Abstract

Background:

Long term reduction and alcohol abstinence have been known to reduce both short and long term mortality in patients with Alcohol associated Liver diseases (AaLD). Naltrexone, despite being known efficacy in Alcohol dependence, has not been tested in liver disease patients. We aimed to evaluate six and twelve month abstinence rates (and new onset decompensation events over 12 months) after 12 weeks of Naltrexone (50 mg) compared with placebo in patients with underlying AaLD.

Methods:

6 and 12 month abstinence rates were analyzed in AaLD patients given take home oral Naltrexone versus placebo; as part of 12 weeks double blind RCT at ILBS hospital, (NCT04391764). Consecutive AaLD patients with no recent decompensation (last 60 days) were given Naltrexone or placebo tablets if they fulfil DSM-5 criteria for AUD. Cirrhosis was confirmed with histology and imaging findings. Self report, family member’s corroboration and blood Ethyl glucoronide testing were done to ascertain abstinence and lapses. Obsessive compulsive drinking scores (OCDS) and self reports of craving (Visual analogue scale-VAS) were used to measure craving at 6 and 12 months. All patients discontinued use of Naltrexone and placebo after the 12 weeks study period; as well as counselling as part of the study.Number of episodes of new onset decompensation was noted. As routine clinical practice all patients received Brief intervention counselling for AUD.

Results:

A total of 147 AaLD patients were screened for inclusion in the study, out of which 100 were included and 56 patients completed 12 months follow up and were analysed (28 in each group). Baseline clinical and alcohol use related parameters were comparable between the two groups. At 12 months, 7.1% (2/28) had new onset hepatic decompensation vs 14.2% (4/28) in the placebo group (aOR=2.34,p=0.04). There was significant improvement in CTP (t=-3.94, p<0.01) and MELD scores (t=-4.07, p<0.01) at 12 months; along with significant reduction in total Bilirubin (t=4.47, p<0.01), INR (t=0.37, p<0.01) and serum GGT levels (t=2.28, p=0.03). Among alcohol use related parameters proportion of patients abstinent at 12 months were higher in Naltrexone as compared to placebo (x²= 0.37, p=0.04). There was reduction in number of lapses in the Naltrexone group (p=0.74) at 12 months. Moreover craving measures including OCDS and VAS were also significantly lower in drug group as compared to placebo. Naltrexone group had lesser number of lapses per month at one year as compared to placebo (3.93 vs 6.50; p=0.26). Both patients with new onset decompensation in Naltrexone continued alcohol consumption. Adverse events were comparable in both the groups (41.4 % vs 26 %; p=0.59) and none required discontinuation of drug.

Conclusion: This is the first placebo controlled RCT using Naltrexone in AaLD patients. It showed that it is a safe and effective drug for improving alcohol use related parameters and new onset decompensation at 6 and 12 months.