Estimating the impact of early hepatitis C virus clearance on hepatocellular carcinoma risk

Abstract

Although achieving sustained virological response (SVR) through antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) attributable to hepatitis C virus (HCV) infection, the impact of early viral clearance on HCC is not well defined. In this study, we compared the risk of HCC among individuals who spontaneously cleared HCV (SC), the referent population, with the risk in untreated chronic HCV (UCHC), those achieved SVR, and those who failed interferon-based treatment (TF). The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV between 1990-2013, integrated with medical visits, hospitalizations, cancers, prescription drugs and mortality data. This analysis included all HCV-positive patients with at least one valid HCV RNA by PCR on or after HCV diagnosis. Of 46 666 HCV-infected individuals, there were 12 527 (26.8%) SC; 24 794 (53.1%) UCHC; 5355 (11.5%) SVR and 3990 (8.5%) TF. HCC incidence was lowest (0.3/1000 person-years (PY)) in the SC group and highest in the TF group (7.7/1000 PY). In a multivariable model, compared to SC, TF had the highest HCC risk (hazard ratio (HR):14.52, 95% confidence interval (CI): 9.83-21.47), followed by UCHC (HR: 5.85; 95% CI: 4.07-8.41). Earlier treatment-based viral clearance similar to SC could decrease HCC incidence by 69.4% (95% CI: 57.5-78.0), 30% (95% CI: 10.8-45.1) and 77.5% (95% CI: 69.4-83.5) among UCHC, SVR and TF patients, respectively. In conclusion, using SC as a real-world comparator group, it showed that substantial reduction in HCC risk could be achieved with earlier treatment initiation. These analyses should be replicated in patients who have been treated with direct acting antiviral therapies.

Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada

“…higher pre-existing medical complications such as diabetes and/or cirrhosis (Supplemental Table 3). 27,39 We observed an elevated risk of colorectal cancer among HBV-infected individuals, as has been reported in previous studies from China and Taiwan. 30,40 In addition to local inflammation, it has been hypothesized that HBV X protein (HBx) could increase the risk of colorectal and other extrahepatic cancers by binding to p53 tumor suppressor and consequently inducing oncogenesis.…”

“…Furthermore, as early HCV treatment initiation could reduce the risk of HCC considerably, therapy with DAA regimens closer to infection acquisition should be considered as a prevention strategy among infected individuals. 27 To our knowledge, this is the first populationbased cohort study in North America that has assessed the risk of multiple gastrointestinal cancers among individuals tested for and diagnosed with HCV, HBV, and HIV (co-)infections. In our study, the large number of individuals who tested negative for all three infections (n = 596,072) provided a comparable group for analyses of risk among the various infection categories.…”

“…In a sensitivity analysis, HCV mono-infected individuals were characterized by their treatment status into four categories including SVR, TF/unknown, SC, and UCHC. 27 To assess the impact of each category on colorectal, liver, and pancreatic cancer, separate adjusted proportional subdistributional hazards models, with SC group as the reference, were constructed. All analyses were performed using SAS version 9.4 (Cary, NC, USA).…”

Untitled

“…Because of this, a role of eEF1A2 in viral replication could be even more pronounced than that of eEF1A1. One cannot exclude that oncogenic eEF1A2 may significantly contribute to elevated expression of viral genomic RNA, infectious virus proliferation and the release of cancer-related RNA-containing viruses, such as viruses of hepatitis B and hepatitis C [85,86], Moloney murine leukemia virus-1 [87] etc.…”

Surgical management of hepatocellular carcinoma—Western versus Eastern attitude

“…The campaign of vaccination against hepatitis B has significantly reduced the incidence of HBV-related cirrhosis in western countries and some areas of Asia ( 2 ). Similarly, the success of the new antiviral drugs ( 3 ) holds the well-grounded promise of eradicating the hepatitis C and the HCV-related HCC in the endemic areas of southern Europe and North America. However, new risk factors for chronic liver disease, including obesity, non-alcoholic steatohepatitis (NASH) and diabetes are rising in the modern society, becoming major indications for liver transplantation (LT) in the US nowadays ( 4 ).…”