CommentaryGaps in Knowledge and Research Priorities for Alcoholic Hepatitis
Section snippets
Demographics, Epidemiology, and Burden of Disease
In the United States, the total cases of AH-related hospitalization have increased from 249,884 (0.66% of total admission) in 2002 to 326,403 (0.83% of total admission) in 2010.2 It is also important to identify whether there are specific populations with a particularly high prevalence. As the baby boomer generation ages, it is also important to determine the spectrum of comorbidities present in those with AH and how they impact outcomes, including the response to therapy. A population that
Histologic and Clinical Classification
Bringing clarity to the nomenclature and classification of AH is critically needed to evaluate fully the true prevalence and health burden owing to AH and to inform methods to prevent and treat this condition.
Biomarker Development
Another area where there has been minimal progress is in the area of biomarker development to identify (1) those at risk for AH, (2) the presence of early phases of the disease, particularly in those who are likely to progress, (3) the optimal molecular targets for therapy, and (4) response to treatment. A recent serum metabolomics analysis of 25 patients with severe AH identified a panel of biomarkers for disease prognosis7; however, future studies in larger cohorts of AH patients are required
Patient-Centered Outcomes for AH
Patient outcomes in AH are generally poor unless patients stop alcohol use in an early phase of the disease. In patients with fatty liver, continued alcohol drinking leads to cirrhosis in about 20% of patients. The 30-day mortality is about 20% in mild and moderate AH but it is >40% in severe AH. Long-term survival at 5 and 10 years varies from 0% to 80%.2 About two-thirds of patients present with decompensated liver disease and 15% develop hepatocellular cancer.
Knowledge gaps in the natural
Treatment of AH
Steroids have been the mainstay of treatment for those with severe AH, particularly in the presence of hepatic encephalopathy. However, they are contraindicated in the presence of infections, which are often concomitantly present. A recent, large, multicenter trial of pentoxyfylline did not show any benefits over placebo. Therefore, the treatment of AH remains largely unsatisfactory.
References (28)
- et al.
Pathological features of fatty liver disease
Gastroenterology
(2014) - et al.
Alcoholic hepatitis: current challenges and future directions
Clin Gastroenterol Hepatol
(2014) - et al.
Alcoholic liver disease: pathogenesis and new therapeutic targets
Gastroenterology
(2011) - et al.
Interactions between the intestinal microbiome and liver diseases
Gastroenterology
(2014) - et al.
A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis
Gastroenterology
(2008) - et al.
Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis
Gastroenterology
(2009) - et al.
Excess weight risk factor for alcoholic liver disease
Hepatology
(1997) - et al.
Harmful effect of adipose tissue on liver lesions in patients with alcoholic liver disease
J Hepatol
(2010) - et al.
Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis
Clin Gastroenterol Hepatol
(2012) - et al.
Alcoholic hepatitis
N Engl J Med
(2009)
Trends in alcoholic hepatitis-related hospitalizations, financial burden, and mortality in the United States
J Clin Gastroenterol
Recurrent severe alcoholic hepatitis: clinical characteristics and outcomes
Eur J Gastroenterol Hepatol
A histologic scoring system for prognosis of patients with alcoholic hepatitis
Gastroenterology
Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways
PLoS One
Cited by (21)
Emerging Biomarkers in Alcohol-associated Hepatitis
2023, Journal of Clinical and Experimental HepatologyCitation Excerpt :Persons of Hispanic ethnicity are at a higher risk for ALD, including AH, than non-Hispanic white and African-American persons, which is at least partially related to genetics.83 PNPLA3 increases the predisposition to developing ALD and is associated with more severe disease.7 A genome-wide association study from the STOPAH trial found that homozygosity for rs738409:G in PNPLA3 independently conferred significant additional risk of medium-term mortality in patients with severe AH with hazard ratio of 1.69.8,84
Current and Future Biomarkers in Alcoholic Hepatitis
2021, Clinics in Liver DiseaseCitation Excerpt :There is no equivalent of an anti–smooth muscle antibody to autoimmune hepatitis in AH, so a high level of clinical suspicion is required and thorough assessment for surreptitious alcohol use by patient interview and/or alcohol biomarkers. Risk factors for AH include female sex, Caucasian race, obesity, binge drinking, and the patatinlike phospholipase domain–containing protein 3 (PNPLA3) genetic polymorphism.6–8 There is a poorly understood relationship between the gut microbiome and development of AH: dysbiosis, increased gut permeability, and bacterial overgrowth seem to contribute to the pathogenesis.9,10
Adipocyte Fatty Acid–Binding Protein as a Predictor of Outcome in Alcohol-induced Acute-On-Chronic Liver Failure
2021, Journal of Clinical and Experimental HepatologyNon-invasive diagnosis and biomarkers in alcohol-related liver disease
2019, Journal of HepatologyMicroRNA 122, Regulated by GRLH2, Protects Livers of Mice and Patients From Ethanol-Induced Liver Disease
2018, GastroenterologyCitation Excerpt :The treatment of ALD is a complex process involving reversal of parenchymal cell injury and suppression of inflammation.54 After 40 years of clinical trials, steroids remain the controversial standard of care, with no new treatments available that are approved by the Food and Drug Administration.2,55–57 Based on our results, we speculate that GRHL2 may serve as a prognostic marker of hepatocyte differentiation or disease progression and that in vivo therapeutic correction of GRHL2 splicing or expression changes in ALD may be beneficial to correct MIR122 dysregulation.
Infection in Severe Alcoholic Hepatitis: Yet Another Piece in the Puzzle
2017, Gastroenterology
Funding Arun J. Sanyal is supported by RO1 AA020758, UO1 AA021891. Bin Gao is supported by the NIAAA intramural program. Gyongyi Szabo is supported by U01AA021907, 1U01AA021893, R01AA017729, 1R01AA020744.
Conflicts of interest The authors disclose the following: Arun Sanyal: Clinical trial site PI for NIAAA-industry sponsored trials for alcoholic hepatitis (Conatus, Intercept, Immuron) and Ad hoc consultant to Intercept +Immuron. The remaining authors disclose no conflicts.