimmune hepatitis (AIH). Glucocorticoid was started with normalized liver function and stable joint symptoms. AIH was thought to be acutely aggravated by the administration of etanercept.     

An overlap syndrome involving autoimmune hepatitis and systemic lupus erythematosus in childhood

We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis (AIH) and systemic lupus erythematosus (SLE). The patient presented with jaundice, hepatosplenomegaly, malaise, polyarthralgia, arthritis and butterfly rash on the face. Laboratory tests revealed severe liver dysfunction, Coombs positive hemolytic anemia and a positive ANA/anti-dsDNA test. Renal biopsy showed class IIA kidney disease, while liver biopsy showed chronic hepatitis with severe in? ammatory activity. The patient satisfi ed the international criteria for both SLE and AIH. Clinical symptoms and laboratory findings of SLE improved with high dose treatment with corticosteroids and azathioprine, however, remission of the liver disease could not be achieved. Repeat biopsy of the liver after three years of therapy revealed ongoing chronic hepatitis with high level of in? ammatory activity. The present case indicates that children with liver dysfunction and SLE should be investigated for AIH. There is much diagnostic and therapeutic dilemma in patients with AIH-SLE overlap syndrome.     

A case of acute liver failure due to hepatitis E virus,liver transplantation,and development of de novo autoimmune hepatitis

Acute hepatitis E virus (HEV) infection could lead to acute liver failure (ALF), which requires liver transplantation (LT). HEV infection could progress to chronic infection in an immunosuppressed host. De novo autoimmune hepatitis (AIH) is a rare occurrence of AIH during post‐LT immunosuppressive therapy in patients who underwent LT due to not AIH but some other etiology. Here, we report the first case of ALF due to HEV infection, the recurrence of HEV after LT that responded to ribavirin therapy, and then the development of de novo AIH showing a complete response to glucocorticoid therapy but multiple relapses after steroid withdrawal. This peculiar case suggests that HEV could have a pathogenic role in the development of the de novo AIH; additionally, this case report could help clinicians make therapeutic decisions in the post‐LT condition.     

Primary biliary cirrhosis with additional features of autoimmune hepatitis: response to therapy with ursodeoxycholic acid

Patients with primary biliary cirrhosis (PBC) may have additional features of autoimmune hepatitis (AIH). Corticosteroids usually contraindicated in PBC have been advocated for these patients. Patients with antimitochondrial antibody (AMA)-positive PBC from two previous randomized, controlled trials were assessed for features of AIH. Their biochemical, immunologic, and histologic responses to ursodeoxycholic acid (UDCA) versus placebo were compared with those without AIH features. The survival of patients testing positive or negative for antinuclear antibodies (ANA) was also examined. Features of AIH were defined by the presence of 2 or more of the following: 1) alanine transaminase (ALT) > 5 x the upper limit of normal (ULN); 2) immunoglobulin G (IgG) > 2 x ULN or positive anti-smooth muscle antibody (ASMA); and 3) moderate to severe lobular inflammation on pretreatment liver biopsy. Testing for AMA, ASMA, and ANA was done by immunofluorescence. The change in serum bilirubin, alkaline phosphatase (ALP), transaminases, IgM, and IgG from baseline to 2 years was compared. Of the 331 patients randomized, 16 (4.8%) had features of AIH (12 UDCA, 4 placebo). The median percent change in serum biochemistry and immunoglobulin values were similar in patients with PBC +/- features of AIH after 2 years of therapy with UDCA. Over 2 years, little change in histologic features of AIH was observed. Survival was similar for patients with PBC with and without ANA. In conclusion, features of AIH in PBC may be transient and response to UDCA therapy similar to patients with PBC without features of AIH.     

Liver cirrhosis due to autoimmune hepatitis combined with systemic sclerosis

Systemic sclerosis (SSc) is a chronic systemic disease that affects the skin, lungs, heart, gastrointestinal tract, kidneys, and musculoskeletal system. Although up to 90% of patients with scleroderma have been estimated to have gastrointestinal involvement, liver disease has been reported only rarely. A 51-year-old woman was hospitalized due to esophageal variceal bleeding. Her serum was positive for anti-nuclear antibody and anti-centromere antibody. Sclerodactyly was noted on both hands, and she had recently developed Raynaud's syndrome. Punch biopsy of the hand showed hyperkeratosis, regular acanthosis, and increased basal pigmentation in the epidermis, and thick pale collagenous bundles in the dermis. Liver biopsy showed chronic active hepatitis with bridging fibrosis. Consequently, she was diagnosed with liver cirrhosis due to autoimmune hepatitis (AIH) combined with SSc. AIH had subsided after administration of prednisolone at 40 mg per day. She received 5-10 mg/day of prednisolone as an outpatient, and her condition has remained stable. Patients with either AIH or SSc should be monitored for further development of concurrent autoimmune diseases. The early diagnosis of AIH combined with SSc will be helpful in achieving optimal management.     

Effect of ursodeoxycholic acid on autoimmune-associated chronic hepatitis C

BACKGROUND: Hypergammaglobulinaemia and various auto-antibodies which are commonly seen in autoimmune hepatitis are also found in patients with chronic hepatitis C. We recently reported that ursodeoxycholic acid (UDCA) improved liver function tests and immunoserological markers in patients with type I autoimmune hepatitis. The aim of this study was to prospectively evaluate the efficacy of UDCA on autoimmune-associated chronic hepatitis C. METHODS: Immunoglobulin G (IgG), anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were determined in 95 patients with chronic hepatitis C. All patients were positive for hepatitis C virus RNA. Autoimmune-associated chronic hepatitis C (C-AIH) was defined by elevated serum IgG level (> or = 2.0 g/dL) and high titres of ANA and/or ASMA (> or = 1 : 160). Nine (9%) of 95 patients were diagnosed as C-AIH. All the C-AIH patients and 30 of the remaining 86 chronic hepatitis C patients without autoimmune features (CHC) were treated with UDCA (600 mg/day) for 1 year. RESULTS: Autoimmune-associated chronic hepatitis C patients included one man and eight women and their AIH scores, as defined by the International Autoimmune Hepatitis Group, were significantly higher than the CHC patients. Before UDCA therapy, there were no significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and y-glutamyl transpeptidase (gamma-GTP) levels between C-AIH and CHC patients. However, after 1 year UDCA therapy, AST, ALT and gamma-GTP were significantly lower in C-AIH patients (P< 0.05) than in CHC patients. In C-AIH, ANA titres in seven of nine patients and ASMA titres in five of seven patients were reduced after 1 year UDCA treatment. CONCLUSIONS: These results suggest that UDCA is a useful therapeutic agent for autoimmune-associated chronic hepatitis C.     

乙型肝炎的自身抗体检测分析及临床意义

目的：检测乙型肝炎自身抗体的阳性率,探讨乙型肝炎自身抗体存在的临床意义。方法：分别采用间接免疫荧光法（IIF）和免疫印迹法（Western-blot）检测453例乙型肝炎、162例自身免疫性肝炎（AIH）和96例正常人抗核抗体（ANA）的阳性率、ANA阳性滴度、核型和抗双链DNA抗体（dsDNA）的阳性率以及肝炎相关自身抗体：抗平滑肌抗体（SMA）、抗肝肾微粒体抗体（LKM）的阳性率。应用酶法检测患者的ALT和AST,实时荧光定量PCR技术检测HBV DNA。结果：①乙肝组ANA的阳性率为22．7％,ANA以低滴度（1：100）为主,仅3例乙肝后肝硬化的滴度为1：320;ANA核型以均质型为主,仅5例为斑点型,显著低于AIH组（P〈0．01）。其中急性乙肝、慢性乙肝、重症乙肝和乙肝后肝硬化ANA的阳性率分别为5．2％、22．8％、24．2％和37．9％,慢性乙肝、重症乙肝和乙肝后肝硬化患者ANA的阳性率显著高于急性乙肝（P〈0．05或P〈0．01）,乙肝后肝硬化组明显高于乙肝炎组（P〈0．05或P〈0．01）。②ANA阳性乙肝患者伴有dsDNA抗体,用Western-blot法检测dsDNA的阳性率为10．34％,显著高于ANA阴性的乙肝患者（P〈0．05）,乙肝组如DNA的阳性率为2．42％与AIH组差异无统计学意义（P〉0．05）。③乙型肝炎存在SMA和LKM,但仅有较低的阳性率分别为4．63％和3．31％,显著低于AIH组（P〈0．01）。④乙型肝炎ANA阳性组的ALT、AST水平和HBVDNA阳性率显著高于ANA阴性组（P〈0．05）;乙肝组ALT、AST水平和HBVDNA阳性率显著高于AIH组（P〈0．01）。结论：HBV感染不仅引起肝组织损害,还诱导产生多种以低滴度为主的自身抗体。自身抗体的产生与肝损伤程度有一定相关性,并与HBV复制水平相关;其在探讨乙肝发生、发展机制和病因研究中有一定的意义。     

Polymyositis associated with autoimmune hepatitis, primary biliary cirrhosis, and autoimmune thrombocytopenic purpura

We describe a 40-year-old woman with polymyositis (PM) who developed autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and autoimmune thrombocytopenic purpura (AITP) concurrently. About 4 years earlier, she suffered from muscle weakness probably due to PM. When she visited our hospital, she had polyarthritis, myalgia, symmetrical proximal limb-muscle weakness, elevated muscle enzymes, and myogenic abnormalities on electromyogram. Pathological findings obtained by muscle biopsy showed histological findings consistent with PM. Her serum liver enzymes were also elevated. The histology obtained by liver biopsy revealed the mixture findings of chronic active hepatitis and biliary cirrhosis. As antibodies to mitochondria M2 and liver/kidney microsome type 1 (LKM-1) were present, we concluded her liver disease was due to an overlap of AIH and PBC. Furthermore, purpura on the legs with thrombocytopenia appeared in parallel with liver dysfunction. She was diagnosed as having AITP by clinical and laboratory findings. Her serum showed a speckled pattern in immunofluorescence antinuclear antibody testing, but the antigen specificities were distinct from those of the known myositis-related autoantigens. This is a first case report of PM accompanied by AIH, PBC, and AITP. It was notable that there was an overlap of disease-associated immunological findings and immunogenetic backgrounds. This case provides a possible insight into the mechanisms and interplay of autoimmune diseases.     

Felty's syndrome with chronic hepatitis and compatible autoimmune hepatitis: a case presentation

A 68-year-old woman with Felty's syndrome was admitted to our hospital due to breathlessness. She was diagnosed as having rheumatoid arthritis at age 59 years. Abdominal computed tomography indicated ascites, splenomegaly and liver atrophy. She had no antigens or antibodies for hepatitis virus, or antibodies for mitochondria with the exception of antinuclear antibody. According to the International Autoimmune Hepatitis (AIH) scoring system, she was diagnosed as having chronic hepatitis, compatible with AIH. The association of Felty's syndrome with AIH is very rare and the most difficult problem to overcome is whether or not steroid therapy is necessary in patients with Felty's syndrome complicated by AIH.     

Rapid-onset primary biliary cirrhosis resembling drug-induced liver injury

A 54-year-old woman was admitted to our hospital because of acute liver injury. Since she had a history of having used a diet product, drug-induced liver injury (DILI) was initially considered. However, the patient was subsequently diagnosed as suffering from primary biliary cirrhosis (PBC) based on the findings of liver histology and serum anti-mitochondrial antibody positivity. Overlap syndrome between PBC and autoimmune hepatitis (AIH) was also suspected, however, serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase became normal three months later, after treatment with combination therapy comprising ursodeoxycholic acid plus bezafibrate. We therefore concluded that the liver disease in this patient was actually PBC, but that it resembled overlap syndrome or DILI. In cases of PBC, a rapid onset, as frequently seen in the case of DILI, viral hepatitis or AIH, is not common. We herein report a rare case of PBC which resembled DILI.     

Polymyositis associated with autoimmune hepatitis,primary biliary cirrhosis,and autoimmune thrombocytopenic purpura

Abstract

We describe a 40-year-old woman with polymyositis (PM) who developed autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and autoimmune thrombocytopenic purpura (AITP) concurrently. About 4 years earlier, she suffered from muscle weakness probably due to PM. When she visited our hospital, she had polyarthritis, myalgia, symmetrical proximal limb-muscle weakness, elevated muscle enzymes, and myogenic abnormalities on electromyogram. Pathological findings obtained by muscle biopsy showed histological findings consistent with PM. Her serum liver enzymes were also elevated. The histology obtained by liver biopsy revealed the mixture findings of chronic active hepatitis and biliary cirrhosis. As antibodies to mitochondria M2 and liver/kidney microsome type 1 (LKM-1) were present, we concluded her liver disease was due to an overlap of AIH and PBC. Furthermore, purpura on the legs with thrombocytopenia appeared in parallel with liver dysfunction. She was diagnosed as having AITP by clinical and laboratory findings. Her serum showed a speckled pattern in immunofluorescence antinuclear antibody testing, but the antigen specificities were distinct from those of the known myositis-related autoantigens. This is a first case report of PM accompanied by AIH, PBC, and AITP. It was notable that there was an overlap of disease-associated immunological findings and immunogenetic backgrounds. This case provides a possible insight into the mechanisms and interplay of autoimmune diseases.     

A 38-year-old African-American woman with an unusually rapid progression of "Primary Biliary Cirrhosis": a missed opportunity!

The case discussed is of a 38-year-old African-American woman who developed upper abdominal symptoms and liver test abnormalities. She underwent cholecystectomy for presumed gallstone disease. This was followed by a worsening of her condition, with the development of jaundice in the next 2 weeks. Results of reevaluation included transaminases around 1000 IU/L with minimal elevation of alkaline phosphatase (ALP), an antimitochondrial antibody (AMA) titer of 1:320, and an elevated immunoglobulin M (IgM). The antinuclear antibodies (ANA) level was positive, but titers were not obtained. There was no suggestion of bile duct obstruction. Liver biopsy findings were believed to be consistent with primary biliary cirrhosis (PBC). She was therefore started on, but failed treatment with, ursodeoxycholic acid. She was transferred to a transplant center 8 weeks later after a brief episode of encephalopathy and hypoglycemia. The clinical findings were consistent with subfulminant hepatic failure secondary to autoimmune hepatitis (AIH) with an ANA titer of 1:1280, an anti-smooth muscle antibody (SMA) titer of 1:40, and an elevated IgG. Review of the biopsy showed panlobular inflammation and bridging necrosis consistent with severe AIH. On imaging, she had ascites and a nodular appearance of the liver. An immediate drop in transaminases followed corticosteroid therapy, but her disease was already irreversible, and she underwent successful liver transplantation. The explanted liver was shrunken and noncirrhotic with massive hepatocellular collapse and contained multiple regenerating nodules, explaining the ultrasonographic appearances. The inflammatory component had greatly diminished compared with the earlier biopsy. The case illustrates the importance of knowledge of the natural course of a specific disease and the careful interpretation of clinical data, including autoimmune markers. PBC would rarely cause liver failure in a young woman; it is not a rapidly progressive disease. The original clinical diagnosis was unduly swayed by a positive AMA, which can be seen in up to 20% of patients with AIH. Markedly elevated transaminases with minimal elevation of ALP and positive ANA in a young woman should have pointed toward AIH at an earlier stage. The academic discussion of AMA-positive AIH versus PBC/AIH overlap syndrome remains intriguing, but prompt institution of aggressive immunosuppressive therapy aimed at the AIH component should not be deferred. In retrospect, an opportunity was missed.