Diagnosis and treatment of alcoholic hepatitis

Alkoholni hepatitis klinički je sindrom karakteriziran akutnim jetrenim oštećenjem i naglom pojavom žutice. Glavni etiološki čimbenik u nastanku AH je pretjerana konzumacija alkohola, a ostali rizični čimbenici su ženski spol, pretilost i genetska predispozicija. Toksično djelovanje alkohola dovodi do razvitka steatoze, fibroze i upalnog odgovora s neutrofilnom infiltracijom u jetri zbog povećane produkcije proupalnih citokina kao npr. TNF-α, IL-8 i IL-17 te posljedičnog oštećenja i uništenja hepatocita. Dijagnoza se postavlja na temelju kliničke slike i abnormalnih laboratorijskih nalaza u pacijenata kod kojih je poznat abuzus alkohola. Za potvrdu dijagnoze u nejasnim slučajevima izvodi se biopsija jetre. Pacijenti se najčešće prezentiraju naglo nastalom žuticom, bolovima u desnom gornjem kvadrantu, hepatomegalijom, pothranjenošću i nespecifičnim simptomima poput vrućice, slabosti, mučnine i povraćanja, a u težim slučajevima može biti prisutan ascites i encefalopatija. Laboratorijski nalazi pokazuju hiperbilirubinemiju, neutrofiliju, povišene razine AST-a s tipičnim AST/ALT omjerom ≥ 2, te produljeno PV i trombocitopeniju. Glavne patohistološke značajke koje se mogu pronaći prilikom biopsije jetre su steatoza, balonirani hepatociti s Malory-Denkovim tjelešcima, lobularna upalna infiltracija i fibroza. Za procjenu težine bolesti koriste se prognostički modeli mDF, GAHS, AIBC i MELD, a Lille model procjenjuje odgovor na kortikosteroidnu terapiju. Liječenje se temelji na apstinenciji, općim suportivnim mjerama i terapiji kortikosteroidima. Kortikosteroidi, unatoč kontroverzama oko njihove primjene, pokazali su se kao jedina trenutno široko dostupna farmakološka terapijska opcija. Zbog slabih dokaza o korisnosti primjene pentoksifilina, njegova upotreba prema najnovijim smjernicama se više ne preporučuje. Istražuje se primjena GCSF-a te N-acetilcisteina u kombinaciji s prednizolonom u liječenju teških slučajeva alkoholnog hepatitisa. Rana transplantacija jetre kao terapijska opcija u paţljivo odabranoj podgrupi pacijenata s teškim alkoholnim hepatitisom trebala bi se razmotriti kao terapijska opcija.Alcoholic hepatitis is a clinical syndrome characterized by an acute liver injury and sudden onset of jaundice. The primary etiological factor that causes alcoholic hepatitis is excessive alcohol consumption, whereas other risk factors are female gender, obesity, and genetic predisposition. Toxic effect of alcohol causes steatosis, fibrosis and inflammatory response with neutrophil infiltration in the liver due to higher production of anti-inflammatory cytokines such as TNF-α, IL-8 and IL-17, which causes damage and destruction of hepatocytes. Diagnosis is established based on the clinical picture and abnormal laboratory results in patients known for alcohol abuse. To confirm the diagnosis in unclear cases, a biopsy of the liver is performed. Patients usually show sudden onset of jaundice, pain in the upper right quadrant, hepatomegaly, malnutrition, and non-specific symptoms such as fever, malaise, nausea and vomiting, and in severe cases ascites and encephalopathy. Laboratory results show hyperbilirubinemia, neutrophilia, high levels of AST with typical AST/ALT ratio ≥ 2, as well as longer PT and thrombocytopenia. The main pathohistological characteristics that can be found during liver biopsy are steatosis, ballooned hepatocytes with Mallory-Denk bodies, lobular inflammatory infiltration and fibrosis. To assess the severity of disease we use prognostic models mDF, GAHS, AIBC, and MELD, while the Lille model is used to assess reaction to corticosteroid therapy. Treatment consists of abstinence, general support and corticosteroid therapy. Corticosteroids, despite controversies surrounding their application, are for the time being the only effective widely available pharmacological therapeutic option. Due to poor evidence of the usefulness of pentoxyfilline, it´s application is no longer recommended. Application of GCSF and N-acetylcysteine combined with prednisolone is studied in the treatment of severe cases of alcoholic hepatitis. Early liver transplant as a therapeutic option in a carefully selected subgroup of patients with severe alcoholic hepatitis should be considered as a therapeutic option