Review article: autoimmune hepatitis - current management and challenges

Abstract

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.

Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome

“…Autoimmune liver diseases can remain silent for variable period of time before developing symptoms [7,8,12,19,26] . Of relevance, viral infections, xenobiotics, drugs and microbes can operate as triggers for the development of liver autoimmunity in genetically predisposed individuals [7][8][9]11,12,14,19,25,27,28] . In all but two patients with chronic HBV and HCV infections described in our study PBC was diagnosed during the follow-up period for viral hepatitis.…”

“…The presence of other liver diseases and in particular of AIH has been appropriately excluded [8,23] .…”

“…In contrast, the prevalence of HCV infection is estimated to be low in our area (0.34%), even though clusters of higher HCV prevalence were recently identified by our group [6] . Coexistence, of autoimmune liver diseases like primary biliary cirrhosis (PBC) [7] or autoimmune hepatitis (AIH) [8] with HCV or HBV infections could be a problem especially in endemic areas for viral hepatitis [8] , since viruses in general have long been associated in some cases with the induction of autoimmune phenomena up to the development of overt autoimmune diseases [8][9][10][11][12][13] .…”

Autoimunski hepatitis: savremeni stavovi o dijagnostici i lečenju

“…Pacijenti sa izraženom nekroinflamacijom (bazirano na histološkom nalazu i elevaciji aminotransferaza i imunoglobulina) sa simptomima bolesti treba da budu lečeni. Prema savetu ovih udruženja i pacijente sa blažom formom bolesti i one sa većim rizikom od neželjenih efekata kortikosteroida treba lečiti (Tabela 5) [21].…”

“…Postoje različiti režimi za indukciju remisije i njeno održavanje. Najčešće se koristi protokol prikazan u Tabeli 6 za postizanje remisije, na osnovu rezultata brojnih kliničkih studija i metaanaliza [21].…”