SUMMARY BackgroundAutoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by interface hepatitis, hypergammaglobulinaemia, circulating autoantibodies and a favourable response to immunosuppression. AimTo review recent advancements in understanding aetiopathogenesis, clinical, serological and histological features, diagnostic criteria and treatment strategies of AIH. MethodsPublished studies on AIH extracted mainly from PubMed during the last 15 years. ResultsAutoimmune hepatitis has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations are variable ranging from no symptoms to severe acute hepatitis and only seldom to fulminant hepatic failure. Autoimmune attack is perpetuated, possibly via molecular mimicry mechanisms, and favoured by the impaired control of regulatory T-cells. A typical laboratory finding is hypergammaglobulinaemia with selective elevation of IgG, although in 15-25% of patients -particularly children, elderly and acute cases -IgG levels are normal. Liver histology and autoantibodies, although not pathognomonic, still remain the hallmark for diagnosis. Immunosuppressive treatment is mandatory and life-saving; however, to meet strict response criteria, the conventional therapy with prednisolone with or without azathioprine is far from ideal. ConclusionsAutoimmune hepatitis remains a major diagnostic and therapeutic challenge. The clinician, the hepato-pathologist and the laboratory personnel need to become more familiar with different expressions of the disease, interpretation of liver histology and autoimmune serology. According to the strict definition of treatment response issued by the 2010 AASLD guidelines, many patients are nonresponders to conventional treatment. Newer immunosuppressive agents targeting pathogenetic mechanisms can improve patient management, which needs to be tailored on a case-by-case basis.

Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.

an internationally acceptable grading system, which has al-A panel of recognized experts in liver transplantation ready been developed for kidney, 3 heart, 4 and lung. 5 At the pathology, hepatology, and surgery was convened for Third Banff Conference on Allograft Pathology, a group of the purpose of developing a consensus document for the specialists in liver transplantation from North America, Eugrading of acute liver allograft rejection that is scientifirope, and Asia met for this purpose. cally correct, simple, and reproducible and clinically useful. Over a period of 6 months pertinent issues were DEFINITION OF ACUTE REJECTION discussed via electronic communication media and a consensus conference was held in Banff, Canada in the In general, organ allograft rejection can be defined as, ''an summer of 1995. Based on previously published data and immunological reaction to the presence of a foreign tissue or the combined experience of the group, the panel agreed organ, which has the potential to result in graft dysfunction on a common nomenclature and a set of histopathologi-and failure.'' 2 This report is specifically concerned with acute cal criteria for the grading of acute liver allograft rejec-rejection, recently defined by the international consensus tion, and a preferred method of reporting. Adoption of document on terminology for hepatic allograft rejection 2 as, this internationally accepted, common grading system ''inflammation of the allograft, elicited by a genetic disparity by scientific journals will minimize the problems associ-between the donor and recipient, primarily affecting interlobated with the use of multiple different local systems. ular bile ducts and vascular endothelia, including portal Modifications of this working document to incorporate veins and hepatic venules and occasionally the hepatic artery chronic rejection are expected in the future. (HEPATOL-and its branches.'' 2 Early rejection, cellular rejection, nonduc-OGY 1997;25:658-663.) topenic rejection, rejection without duct loss, and reversible rejection are synonyms for acute rejection that appear in the literature, but their use is discouraged. The general clinical, The success of hepatic transplantation has resulted in its laboratory, and histopathological abnormalities listed below widespread use for treatment of many patients with endstage were derived from the international consensus document.2 liver disease; it is currently offered by more than 100 centers worldwide. One-year survival rates range from 70% to 90%; CLINICAL AND LABORATORY FINDINGSand long-term survival of 50% to 60% of patients is not unViewed from a biological perspective, any recipient's imcommon.1 Therefore, an increasing number of physicians, inmune system will likely be perturbed after transplantation, cluding pathologists, many of whom have no specific training resulting in immune activation. 2 However, viewed from a in transplantation biology, will become involved in the care clinical perspective, because of baseline immunosuppressive of organ all...

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