Comparison of Clinical Manifestations and Outcomes between Hepatitis B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma: Analysis of a Nationwide Cohort

Abstract

BackgroundWe analyzed whether difference exist in the clinical manifestations and outcomes of hepatocellular carcinoma (HCC) according to the two major etiologies of HCC from a nationwide, population-based, random HCC registry.MethodsOf the 31,521 new HCC cases registered at the Korea Central Cancer Registry between 2003 and 2005, 4,630 (14.7%) were randomly abstracted, and followed up until December 2011. Of those, 2,785 hepatitis B virus (HBV)-related and 447 hepatitis C virus (HCV)-related HCC patients were compared.ResultsThe mean annual incidence rates of HBV- and HCV-related HCC incidence per 100,000 persons were 20.8 and 4.9, respectively. The annual incidence rate of HBV-related HCC peaked at 50–59 age group (46.5 per 100,000 persons), while the annual incidence rate of HCV-related HCC increased gradually to the ≥70 year age group (13.2 per 100,000 persons). Large tumors (≥5 cm) and portal vein invasion at initial diagnosis were more frequent in HBV-related HCC, while multiple tumors were more frequent in HCV-related HCC. In outcome analysis, HBV-related HCC showed poorer survival than HCV-related HCC [median survival: 1.34 vs. 2.17 years, adjusted hazard ratio (95% confidence interval): 0.88 (0.78–0.98), P = 0.03, adjusted for age, gender, Child-Pugh class, AJCC/mUICC stage, and initial treatment modality]. However, when divided according to the AJCC/mUICC stage, survival difference was observed only for those with AJCC/mUICC stage IV tumor, but not for AJCC/mUICC stage I, II or III tumors. The treatment outcome of each modality (resection, ablation, and transartherial chemoeombolization) was comparable between the two etiologies.ConclusionHBV-related and HCV-related HCC have clear differences in clinical manifestation, requiring different screening strategy according to etiology to optimize HCC surveillance in HBV-endemic area. However, etiology did not affect treatment outcomes and long-term survival within the same stage except for far advanced tumors.

Survival Analysis of Single Large (>5 cm) Hepatocellular Carcinoma Patients: BCLC A versus B

“…This study was conducted in Korea, where most of tumor are hepatitis B virus (HBV)-related HCCs. HCC shows different characteristics according to the underlying disease [35], and potent nucleos(t)ide analogues are available to preserve liver function during HCC treatment. Therefore, generalizability should be validated in area where major etiology of HCC is not HBV.…”

Comparison of hepatocellular carcinoma in Eastern versus Western populations

“…Patients with HBV-related HCC tended to be younger (because of the higher rates of vertical HBV transmission), had larger or bilobar tumors, and were less likely to meet the Milan criteria for transplantation; whereas those with HCV-related HCC tended to have worse liver function at diagnosis, because cirrhosis usually accompanies chronic HCV infection and precedes hepatocarcinogenesis. [106][107][108] Differences in treatment approaches can partly explain some of the differences in treatment outcomes between Asian and non-Asian patients with HCC in global clinical trials. 106 Patients with HBV-HCC in that study also had more aggressive tumors that were larger (5 cm), and they had portal vein invasion at diagnosis as well as poorer survival (median, 1.34 vs 2.17 years; adjusted hazard ratio [HR], 0.88; P 5 .03).…”

Stereotactic body radiation therapy in hepatocellular carcinoma: Optimal treatment strategies based on liver segmentation and functional hepatic reserve

“…Sinn et al 35 reported that HBV-related HCC and HCV-related HCC have different oncogenic pathways. In HBV infection, the integration of HBV DNA into the patient's hepatocyte DNA will transactivate human oncogenes, while in HCV infection, chronic inflammation is the major pathway in oncogenesis.…”

“…In HBV infection, the integration of HBV DNA into the patient's hepatocyte DNA will transactivate human oncogenes, while in HCV infection, chronic inflammation is the major pathway in oncogenesis. [35][36][37] Although HCV-related HCC has a higher recurrence rate than HBV-related HCC 38 , HBV-related HCC is more aggressive than HCV-related HCC, especially in the advanced stages. 35,39 In patients with underlying HBV or HCV infection, hepatitis reactivation is a concern as such patients are at a much higher risk of RILD during treatment.…”

“…[35][36][37] Although HCV-related HCC has a higher recurrence rate than HBV-related HCC 38 , HBV-related HCC is more aggressive than HCV-related HCC, especially in the advanced stages. 35,39 In patients with underlying HBV or HCV infection, hepatitis reactivation is a concern as such patients are at a much higher risk of RILD during treatment. Patients with HBV have a significantly greater susceptibility to RILD after radiotherapy than patients with HCV.…”