Elsevier

Journal of Hepatology

Volume 70, Issue 2, February 2019, Pages 328-334
Journal of Hepatology

Review
Liver transplantation for alcoholic hepatitis

https://doi.org/10.1016/j.jhep.2018.11.007Get rights and content

Summary

While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called ‘6-month rule’) by many centres made AH a contraindication to LT. Given the high short-term mortality of severe AH, the lack of effective medical therapies and an increasing recognition that the 6-month rule unfairly excluded otherwise favourable candidates, a seminal European pilot study of LT for AH was performed. The success of the European study, which has been corroborated in retrospective analyses from the United States, represented a paradigm shift in therapy for highly selected patients with severe AH who are not responding to medical therapy. However, prospective studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder.

Section snippets

Alcoholic hepatitis as an indication for liver transplantation – a brief history

In 1983, the National Institutes of Health convened a consensus development conference about liver transplantation (LT).1 The consensus statement, which declared LT a ‘therapeutic modality for end-stage liver disease that deserves broader application’, was a key turning point in the establishment of LT within mainstream therapeutics in the United States (US). In addition, the assembled experts offered the following assessment regarding ‘alcohol-related liver cirrhosis and alcoholic hepatitis’:

The ‘6-month rule’

Even while the need to understand AUD became more widespread within the transplant community, LT as a therapy for patients with severe AH remained ‘beyond the pale’. The key to this attitude was a resistance to offering LT to patients who had a short, or no, interval of abstinence. The origin of the 6-month abstinence requirement prior to LT is obscure. In a survey conducted in 1996, 85% of responding LT programmes in the US said that they required at least 6 months abstinence as a

The present era

Within this historical perspective, the 6-month rule and with it the interdiction of LT for patients with ALD and short intervals of abstinence has persisted in the US. The change in attitude arose in Europe, most significantly in France, where a consensus conference in 2005 came to the conclusion that a therapeutic trial of early LT in patients not responsive to corticosteroid therapy was recommended ‘despite the brevity of the required abstinence’.14 This important determination prepared the

Database studies

It is possible to gain insight into the success of LT for AH by examining what has already been done, in some cases unknowingly. In 2002, Tome et al. reported a review of liver explants from 68 patients transplanted for ALD and compared them to 101 explants from patients transplanted for miscellaneous non-ALD causes in Spain.18 The authors looked for histologic evidence of alcoholic steatohepatitis (ASH) in explants, implying more recent alcohol use (perhaps hidden) at the time of LT. There was

Landmark French-Belgian trial

In 2011, a pioneering study demonstrated a significant survival benefit in patients receiving liver transplants for severe alcoholic hepatitis, which would encourage further study in Europe and the US.

This call was answered in 2011. Mathurin et al., performed a prospective study of LT for severe AH carried out at 7 liver transplant centres (6 across France, 1 in Belgium) that included patients with severe AH not responding to medical therapy (DF >32, Lille ≥0.45) and stringent selection

Liver transplantation for alcoholic hepatitis crosses the Atlantic

The US response to the French-Belgian trial was more hesitant, with only a handful of centres reporting on single-centre pilot studies initiated in response. (Table 3) The initial report came in 2016, with Im et al. reporting on the Mount Sinai experience with LT for severe AH in a single-centre report of 9 patients compared to a matched control group that were managed medically, similar to the French-Belgian trial.25 Out of 111 patients with severe AH from 2012–2015, 94 patients with severe AH

Impact of liver transplantation for alcoholic hepatitis

Coinciding with highly effective therapies for hepatitis C virus infection and despite the rising burden of non-alcohol-related fatty liver disease, ALD is now the most common liver disease aetiology for patients waitlisted and undergoing LT in the US.[29], [3] LT for AH is likely contributing to this trend. Two surveys of LT centre directors in the US, reflecting data from 2014 and 2017 with similar response rates, illustrate the broader interest in LT for AH.[30], [31] Over 3 years, the

Improving candidate selection

Distinguishing between AH, decompensated AC and acute-on-chronic liver failure can be difficult. The diagnostic criteria outlined by the NIAAA can be useful for classifying patients as having definite, probable or possible AH.36 Liver biopsy should be performed, usually by transjugular route, when there is diagnostic uncertainty (like in possible AH) and treatment is being considered (including LT for AH), as recommended by clinical guidelines.[37], [38]

The French-Belgian trial set very

Areas of future study

As with any new indication for LT, a learning curve for candidate selection is expected. Akin to the early days of LT for hepatocellular carcinoma, the search for pre-LT psychosocial “Milan criteria” informing and pushing the boundaries for optimal selection in LT for AH should be pursued by the transplant community in well-designed prospective studies. Equally important, studies of AUD treatment (psychosocial and/or pharmacologic) after LT are needed. Since AUD is not cured by LT, early or

Financial support

GYI: Nothing to disclose. AMC: Nothing to disclose. MRL: Nothing to disclose

Conflict of interest.

GYI: Nothing to disclose. AMC: Nothing to disclose. MRL: Nothing to disclose.

Please refer to the accompanying ICMJE disclosure forms for further details.

Authors’ contributions

GYI: Writing of manuscript, critical edits. AMC: Writing of manuscript, critical edits. MRL: Writing of manuscript, critical edits.

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