Autoimmune chronic active hepatitis: anatomoclinic's study of 50 patients

PURPOSE: To analyse anatomoclinic and evolutive aspects of autoimmune hepatitis (AIH) through 50 observations collected in two Internal Medicine departments in Algiers from 1998 to 2002 and to make a review of the literature. METHODS: The study is prospective. The diagnosis of autoimmune hepatitis (AIH) is established according to the recommendations of the score of the International Autoimmune Hepatitis Group (1991) or/and hepatitic damage confirmed by histology. RESULTS: Fifty patients were studied: (32 women-18 men) and the mean age was 38 years (17 to 73). Autoimmune extra-hepatitic manifestations were associated in 26%. The AIH type 1 has been noted in 58%. AIH were type 2 in only 6%. In 22% of the cases AIH were sero-negative and the others AIH represented 14% were classed as overlap-syndrome (5 cases of primary biliary cirrhosis and 2 cases of primary sclerosing cholangitis hepatitis overlap syndrome). The first liver biopsy tissue showed strong necrotic-inflammatory activity in 56% and cirrhosis was identified in 19 patients (38%). The treatment (azathioprine and corticosteroid) was prescribed in 37 patients (74%) in active chronic hepatitis or in compensed cirrhosis. Follow-up: 28% of the patients died (9-36 months) because cirrhosis's complications or because complications of hepatocarcinoma (3 cases). CONCLUSION: The diagnosis of AIH must be established early for each patient with chronic liver disease particularly is those are supposed as a crypto genetic hepatitis. The prognosis is compromised by delayed diagnosis and the mortality in middle following up is high.     

自身免疫性肝炎合并淋巴结肿大14例分析

目的分析自身免疫性肝炎（autoimmunehe patitis，AIH）合并淋巴结肿大的临床特点及探讨可能形成原因。方法回顾性分析2000年1月～2008年1月在天津医科大学总医院确诊的114例AIH患者的临床资料。结果114例A1H患者分为两组，其中A组无淋巴结肿大100例，B组合并淋巴结肿大14例，二者对比分析。A、B两组比较，B组易出现肝硬化（57／100vs12／14，P〈0．05），两组白细胞、血小板差异有统计学意义（P〈0．05）。结论AIH可合并淋巴结肿大，且合并淋巴结肿大者较易出现肝硬化，表现脾功能亢进，可能是AIH预后不良的一个指标。     

Autoimmune hepatitis: a review

Autoimmune hepatitis (AIH) is an inflammatory liver disease that predominantly affects females. The disease is characterized histologically by interface hepatitis, biochemically by increased aspartate and alanine aminotransferase levels, and serologically by the presence of autoantibodies and elevated levels of immunoglobulin G. AIH affects both adults and children, and is particularly aggressive in the latter group. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. Treatment is often successful at inducing remission of disease, and this can lead to a normal life expectancy. However, progression to cirrhosis can and does occur in some. For those with advanced-stage disease and complications, consideration of liver transplantation is appropriate.     

Autoimmune hepatitis. Part A: pathogenesis

Autoimmune hepatitis is a consequence of a triggering antigen and genetic factors that favor the presentation of autoantigens, polymorphisms that affect immunocyte activation and durability, cytokine alterations that promote proliferation of liver-infiltrating cytotoxic T cells, and perturbations in the number and function of immune-regulatory cell populations, including T regulatory cells and natural killer T cells. The triggering epitope is probably a short sequence peptide that is common in multiple infectious or toxic agents. Homologies between this epitope and self-antigens (molecular mimicry) may stimulate humoral and cellular responses that are cross-reactive. Sensitized immunocytes extend and perpetuate the inflammation through imprecise targeting of self-antigens that resemble foreign antigens (promiscuous behavior). The occurrence and clinical phenotype of the disease may relate to genetic susceptibility factors that favor protracted exposure to indigenous etiological agents, and these genetic factors can vary in different geographical regions and ethnic groups. The clinical phenotype within a population can be modified further by genetic polymorphisms that are not disease specific and that affect immunocyte activation, differentiation, proliferation and programmed death (apoptosis). Autoimmune hepatitis is a model of autoreactivity that reflects multiple disturbances in the counter-regulatory mechanisms essential for immune homeostasis.     

Autoimmune hepatitis: the role of environmental risk factors: a population-based study

Purpose

The etiology of autoimmune hepatitis (AIH) likely involves a complex interaction of genetic and environmental factors. We aim to investigate the associations between exposure to putative environmental factors and AIH and to quantify AIH risk in a first-degree relative.

Methods

We conducted a population-based case-control study. Cases were AIH patients who were alive and resided in Canterbury, New Zealand, between 1 July 2011 and 30 June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used.

Results

72 AIH cases and 144 controls were included. We found that exposure to antibiotics within 12 months prior to AIH diagnosis (OR 12.98, 95 % CI 2.49–67.67, p < 0.01) was an independent risk factor for the development of AIH. Alcohol consumption (OR 0.43, 95 % CI 0.28–0.68, p < 0.01) and childhood home with wood heating (OR 0.30, 95 % CI 0.14–0.63, p < 0.01) were independently associated with reduced risks of later development of AIH. The crude risk of AIH in first-degree relatives of a patient with AIH was 0.2 % (95 % CI <0.1–2.0).

Conclusions

We found that antibiotics are an independent risk factor for the development of AIH, whereas alcohol consumption and living in a childhood home with wood heating are independent protective factors against the later development of AIH.     

Autoimmune hepatitis. Part B: diagnosis

Diagnostic criteria have been codified by the International Autoimmune Hepatitis Group, and a scoring system can quantify the strength of the diagnosis and over-ride the impact of absent or inconsistent features. The absence of a definable etiologic agent and precise diagnostic test, implies that the diagnosis may be missed or misapplied. Centrilobular (zone 3) necrosis may be an early form of autoimmune hepatitis and this pattern can transform to the classical pattern of interface hepatitis. An acute severe or fulminant presentation is possible, and different ethnic groups may have different manifestations and outcomes. Asymptomatic patients at presentation commonly become symptomatic, and treatment decisions must be based on objective features of disease severity and not the presence or absence of symptoms. Concurrent autoimmune diseases are frequent, and they may constitute an autoimmune polyglandular syndrome associated with a single gene mutation. Emerging autoantibodies of possible prognostic value are antibodies to soluble liver antigen/liver pancreas, asialoglycoprotein receptor, actin, and liver cytosol type 1. HLA DRB1*03, *04, *03–*04, *07, *13 and DQB1*02 are associated with the occurrence, clinical phenotype and outcome of autoimmune hepatitis. Variant syndromes should be suspected if cholestatic features are prominent and conventional treatment is ineffective.     

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.     

Autoimmune hepatitis in patients with a diagnosis of multiple sclerosis

Autoimmune hepatitis (AIH) is a chronic necroinflammatory liver disorder associated with hypergammaglobulinemia and circulating autoantibodies. Two patients previously diagnosed with multiple sclerosis who developed AIH are reported. One patient showed acute presentation with fulminant hepatic failure requiring liver transplantation. Serum autoantibodies were negative in both patients but a characteristic clinical course in the first patient as well as the hepatic histological features with typical pathological changes of AIH in both patients and a score compatible with AIH established the diagnosis.     

Autoimmune chronic active hepatitis in a family.

A positive family history of autoimmune disease is common among patients with autoimmune chronic active hepatitis, but usually autoimmunity is directed at organs other than the liver. We document for the first time the multiple occurrence of autoimmune chronic active hepatitis in a family. Out of a sibship of seven, three sisters developed this, one sister developed coeliac and autoimmune thyroid disease, one sister showed serological signs of autoimmunity, while the two brothers were well with no signs of autoimmunity. HLA typing showed that in association with the female sex DR3 seems to be more important than B8 in conferring susceptibility to autoimmune chronic active hepatitis, at least in this family.     

Autoimmune hepatitis

Autoimmune hepatitis was one of the first liver diseases for which an effective treatment was developed and the benefit proven by randomized controlled trials. Nonetheless, both the diagnosis and the treatment of autoimmune hepatitis remain full of challenges. The clinical spectrum is very wide, ranging from subclinical non-progressive disease to fulminant hepatic failure. Diagnostic criteria based on elevation of IgG, demonstration of characteristic autoantibodies, and histological features of hepatitis in the absence of viral disease are very helpful. However, in some patients, diagnosis remains a clinical challenge. Adequately dosed steroids are the mainstay of remission induction treatment, while remission maintenance is best achieved by azathioprine. Therapeutic alternatives are required in a small group of patients responding insufficiently to these drugs or intolerant to their side effects.     

Autoimmune hepatitis

Autoimmune hepatitis (AIH) is an inflammatory liver disease that mainly affects females. It is characterized histologically by interface hepatitis, biochemically by increased aspartate and alanine aminotransferase levels, and serologically by the presence of autoantibodies and increased levels of immunoglobulin G. AIH affects both adults and children, and is particularly aggressive in the latter group. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. With appropriate treatment 80% of patients achieve remission and long-term survival. Those patients who progress to end-stage liver disease because they are unresponsive or nonadherent to treatment, and those with fulminant liver failure (encephalopathy grade II-IV) at diagnosis, require liver transplantation. Seropositivity for smooth muscle and/or antinuclear antibodies defines type 1 AIH, while positivity for liver kidney microsomal type 1 antibodies defines type 2 AIH. The primary cause of AIH is unknown; however, considerable knowledge about the mechanisms of liver damage involved has been gathered over the past 30 years, which is likely to provide the basis for specific modes of treatment and a possible cure.     

自身免疫性肝炎

自身免疫性肝炎 (AIH)是一类病因未明 ,但均具有自身免疫基础的慢性炎症坏死的肝脏疾病 ,如高丙种球蛋白血症、自身免疫性抗体阳性及糖皮质激素治疗有效。病理学上肝实质呈渐进性的损害 ,以汇管区和小叶间隔周围肝细胞呈小碎片样坏死以及炎性细胞浸润为特征。此病发病率约 2 0～ 3 0 /百万 ,占慢性肝炎的 10 %～ 2 0 % ,是慢性非病毒性肝炎中较常见的一种疾病。随着先进的分子生物学和病毒学诊断方法的应用 ,目前对AIH概念有了进一步的认识[1] 。近年来国际上推出的AIH的诊断计分系统和一些自身免疫指标 ,将有助于AIH的诊断和鉴别诊断…