Comment to “Liver transplantation for patients with alcoholic liver disease: An open question”

Abstract

We read the excellent paper by Gramenzi et al. [[1]Gramenzi A. Gitto S. Caputo F. et al.Liver transplantation for patients with alcoholic liver disease: an open question.Digestive and Liver Disease. 2011; 43: 843-849Abstract Full Text Full Text PDF Scopus (19) Google Scholar]; liver transplantation (LT) for alcoholic liver disease has a favourable outcome, better than for hepatitis C infection. Alcoholic hepatitis (AH) generally occurs after decades of heavy alcohol use; less severe forms of acute AH (AAH) frequently respond to alcohol abstinence, whereas the prognosis of severe AAH is poor: up to 40% die within 6 months. Patients who do not respond to steroids have a 6-month survival of 25–30%, and patients with hepatorenal syndrome (HRS) have a 3-month mortality rate above 90%, unless treated with liver transplantation [[2]Testino G. Ferro C. Sumberaz et al.Type-2 hepatorenal syndrome and refractory ascites: role of transjugular portosystemic stent shunt in eighteen patients with advanced cirrhosis awaiting orthotopic liver transplantation.Hepatogastroenterology. 2003; 50: 1169-1171PubMed Google Scholar].Liver transplantation is a possible therapeutic option for severe AAH, but it is rarely used because a 6-month abstinence period is required before listing for LT; however this duration is arbitrary and has never been demonstrated as affecting survival post-LT. Even where there is evidence that shorter prelisting abstinence correlates to shorter time to first drink post-transplant, an optimal period of pre-transplant abstinence remains unclear. The United Network for Organ Sharing and the French Consensus Conference state that in case of end-stage alcoholic liver disease, 6 months of abstinence before LT should no longer be the absolute rule and should not be considered the determining factor for graft access. Since patients who do not recover within the first 3 months of abstinence are unlikely to survive, a shorter period (i.e., 3 months instead of 6) pre-LT seems more reasonable. In case of severe drug-resistant AAH, a 6-month sobriety period is clearly inadequate, and the high risk of early death in these patients requires that liver transplantation be a therapeutic option. In our experience seven non-responder patients (median age, 49 years), with clinical evidence of severe AAH (MELD > 21 and DF > 32) and type 1 HRS, underwent transjugular intrahepatic portosystemic shunt (TIPS), and then were successfully transplanted (30–45 days later). None of the patients relapsed over 5 years (unpublished data). Mathurin et al. [[3]Mathurin P. Moreno C. Samuel D. et al.Early liver transplantation for severe alcoholic hepatitis.New England Journal of Medicine. 2011; 365: 1790-1800Crossref PubMed Scopus (579) Google Scholar] listed 26 non-responder patients (median age, 47.4 years) for liver transplantation, within 15 days after non-response to medical therapy. Transplantation was performed soon after listing (median, 9 days later; range, 5–11 days). Non-response to steroids was defined as a Lille score of 0.45 or more or as a worsening of liver function within 7 days from presentation. The 6-month survival rate among patients undergoing transplantation was 77 ± 8%, higher than among non-randomised case-matched controls (6-month survival rate, 23 ± 8%). Only 3/26 patients resumed drinking alcohol (showing a low rate of relapse), none had graft dysfunction. Shawcross and O’Grady [[4]Shawcross D. O’Grady J.G. The 6-month abstinence rule in liver transplantation.The Lancet. 2010; 376: 216-217Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar] underlined that a teenager who develops acute liver failure after a deliberate paracetamol overdose, Ecstasy ingestion, or after contracting hepatitis B through irresponsible sexual behaviour will have open access to LT. Why should their peer, with alcoholic hepatitis, be treated differently? A strict application of a period of sobriety as a policy for transplant eligibility is unfair to such patients, as most of them will have died before 6 months. In our opinion, patients with severe AAH and decompensated liver disease should be listed for transplantation after a 3-month abstinence period. Determining factors for graft access might be: strong social support and the absence of psychiatric or personality disorders. Post-LT, patients with limited comorbidities and good support systems should be offered individual cognitive behavioural therapy; patients with significant comorbidities and/or limited social support should have access to multicomponent programmes (multidimensional family therapy, functional family therapy, brief strategic family therapy). Participation to self-help groups (i.e., Alcoholics Anonymous and Clubs of Alcoholics in Treatment) should be mandatory. We agree with Kotlyar et al. [[5]Kotlyar D.S. Burke A. Campbell M.S. et al.A critical review of candidacy for orthotopic liver transplantation in alcoholic liver disease.American Journal of Gastroenterology. 2008; 103: 734-743Crossref PubMed Scopus (87) Google Scholar]: in patients with AAH not responding to medical therapy the lack of pre-LT abstinence alone should not be considered a barrier against being listed. No source of support in the form of grants, equipment, drugs, or all of the above, was used.