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Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review
Hamzah Z Farooq1, Michael James2, Jane Abbott2
1Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom. hamzah.farooq@qmul.ac.uk.
Insights
Hepatitis C virus genotype-3 (HCV-G3) infection increases hepatocellular carcinoma (HCC) risk. Cirrhosis and age are identified risk factors, but more research is needed to fully understand HCC development in HCV-G3 patients.
Area of Science:
- Hepatology
- Virology
- Oncology
Background:
- Hepatitis C virus (HCV) affects 79 million globally, causing significant morbidity and mortality.
- Chronic HCV infection can lead to cirrhosis and hepatocellular carcinoma (HCC).
- HCV genotype-3 (HCV-G3) accounts for 17.9% of infections and is less responsive to antivirals, with increased HCC risk even without cirrhosis.
Purpose of the Study:
- To systematically review and critically appraise risk factors for HCC secondary to HCV-G3.
- To synthesize existing literature on risk factors for HCC due to HCV-G3 from 1946 to 2023.
Main Methods:
- Systematic review of published studies on risk factors for HCC secondary to HCV-G3.
- Searched Web of Science, Medline, EMBASE, and CENTRAL databases for relevant publications (1946-2023).
- Included seven studies (3 case-control, 2 cohort, 1 cross-sectional) with a total of 9621 participants.
Main Results:
- Cirrhosis was identified as a risk factor for HCC in all seven studies.
- Higher age was a risk factor in five studies.
- Male sex, high alpha-fetoprotein, directly-acting antiviral treatment, and sustained virologic response were risk factors in two studies each.
Conclusions:
- HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death.
- Limited evidence exists for specific risk factors of HCC secondary to HCV-G3.
- Cirrhosis and age are associated risk factors, but further research is required due to the small number of studies.
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 HCV-G3 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.
