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Nonalcoholic Fatty Liver Disease Risk Factors Affect Liver-Related Outcomes After Direct-Acting Antiviral Treatment for Hepatitis C

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Abstract

Introduction

In hepatitis C (HCV) patients, obesity and/or diabetes may increase the risk of liver-related outcomes. We aimed to determine whether diabetes and/or obesity are associated with adverse outcomes in direct-acting antiviral (DAA)-treated HCV patients.

Methods

We conducted a retrospective study of 33,003 HCV-infected, DAA-treated Veterans between 2013 and 2015. Body mass index was used to categorize patients into underweight (< 18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), obesity I (30 to < 35 kg/m2), and obesity II–III (> 35 kg/m2). Diabetes was defined by ICD-9/10 codes in association with hemoglobin A1c > 6.5% or medication prescriptions. Patients were followed from 180 days post-DAA initiation until 2/14/2019 to assess for development of cirrhosis, decompensations, hepatocellular carcinoma (HCC), and death. Multivariable Cox proportional hazards regression models were used to determine the association between diabetes and/or obesity and outcomes.

Results

During a mean follow-up of 3 years, 10.1% patients died, 5.0% were newly diagnosed with cirrhosis, 4.7% had a decompensation and 4.0% developed HCC. Diabetes was associated with an increased risk of mortality (AHR = 1.25, 95% CI 1.10–1.42), cirrhosis (AHR = 1.31, 95% CI 1.16–1.48), decompensation (AHR = 1.74, 95% CI 1.31–2.31), and HCC (AHR = 1.32, 95% CI 1.01–1.72) among patients without baseline cirrhosis. Compared to normal-weight persons, obese persons had a higher risk of cirrhosis, but overweight and obese persons had lower risk of mortality and HCC.

Conclusions

In this large DAA-treated Veterans cohort, pre-DAA diabetes increases mortality and liver-related events independent of SVR. Continued vigilance is warranted in patients with diabetes despite SVR. Elevated BMI categories appear to have improved outcomes, although further studies are needed to understand those associations.

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Acknowledgments

We would like to thank Dr. Kristin Wyatt for her statistical support and critical review of the manuscript.

Funding

This study was funded in part by NIH/NCI Grant Number R01CA196692 and VA CSR&D Grant Number I01CX001156 to Dr. George N. Ioannou, JBN-AASLD and UCLA: DDRC Pilot and Feasibility of the National Institutes of Health under award number DKP3041301 and the National Center for Advancing Translational Sciences at UCLA, CTSI Grant ULTR001881, JRP-NIH NIDDK P30DK41301 and Department of Veterans Affairs BX004560-01, FS-NIH T32 DK007742-2, AMM – NIH T32 DK007634.

Author information

Authors and Affiliations

  1. Pfleger Liver Institute, University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA, 90095, USA

    Jihane N. Benhammou

  2. Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA

    Jihane N. Benhammou & Joseph R. Pisegna

  3. Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, 130 Mason Farm Road, Bioinformatics Building CB#7080, Chapel Hill, NC, 27599-7080, USA

    Andrew M. Moon & George N. Ioannou

  4. Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA

    Feng Su & Philip Vutien

  5. Division of Gastroenterology, Veterans Affairs Health System, Durham, NC, USA

    Cynthia A. Moylan

  6. Division of Gastroenterology, Duke University Health System, 905 Lasalle St., Gsrb 1 DUMC 3256, Durham, NC, 27710, USA

    Cynthia A. Moylan

  7. Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA, 98108, USA

    George N. Ioannou

  8. Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, S-111-Gastro, 1660 S. Columbian Way, Seattle, WA, 98108, USA

    George N. Ioannou

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  1. Jihane N. Benhammou
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Contributions

JNB is the guarantor for the article. JNB was involved in the study concept and design, interpretation of the data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. AMM was involved in the interpretation of the data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. JRP, FS, and PV were involved in the critical revision of the manuscript. CAM was involved in the drafting of the manuscript and critical revision of the manuscript for important intellectual content. GNI was involved in the study concept and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and study supervision. All authors have revised and approved the final version of the manuscript.

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Correspondence to Jihane N. Benhammou.

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Benhammou, J.N., Moon, A.M., Pisegna, J.R. et al. Nonalcoholic Fatty Liver Disease Risk Factors Affect Liver-Related Outcomes After Direct-Acting Antiviral Treatment for Hepatitis C. Dig Dis Sci 66, 2394–2406 (2021). https://doi.org/10.1007/s10620-020-06457-2

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