Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1596
Peer-review started: November 17, 2023
First decision: December 11, 2023
Revised: December 21, 2023
Accepted: January 23, 2024
Article in press: January 23, 2024
Published online: April 15, 2024
Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.
To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.
This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023.
Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.
Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.
Core Tip: Hepatitis C virus (HCV) genotype-3 accounts for 17.9% of HCV infections with an increased risk of hepatocellular carcinoma (HCC) globally. In this systematic review and meta-analysis, we screened 4144 records to find only seven studies which study risk factors for HCC. Conducted primarily in Global South hospital settings, the studies encompassed 9621 participants, revealing cirrhosis and age as consistent risk factors for HCC. While cirrhosis and age emerge as contributors, the scarcity of studies underscores the urgent need for expanded research. Limited evidence exists on other factors, emphasising the need for further research to understand specific risk contributors to HCC secondary to HCV Genotype-3.