Hepatitis C Virus Genotypes and Risk of Hepatocellular Carcinoma in Cirrhosis: A Prospective Study

Abstract

approximately 3%. 3,4 Early detection of HCC in cirrhotic pa-A prospective study was performed to establish tients can usually be achieved by screening with noninvasive whether infection with specific hepatitis C virus (HCV) techniques, such as ultrasound (US) scan and serum a-fetogenotypes was associated with an increased risk of protein (AFP) concentration. 5,6 development of hepatocellular carcinoma (HCC) in cirOver the years, several lines of experimental evidence indirhosis. A cohort of 163 consecutive hepatitis C virus anticated that male sex, age, and alcohol consumption 4,7,8 were body (anti-HCV)-positive cirrhotic patients was proclosely associated with the development of HCC in cirrhotic spectively evaluated for the development of HCC at patients. The identification of additional variables associated 6-month intervals by ultrasound (US) scan and awith an increased risk of developing HCC would be particufetoprotein (AFP) concentration. HCV genotypes were larly important to optimize preventive medical programs in determined according to Okamoto. Risk factors associthis setting. Recent studies suggested a possible role for HCV ated with cancer development were analyzed by univarigenotype in chronic liver disease outcome and, specifically, ate and multivariate statistics. At enrollment, 101 pa-HCV type 1 was more frequently found in advanced liver tients (62%) were infected with type 1b, 48 (29.5%) were disease, such as cirrhosis and HCC, 9-11 and was associated infected with type 2a/c, 2 (1.2%) were infected with type with a more rapid deterioration of liver histology in chronic 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a hepatitis. 12 We have studied the distribution of HCV genomixed-type infection, and, in 8 patients (4.9%), genotype types in a cohort of patients with cirrhosis prospectively folcould not be assigned. After a 5-to 7-year follow-up (melowed for early detection of HCC, and we performed multivardian, 68 months), HCC developed in 22 of the patients, iate analysis to evaluate the independent risk for tumor 19 infected with type 1b and 3 with type 2a/c (P õ .005).development associated with specific HCV types and with Moreover, HCC developed more frequently in males (P other variables, including interferon treatment, which has õ .01), patients with excessive alcohol intake (P õ .01), been recently reported to reduce the cancer risk in HCVthose over 60 years of age (P õ .02), and in patients who induced cirrhosis. ated with the development of cirrhosis. 1 HCV infection alone was also calculated. Aliquots of sera collected at entry were stored accounts for over 25% of all cases of cirrhosis in Italy, 2 a at 030ЊC for further serological and molecular analysis. When hepacondition that is associated with an increased risk of hepato-titis C virus antibody (anti-HCV) serology became available, sera cellular carcinoma (HCC), with a yearly incidence rate of from 472 of 501 patients were tested by second-generation enzyme immunoassay (Ortho Diagnostic Systems, Raritan, NJ), and 240 sub...

Which patients with hepatitis C develop liver complications?

“…Age could also explain the lower rate of complications, only 2%, that was evident among the 198 patients who acquired HCV from IDU, a finding consistent with the observations of Gordon et al 22 In this and other studies, 13,28 gender had no effect on liver-related complications other than the development of HCC, which as observed in many diseases is more common in men. [35][36][37][38] In this study, HCV acquired from BT and cases without identified risk factors (sporadic cases) were at higher risk of liver-related complications compared with IDU cases. However, only ''sporadic'' was an independent predictor of liverrelated complications.…”

Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas #

“…The need for closer monitoring of patients with chronic hepatitis who have a high risk of developing HCC during the course of the disease 19 has long been stated. In these patients, sAFP has been a particularly unsatisfactory screening tool for early detection of HCC.…”

Sustained activation of the Raf/MEK/Erk pathway in response to EGF in stable cell lines expressing the Hepatitis C Virus (HCV) core protein

“…Using an antiphospho-Erk1/2 MAP Kinases antibody (New England Biolabs), that speci®cally recognizes activated Erk1/ Erk2, we showed that HCV core type 1 activates endogenous ERKs (Figure 1a, top panel, lane 3), whereas the pCDNA3-HA empty vector and the pCDNA3-GFP expression vector (Figure 1a, top panel, lanes 1 and 2) have no e ect. Although it has been proposed that HCV genotypes may have a di erent impact on the natural history of the infection and on the risk of HCC development (Bruno et al, 1997) we observed that type 3 HCV core activates at the same extent endogenous Erk1/2 ( Figure 1a, top panel, lane 4).…”