Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2022; 28(45): 6380-6396
Published online Dec 7, 2022. doi: 10.3748/wjg.v28.i45.6380
Best therapy for the easiest to treat hepatitis C virus genotype 1b-infected patients
Dorota Zarębska-Michaluk, Michał Brzdęk, Jerzy Jaroszewicz, Magdalena Tudrujek-Zdunek, Beata Lorenc, Jakub Klapaczyński, Włodzimierz Mazur, Adam Kazek, Marek Sitko, Hanna Berak, Justyna Janocha-Litwin, Dorota Dybowska, Łukasz Supronowicz, Rafał Krygier, Jolanta Citko, Anna Piekarska, Robert Flisiak
Dorota Zarębska-Michaluk, Michał Brzdęk, Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-317, Poland
Jerzy Jaroszewicz, Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice 40-055, Poland
Magdalena Tudrujek-Zdunek, Department of Infectious Diseases, Medical University of Lublin, Lublin 20-059, Poland
Beata Lorenc, Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk 80-214, Poland
Jakub Klapaczyński, Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warszawa 00-241, Poland
Włodzimierz Mazur, Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów 41-500, Poland
Adam Kazek, ID Clinic, Mysłowice 41-400, Poland
Marek Sitko, Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 31-088, Poland
Hanna Berak, Hospital for Infectious Diseases, Hospital for Infectious Diseases, Warszawa 02-091, Poland
Justyna Janocha-Litwin, Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 50-367, Poland
Dorota Dybowska, Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
Łukasz Supronowicz, Robert Flisiak, Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
Rafał Krygier, Infectious Diseases and Hepatology Outpatient Clinic, Gemini NZOZ, Żychlin 62-571, Poland
Jolanta Citko, Medical Practice of Infections, Regional Hospital, Olsztyn 10-561, Poland
Anna Piekarska, Department of Infectious Diseases and Hepatology, Medical University Łódź, Łódź 90-419, Poland
Author contributions: Zarębska-Michaluk D and Flisiak R conceived the study design, acquired the data; Zarębska-Michaluk D and Brzdęk M analyzed and interpreted the data; Zarębska-Michaluk D drafted the manuscript; Brzdęk M prepared tables and figures; Jaroszewicz J acquired the data, performed statistical analysis; Flisiak R prepared figures; Tudrujek-Zdunek M, Lorenc B, Klapaczyński J, Mazur W, Kazek A, Sitko M, Berak H, Janocha-Litwin J, Dybowska D, Supronowicz Ł, Krygier R, Citko J, Piekarska A acquired the data and approved the final version of the manuscript.
Institutional review board statement: According to local law (Pharmaceutical Law of 6th September 2001, art. 37al), non-interventional studies do not require ethics committee approval.
Informed consent statement: All study participants provided informed consent for treatment and processing of personal data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Dataset available upon reasonable request to the corresponding author at dorota1010@tlen.pl.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dorota Zarębska-Michaluk, MD, PhD, Professor, Department of Infectious Diseases, Jan Kochanowski University, Radiowa 7, Kielce 25-317, Poland. dorota1010@tlen.pl
Received: August 26, 2022
Peer-review started: August 26, 2022
First decision: September 25, 2022
Revised: October 1, 2022
Accepted: November 19, 2022
Article in press: November 19, 2022
Published online: December 7, 2022
Processing time: 97 Days and 17.9 Hours
Abstract
BACKGROUND

The revolution in treatment of patients with chronic hepatitis C virus (HCV) infection dates back to the introduction of direct-acting antivirals (DAAs). The increase in efficacy was most pronounced in patients infected with genotype (GT) 1b, as this was the most poorly responsive population to treatment during the interferon era.

AIM

To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.

METHODS

This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database. Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses (SVR). Assessment of the safety was based on the evaluation of the course of therapy, the occurrence of adverse events including serious ones, deaths during treatment and in the post 12-wk follow-up period.

RESULTS

The studied population consisted of 11385 patients with a mean age of 53 ± 14.8 years and a female predominance (53.4%). The majority of them were treatment-naïve (74.6%) and patients with cirrhosis accounted for 24.3%. Of the DAA regimens used, 76.9% were GT-specific with ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin being the most used option (32.4%). A total of 10903 patients responded to treatment resulting in a 98.1% in the per-protocol analysis after excluding 273 patients without SVR data. The effectiveness of all regimens exceeded 90% and the highest SVR of 98.9% was achieved in patients treated with a combination of glecaprevir/pibrentasvir. Logistic regression analyses showed that the virologic response was independently associated with female sex [odds ratio (OR) = 1.67], absence of decompensated cirrhosis at baseline (OR = 2.42) and higher baseline platelets (OR = 1.004 per 1000/μL increase), while the presence of human immunodeficiency virus (HIV) coinfection significantly decreased the odds of response (OR = 0.39). About 95%-100% of patients completed therapy irrespective of the drug regimen. At least one adverse effect occurred in 10.9%-36.3% and most of them were mild. No treatment related deaths have been reported.

CONCLUSION

We documented very high effectiveness and a good safety profile across all DAA regimens. Positive predictors of SVR were female sex, absence of decompensated cirrhosis at baseline and higher platelet count while HIV coinfection reduced the effectiveness.

Keywords: Hepatitis C, Genotype 1b, Direct-acting antivirals, Pangenotypic, Genotype-specific, Sustained virologic response

Core Tip: Our real-world analysis focused on a population of patients chronically infected with the genotype 1b of hepatitis C virus. In the interferon era, this was considered to be difficult to treat due to low cure rates. Although we documented the very good effectiveness of all interferon-free regimens, we have shown that in what is now described as the easiest to treat population, the chance of response to antiviral treatment is reduced by coinfection with human immunodeficiency virus, while female sex, absence of decompensated cirrhosis and higher platelets count at baseline, increase the chances of a cure.