Hepatitis C, Liver cirrhosis, Sofosbuvir, Daclatasvir, Patient-reported outcome measures, Clinical pharmacy, Quality of life

Hepatitis C virus (HCV) remains a major contributor to chronic liver disease and related complications globally and continues to significantly impact morbidity, mortality, and healthcare expenditures [1,2]. If left untreated or inadequately managed, over time, HCV infection can progress to severe hepatic complications such as hepatocellular carcinoma, fibrosis, and cirrhosis [3,4]. HCV infection poses a major public health challenge, particularly in low- and middle-income countries (LMICs), where timely diagnosis and access to standardized care remain constrained [5,6]. Recent global estimates show that HCV has affected more than 185 million people worldwide—an increase of nearly 2.8% in the past decade and a half [7]. In Pakistan, where the national prevalence of chronic HCV exceeds 5%, the burden is particularly high. Punjab, the country’s most populous province, has reported prevalence rates as high as 6.5% [8]. Transmission primarily occurs through unsafe injection practices, transfusions, needlestick injuries, and intravenous drug use [9].

The primary objective in managing HCV is to achieve a virological cure, either through a sustained virological response (SVR)—defined as undetectable viral levels at 12 weeks (SVR12) or 24 weeks (SVR24) posttherapy—or by achieving an end-of-treatment response (ETR) [10]. With the advent of treatment modalities such as direct-acting antivirals (DAAs), the clinical landscape of HCV management has undergone a paradigm shift. Compared with earlier interferon-based therapies, DAAs, such as sofosbuvir (SOF)-based regimens, offer high rates of SVR, shorter treatment durations, improved tolerability, and minimal adverse effects [11,12]. Current clinical guidelines aim for SVR12, which is widely accepted as a surrogate marker for virologic cure [13]. These therapies have been proven effective across a wide range of patient profiles, including naïve to treatment, experienced treatment, and those with compensated liver cirrhosis [14,15].

Nevertheless, while clinical outcomes such as SVR and liver function normalization are well documented, there remains a critical gap in understanding how these treatments influence patients’ lived experiences, particularly in LMICs such as Pakistan [16,17]. Patient-reported outcomes (PROs), which highlight the perspectives of patients without clinician interpretation, are increasingly recognized as essential components of treatment evaluation [18,19]. While viral eradication remains the cornerstone of therapeutic success, it does not fully capture how patients perceive their recovery, nor does it reflect the treatment's influence on daily functioning, mental well-being, social participation, and work productivity [20,21].

Notably, advanced liver disease presents complex clinical challenges, and patients with cirrhosis may experience different therapeutic responses, symptom burdens, and quality-of-life outcomes than those without cirrhosis. There is a lack of empirical data from Pakistan exploring distinctions, especially concerning PROs. The lack of such data limits the development of evidence-based, patient-centered treatment strategies across healthcare systems globally. Therefore, this study compared both patient-reported treatment experiences and clinical outcomes among chronic hepatitis C patients with and without cirrhosis receiving standard DAA therapy. By integrating clinical indicators such as SVR12 with PROs assessed through the EuroQol 5-Dimensions 3-Levels (EQ-5D-3 L) and Work Productivity and Activity Impairment (WPAI) instruments, this study aims to generate holistic, locally relevant evidence to inform treatment guidelines, clinical counseling, and public health strategies in Pakistan.

2.1. Study design and duration

This prospective cohort study was carried out over a six-month period spanning from May to November 2020.

2.2. Ethics approval

This study obtained ethics clearance from the Services Institute of Medical Sciences (SIMS), Lahore (No. IRB/2020/734/SIMS), and was approved by the Institutional Review Board (IRB) of Lahore College for Women University (LCWU), Lahore.

2.3. Study settings

This study was conducted at the Services Hospital, Lahore, a 1325-bed tertiary care referral and teaching hospital located in Lahore, Pakistan [22]. The hospital has a specialized clinic for liver and hepatitis, offering outpatient services for diagnosing, treating, and managing hepatitis C and other chronic liver diseases.

2.4. Sample size and sampling technique

The study sample was obtained via the OpenEpi online sample size calculator (version 3.01) [23], with a minimum of 101 participants per group calculated on the basis of a 95% confidence level, a 5% margin of error, and an anticipated proportion of 93% [24]. To increase the study's statistical power, the sample size was expanded to 150 participants per group, totaling 300 chronic HCV patients—150 with cirrhosis and 150 without cirrhosis—selected through a nonprobability purposive sampling technique.

2.5. Selection criteria

The study recruited adults (≥ 18 years) diagnosed with chronic hepatitis C, verified through detectable levels of HCV ribonucleic acid (RNA). Both naïve to treatment and experienced patients for treatment were included, provided that they had not previously received DAA therapy. Patients with or without cirrhosis, as confirmed through clinical or radiological evaluation, were enrolled. All participants needed to be eligible for the standard antiviral regimen of daclatasvir (DCV) and SOF, with or without ribavirin (RBV), and had to provide informed consent for enrollment and follow-up assessments at baseline and 12 weeks posttreatment. Patients with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) coinfection, hepatocellular carcinoma, decompensated liver disease, pregnancy, lactation, treatment with investigational or nonstandard HCV therapies, or psychiatric or cognitive impairments that could obstruct the completion of PRO questionnaires were excluded.

2.6. Data collection procedure

All patients with chronic hepatitis C were screened for cirrhosis via the aspartate aminotransferase-to-platelet ratio index (APRI). Laboratory values for platelet count and aspartate aminotransferase (AST) levels were obtained from patient records. An APRI score of ≥ 1.5 was used to classify patients as cirrhotic, whereas a score < 1.5 indicated noncirrhosis [25,26].

The patients were categorized into two groups: Group A included individuals with chronic hepatitis C without cirrhosis, whereas Group B included those with cirrhosis. All patients received a standardized treatment regimen consisting of SOF 400 mg once daily and DCV 60 mg once daily. RBV 400 mg was additionally administered either twice or three times daily on the basis of clinical judgment and the specific characteristics of each patient. The treatment protocol was the same for both naïve patients and experienced patients; the latter had previously received interferon-based regimens but not DAAs [27]. Participants were prospectively followed over the 12-week treatment course to monitor their clinical response and assess changes in PROs at baseline and posttreatment.

2.7. Data collection tools

The EQ-5D-3 L is a commonly used instrument for evaluating health-related quality of life (HRQoL) [28]. It consists of two primary sections: a descriptive system of health states and a self-rated health assessment. The descriptive system includes five areas: self-care, mobility, pain/discomfort, usual activities, and anxiety/depression. Participants assessed their overall health status via a visual analog scale (VAS) at the time of evaluation.

The WPAI questionnaire is a well-established tool for assessing disruptions in both work performance and daily activities [29]. In this study, participants provided insights into how the hepatitis C virus (HCV) affects their productivity at work and in routine daily tasks. The work impairment score reflects the combined impact of missed work (absenteeism) and reduced efficiency while on the job (presenteeism) and was evaluated only for those who identified as employed. Conversely, the activity impairment score captures limitations in nonwork-related daily functions and was assessed across all participants, irrespective of their job status. Notably, high scores on this instrument correspond to worse health-related outcomes.

Each domain was calculated as a percentage (%) via the standard WPAI scoring formula:

Conceptualization, IAU, FA, SA, YA, VP, and AHK; methodology, IAU, FA, SA, YA, VP, and AHK; software, IAU, FA, SA, and YA; validation, VP, and AHK; formal analysis, IAU, FA, SA, and YA; investigation, IAU, FA, SA, and YA; resources, IAU, FA, SA, and AHK; data curation, IAU, FA, SA, and YA; writing—original draft preparation, IAU, FA, SA, YA, VP, and AHK; writing—review and editing, IAU, FA, and SA; visualization, IAU, FA, SA, and YA; supervision, VP, and AHK; project administration, IAU, FA, and YA. All authors have read and agreed to the published version of the manuscript.

This research received no specific grant from the public, commercial, or not-for-profit funding agencies.

This study obtained ethics clearance from the Services Institute of Medical Sciences (SIMS), Lahore (No. IRB/2020/734/SIMS).

Not Applicable.

The data supporting this study's findings are available from Iram Aman Ullah upon reasonable request.

None.

The authors declare no conflicts of interest.

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