Determinants of long-term outcome in severe alcoholic hepatitis

Potts, Jonathan R.; Goubet, Stephanie; Heneghan, Michael A.; Verma, Sumita

doi:10.1111/apt.12427

Cited by 107 publications

(114 citation statements)

References 39 publications

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“…3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 17 Fourth: the study provides clear evidence supporting the primacy of drinking behaviour as a determinant of medium-term outcome in patients with severe alcoholic hepatitis who survive the initial illness [15,16]. Individuals who maintain abstinence have significantly lower mortality than individuals who resume drinking, at any level.…”

Section: Discussionmentioning

confidence: 92%

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Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis

Atkinson

Way

McQuillin

et al. 2017

Journal of Hepatology

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Background & Aims: Carriage of rs738409:G in PNPLA3 is associated with an increased risk of developing alcohol-related cirrhosis and has a significant negative effect on survival. Short-term mortality in patients with severe alcoholic hepatitis is high; drinking behaviour is a major determinant of outcome in survivors. The aim of this study was to determine whether carriage of rs738409:G has an additional detrimental effect on survival in this patient group. Methods: Genotyping was undertaken in 898 cases with severe alcoholic hepatitis, recruited through the UK Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial, and 1,188 white British/Irish alcohol dependent controls with no liver injury recruited via University College London. Subsequent drinking behaviour was classified, in cases surviving ≥90 days, as abstinent or drinking. The relationship between rs738409 genotype, drinking behaviour and survival was explored. Results: The frequency of rs738409:G was significantly higher in cases than controls (29.5% vs. 18.9%;). Case-mortality at days 28, 90 and 450 was, 16%, 25% and 41% respectively. There was no association between rs738409:G and 28-day mortality. Mortality in the period day 90-450 was higher in survivors who subsequently resumed drinking (Hazard Ratio [HR] 2.77, 95% Confidence Interval [CI] 1.79-4.29; p<0.0001) and individuals homozygous for rs738409:G (HR 1.69, 95% CI 1.02-2.81, p=0.04). Conclusion: Homozygosity for rs738409:G in PNPLA3 confers significant additional risk of medium-term mortality in patients with severe alcoholic hepatitis. Rs738409 genotype may be an additional factor when considering treatment options in these patients.Response to Reviewers: Reviewer statistics 1.Imputing missing drinking behavior at 90 days based on observed values at 1 year is tricky, even in sensitivity analyses. Actually, this corresponds to sort of conditioning on the future, which should be avoided because it may lead to biased results (see works by Terry Therneau, for instance). Since it is a sensitivity analyses, the issue is less severe than for a primary analysis, but the limit should be stated. 2.The authors explain that now they only kept subgroup analyses where a significant interaction was found, but in the manuscript, it remains "Separate models were fitted for clinically relevant features and biochemical parameters", thus without conditioning on a significant interaction. 3.My point on the sentence "Individuals homozygous for rs738409:G had a significantly lower 450-day survival, even if abstinent" has been misunderstood, and it is certainly because I was not clear enough. I did not mean that there was no significant difference in any of the whole population and the subgroup analyses, but that it was not possible to claim that 450 days mortality would be lower in patients homozygous for rs738409:G because this was not analyzed. What the study shows is that among patients still alive at 90 days, the 450 days mortality was different, which is different. Simply stating "450 day...

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Section: Discussionmentioning

confidence: 92%

“…The long-term prognosis is influenced by several factors including gender, disease severity at presentation, the presence of/evolution to cirrhosis and subsequent drinking behaviour [9,12,13,15,16].…”

Section: Introductionmentioning

confidence: 99%

Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis

Atkinson

Way

McQuillin

et al. 2017

Journal of Hepatology

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“…Ascites is the most the common complication of cirrhosis, seen in approximately 90% of individuals with end stage liver disease (ESLD) (1). It results in frequent, repeated hospitalisations due to symptoms such as pain and breathlessness.…”

Section: Introductionmentioning

confidence: 99%

“…Unresponsiveness to, or intolerance of, diuretics [refractory ascites, (RA)] is a poor prognostic sign in ESLD; without liver transplantation (LT) median life expectancy is six months (2, 3). We and others have shown less than ten percent of patients with advanced cirrhosis are eligible for LT due to comorbidity, alcohol recidivism, substance misuse and psychosocial issues (1,4). Thus in many with RA and ESLD the management remains palliative.…”

Section: Introductionmentioning

confidence: 99%

Palliative long-term abdominal drains in refractory ascites due to end-stage liver disease: A case series

et al. 2016

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Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. MeSH headings/keywords

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“…This increasingly common condition is associated with poor survival, and a recent meta‐analysis of 77 studies, which included data from a total of 8,184 patients, showed mortality rates from SAH as 26% at 28 days, 29% at 90 days, and 44% at 180 days 1. Even after decades of debate and research, SAH continues to be a treatment enigma, and abstinence remains the only independent predictor of long‐term survival 2. The shortage of novel therapeutic strategies in SAH is attributable to being clinically understudied in comparison with other liver diseases, the lack of significant research funding historically, and the inability of recapitulating this complex, inflammatory yet immunodeficient, multifactorial disease in animal models.…”

mentioning

confidence: 99%

Can we reliably predict response to corticosteroid treatment in severe alcoholic hepatitis?

Chokshi

2018

Hepatology Communications

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Determinants of long-term outcome in severe alcoholic hepatitis

Abstract: SUMMARY BackgroundAlthough short-term outcome in severe alcoholic hepatitis (SAH) is well described, its long-term course remains uncharacterised.

Cited by 107 publications

References 39 publications

Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis

Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis

Palliative long-term abdominal drains in refractory ascites due to end-stage liver disease: A case series

Can we reliably predict response to corticosteroid treatment in severe alcoholic hepatitis?

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