Current and emerging therapies for alcohol-associated hepatitis

Alcohol-related liver disease(ALD)encompasses a spectrum of diseases caused by excessive alcohol consumption.ALD includes hepatic steatosis,steatohepatitis,variable degrees of fibrosis,cirrhosis,and alcohol-associated hepatitis(AH),the latter being the most severe acute form of the disease.Severe AH is associated with high mortality(reaching up to 30%e50%)at 90 days.The cornerstone of ALD,and particularly AH,treatment continues to be abstinence,accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome(AWS).In severe AH with model for end-stage liver disease(MELD)score21,corticosteroids can be used,especially MELD score between 25 and 39,where the highest benefit is achieved.Other key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver transplantation.The development of new therapies based on the pathophysiology and mechanisms of liver injury are underway.This includes the modulation and management of the innate immune response,gut dysbiosis,bacterial translocation,and bacteria-derived products from the intestine.These hold promise for the future of AH treatment.

COVID-19 and Indirect Liver Injury:A Narrative Synthesis of the Evidence

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)infection.The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase,with a prevalence of 16-53%among patients.Cases with severe coronavirus disease 2019(COVID-19)seem to have higher rates of acute liver dysfunction,and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization.Patients with chronic liver diseases also have a higher risk of severe disease and mortality(mainly seen in patients with metabolic-associated fatty liver disease).Several pathways of damage have been proposed in the liver involvement of COVID-19 patients;although,the end-cause is most likely multifactorial.Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection.This enzyme is expressed widely in cholangiocytes and less in hepatocytes.Other factors attributed to liver damage include drug-induced liver injury,uncontrolled release of proinflammatory molecules(“cytokine storm”),pneumonia-associated hypoxia,and direct damage by the infection.Hepatic steatosis,vascular thrombosis,fibrosis,and inflammatory features(including Kupffer cell hyperplasia)are the most common liver histopathological findings in deceased COVID-19 patients,suggesting important indirect mechanisms of liver damage.In this translational medicinebased narrative review,we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19,the histopathological findings,and the impact of these mechanisms in patients with chronic liver disease.

Sending an SOS: Healing the Liver with the Bone Marrow

Citation of this article:Ayares G,Arab JP,Singal AK.Sending an SOS:Healing the Liver with the Bone Marrow.J Clin Transl Hepatol 2022;10(1):1-3.doi:10.14218/JCTH.2021.00557.Cirrhosis,an end stage of any chronic liver disease is a form of impaired regeneration leading to progressive dif-fuse hepatic fibrosis.The healthcare burden of cirrhosis is increasing,and it is currently the 13th leading cause of death globally.The progression of liver injury and fibrosis results in portal hypertension and hepatic insufficiency.