The proportion of U.S. liver transplants for alcoholic liver disease (ALD) rose steadily from 2002 to 2016, making ALD the leading indication for liver transplant, researchers reported.
In 2002, ALD accounted for 24.2% of all U.S. liver transplants, increasing to 27.2% in 2010 and 36.7% in 2016, according to Norah A. Terrault, MD, of the University of California San Francisco, and colleagues.
The increase may be driven by a decline in hepatitis C virus (HCV) infection thanks to direct-acting antivirals and younger age at transplant for ALD. It may also reflect a broader acceptance of ALD as an indication for transplantation and less stringent pre-transplant abstinence requirements, they wrote in JAMA Internal Medicine.
Nevertheless, the analysis of trends and long-term outcomes revealed that 5-year post-transplant survival in ALD patients was 11% lower than in liver recipients with other indications, suggesting a need to identify patient profiles associated with best outcomes. Moreover, regional disparities in transplant access pointed to heterogeneous policies on liver transplant for ALD and a need for a federal strategy.
“The rapid emergence of ALD as the leading indication for liver transplant may be associated with the decrease in HCV infection, and shifting attitudes toward the length of pre-liver transplant sobriety necessary to undertake liver transplant for ALD,” Terrault’s group wrote, adding that these factors may continue to increase the proportion of transplants performed in ALD patients.
Using statistics from the United Network for Organ Sharing (UNOS) database, their multicenter, prospective, national cohort study evaluated all liver transplants performed in the U.S. from 2002 to 2016. The cohort consisted of 32,913 patients across 11 UNOS regions, including 9,438 with ALD and 23,475 without, excluding patients with HCV infection and/or hepatocellular carcinoma. The median age of both ALD and non-ALD patients was 54. ALD patients were more likely to be men (76.2% vs 50.1%) and more frequently white (80% vs 73.5%).
ALD patients more often had Medicaid insurance (17% vs 12%), had higher median model for end-stage liver disease (MELD) scores (26 vs 24), and more often required renal replacement therapy at transplant (20.3% vs 15.2%). In the ALD group, 1.6% had a secondary listing diagnosis of nonalcoholic steatohepatitis, and 1.6% in the non-ALD group had a secondary listing diagnosis of ALD.
Patients with a primary diagnosis of alcoholic hepatitis versus alcohol-associated cirrhosis were younger (median age 47) and more likely to be women (31.4% vs 23.7%). They also had more severe disease, including higher median MELD scores (36 vs 26) and were more often hospitalized at the time of liver transplant (74.5% vs 41.5%).
The number of liver transplants for ALD increased from 433 of 1,791 in 2002 to 556 of 2,044 in 2010, and 1,253 of 3,419 in 2016. With HCV co-infection included, the proportions of ALD-related liver transplant were 15.3% in 2002, 18.6% in 2010, and 30.6% in 2016, representing a 100% increase in transplantation for this indication. The researchers estimated that 48% of this increase was associated with a decrease in transplants for HCV infection, likely due to the use of direct-acting antiviral therapy.
The magnitude of increase varied by region and was associated with changing patient characteristics suggestive of alcoholic hepatitis, such as decreasing age and increasing MELD scores.
With regard to survival, cumulative unadjusted 5-year post-transplant survival was similar for both disease groups: 79% for ALD and 80% for non-ALD. Cumulative unadjusted 10-year survival was 63% for ALD versus 68% for non-ALD (P=0.006). In multivariable analysis, ALD was associated with increased risk of late death after liver transplant, for an adjusted hazard ratio of 1.11 (P=0.006).
Study limitations included its use of registry data, which restricted conclusions to the associative rather than the causal. In addition, the registry may have contained potential inaccuracies in coding and may also have lacked some relevant data.
In an invited commentary, Mack C. Mitchell, MD, and Willis C. Maddrey, MD, of the University of Texas Southwestern Medical Center in Dallas noted that the increase from 2010 to 2016 coincided with a landmark 2011 European trial showing excellent short-term survival after early transplant in carefully selected patients with acute alcoholic hepatitis but no mandated sobriety period — findings later confirmed in a pilot program for U.S. patients with severe alcoholic hepatitis.
Yet, as the authors pointed out, the observed increases in the UNOS study did not seem directly related to alcoholic hepatitis because this condition as a listing diagnosis accounted for <1% of transplants performed.
As for the easing of the 6-month pre-transplant abstinence rule, Mitchell and Maddrey wrote, “Perhaps there is less stigma around heavy alcohol consumption as a cause of advanced liver disease requiring transplant.” They added, however, that over the past 30 years, several studies have found the likelihood of alcoholic relapse in transplanted ALD patients is related to factors other than a specific duration of sobriety. Such data have diminished but not eliminated anti-ALD bias.
“Transplant centers must develop better understanding of the psychosocial and other medical needs of potential transplant recipients with ALD to select appropriate candidates for this life-saving treatment,” they wrote.
Although 5- and 10-year survival was lower in ALD graft recipients, the commentators cautioned against any conclusion that an increase in late deaths due to recidivism is reason to return to an arbitrary abstinence requirement or a reduction in ALD transplants. “We should consider other options to improve outcomes that also meet expectations of beneficence and maximize overall good,” they wrote.
With cancer and infection being common causes of death in ALD patients, they called for more aggressive screening for treatable types of cancer such as skin, colon, breast, and lung in all transplant recipients.
With respect to the possibly attitude-based regional disparities, the authors wrote that “this finding highlights the value of a national policy for liver transplant in ALD to abrogate any potential inequity in healthcare access for liver transplant related to the patient’s geographical region and the liver transplant policy of the local center.”
A 2018 study showed that Hispanics were less likely than non-Hispanic whites to receive liver transplants, while blacks were more likely to die after transplant.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the UCSF Liver Center.
Terrault and co-authors disclosed no relevant relationships with industry.
Mitchell disclosed support from the National Institute of Alcohol and Alcohol Abuse and the Alcoholic Beverage Medical Research Foundation. Maddrey reported no conflicts of interest.