CommentaryStandard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia
Section snippets
Natural History of AH
Alcohol-related steatosis is the most common manifestation of heavy drinking. A “standard drink” in the United States (12 oz of beer, 5 oz of wine, or 1 oz of liquor) contains 14 g of alcohol; volunteers drinking approximately 10 drinks per day for 2-3 weeks consistently developed steatosis.1 This level of drinking, often for decades, is observed in AH,2, 3 but only a minority of such drinkers develop AH. The best established risk factors are female sex and increased body mass index; these and
Diagnostic Definition of AH
AH is a clinical entity with rapid onset of jaundice with elevated serum aspartate transaminase (AST), arising on the background of heavy alcohol use. Liver biopsy usually reveals ASH, cholestasis, and severe fibrosis The thresholds for amount and duration of alcohol use causing AH are not known, although an average consumption of more than 3 drinks (∼40 g) per day for women and 4 drinks (∼50–60 g) per day for men are reasonable minimal thresholds for the diagnosis of AH. Patients typically
Inclusion Criteria
We recommend the following inclusion criteria for clinical studies (Table 1). However, we recognize that biopsy may not be feasible in all situations. Thus, liver biopsy confirmation of ASH should be required only for patients with clinical AH classified as possible AH (see below).
- 1.
Definite AH: Clinically diagnosed and biopsy proven. In the future, imaging techniques and biomarkers may replace liver biopsy for definite diagnosis of AH. However, biopsy may have a role in determining molecular
Outcomes
A 90-day mortality endpoint is preferred to the traditional 30-day mortality in light of recent trials. In addition to mortality, endpoints that reflect improvements in liver function (eg, change in Maddrey discriminant function or MELD score) should be considered for the less severely ill group of patients with AH. There is no instrument currently available that measures disease-specific quality of life in AH. Measures of functional status and quality of life; well-being (eg, WHO Performance
Recommended Common Datasets for Patients in Clinical Trials for AH: Endpoints, Outcomes, and Adverse Events
Suggested common datasets for patients in clinical trials are listed in Table 2: they include usual blood tests for severe liver injury, potential risk factors for AH, and measures related to alcohol consumption before and after the onset of AH. The timing of these measurements will vary between the short term (the traditional measures) and longer term, depending on the outcomes defined (late deaths, complications of cirrhosis). Adverse events include the usual complications of severe liver
Common Data Elements for Capturing and Reporting Adverse Events
All clinical trials use standard data elements such that safety of the tested compound is rigorously investigated. Requirements for safe conduct and reporting results of human research in the United States are dictated by the Code of Federal Regulation (CFR) Title 21. These include (1) drug trial having an investigational new drug approval from the Food and Drug Administration (FDA); (2) registration on Clinicaltrials.gov; (3) adherence to the principles of good clinical practices; (4) having a
Acknowledgements
The NIAAA Alcoholic Hepatitis Consortia were established in 2012 to expedite the translation of emerging findings that could advance the development of new or existing treatments for AH. It consists of 15 translational and clinical projects that are funded through four individual U01 Cooperative Agreements (AA 021840, AA 021893, AA021908, and AA 021886).
D.W.C. is the corresponding author, all other authors are listed alphabetically.
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Conflicts of interest The authors disclose no conflicts.