**1. Introduction**

Chronic infection with the hepatitis C virus (HCV) seems to be one of the significant health problems worldwide. Approximately 71 million people are affected globally, of whom 400,000 died annually due to the consequences of the disease [1]. The most severe complications of chronic hepatitis C (CHC) with a risk of death are liver cirrhosis and hepatocellular carcinoma (HCC). The development of liver fibrosis leading to cirrhosis occurs in nearly 20% of patients, and, on average, two decades of HCV infection are needed for this [2]. However, the rate of progression of fibrosis varies between different patients and depends on both viral and host predictors [2]. Male gender, the age of infection over 40 years, coinfection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV), obesity, alcohol abuse are listed among variables related to the infected person, whereas the most important viral predictor for the accelerated fibrosis is genotype (GT) 3 HCV, which is second in frequency worldwide accounting for 25–30% all HCV cases [3–6]. In the era of interferon (IFN) based therapy, patients with liver cirrhosis had limited access to antiviral treatment due to safety issues and low effectiveness [7]. The implementation of the IFN-free DAA regimens has removed those safety-related limitations, but sofosbuvir (SOF) plus ribavirin (RBV), the only option available initially for GT3 patients, had still relatively low efficacy as compared to the cure rate achieved with DAA therapies in other GTs-infected individuals and treatment with daclatasvir (DCV) plus SOF was not available worldwide [8–10]. Therefore, at the beginning of the IFN-free era, cirrhotics infected with GT3 were assumed to be the most difficult-to-treat patients with CHC. The latest development in the antiviral treatment of this subpopulation was the registration of pangenotypic regimens. According to the recent guidelines, two options are recommended in patients with liver cirrhosis in the course of GT3 infection, the combination of protease inhibitor glecaprevir (GLE) with the inhibitor of non-structural protein 5A (NS5A) pibrentasvir (PIB), and SOF, polymerase inhibitor with velpatasvir (VEL), acting by inhibition of NS5A HCV [11–14]. However, available data in this population are based on limited studies, which usually included a small number of patients. The current study aimed to evaluate the efficacy of pangenotypic regimens in patients with liver cirrhosis infected with GT3 in the real-world experience.

#### **2. Materials and Methods**

The analyzed population consisted of CHC patients with liver cirrhosis infected with GT3 HCV selected from EpiTer-2 database. This sizeable national project supported by the Polish Association of Epidemiologists and Infectiologists includes 13,554 individuals treated with DAA regimens in 22 Polish hepatology centers between 1 July 2015 and 31 December 2020. Clinical data, including the severity of liver disease, the presence of the extrahepatic manifestations, coexisting medical conditions, concomitant medications, coinfections, the history of previous antiviral treatment and currently used regimen, and laboratory parameters were collected at baseline.

The severity of liver disease was assessed based on the non-invasive fibrosis evaluation either by transient elastography (TE) or shear-wave elastography (SWE), and cirrhosis was diagnosed according to recommendations of the European Association for the Study of the Liver (EASL) if liver stiffness ≥13 kilopascals corresponding to a METAVIR score of F4 [11]. In addition, cirrhotic patients were assessed for the oesophageal varices, past or present hepatic decompensation, history of liver transplantation, and scored in Child-Pugh (CP) scale and Model of End Stage Liver Disease (MELD).

HCV RNA was measured at baseline, at the end of treatment (EOT), and 12 weeks after therapy completion. The efficacy endpoint was sustained virologic response (SVR) defined as undetectable HCV RNA post-treatment week 12. The intent-to-treat (ITT) population included all patients who initiated the treatment, whereas per-protocol (PP) analysis was performed after excluding lost follow-up patients considered to be a non-virologic failure. Safety data in terms of adverse events (AE) and deaths were collected during the treatment course and in the 12-weeks follow-up period. Data were collected retrospectively and submitted by an online questionnaire administered by Tiba sp. z o.o.
