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Abstract

BACKGROUND
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.

AIM
To systematically review and critically appraise all risk factors for HCC secondary to HCVG3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.

METHODS
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.

RESULTS
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.

CONCLUSION
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.

Publication Type:	Article
Additional Information:	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/ Farooq HZ, James M, Abbott J, Oyibo P, Divall P, Choudhry N, Foster GR. Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review. World J Gastrointest Oncol 2024; 16(4): 1596-1612 [DOI: 10.4251/wjgo.v16.i4.1596]
Publisher Keywords:	Hepatocellular carcinoma; Hepatitis C; Genotype 3; Systematic review; Bloodborne viruses; Liver cancer
Subjects:	Q Science > QR Microbiology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Departments:	School of Health & Psychological Sciences School of Health & Psychological Sciences > Healthcare Services Research & Management
SWORD Depositor:	Symplectic Administrator

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