Risky Alcohol Use Does Not Impact HCV Treatment Efficacy But Is Linked to Cirrhosis

Paul Clark, MHB, MPHB

Credit: Maters Online

Hepatitis C virus (HCV) treatment with direct-acting antiviral (DAA) therapy is equally efficacious in patients with risky alcohol use compared to those without, according to findings from a recent study.¹

Results from OPERA-C, a prospective multicenter study conducted across 26 hospital-based liver clinics in Australia, showed equivalent rates of sustained virologic response (SVR) regardless of alcohol use. However, patients with risky alcohol use had greater rates of cirrhosis and more than one-third of patients with cirrhosis continued to consume alcohol, most of whom were not offered pharmacological therapy for alcohol dependence.¹

“Despite the increased prevalence of alcohol problems in patients with HCV infection, and the additional increased harm from alcohol in terms of liver disease, liver clinics typically offer limited therapeutic opportunities to help patients with HCV infection to address their alcohol problems,” Paul Clark, MHB, MPHB, director of the Alcohol and Drug Assessment Unit at the Princess Alexandra Hospital and an associate professor with the School of Medicine at the University of Queensland, and colleagues wrote.¹ “Missing these therapeutic opportunities fails to avert continued liver injury and contributes to consequent poorer liver disease outcomes obviating some of the benefits from HCV cure.”

The World Health Organization estimates a global 50 million people have chronic HCV infection, with about 1 million new infections occurring each year. Although there is no vaccine for hepatitis C, it can be effectively treated with antiviral medications to prevent serious liver damage and improve long-term health. Alcohol avoidance is generally recommended in patients with HCV, but the impact of high-risk alcohol use on treatment outcomes is not well understood.²

To examine the impact of alcohol use on HCV treatment outcomes and the clinical course of liver disease, investigators recruited adult patients with HCV who received DAA therapy from 26 hospitals in Australia from 2016-2021.¹ For inclusion, patients were required to be ≥ 18 years of age, have an HCV diagnosis confirmed on viral RNA using highly sensitive polymerase chain reaction, and receive DAA therapy according to HCV treatment guidelines.³

Investigators defined high-risk alcohol exposure through a combination of self-reported consumption of ≥ 40 g/day of ethanol, physician-reported history of problematic alcohol use, and anti-craving medication prescription via population-based database linkage. Liver fibrosis was assessed using Fibrosis-4 (FIB-4) scores, the aspartate aminotransferase to platelet ratio index (APRI), and transient elastography (liver stiffness measurement [LSM]). FIB-4 test >3.25 and APRI >1 were considered advanced liver fibrosis, and LSM between 8 and 12.5 kPa was defined as moderate or advanced fibrosis while >12.5 kPa was considered cirrhosis. All cases were followed from DAA treatment initiation until the date of death, liver transplant, or end of study follow-up 2 years after treatment initiation.¹

In total, OPERA-C recruited 3729 patients, of whom 3630 initiated DAA therapy and 2624 were included in the present analysis. Investigators pointed out the majority of patients had a history of risky alcohol use (62.3%), noting men (77.2% vs 53.8%; P <.001) and individuals born in Australia (86.6% vs 78.3%; P <.001) were overrepresented in those with a history of risky alcohol use compared to those without. Among these patients, 24.6% reported a current intake of ≥40 g/day of alcohol, 98.3% had physician documentation of a history of significant alcohol use, and 4.1% were dispensed naltrexone or acamprosate 12 months prior to and/or during DAA therapy.¹

Additionally, patients with a history of risky alcohol use had features of more advanced liver disease across multiple indices, including elevated FIB-4 (P <.001), APRI (P <.001), LSM (P <.001), AST (P <.001), alanine transaminase (P <.001), bilirubin (P <.001), gamma-glutamyl transferase (P <.001), and had higher rates of cirrhosis (44.2% vs 23.6%; P <.001).¹

Among 716 patients with risky alcohol use and cirrhosis, 22.5% reported ≥40 g/day of alcohol, and 3.3% were dispensed anti-craving medication. Of note, 4.3% of patients with cirrhosis and current alcohol use of ≥40 g per day were prescribed anti-craving medications for alcohol dependence in the 12 months prior to and during DAA therapy.¹

Further analysis revealed risky alcohol use was associated with advanced fibrosis (adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.32–2.17). Additionally, cirrhosis (45.1% vs 25.6%; P <.001) and hepatocellular carcinoma (5.7% vs 2.5%; P <.001) were significantly overrepresented among patients with a history of risky alcohol use.¹

Multivariable analysis adjusting for age, genotype 3, FIB-4, and cirrhosis at enrollment showed SVR did not vary significantly based on history of risky alcohol use (P = .319). Investigators also noted risky alcohol use was not associated with 2-year survival (adjusted HR, 1.98; 95% CI, 0.84-4.63).¹

Investigators outlined multiple limitations to these findings, including their reliance on self-reported alcohol consumption; the inability to identify very-high alcohol exposure or alcohol-dependent patients; the lack of long-term follow-up beyond 2 years; the lack of data on non-Medicare funded alcohol counseling; and the potential lack of generalizability to patients treated in community clinics or living in more remote areas.¹

“The use of more holistic, multi-disciplinary approaches integrating addiction medicine skills into liver clinics and gastroenterology training programs may improve patient outcomes,” investigators concluded.¹ “Likewise, better integration of both alcohol dependence assessment and recognition of liver disease into community primary care may increase opportunities to proactively manage these conditions concurrently at an early stage and improve public health outcomes.”

References

1. ^{Clark PJ, Valery PC, Strasser SI, et al. Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C). Drug and Alcohol Review. https://doi.org/10.1111/dar.13914}
2. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed August 14, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}
3. ^{Clark PJ, Valery PC, Strasser SI, et al. Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort. Dig Dis Sci.. https://doi.org/10.1007/s10620-022-07483-y}