Is a liver biopsy necessary in alcoholic hepatitis?

Forrest, Ewan; Gleeson, Dermot

doi:10.1016/j.jhep.2011.12.028

Cited by 24 publications

(19 citation statements)

References 9 publications

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“…Liver biopsy remains the gold standard for the definitive diagnosis of AH, defined histologically by the presence of neutrophilic lobular inflammation and hepatocyte degeneration (ballooning and Mallory‐Denk bodies) in a background of steatosis and “chicken‐wire” fibrosis . However, biopsy is not routinely recommended because of its associated risks, costs, and lack of availability in many communities . In the absence of histology, AH may be overdiagnosed in 25%‐50% of alcoholic patients who have jaundice due to other acute or acute‐on‐chronic patterns of liver injury .…”

Section: Introductionmentioning

confidence: 99%

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy

Roth

Saberi

Macklin

et al. 2017

Hepatology Communications

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The clinical presentation of alcoholic hepatitis (AH) can be mimicked by other alcoholic liver diseases. The aim of this study was to identify clinical features that predict AH on liver biopsy. Biopsies from patients hospitalized for presumed severe AH were used to identify a derivation cohort (101 patients) and validation cohort (71 patients). Using histologic scores for hepatocyte ballooning, Mallory‐Denk bodies, and lobular inflammation, 95 patient biopsies (55%) were classified as definite AH, 55 (32%) as possible AH, and 22 (13%) as no AH. Survival was similar among the groups, but mortality was significantly increased for patients with fatty change ≤50% on initial liver biopsy. An analysis limited to uninfected patients with definite AH or no AH in the derivation cohort identified a greater leukocyte count at admission and radiographic evidence of liver surface nodularity as independent predictors of definite AH on biopsy (P < 0.05). In the derivation cohort, the leukocyte count thresholds for ensuring 100% specificity for diagnosing definite AH were 10 × 109/L if the liver surface was nodular and 14 × 109/L if the liver surface was smooth, with a sensitivity of 76% and an area under the receiver operator characteristic curve of 0.88. In the validation cohort, these thresholds had a specificity of 86%, a sensitivity of 59%, and an area under the receiver operator characteristic curve of 0.72. Conclusion: The combination of an elevated leukocyte count and a nodular liver surface in the absence of active infection retrospectively identified patients with a high likelihood of histologic AH for whom liver biopsy may not be necessary. For patients with suspected severe AH who do not fulfill these criteria, liver biopsy is important to exclude other variants of alcoholic liver disease. (Hepatology Communications 2017;1:1070–1084)

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Section: Introductionmentioning

confidence: 99%

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy

Roth

Saberi

Macklin

et al. 2017

Hepatology Communications

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“…Other trials in this field 22,55 have required liver biopsy and histological confirmation of the diagnosis prior to inclusion; however, in the UK, the USA and much of Europe, liver biopsy is rarely performed for diagnostic confirmation and reserved only for diagnostic uncertainty. This strategy is vindicated by a number of studies 22,[55][56][57] that show that clinicians can accurately judge the diagnosis by the recent use of alcohol and also applying of strict criteria on the duration of jaundice. A trial requiring liver biopsy could not have recruited this number of subjects, as many centres do not have access to the transjugular technique that would be required in this group of patients or would have considered the procedure to be unethical.…”

Section: Discussionmentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial

Thursz

Forrest

Roderick

et al. 2015

Health Technol Assess

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BackgroundAlcoholic hepatitis (AH) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods, which is characterised by jaundice and liver failure. Severe disease is associated with high short-term mortality. Prednisolone and pentoxifylline (PTX) are recommended in guidelines for treatment of severe AH, but trials supporting their use have given heterogeneous results and controversy persists about their benefit.ObjectivesThe aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX.DesignThe trial was a randomised, double-blind, 2 × 2 factorial, multicentre design.SettingSixty-five gastroenterology and hepatology inpatient units across the UK.ParticipantsPatients with a clinical diagnosis of AH who had a Maddrey’s discriminant function value of ≥ 32 were randomised into four arms: A, placebo/placebo; B, placebo/prednisolone; C, PTX/placebo; and D, PTX/prednisolone. Of the 5234 patients screened for the trial, 1103 were randomised and after withdrawals, 1053 were available for primary end-point analysis.InterventionsThose allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days.OutcomesThe primary outcome measure was mortality at 28 days. Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year. Rates of recidivism among survivors and the impact of recidivism on mortality were assessed.ResultsAt 28 days, in arm A, 45 of 269 (16.7%) patients died; in arm B, 38 of 266 (14.3%) died; in arm C, 50 of 258 (19.4%) died; and in arm D, 35 of 260 (13.5%) died. For PTX, the odds ratio for 28-day mortality was 1.07 [95% confidence interval (CI) 0.77 to 1.40;p = 0.686)] and for prednisolone the odds ratio was 0.72 (95% CI 0.52 to 1.01;p = 0.056). In the logistic regression analysis, accounting for indices of disease severity and prognosis, the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 (95% CI 0.41 to 0.91;p = 0.015). At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups. Serious infections occurred in 13% of patients treated with prednisolone compared with 7% of controls (p = 0.002). At the 90-day follow-up, 45% of patients reported being completely abstinent, 9% reported drinking within safety limits and 33% had an unknown level of alcohol consumption. At 1 year, 37% of patients reported being completely abstinent, 10% reported drinking within safety limits and 39% had an unknown level of alcohol consumption. Only 22% of patients had attended alcohol rehabilitation treatment at 90 days and 1 year.ConclusionsWe conclude that prednisolone reduces the risk of mortality at 28 days, but this benefit is not sustained beyond 28 days. PTX had no impact on survival. Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection.Trial registrationThis trial is registered as EudraCT 2009-013897-42 and Current Controlled Trials ISRCTN88782125.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 102. See the NIHR Journals Library website for further project information. The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding.

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“…First, the diagnosis of AAH was made on clinical grounds, and only three patients underwent liver biopsy. While prior studies have confirmed the utility of liver biopsy in AAH (Mookerjee et al, 2011), a recent meta-analysis of therapeutic trials requiring biopsy-proven AAH for inclusion demonstrated 96% histologic confirmation in patients with serum bilirubin > 80 μmol/L (4.7 mg/dl) (Forrest and Gleeson, 2012). Next, our analysis was not sufficiently powered to detect acute kidney injury and hepatorenal syndrome, and future, larger investigations are planned to detect the effect of lipid metabolism on renal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Stratification of Risk of Death in Severe Acute Alcoholic Hepatitis Using a Panel of Adipokines and Cytokines

Rachakonda

Gabbert

Raina

et al. 2014

Alcoholism Clin & Exp Res

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Background: Dysregulated adipose tissue metabolism has been implicated in the pathogenesis of alcoholic liver disease in murine models. We aimed to characterize serum markers of adipose tissue metabolism and inflammation in patients with severe acute alcoholic hepatitis (AAH) and determine their utility to predict survival in severe AAH. Methods: A prospective, case control study design was used. Seventy-six patients hospitalized with severe AAH and twenty-five ambulatory patients with alcoholic cirrhosis as controls were included. Serum samples were collected for biochemical analyses. Patients were followed for 180 days after enrollment to determine survival. Results: AAH patients exhibited higher serum glycerol and free fatty acid levels, suggesting enhanced adipose tissue triglyceride hydrolysis. Patients with AAH demonstrated a distinct serum lipidomic profile compared with alcoholic cirrhosis but not in systemic and adipose-specific insulin resistance. AAH patients had higher serum resistin and plasmin activation inhibitor-1 levels, while serum leptin was decreased. Serum levels of the prolipolytic cytokines tumor necrosis factor α (TNF- α), interleukin (IL)-6, IL-8 and IL-15 were significantly higher in AAH patients. Only 53% of AAH patients survived 180 days after admission, while all cirrhotic patients were alive at the end of the study period. Among patients with severe AAH, white blood cell count, hemoglobin, resistin, IL-6, and TNF-α were associated with 180-day survival, and all five markers demonstrated accuracy by area under receiver-operator curve (AUC) analysis. Serum IL-6 levels ≥ 38.66 pg/ml most precisely identified deaths in severe AAH. Patients with IL-6 ≥ 38.66 pg/ml had significantly decreased mean survival compared to those with lower levels. Conclusions: AAH patients demonstrate evidence of increased adipose tissue lipolysis and altered serum lipidomic profile compared with alcoholic cirrhosis patients. IL-6 may be a useful biomarker to risk-stratify severe AAH patients at the highest risk of mortality.

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Is a liver biopsy necessary in alcoholic hepatitis?

Cited by 24 publications

References 9 publications

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial

Stratification of Risk of Death in Severe Acute Alcoholic Hepatitis Using a Panel of Adipokines and Cytokines

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