Syphilitic Hepatitis

Liver involvement in syphilis varies with the stage of the disease. The presence of fibrosis. gumma and hepar lobatum are well described in patients with late and congenital syphilis.¹ On the other hand since Hahn's review of 1943,² only eight cases with secondary syphilis have been described in the literature.^3–11 With the new acceptance of aberrant sexual practice there has been an increase in the prevalence of venereal diseases and emergence of new syndromes related to homosexuality.¹²
This case report illustrates one of the manifestations of syphilis that may be easily confused with other causes of jaundice.     

Diagnosis and Treatment of Autoimmune Hepatitis

Autoimmune hepatitis is a chronic liver disease characterized by elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. Recent advances include new practice guidelines that redefine criteria for remission to require complete biochemical and histological normalization on therapy; comparisons between the revised original and simplified diagnostic scoring systems; refined characterization of autoantibodies and their diagnostic performance parameters; proof of the safety and efficacy of combination budesonide and azathioprine therapy for non-cirrhotic patients; scrutiny of overlap syndromes; further analyses of the outcomes of orthotopic liver transplantation and the diagnosis and treatment of recurrent and de novo autoimmune hepatitis after transplantation. Anticipated consequences of the application of the new definition of therapeutic remission include a reduction in the proportion of patients achieving remission with conventional immunosuppression regimens and a corresponding increase in the need for alternative therapies.     

自身免疫性肝炎

自身免疫性肝炎(autoimmune hepatitis,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[1]。此病多见于女性(男女比例为 1:3.6),任何年龄均可发病。如不治疗易发展为肝硬化,免疫抑制剂对其显示一定疗效。病因及发病机制自身免疫性肝炎的病因及发病机制尚不清楚,遗传易感性被认为是主要因素,而病毒感染、环境和药物则可能是在遗传易感基础上的促发因素[2~3]。激发AIH的抗原目前尚不清楚,表达在肝细胞表面的肝…     

自身免疫性肝炎的诊断和治疗进展

自身免疫性肝炎（AIH）是由异常自身免疫反应介导的肝实质炎症性病变,多发于女性。以高丙种球蛋白血症、血清自身抗体阳性和对免疫抑制治疗应答为特点。早期诊断和治疗可显著缓解肝内炎症和纤维化,并能改善患者的预后和生活质量。     

Dichlorvos Induced Autoimmune Hepatitis: A Case Report and Review of Literature

Introduction:

Drug-induced liver injury is a frequent cause of hepatic dysfunction. Several drugs have been identified to cause autoimmune hepatitis (AIH). Environmental chemicals are capable of triggering a certain degree of liver injury. However, toxin induced AIH is rare.

Case Presentation:

We reported a woman with chronic (long-term) exposures to dichlorvos, which resulted in liver injury and cirrhosis. She was diagnosed after a second liver biopsy, which was correlated with laboratory findings. At the same time, she experienced hepatic cortical blindness during her first admission.

Conclusions:

Chronic (long-term) exposures to dichlorvos can lead to AIH. A detailed inquiry of medical history and liver biopsy are necessary for the diagnosis of toxin-induced AIH. Corticosteroid therapy is associated with favorable evolution.     

Autoantibody-Negative Autoimmune Hepatitis

Autoimmune hepatitis has a variable clinical phenotype, and the absence of conventional autoantibodies does not preclude its diagnosis or need for treatment. The goals of this review are to describe the frequency and nature of autoantibody-negative autoimmune hepatitis, indicate its outcome after corticosteroid treatment, and increase awareness of the diagnosis in patients with unexplained acute and chronic hepatitis. The frequency of presumed autoantibody-negative autoimmune hepatitis in patients with acute and acute severe presentations is ≤7%, and its frequency in patients with chronic presentations is 1–34%. Patients with acute presentations can have normal serum γ-globulin levels, centrilobular zone 3 necrosis, and low pre-treatment international diagnostic scores. Liver tissue examination is essential for the diagnosis, and hepatic steatosis can be a co-morbid feature. The comprehensive international scoring system can support but never override the clinical diagnosis pre-treatment, and non-standard serological markers should be sought if the clinical diagnosis is uncertain or the diagnostic score is low. A 3-month treatment trial with corticosteroids should be considered in all patients, regardless of the serological findings, and improvements have occurred in 67–87% of cases. Autoantibody-negative autoimmune hepatitis may be associated with an autoantibody outside the conventional battery; it may have a signature autoantibody that is still undiscovered, or its characteristic autoantibodies may have been suppressed or have a delayed expression. The pathogenic mechanisms are presumed to be identical to those of classical disease. Autoantibody-negative autoimmune hepatitis is an infrequent but treatable disease that must be considered in unexplained acute and chronic hepatitis.     

Use of Sirolimus in the Treatment of Refractory Autoimmune Hepatitis

BackgroundCorticosteroids and azathioprine are widely accepted as the initial therapy for autoimmune hepatitis. However, the disease is refractory to steroids in about 10%-20% of patients, for whom currently there is no standardized treatment. Here we describe our experience with sirolimus in treatment of steroid refractory autoimmune hepatitis.MethodsThis is a longitudinal follow-up study. Between November 2007 and January 2014, 5 subjects with steroid refractory autoimmune hepatitis were treated with sirolimus at our institution.ResultsA response, defined as a sustained >50% fall in alanine aminotransferase (ALT) levels, was achieved in 4/5 patients. A complete response, sustained normalization of ALT levels, was achieved in 2/5 patients. The need for steroids was significantly reduced in all patients (P < .05).ConclusionsIn this small series, sirolimus appears to be useful in the treatment of patients with steroid refractory autoimmune hepatitis.     

Impact of Immunosuppressive Treatment on Liver Fibrosis in Autoimmune Hepatitis

The impact of treatment on progression of fibrosis in autoimmune hepatitis (AIH) is unknown. We assessed the changes in liver fibrosis before and after treatment among these patients. Nineteen AIH patients who had paired liver biopsies were studied. Of these, seven had been treated with 6 months of cyclosporine A and the rest with 6 months of prednisolone for induction of remission. Thereafter all had been maintained on azathioprine. Biopsy specimens before and after treatment were reviewed by one pathologist and scored by the Ishak method. Mean fibrosis stages before and after treatment were compared. Also, factors predicting significant fibrosis (stage 3) and cirrhosis (stage 5) at presentation were assessed. Mean interval between biopsies was 3.38 years. Mean fibrosis stage decreased from 4.53 to 2.16 following treatment (P < 0.001). Mean decrement in inflammatory grade was 8 scores (range, 4–10) in patients in whom fibrosis improved, and 2 scores (range, 0–4) in patients in whom fibrosis did not decrease after treatment (P < 0.001). ALT-to-platelet ratio was the best predictor of significant fibrosis and also cirrhosis. Fibrosis commonly improves after immunosuppressive treatment in AIH. ALT-to-platelet ratio can predict accurately the presence of significant fibrosis and cirrhosis in AIH.     

Autoimmune Hepatitis Induced by Syngeneic Liver Cytosolic Proteins Biotransformed by Alcohol Metabolites

Background and aims: Aldehydes that are produced following the breakdown of ethanol (acetaldehyde) and lipid peroxidation of membranes (malondialdehyde) have been shown to bind (adduct) proteins. Additionally, these two aldehydes can combine (MAA) on nonsyngeneic and syngeneic proteins to initiate numerous immune responses to the unmodified part of the protein in the absence of an adjuvant. Therefore, these studies provide a potential mechanism for the development of antigen‐specific immune responses resulting in liver damage should syngeneic liver proteins be adducted with MAA. Methods: This study sought to test whether MAA‐modified syngeneic liver cytosolic proteins administered daily in the absence of adjuvant into C57BL/6 mice abrogates tolerance to initiate a MAA‐induced autoimmune‐like hepatitis. Results: In mice immunized with MAA‐modified cytosols, there was an increase in liver damage as assessed by aspartate aminotransferase/alanine aminotransferase levels that correlated with liver pathology scores and the presence of the pro‐fibrotic factors, smooth muscle actin, TGF‐β, and collagen. IgG antibodies and T‐cell proliferative responses specific for cytosolic proteins were also detected. Pro‐inflammatory cytokines were produced in the livers of animals exposed to MAA‐modified cytosols. Finally, transfer of immunized T cells to naïve animals caused biochemical and histological evidence of liver damage. Conclusions: These data demonstrate that a disease with an autoimmune‐like pathophysiology can be generated in this animal model using soluble MAA‐modified syngeneic liver cytosols as the immunogen. These studies provide insight into potential mechanism(s) that the metabolites of alcohol may play in contributing to the onset of an autoimmune‐like disease in patients with alcoholic liver disease.     

Update on Autoimmune Hepatitis

Autoimmune hepatitis (AIH), a liver disorder affecting both children and adults, is characterized by inflammatory liver histology, elevated transaminase levels, circulating nonorganspecific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is mainly a paediatric disease, though it does occasionally affects young adults. AIH should be considered during the diagnostic workup of any patient with increased liver enzyme levels. AIH is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine, with symptom free long-term survival for the majority of patients. For those who do not respond to standard treatment, or who are difficult-to-treat, mycophenolate mofetil and, in the absence of a response, calcineurin inhibitors should be tried in addition to steroids. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens.     

Lupus Hepatitis and Autoimmune Hepatitis (Lupoid Hepatitis)

Liver dysfunction occurs in approximately 50% of patients with systemic lupus erythematosus (SLE), and patients with SLE and elevated liver enzymes can present a complicated and difficult differential diagnosis. Lupus hepatitis and autoimmune hepatitis are 2 immunologic conditions involving the liver, which can have similar clinical, laboratory and systemic presentations, leading to difficulties in diagnosis. Physicians need to be aware of these 2 hepatic diseases as diagnosis and appropriate therapy need to occur early in the disease course to prevent progression to advanced liver disease. We review the liver diseases associated with SLE and discuss the approach to the diagnostic evaluation of these patients. In particular, differentiation between lupus hepatitis and autoimmune hepatitis requires careful clinical and often histologic evaluation.