Outcome of Direct-Acting Antiviral Drugs on Treatment of Naïve Cirrhotic and Non-cirrhotic HCV Patients in Assir Region, Saudi Arabia: A Retrospective Cohort Study

Abstract

Context: 

Direct-acting antiviral drugs (DAAs) have revolutionized HCV treatment, but their long-term impact on liver disease severity, fibrosis progression, and hepatocellular carcinoma (HCC) incidence among treatment-naïve cirrhotic and non-cirrhotic patients in Saudi Arabia remains underexplored. This study evaluated the sustained virological response (SVR), liver disease severity, fibrosis progression, and HCC incidence among treatment-naïve cirrhotic and non-cirrhotic HCV patients treated with DAAs in Saudi Arabia.

Methods and Materials: 

A retrospective cohort study was conducted at Assir Central Hospital, Saudi Arabia, from March 2019 to December 2022. The study enrolled 52 adults (>18 years) comprising both cirrhotic and non-cirrhotic HCV patients who had received DAA treatment at least 6 months (24 weeks) prior. Demographic data, laboratory results, HCV genotype, and viral load were collected. Liver fibrosis was assessed using Fibroscan, while liver disease severity was evaluated using Model for End-stage Liver Disease (MELD) and Child-Pugh scores. HCC screening was performed using alpha-fetoprotein (AFP), ultrasound, and triphasic CT abdomen.

Results: 

Findings included no significant changes in laboratory values (INR, bilirubin, albumin, liver enzymes) before and after treatment. However, cirrhosis cases increased post-treatment (P = 0.033), while HCC incidence remained stable. The most prevalent HCV genotype was 4 (64%), with Sofosbuvir/Daclatasvir being the most prescribed medication (44%).

Conclusion: 

DAA treatment in treatment-naïve cirrhotic and non-cirrhotic HCV patients in Saudi Arabia demonstrated efficacy in achieving SVR and maintaining liver function. However, continued monitoring is crucial post-treatment, particularly for detecting fibrosis progression and cirrhosis development.

BACKGROUND

Hepatitis C virus (HCV) infection is a significant global health challenge, with an estimated 71 million people living with chronic HCV infection worldwide.^[1,2] The prevalence of HCV varies geographically, with certain regions experiencing a higher disease burden, including the Middle East and North Africa (MENA) region, including Saudi Arabia.^[2,3] HCV infection is a leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality, making it a priority area for public health interventions and research efforts.^[4,5]

In Saudi Arabia, the prevalence of HCV infection has been a cause for concern, with studies indicating varying prevalence rates across different population groups.^[6,7] Studies estimated the overall prevalence of HCV antibodies among the general population at 1.65%. However, prevalence rates were higher among specific subpopulations, such as hemodialysis patients, where prevalence rates ranged from 8% to 57.7%.^[8,9]

The transmission routes of HCV are diverse and include blood transfusions, healthcare-related exposures, injection drug use, and unsafe injection practices.^[6,8] Implementing stringent blood safety measures, including screening of blood donors for HCV antibodies and nucleic acid testing, has significantly reduced the risk of transfusion-related HCV transmission. However, challenges persist in other transmission routes, highlighting the importance of targeted prevention and control strategies.^[5,8,9]

Historically, the treatment landscape for HCV relied heavily on interferon-based regimens, which were associated with significant side effects, low efficacy rates, and long treatment durations. The advent of direct-acting antiviral drugs (DAAs) marked a paradigm shift in HCV therapy, offering highly effective, well-tolerated, and shorter-duration treatment options.^[10,11]

DAAs target specific viral enzymes and proteins in the HCV replication cycle, disrupting viral replication and leading to sustained virological response (SVR) rates exceeding 95%. The introduction of DAAs has transformed HCV treatment, enabling cure rates previously considered unattainable and reducing the burden of chronic liver disease and its associated complications.^[10,12,13]

Several studies have demonstrated the real-world effectiveness of DAAs in achieving SVR and improving clinical outcomes among HCV-infected individuals. Studies assessed the efficacy and safety of DAAs across various patient populations and genotypes, reporting overall SVR rates exceeding 95%. These findings underscore DAA therapy’s high cure rates and clinical benefits.^[10,14,15]

Furthermore, DAAs have shown efficacy in diverse patient populations, including treatment-naïve and treatment-experienced individuals, as well as those with advanced liver disease, such as cirrhosis and compensated or decompensated liver function. The improved tolerability and shorter treatment durations of DAAs have also contributed to higher treatment adherence and patient satisfaction compared to interferon-based regimens.^[16,17]

Despite the remarkable success of DAAs in HCV treatment, challenges remain, particularly in addressing access barriers, optimizing treatment strategies for specific patient populations, and addressing emerging issues such as drug resistance and reinfection.^[10-13] Additionally, the long-term impact of DAAs on liver disease progression, fibrosis regression, and HCC incidence requires further investigation through longitudinal studies with extended follow-up periods.^[12,13,15]

STUDY AIM

To evaluate the long-term outcomes of DAAs on treatment-naïve cirrhotic and non-cirrhotic HCV patients in Saudi Arabia, focusing on fibrosis severity, liver disease severity, and the incidence of HCC. The long-term outcomes are (1) the SVR rates at least 24 weeks after DAA treatment, (2) the severity of liver disease post-HCV eradication using Model for End-stage Liver Disease (MELD) and Child-Pugh scores, (3) the degree of liver stiffness measurement post-HCV eradication using Fibroscan, and (4) the incidence of HCC post-HCV eradication.

METHODOLOGY Study design

The aim of this retrospective cohort study was to evaluate the outcomes of DAAs in treatment-naïve cirrhotic and non-cirrhotic HCV patients. The study design facilitated data collection at a single point in time, providing a snapshot of treatment outcomes and associated factors in the study population.

Study setting

The study was conducted at Assir Central Hospital in Saudi Arabia, a tertiary care facility with advanced diagnostic and treatment modalities for liver diseases, including HCV management.

Sampling technique

The study employed a total coverage sampling technique for all eligible patients after carefully screening them through the inclusion and exclusion criteria. More than 500 patients were treated at the hospital, and after applying the selection criteria and obtaining consent to participate in the study, a final sample size of 52 was achieved.

Study population

The study included adult patients (>18 years) with a confirmed diagnosis of HCV who were treatment-naïve and had not undergone liver transplantation prior to DAA therapy. The participants were both cirrhotic and non-cirrhotic individuals who had received DAA treatment at least 6 months (24 weeks) before the study period.

Inclusion criteria

Participants included treatment-naïve chronic HCV patients who had successfully completed DAA treatment at least 6 months (24 weeks) prior to the study, who were willing and able to comply with study procedures, and provided informed consent.

Exclusion criteria

Patients with a history of liver transplantation prior to HCV therapy, co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV), non-alcoholic steatohepatitis (NASH) biopsy-proven diagnosis, body mass index (BMI) > 35, active use of hepatotoxic medications, evidence of HCC or any hepatic lesion before HCV treatment, and previous treatment failure with peg-interferon plus ribavirin or first-generation DAAs were excluded from the study.

Data collection tool