title: New paradigms in management of alcoholic hepatitis: a review.
abstract: Severe alcoholic hepatitis (SAH) is defined by modified Maddrey discriminant function ≥32 or Model for End-Stage Liver Disease (MELD) >21 and/or hepatic encephalopathy. It has a 3-month mortality rate ≥30-70 %. Patients with severe alcoholic hepatitis need combined, i.e., static (MELD score) and dynamic (Lille's score), prognostication. Systemic inflammation and poor regeneration are hallmarks of SAH, rather than intrahepatic inflammation. SAH is characterized by dysregulated and uncontrolled systemic inflammatory response followed by weak compensatory antiinflammatory response that leads to increased susceptibility to infection and multiple organ failure. Massive necrosis of hepatocytes exceeds the proliferative capacity of hepatocytes. Liver progenitor cells proliferate to form narrow ductules which radiate out into the damaged liver parenchyma. Corticosteroids have been the standard-of-care therapy, albeit controversial. However, the recent Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial revealed that prednisolone was not associated with a significant reduction in 28-day mortality, with no improvement in outcomes at 90 days or 1 year. A paradigm shift from antiinflammatory therapy such as corticosteroids to liver regeneration treatment, e.g., granulocyte-colony stimulating factor, molecular targeted treatments, and fecal microbiota transplantation, for severe alcoholic hepatitis is taking place. Liver transplantation should be offered to select patients with severe alcoholic hepatitis who are nonresponsive to medical treatment.
authors.affiliation: Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India. sandeepsidhu1963@gmail.com.
authors.forename: Sandeep Singh
authors.initials: SS
authors.lastname: Sidhu
authors.affiliation: Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India.
authors.forename: Omesh
authors.initials: O
authors.lastname: Goyal
authors.affiliation: Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India.
authors.forename: Harsh
authors.initials: H
authors.lastname: Kishore
authors.affiliation: Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India.
authors.forename: Simran
authors.initials: S
authors.lastname: Sidhu
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000069467:Fecal Microbiota Transplantation / Q000379:methods; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006501:Hepatic Encephalopathy / Q000150:complications / Q000453:epidemiology / Q000209:etiology; D006519:Hepatitis, Alcoholic / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008107:Liver Diseases / Q000188:drug therapy; D008115:Liver Regeneration / Q000187:drug effects*; D016031:Liver Transplantation / Q000379:methods; D008297:Male; D051379:Mice; D023421:Models, Animal; D058990:Molecular Targeted Therapy / Q000379:methods; D009336:Necrosis / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D010726:Phosphodiesterase Inhibitors; D016179:Granulocyte Colony-Stimulating Factor; D011239:Prednisolone; C072115:nartograstim; D010431:Pentoxifylline
keywords: Alcoholic hepatitis; Corticosteroids; Granulocyte-colony stimulating factor; Liver transplantation; Molecular targeted therapy