Early liver transplantation beneficial, feasible in severe alcoholic hepatitis
Early liver transplantation (LT) should be considered in selected patients with severe alcoholic hepatitis (SAH) as it significantly improves survival with a low impact on the donor pool, according to recent data presented at the Asian Pacific Digestive Week (APDW) 2017 held in Hong Kong.
“While LT can be considered for patients with SAH who are not responding to or are contraindicated for corticosteroid therapy, a 6-month period of abstinence from alcohol is usually required to see whether patients will remain abstinent and whether the liver will recover. However, most patients with SAH will die within 6 months,” said Dr James Fung of the Department of Surgery, Queen Mary Hospital and the Department of Medicine, The University of Hong Kong. [Gastroenterology 2016;150:1823-1334]
“Early LT should be considered in selected patients with SAH as recent data showed survival benefit in those not responding to medical therapy,” suggested Fung. “Importantly, allowing early LT in this group of patients did not open the floodgates to more LTs or cause a big drain on resources.”
For example, in a study in 26 patients with SAH not responding to medical therapy who underwent early LT at seven French centres, cumulative 6-month survival rate was 77 percent compared with 23 percent in controls (p<0.001). The survival benefit of early LT was maintained at 2-year follow-up (hazard ratio, 6.08; p=0.004). [N Engl J Med 2011;365:1790-1800]
In the study, patients selected for early LT were required to have SAH as the first liver decompensating event. They were also required to have close supportive family members, no severe coexisting conditions or psychiatric disorders, and a commitment to lifelong alcohol abstinence. “The patient selection process consisted of four-tier medical group assessment,” said Fung. “Because of the strict criteria, less than 2 percent of patients admitted for SAH were selected, using up only 2.9 percent of available grafts. Three patients resumed alcohol consumption 2 years after LT.”
A more recent single-centre study showed similar results. Among 94 patients with SAH not responding to medical therapy, 9.6 percent underwent early LT, comprising 3 percent of all adult LTs during the study period. At 6 months, survival rate was 89 percent in those receiving early LT compared with 11 percent in controls (p<0.001). [Am J Transplant 2016;16:841-849]
“It is therefore time to consider optimal use of LT for patients with SAH and decompensated alcoholic liver disease, with evidence-based decision making based on the most recent data,” said Fung.
“Therapeutic options are limited for patients with alcoholic liver disease. Management comprises abstinence and nutritional support, with enteral nutrition being the best option,” he noted. “In patients with SAH, corticosteroids with or without N-acetylcysteine significantly improve short-term survival at 28 or 30 days.” [Gut 2011;60:255-260; N Engl J Med 2011;365:1781-1789]
However, corticosteroids also increase the risk of infections in patients with SAH. New data from a retrospective analysis of a multinational cohort of 163 patients with SAH and a discriminant function (DV) of ≥32 showed that assessment by the Lille Model on day 4 (LM4; cut-off value, 0.45) is as accurate as day 7 (LM7; cut-off value, 0.45) in predicting response to prednisolone as well as 28-day and 90-day mortality. [Am J Gastroenterol 2017;112:306-315]
“Earlier assessment of the efficacy of prednisolone can thus avoid more prolonged futile use of the therapy,” said Fung.
“Anti-inflammatory agents, immunomodulatory agents, anti-infectives, correction of gut dysbiosis and liver regeneration are potential future directions in treatment of alcoholic liver disease. Different agents are currently being evaluated in phase II and III studies,” he added. [Curr Opin Gastroenterol 2017;33:142-148]