Possible benefit of splenectomy in liver transplantation for autoimmune hepatitis

Liver transplantation for autoimmune hepatitis (AIH) is usually successful with excellent long-term outcomes, but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy. Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.     

Autoimmune hepatitis: East meets west

Autoimmune hepatitis (AIH) is an inflammatory liver disease with diverse clinical spectrum, which predominantly affects females. This review provides detailed comparisons of epidemiology, genetic predispositions, clinical features, risk factors of hepatocellular carcinoma, and mortality in AIH patients between eastern and western countries. AIH prevalence and incidence are lower in Asia‐Pacific area than in Europe and America. European and American patients seem to have more severe disease, characterized with human leukocyte antigen‐DR3 haplotype, younger age, more AIH‐induced “cirrhosis” at diagnosis, higher elevated serum immunoglobulin G levels, and positive rate of antisoluble liver antigen/liver pancreatitis. The overall AIH diagnostic accuracy of revised original criteria and simplified scoring system are similar in European/American populations and Asian. Cirrhosis at presentation and non‐response to immunosuppressive therapy within 1 year are the most important predictors for poor prognosis of AIH patients.     

Adoptive cell transfer in autoimmune hepatitis

Adoptive cell transfer is an intervention in which autologous immune cells that have been expanded ex vivo are re-introduced to mitigate a pathological process. Tregs, mesenchymal stromal cells, dendritic cells, macrophages and myeloid-derived suppressor cells have been transferred in diverse immune-mediated diseases, and Tregs have been the focus of investigations in autoimmune hepatitis. Transferred Tregs have improved histological findings in animal models of autoimmune hepatitis and autoimmune cholangitis. Key challenges relate to discrepant findings among studies, phenotypic instability of the transferred population, uncertain side effects and possible need for staged therapy involving anti-inflammatory drugs. Future investigations must resolve issues about the purification, durability and safety of these cells and consider alternative populations if necessary.     

Autoimmune chronic active hepatitis developing after acute type B hepatitis

Summary A case of autoimmune type chronic active hepatitis which developed in a 24-year-old female as a sequel of acute type B hepatitis is described. At least in some cases of autoimmune hepatitis, infection with HBV may be the initiating factor.     

Autoimmune liver disease in children

BACKGROUND AND AIM: Autoimmune liver disease (AILD) in children progresses to cirrhosis and liver failure if not diagnosed and managed in time. We prospectively analyzed our patients with liver disease for autoimmune etiology and their outcome with treatment. METHODS: All patients with liver disease were evaluated with liver function tests, abdominal ultrasonography, endoscopy, liver biopsy, viral markers and investigations for Wilson's disease. Immunoglobin (Ig)M hepatitis A virus, hepatitis E virus (HEV) and IgM hepatitis B core antibody were tested if acute viral hepatitis was suspected. Antinuclear antibody (ANA), antismooth muscle antibody (SMA), and liver kidney microsomal antibody (anti-LKM-1) were done in all cases. Autoimmune liver disease was diagnosed when one or more autoantibodies tested positive (> 1:40), and no other etiology of liver disease was identified. We also applied criteria proposed by the International Autoimmune Hepatitis Group. Cases diagnosed to have AILD were treated with immunosuppressive drugs. RESULTS: Autoimmune liver disease constituted 3.9% (6/153; median age and duration of illness 8.5 years and 3 months, respectively) of chronic liver disease cases. Four patients had acute hepatitis-like presentation. Of the six cases, two each were ANA and SMA +; one was anti-LKM-1 +, and the other was positive for both SMA and anti-LKM-1. Three of the patients achieved remission with combination therapy of oral prednisolone (OP) and azathioprine (AZT), and one with only OP. The other two patients were not treated. Two of the patients in remission have been weaned off from immunosuppressive therapy, and one is in a withdrawal phase. Another patient, while in biochemical remission developed superimposed anicteric acute HEV infection. CONCLUSION: Although AILD is uncommon in children, its search is rewarding, as remission is achieved with immunosuppressive therapy. Superimposed acute viral hepatitis can occur in endemic areas.     

Autoimmune hepatitis in Singapore: a rare syndrome affecting middle-aged women

BACKGROUND AND AIM: The prevalence of autoimmune hepatitis in Singapore is unknown. Over a period of 7 years, 24 cases were diagnosed in a district general hospital in Singapore (Toa Payoh Hospital) by using the scoring system proposed by the International Autoimmune Hepatitis Group in 1993. The aims of our study were to determine the prevalence of autoimmune hepatitis in Singapore, and to investigate the characteristics and prognosis in the mainly Chinese population. METHODS: The case records of all 24 patients were reviewed, and the following parameters were recorded: age at presentation, sex, symptoms and signs at presentation, past exposure to hepatotoxic drugs, alcohol intake, blood transfusion laboratory and histological tests used to determine autoimmune hepatitis, response to treatment, complications, and survival. RESULTS: The mean age of patients was 57 years old. There was a female-male ratio of 11:1. Forty-two percent of the patients were cirrhotic at presentation. The prevalence of autoimmune hepatitis was four per 100 000, with no significant difference between Chinese, Malay and Indian patients (Odds ratio of 0.38 by the chi-squared test). Eighty-nine percent of the patients responded to treatment with the induction of prednisolone, but the relapse rate was 61%. Treatment failure occurred in one patient. The mortality rate during the 7 years of follow up was 21%, and all were caused by complications of cirrhosis. The survival at 5 years was 71%, with a standard error of 0.13. CONCLUSION: Autoimmune hepatitis in Singapore is mainly a disease in older women. The response to steroid treatment is good, with a 5-year survival rate of 71%.     

自身免疫性肝炎86例临床、病理特点分析

为提高对自身免疫性肝炎(AIH)的诊治水平,采用国际自身免疫性肝炎小组(IAIHG)新修订的描述性诊 断标准和计分系统,对符合诊断的患者进行临床、生化、病理特点分析。86例AIH患者,女75例,男11例,高发年 龄为40～60岁,其中Ⅰ型80例(93．020k),Ⅱ型3例(3．49％);Ⅲ型3例(3．49％);肝功能生化检查表现为肝炎样改 变;实验室检查主要表现为高γ球蛋白血症,高IgG、ALP、γ-GT及甘油三酯增高,81．5％患者抗核抗体阳性:病理改 变以界板性肝炎,浆细胞浸润为主,78％的患者对免疫抑制剂治疗效佳。AIH患者多为中年女性,以血清自身抗体、 高γ球蛋白血症和肝组织活检呈界板性肝炎、浆细胞浸润,对免疫抑制治疗反应良好为特点。     

Autoimmune hepatitis in the Indian subcontinent: 7 years experience

BACKGROUND: Autoimmune hepatitis (AIH) is presumed to be rare in India. The present prospective study was carried out to determine the prevalence, clinical, biochemical and histological profile of patients with AIH in India. METHODS: Consecutive patients with chronic liver disease suspected to be AIH, were screened for antinuclear antibodies (ANA), antismooth muscle antibodies (ASMA), antimitochondrial antibody (AMA), and anti-liver kidney microsomal antibodies (anti-LKM-1). Serum protein electrophoresis and liver biopsy were done. Autoimmune hepatitis was diagnosed according to the International Autoimmune Hepatitis Group criteria. RESULTS: Fifty of 1358 (3.43%) patients with chronic liver disease were diagnosed as autoimmune liver disease; 39 with AIH, two with overlap syndrome, five with primary sclerosing cholangitis, and four with primary biliary cirrhosis. Twenty-nine patients were categorized as definite AIH and 10 as probable AIH. Autoimmune hepatitis was common in females (males : females 1:3), with a mean age of 31 +/- 17 years. Patients often presented with fatigue, jaundice and anorexia. Skin lesions (58%), joint symptoms (30%), and menstrual abnormalities (26%) were not uncommon. Mildly elevated alkaline phosphatase and hyper gamma globulinemia were seen in 78 and 91% patients, respectively. Eighty percent of patients were type I AIH, while 20% of cases remained unclassified. Histopathological changes included piecemeal necrosis (100%), plasma cell infiltration (91%), rosette formation (82%), and cirrhosis (76%). Overall mortality was 25% during a mean follow up of 15.7 +/- 17.0 months. CONCLUSIONS: Our results clearly demonstrate that: (i) AIH is not uncommon in India; and (ii) while the profile and spectrum of AIH resembles that seen in the West, Indian patients present late, often in a cirrhotic state.     

Autoimmune serology in liver disease: methodology and interpretation

Abstract   Accurate measurement of levels of autoantibodies in serum is critical for the diagnosis of autoimmune hepatitis. The major reactivities include anti-nuclear antibody (ANA), smooth muscle antibody (SMA), antibody to liver kidney microsomes type-1 (anti-LKM1); other relevant reactivities include antibodies to liver cytosol 1 (anti-LC1), soluble liver antigen (anti-SLA), and neutrophil cytoplasmic antigens (ANCA). In addition to the classical indirect immunofluorescence technique, automatic assays based on recombinant antigens are now available, which allow detection of antibodies not visible on immunofluorescence, like anti-SLA, and assist in the interpretation of at times problematic immunofluorescence patterns, like anti-LKM1 or anti-LC1.     

Autoimmune hepatitis in a demographically isolated area of Australia

Background: Previous studies describing autoimmune hepatitis (AIH) come from liver transplant centres in which a skewed distribution of cases may give a misleading picture of the incidence of AIH and its natural history. This series describes AIH in a stable and demographically discrete population of patients in the Australian Capital Territory (ACT) and the surrounding region. Methods: In 42 patients with type 1 AIH (point prevalence 8 per 100 000 population), clinical, laboratory and histological features at presentation, response to initial therapy, details of maintenance therapy and outcome were recorded. Results: Consistent with other publications, the male‐to‐female ratio was 1:3, mean age at presentation was 53 years and 24% had cirrhosis at diagnosis. Most patients (86%) responded to initial therapy and 67% went into long‐term remission. One patient died from liver failure and none required liver transplantation. Azathioprine was included in the treatment regimen in 74% of cases with doses generally <2 mg/kg. Azathioprine dose greater than or equal to 2 mg/kg was associated with better clinical outcome, but this did not reach statistical significance. A higher proportion of female patients had cirrhosis at presentation (9/10 vs 1/10; P= 0.24). Conclusion: In this Australian community‐based study, type 1 AIH was primarily a disease of later life, responded to conventional immunosuppressive therapy and generally has a good prognosis. Further study of the use of azathioprine is warranted to determine the optimal dose.     

Autoimmune hepatitis in childhood

Autoimmune hepatitis (AIH) is a generally progressive inflammatory liver disease of unknown etiology that occurs in adults and children. Although the peak age of incidence is in prepubertal girls, AIH has been diagnosed as early 6 months of age. Two types of AIH are recognized according to the nature of the autoantibody detected in children at the time of diagnosis. The diagnosis of AIH is based on histological abnormalities, characteristic clinical and biochemical findings, and abnormal levels of serum globulin due almost exclusively to markedly increased immunoglobulin G including various autoantibodies. A genetic predisposition is suggested by the increase frequency of human leukocyte antigen (HLA) haplotypes HLA-B8/DR3, and allotypes DR3 and DR4. However, the incidence of these HLA types is different in each country.Proposed triggers of AIH that may initiate the inflammatory process include some viral infections and some drugs. There is much information about adults with AIH, however, little information on AIH in children, especially in Japanese children. To clarify the clinicohistological features of AIH in Japanese children, we analyzed the clinical, pathological features and response to treatment in 12 Japanese children with AIH. Furthermore, we discuss several problems for diagnosis and treatment for AIH in children.     

Autoimmune hepatitis: Unveiling faces

Autoimmune hepatitis (AIH) is a complex multifactorial liver disease with unknown etiology. It may be induced by certain triggers that cause immune disorders and autoimmune attack in genetically susceptible individuals, which ultimately results in chronic persistent interface inflammation of the liver. The diagnosis of AIH is made based on comprehensive evaluation score system. All AIH patients should receive interventions and the mainstay therapy is prednisone alone or in combination with azathioprine. Further exploratory researches on refractory AIH have been developed. Liver transplantation is still the only effective option for patients with decompensated cirrhosis or hepatic failure.     

自身免疫性肝炎与肝移植

AIH是一类以自身免疫反应为基础,以高丙种球蛋白血症、高血清自身抗体为特征的肝脏炎症性病变,汇管区大量浆细胞浸润并向周围肝实质侵入形成界板炎症是其典型病理组织学特征。此病多见于女性(男女比例为1.0:3.6),任何年龄均可发病。免疫抑制剂是治疗AIH的常用药物,但部分患者仍然会发展至终末期肝硬化,或出现暴发性肝衰竭。此时,肝移植术成为治疗终末期AIH患者的有效方法,约占肝移植总数的5%。AIH肝移植患者的5年存活率和移植     

Autoimmune hepatitis: diagnostic and management challenges

Abstract   There are two main types of autoimmune hepatitis (AIH): AIH type 1, characterized by anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies; and AIH type 2, positive for anti-liver kidney microsomal antibody type 1 (LKM1). AIH type 1 affects equally adults and children, while AIH type 2 affects mainly children. There is a female preponderance for both; AIH type 1 is associated with the HLA haplotype DR3, while AIH type 2 is associated with DR7. In young patients, both types of AIH frequently present with features of acute hepatitis. The diagnosis must be suspected and the appropriate tests sought promptly, because treatment should be started as soon as possible to avoid rapid progression to cirrhosis and liver failure. Though new drugs have been used for the treatment of AIH, including ciclosporin A, the standard treatment with prednisolone, to which azathioprine may be added as a steroid sparing agent, remains the best, with excellent short and long term results. Treatment, however, has to be finely tuned, to avoid severe steroid side effects.     

Autoimmune hepatitis versus viral hepatitis C

Abstract: Numerous viruses are capable of inducing the syndrome of chronic hepatitis. Among them are the hepatitis B, C and D viruses. Out of the most common agents of chronic hepatitis, the hepatitis C virus has been found to be strikingly associated with autoimmune diseases and serological markers of autoimmunity. Conversely, the syndrome of genuine autoimmune hepatitis lacks evidence of previous or ongoing virus infection and is diagnosed by additionally excluding metabolic, toxic, and genetic causes of chronic hepatitis, and by the response to immunosuppressive treatment. This review article summarizes the current knowledge of hepatotropic virus-induced autoimmunity. It focuses on the present molecular and immunological definitions, the clinical and molecular distinction between autoimmune hepatitis and chronic viral hepatitis and the implications for the safe and efficacious therapy of these disease entities.     

Autoimmune hepatitis and pregnancy: a rheumatologist's dilemma

OBJECTIVES: To review the course, predisposing risk factors, treatment employed, and complications of autoimmune hepatitis (AIH) during pregnancy. Maternal and fetal outcomes will be discussed. METHODS: We reviewed the literature from February 1966 to January 2004 using MEDLINE and the key words autoimmune hepatitis, chronic active hepatitis, lupoid hepatitis, and pregnancy. An additional case of ours was included as she had AIH since childhood with worsening of liver disease during pregnancy. RESULTS: Including the present case, 58 pregnant women with AIH were reported in 17 case reports and series. In the 101 pregnancies documented in these cases, there were 47 flare-ups, 5 clinical improvements, 45 stabilizations of the disease during pregnancy, and 4 cases in which the disease course was not reported. Two maternal deaths occurred. A perinatal mortality of 4% and 19 fetal deaths were described. Most women were treated with prednisone alone; however azathioprine was used in a number of patients. CONCLUSIONS: Pregnancy course in patients with AIH is unpredictable. AIH exacerbates in some patients and is associated with a high rate of fetal complications including prematurity and death. Low-dose prednisone seems to be the preferred treatment. The use of azathioprine must be individualized and further studies are needed to better define its role and safety during pregnancy in patients with AIH. RELEVANCE: A better understanding of the course of pregnancy in patients with AIH should help design appropriate therapeutic schemes to improve pregnancy outcomes for both mother and fetus.