Tumor aggression among hepatitis-C related hepatocellular carcinoma patients: an observational study regarding the impact of anti-HCV therapy

Abstract

Background: 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, 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. Methods: Hepatocellular 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. Results: Out 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). Conclusion: We 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.

No evidence of a more aggressive pattern of hepatocellular carcinoma after direct acting antivirals –results from a single center observational study

“…For instance, a recent article by Fayoume et al found that multiplicity and infiltrative patterns were more common in DAAs-treated HCC patients compared to naïve HCC patients (13). Another study revealed that malignant PVT and lymphadenopathy were significantly more frequent in DAAstreated HCC patients (14). On the contrary, we found a more aggressive behavior of HCC among untreated patients from group II compared to group I.…”

Long-term Risk of Hepatocellular Carcinoma Following Direct-Acting Antiviral Therapy in Compensated Liver Cirrhosis Induced by Hepatitis C Virus Infection

“…Although there are abundant data regarding the HCC occurrence and recurrence after DAAs, few reports assessed the behavior of HCC and access to curative therapy after the DAA treatment (25)(26)(27)(28)(29)(30)(31). Regarding tumor aggression, the patients with HCC in the present study revealed aggression less frequently than those reported in other studies.…”

Patterns of Hepatocellular Carcinoma After Direct Antiviral Agents and Pegylated-Interferon Therapy

“…Hepatitis C Virus (HCV) which is a leading cause of chronic liver disease (CLD) and decompensated liver disease (DCLD) affects about 170-200 million individuals worldwide [ 1 ]. In Pakistan, approximately 10 million individuals are infected with HCV and this burden is expected to grow in the coming years [ 2 ].…”

“…These have transformed the treatment of HCV. DAAs have been so successful that sustained viral response (SVR) is achieved in more than 90% of the cases [ 1 ]. However, few studies have linked it to hepatocellular carcinoma (HCC).…”

“…Worldwide, HCC accounts for 700,000 new cases every year with a mortality rate of >90%. There are many risk factors associated with it like autoimmune disease, consumption of aflatoxin-contaminated commodities, chronic viral hepatitis caused by hepatitis B and C viruses (HBV and HCV, respectively), and excessive alcohol intake but the link with DAA is the most shocking [ 1 ]. It is more concerning because the achievement of SVR should be associated with a decreased risk of cancer.…”