Abstract
BackgroundHepatitis C virus (HCV) represents a major risk factor for hepatocellular carcinoma (HCC) development and anti-HCV therapy is a significant measure to reduce the incidence of HCC, however development of HCC in HCV treated patients is an emerging clinical problem which needs to be investigated. In this study we aim to analyze association between anti-HCV therapy and tumor pattern of HCV related HCC patients.MethodsHepatocellular Carcinoma (HCC) patients with seropositivity for hepatitis C virus (HCV) antibodies, registered at three tertiary care hospitals of Rawalpindi and Islamabad, Pakistan during August 2017 to July 2018 were enrolled. Selected patients were then segregated in two groups on the basis of their HCV treatment history i.e., “TN” (HCV Treatment Naïve i.e. having no history/medical record for treatment prior to HCC diagnosis) and “TH” (Treated for HCV infection). Aggressiveness index (AgI) scoring system was applied to determine the tumor pattern. Univariate and multivariate analysis was carried out to analyze the independent effect of anti-HCV therapy on tumor pattern.ResultsOut of 234 consecutive HCC patients, 171 HCV-related HCC patients were enrolled in final analysis and labeled as “TN” (n = 120) and “TH” (n = 51). Tumor pattern was found to be significantly aggressive (P = 0.02) in the treated cohort with an adjusted odds of 2.47 for aggressive and 6.92 for highly aggressive tumor. Neutrophil to lymphocyte ratio (NLR) was strongly associated with highly aggressive tumor pattern (P = 0.012). Patients in TN group were found to be marginally older than those in the TH group (59.5 vs. 55 years) where mean age of the patients treated with direct acting anti-viral agents was found to be visibly lower than mean age of patients who received interferon based treatment (53.5 vs. 57 years) with significant masculine predominance (62.1 vs. 37.9%, P = 0.049).ConclusionWe observed raised neutrophil to lymphocyte ratio and prominence of younger age with aggressive tumor biology in HCV treated HCC patients. These observations highlight the need for a longitudinal prospective study on HCV positive subjects treated with antivirals, irrespective of treatment response.
Highlights
Hepatitis C virus (HCV) represents a major risk factor for hepatocellular carcinoma (HCC) development and anti-HCV therapy is a significant measure to reduce the incidence of HCC, development of HCC in HCV treated patients is an emerging clinical problem which needs to be investigated
Six patients having co-infection with Hepatitis B virus (HBV) and nine patients with failed HCV treatment were excluded from the final analysis (Fig. 1)
Majority of the patients were diagnosed for HCC symptomatically (85.4%), where all were cirrhotic with a greater proportion of male gender (63.2%)
Summary
Hepatitis C virus (HCV) represents a major risk factor for hepatocellular carcinoma (HCC) development and anti-HCV therapy is a significant measure to reduce the incidence of HCC, development of HCC in HCV treated patients is an emerging clinical problem which needs to be investigated. In this study we aim to analyze association between anti-HCV therapy and tumor pattern of HCV related HCC patients. Hepatocellular carcinoma (HCC) accounts for 700,000 new cases worldwide with mortality rate of > 90% [1]. It is the fourth leading cause of cancer related deaths and ranked sixth in incident cases [2]. Aggressiveness Index (AgI) is a recently introduced scoring system for HCC tumor patterns which takes accounts of four tumor-related parameters i.e., maximum tumor diameter (MTD), number of tumor nodules, portal vein thrombosis (PVT) and serum alphafetoprotein (AFP) level. Studies have shown that higher AgI score is associated with poor prognosis [8, 9]
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