Alcoholic hepatitis and liver transplantation: the good news and what to do about it

A commentary on

Early liver transplantation for severe alcoholic hepatitis
by Mathurin, P., Moreno, C., Samuel, D., Dumortier, J., Salleron, J., Durand, F., Castel, H., Duhamel, A., Pageaux, G. P., Leroy, V., Dharancy, S., Louvet, A., Boleslawski, E., Lucidi, V., Gustot, T., Francoz, C., Letoublon, C., Castaing, D., Belghiti, J., Donckier, V., Pruvot, F. R., and Duclos-Vallée, J. C. (2011). N. Engl. J. Med. 365, 1790–1800.

A recent French trial in the New England Journal of Medicine (Mathurin et al., 2011) reported that early orthotopic liver transplantation (OLTx) improves survival in patients with a first episode of severe alcoholic hepatitis (AH) not responding to medical therapy. In this trial, 26 patients with severe AH at high risk of death were selected (i.e., <2% of patients admitted for an episode of severe AH). The results of this trial are very encouraging as the cumulative 6-month survival rate was higher among patients who received early transplantation than among those who did not (P < 0.001). Notably, this benefit of early transplantation was maintained through 2 years of follow-up (P = 0.004).

Alcoholism is still considered by many individuals and clinicians, as a bad habit and there is a general reluctance to transplant alcoholic individuals who still drink. However, research in neuroscience has improved dramatically in the last decades, and we do know by now that alcoholism is a chronic relapsing medical disease of the brain, and not a bad behavior. Let’s make a comparison with hepatitis C virus (HCV). We all know that given the presence of extrahepatic sites of HCV replication, the new transplant liver is infected by HCV in virtually all patients, with a 10- to 20-fold increase in levels of viremia after liver transplantation, and progression to HCV-related cirrhosis is estimated to reach 20–30% at 5-year follow-up (Gruener et al., 2004). No one, however, would deny an OLTx to an HCV-infected patient because of the “risk” of the re-infection after surgery.

As for alcoholic patients, at present, a minimum of 6 months of total alcohol abstinence before OLTx is required to reduce the risk of alcohol recidivism. Notably, in the French trial (Mathurin et al., 2011) not only survival rate was higher in patients receiving early OLTx, but also a very low number of patents (n = 3; 11.5%) relapsed, i.e., one at 720 days, one at 740 days, and one at 1140 days after transplantation (Mathurin et al., 2011). The take home message of this trial is very important and has significant clinical implications. This trial, in fact, clearly suggests the need to re-consider the 6-month rule. Alcoholic patients who receive OLTx might have a better survival rate if the transplant is performed sooner. As such, it is important, at least in selected cases, to consider the possibility to perform the OLTx the soonest possible in alcoholic patients with severe AH. The possibility to re-consider the 6-month rule, however, needs to be discussed by the scientific and clinical community, together with the need to provide more effective monitoring and treatments for alcoholism both before and after the OLTx. As such, there is a crucial need to develop a more integrated approach in the management of these patients, including the need to follow-up these patients by team players coming from different fields (e.g., hepatology, psychiatry, addiction medicine, surgery).

References

Gruener, N. H., Jung, M. C., and Schirren, C. A. (2004). Recurrent hepatitis C virus infection after liver transplantation: natural course, therapeutic approach and possible mechanisms of viral control. J. Antimicrob. Chemother. 54, 17–20.

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Mathurin, P., Moreno, C., Samuel, D., Dumortier, J., Salleron, J., Durand, F., Castel, H., Duhamel, A., Pageaux, G. P., Leroy, V., Dharancy, S., Louvet, A., Boleslawski, E., Lucidi, V., Gustot, T., Francoz, C., Letoublon, C., Castaing, D., Belghiti, J., Donckier, V., Pruvot, F. R., and Duclos-Vallée, J. C. (2011). Early liver transplantation for severe alcoholic hepatitis. N. Engl. J. Med. 365, 1790–1800.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text