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.     

药物诱导的自身免疫性肝炎3例报告

<正>由药物触发的自身免疫反应引起的肝细胞损伤,称之为药物诱发的自身免疫性肝炎(drug-induced autoimmune hepatitis,DAIH)。近几年来药物性肝损害的患者越来越多,由药物性肝损害发展为DAIH的患者也逐年增加,然而由于其发病率低,临床特征不典型,容易被忽视,且易与普通药物性肝损害混淆[1]。本文报道3例药物诱发的自身免疫性肝炎。1临床资料     

Psychological stress is associated with relapse in type 1 autoimmune hepatitis

Background/aim: The pathophysiological basis of relapse and recrudescence in type 1 autoimmune hepatitis (AIH) is poorly understood. This study examined factors associated with biochemical relapse in type 1 AIH, and specifically addressed whether psychological stress was associated with a relapsing‐remitting disease course. Methods: A case–control study design was used to analyse 33 patients with AIH followed at the Yale Liver Clinic during a 4‐year period. Twenty‐two patients with 46 episodes of relapse or recrudescence (cases) and 11 controls in long‐term remission were identified during this period. Clinical variables were collected to establish factors associated with relapse. All patients were administered the Social Readjustment Rating Scale (SRRS), a psychological stress questionnaire consisting of 43 weighted life events. Stress is judged to be low when the score is 0–150; mild, 151–200; moderate, 201–300 and major >300. Results: AST, ALT, prednisone dose and SRRS score were all significantly different between cases and controls. The mean SRRS score for cases with relapse/recrudescence was 239 vs 152 for the control group, P=0.048 and remained significant on ancova analysis which accounted for covariables, P=0.05. Cases also identified additional stressors not represented in the SRRS at a significantly higher rate than controls. Conversely, the controls spontaneously identified coping strategies that may have allowed them to manage stress more effectively. Conclusion: Psychological stress is a significant factor that is associated with relapse in type 1 autoimmune hepatitis. Management of AIH may benefit from strategies to reduce stress and promote psychological well being.     

Postinfantile giant-cell hepatitis associated with ulcerative colitis and autoimmune hepatitis

Postinfantile giant cell hepatitis (PGCH) is rare. It is characterized by the presence of multinucleated giant cells in liver biopsy, and although it has been associated with several etiological agents, in many cases its etiology remains unclear. The case is presented herein of an adult woman with PGCH in the setting of ulcerative colitis and autoimmune hepatitis. The presence of autoimmune hepatitis in the patient is consistent and supports the autoimmune pathogenesis of PGCH in a subgroup of patients. Furthermore, this finding, along with others, suggests that PGCH may be included in the list of hepatic complications of inflammatory bowel disease.     

Case of mixed connective tissue disease associated with autoimmune hepatitis

Summary A 56-year-old female with mixed connective tissue disease (MCTD) who developed autoimmune hepatitis is described. Hepatitis was controlled effectively by the corticosteroid therapy. Biopsy of the liver revealed swelling and hydropic degeneration of hepatocytes, accompanied by Councilman's body formation and focal necrosis. These histological findings differ from those in three previously described cases. A relationship between MCTD and liver involvement appears possible.     

药物诱发自身免疫性肝炎的研究进展

随着药物(或中草药、保健品)的滥用和“被用”,药物性肝损害不断增加.某些药物本身或代谢产物可与蛋白结合形成半抗原,刺激机体发生免疫反应,和(或)由于宿主的遗传易感性、女性、高龄等因素,导致药物诱发自身免疫性肝炎( drug-induced autoimmune hepatitis,DIAIH)的发生.DIAIH的临床症...     

The international autoimmune hepatitis score in chronic hepatitis C

SUMMARY. Clinical and laboratory findings of autoimmunity are common in chronic hepatitis C. Autoimmune hepatitis (AIH), a disease of unknown cause, has been defined by use of the International Autoimmune Hepatitis Group Score (AIH score), which quantifies clinical and laboratory parameters. To further validate the specificity of the International AIH score and investigate the similarities between hepatitis C and AIH, we measured the International Autoimmune Hepatitis Group Score in patients with well-defined chronic hepatitis C. Thirty consecutive non-cirrhotic patients with chronic hepatitis C were evaluated. Scoring was performed using both components of the AIH score: a set of minimum required parameters including laboratory and historical data and a second set of additional parameters dominated by histological criteria. Autoantibodies were positive in 21 of 30 hepatitis C patients and associated (patient or first-degree relative) autoimmune diseases were present in eight of 30 patients. Histologically, chronic active hepatitis with periportal piecemeal necrosis was seen in 24 of 30 patients and lymphoid follicles in 16 of 30 patients. No patient scored as probable or definite AIH using the minimum required parameters of the AIH score. When histological parameters were included, four of 30 patients scored as probable AIH but none as definite AIH. Therefore, AIH was excluded by the minimal and additional criteria of the AIH score in 86% of patients with hepatitis C despite a high prevalence of autoantibodies in these patients. We conclude that the criteria set forth by the International AIH scoring system defines a distinct disease although it shares some features with chronic hepatitis C. Modification of the AIH scoring system to include other commonly accepted risk factors for hepatitis C and additional histological parameters would further improve its specificity.     

丙型肝炎抗体阳性的自身免疫性肝炎1例报告

正1病例资料患者女性,50岁,因"反复右胁部隐痛不适伴乏力1年余,加重1个月"入院。患者1年前无明显诱因下出现右胁部隐痛,伴乏力、腹胀、呃逆,呈进行性加重,自行服用中草药"鱼腥草",症状未见好转,后出现身目黄染,小便洗肉水样,至当地人民医院就诊,期间查"ALT900 U/L",诊断为"慢性丙型肝炎"。服用"多烯磷脂酰胆碱、复方甘草酸苷、双环醇、葡醛内酯、复合维生素B",病情控制欠佳。1年内反复5次转氨酶升     

Factors associated with progression of the disease before transplantation in patients with autoimmune hepatitis

Abstract: Aims/Background: Studies on transplanted patients may provide clinically useful data on factors influencing progression of autoimmune hepatitis (AIH) since transplantation rather than death may now be considered as the most likely end-point of the disease. The aim of this work was to analyze risk factors related to progression of AIH before transplantation and provide guidelines for further prognostication with regards to the timing of transplantation. Methods: 80 liver transplants in 68 patients with AIH were performed in our unit. The diagnosis was established on conventional clinical criteria. Parameters such as sex, age at diagnosis and transplantation or duration of the disease were evaluated in relation to: patient HLA DR status, disease presentation (aggressive or non-aggressive), presence of anti-LKM antibodies and concurrent immune disease. Results: AIH with concurrent immune disease occurred more commonly in females (90 vs. 61%; p= 0.0075) and was linked with markedly slower progression of the disease (125 vs. 66 mo; p=0.002) as compared to subjects without such association. AIH without concurrent autoimmune disease occurred significantly more commonly in patients with DR3 phenotype (p= 0.01). Patients with positive anti-LKM autoantibodies were younger at transplantation (25.6 vs 43.5 yr; p= 0.006) and had more rapid progression of their disease (14.3 vs. 103 mo; p= 0.001). Unlike previously reported series of non-transplanted patients, all anti-LKM positive subjects had no concurrent autoimmune disease. Conclusions: Coincidence with another autoimmune disease is associated with a significantly longer disease history prior to transplantation and may possibly reflect greater responsiveness to immunosuppressive therapy before grafting. AIH without concurrent autoimmune disease, particularly if associated with DR4 negative phenotype, male sex and anti-LKM antibodies may characterize patients with rapid progression of the disease. None of these factors had a significant influence on 5 year survival after surgery.     

Risk factors associated with relapse of type 1 autoimmune hepatitis in Japan

Aim: Patients receiving corticosteroid therapy on a tapered schedule occasionally suffer autoimmune hepatitis (AIH) relapses. The aim of this study was to assess the frequency and features of relapses, explore risk factors associated with relapses, and evaluate the effectiveness of azathioprine (AZP) therapy against relapses in Japanese patients with type 1 AIH. Methods: We assessed clinical characteristics and therapeutic processes in 67 patients diagnosed with AIH. Results: Twenty patients (29.9%) suffered from relapses during tapering of corticosteroid therapy. The remaining 47 patients sustained their remission. At the onset of disease, risk factors associated with relapse were: age of 50 years or older; total bilirubin of 1.5 mg/dL or more; aspartate aminotransferase levels of 250 IU/L or more; alanine aminotransferase levels of 250 IU/L or more; prothrombin activity of 80% or more; γ‐globulin levels of 3.4 g/dL or more; and International Autoimmune Hepatitis Group (IAIHG) score of 17 or more in univariate analysis. Grading of histological interface hepatitis is not significantly associated with relapse. Multivariate analysis revealed that IAIHG scores of 17 or more were significantly associated with relapse (odds ratio = 6.57, 95% confidence interval = 1.19–36.33). Seven patients who relapsed were treated with AZP and prednisolone (PSL), and all sustained remission (100%). Of the remaining 13 relapse patients who received only PSL, eight (61.5%) suffered additional relapses. Conclusion: Our results demonstrate the risk factors associated with relapse of AIH. We also show that early administration of AZP after the first relapse may help to prevent additional relapses.     

自身免疫性肝炎发病机制研究进展

自身免疫性肝炎的病因及发病机制尚未完全阐明,目前多数学者认为具有遗传易感性的个体在多种诱因作用下,自身免疫耐受机制遭到破坏,机体逐渐不能耐受自身抗原,从而导致出现疾病特异性的自身抗体并在肝脏内出现免疫细胞浸润。深入研究发病机制,有助于在诊断、治疗及预防上取得根本性突破。本文就自身免疫性肝炎发病机制的研究进展作一综述     

Identification and characterization of IgG4‐associated autoimmune hepatitis

Background: Autoimmune hepatitis (AIH) and autoimmune pancreatitis (AIP) share clinical and pathological features such as high serum levels of immunoglobulin (Ig) G and autoantibodies, and lymphoplasmacytic infiltration, suggesting the presence of common immunological abnormalities. However, little is known about the possible involvement of IgG4, a hallmark of AIP, in AIH. Aims: In this study, we examined whether the IgG4 response contributes to the histopathological and clinical findings in AIH. Methods: Liver sections from 26 patients with AIH, 10 patients with primary biliary cirrhosis (PBC), three patients with primary sclerosing cholangitis (PSC) and 20 chronic hepatitis patients with hepatitis C virus (HCV) infection were immunostained for IgG4. We investigated the relationship among the histopathology, the responses to steroid therapy and the IgG4 staining. Results: Nine of the 26 liver specimens from patients with AIH showed positive staining for IgG4 whereas none of the 10 samples from patients with PBC, the three samples from patients with PSC or the 20 samples from patients with HCV hepatitis were positive. Patients with IgG4‐positive AIH also showed increased serum levels of IgG. The numbers of T cells, B cells and plasma cells were significantly increased in the livers of patients with IgG4‐positive AIH as compared with those patients with IgG4‐negative AIH. Patients with IgG4‐positive AIH also showed a marked response to prednisolone therapy. Conclusions: AIH may be classified into either an IgG4‐associated type or an IgG4 non‐associated type with the former showing a marked response to prednisolone treatment.