HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis (original) (raw)
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Hepatology, 1997
both virus and host factors. The hepatitis C virus exists as The influence of the hepatitis C virus (HCV)-genotype a family of distinct variants that have been classified recently on liver disease severity was evaluated in 429 consecuinto at least 6 major genotypes on the basis of genomic nucleotive patients with chronic hepatitis C, including 109 with tide sequence-analysis. 9-14 Some evidence has been provided cirrhosis who were followed up prospectively, allowing that the genotype of HCV may be one of the factors influencfor the assessment of the role of the HCV-genotype on ing the severity and outcome of liver disease. 15-17 Genotype disease outcome and on the development of hepatocellu-1b, the most prevalent variant found in several parts of the lar carcinoma (HCC). HCV-1 was detected in 147 (46%) world, including the United States, Europe, and Japan, has patients without cirrhosis and in 47 (43%) with cirrhosis been associated with more advanced liver damage, with cir-(P: not significant), being mainly HCV-1b. HCV-2 was rhosis, and with HCC, 18-20 leading to the conclusion that its found in 103 (32%) cases without cirrhosis and in 30 (27.5) pathogenicity may be greater than that of other HCV types, with cirrhosis (P: not significant), being mainly HCV-2a.
European Journal of Gastroenterology & Hepatology, 2001
Objective To assess the in¯uence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2307 patients. Results The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P < 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P < 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P < 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2307 patients, only genotype 1b was associated signi®cantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P < 0.01) and a lower cumulative hazard for HCC (P < 0.01). Conclusions Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not con®rm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.
Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: A prospective study
Hepatology, 1997
A prospective study was performed to establish whether infection with specific hepatitis C virus (HCV) genotypes was associated with an increased risk of development of hepatocellular carcinoma (HCC) in cirrhosis. A cohort of 163 consecutive hepatitis C virus antibody (anti- HCV)-positive cirrhotic patients was prospectively evaluated for the development of HCC at 6-month intervals by ultrasound (US) scan and α-fetoprotein (AFP) concentration. HCV genotypes were determined according to Okamoto. Risk factors associated with cancer development were analyzed by univariate and multivariate statistics. At enrollment, 101 patients (62%) were infected with type 1b, 48 (29.5%) were infected with type 2a/c, 2 (1.2%) were infected with type 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a mixed-type infection, and, in 8 patients (4.9%), genotype could not be assigned. After a 5- to 7-year follow-up (median, 68 months), HCC developed in 22 of the patients, 19 infected with type 1b and 3 with type 2a/c (P < .005). Moreover, HCC developed more frequently in males (P < .01), patients with excessive alcohol intake (P < .01), those over 60 years of age (P < .02), and in patients who did not receive interferon treatment (P < .02). Multivariate analysis showed that type 1b was the most important risk factor associated with tumor development (odds ratio 6.14, 1.77-21.37 95% confidence interval). Other independent risk factors were older age and male sex. Cirrhotic patients infected with HCV type 1b carry a significantly higher risk of developing HCC than patients infected by other HCV types. The latter may require a less intensive clinical surveillance for the early detection of neoplasia.
Hepatology, 2007
worldwide suggesting an association between HCV genotype 1 and the risk of HCC, no consensus has emerged yet on this matter, which is still controversial. In an attempt to clarify this issue, a prospective study of 163 consecutive HCV-positive patients with cirrhosis, who were enrolled between January 1989 and December 1990, was carried out. HCC occurrence was detected by ultrasound surveillance every 6 months. Independent predictors of HCC were assessed with a Cox regression analysis. After a median follow-up of 10.7 years, 44 [4.26/100/year, confidence interval (CI) ؍ 3.11-5.68/100/year] of 104 patients infected with genotype 1b developed HCC versus 10 (1.69/100/year, CI ؍ 0.82-3.09/100/year) of 52 patients infected with genotype 2a/c (P ؍ 0.0001). Multivariate analysis showed that HCV genotype 1b was independently associated with HCC development [hazard ratio (HR) ؍ 3.02, 95% CI ؍ 1.40-6.53]. Other predictors of HCC were esophageal varices (HR ؍ 2.15, 95% CI ؍ , male gender (HR ؍ 2.12, 95% CI ؍ 1.10-4.11), and age over 60 years (HR ؍ 5.96, 95% CI ؍ 1.23-28.8). Conclusion: HCV genotype 1b is associated with a statistically significant higher risk of developing HCC. Patients with cirrhosis that are infected with this genotype require more intensive surveillance for the early detection and aggressive management of neoplasia. (HEPATOLOGY 2007;46:1350-1356
Gut, 1999
Background-The severity, clinical course, and risk of hepatitis C virus (HCV) related chronic liver disease are still rather poorly defined. Aims-To investigate the prevalence, risk factors, and severity of HCV related liver disease in the general population, and investigate whether infection with a specific genotype is associated with an increased risk of cirrhosis or hepatocellular carcinoma. Methods-HCV RNA determination by polymerase chain reaction (PCR) and HCV genotyping were performed in all anti-HCV positive subjects belonging to the Dionysos study (6917 subjects). Diagnosis of cirrhosis and hepatocellular carcinoma was established by liver biopsy in all cases. All the data were analysed by univariate and multivariate statistics in all the cohort. To investigate the natural history of HCV infection, anti-HCV positive subjects were followed up every six months for three years with liver function tests and ultrasonograms. Results-The overall prevalence of HCV RNA positivity was 2.3%. Positivity increased progressively with age, and was higher in women (ratio of men to women = 0.7). Genotypes 1b and 2a were the most frequent (42 and 24% of HCV RNA positive patients), with a prevalence of 1 and 0.6% respectively. Intravenous drug use, blood transfusions received before 1990, history of previous hepatitis among the cohabiting, and history of animal (mainly dogs) bites were significantly (p<0.05) associated with HCV infection, independently of age and sex. Multivariate analysis showed that, independently of age, sex, and alcohol intake, genotype 1b infection, with or without coinfection with other genotypes, is the major risk factor associated with the presence of cirrhosis and/or hepatocellular carcinoma. During the three years of follow up, 57 (35%) of the HCV RNA positive subjects had consistently normal alanine aminotransferase and -glutamyltransferase values. Two of the 22 HCV RNA positive cirrhotic patients, all drinking more than 90 g of alcohol a day, developed hepatocellular carcinoma (incidence rate = 3.0% per year).
American Journal of Gastroenterology, 2017
Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classifi ed, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes. METHODS: This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person-years of various HCV genotypes was estimated by dividing the new HCC cases to the person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confi dence intervals (CIs) were estimated by Cox's proportional hazards models. RESULTS: After 4072 person-years of follow-up, there were 96 newly-developed HCC cases, confi rming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9 vs. 2.2% for those without cirrhosis (P =0.45) and 76.2% (95% CI: 55.6-96.8%) vs. 36.2% (95% CI: 28.7-39.1%) for those with cirrhosis (P <0.05), respectively. Among patients with cirrhosis, HCV genotype 6 was signifi cantly associated with HCC compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33-3.39), P <0.05. In a model treating patients with genotypes other than 1 or 6 as the reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56-2.27) and 2.34 (1.12-4.86), respectively. CONCLUSIONS: Among patients with cirrhosis, those with HCV genotype 6 infection should be given high priority for antiviral therapy to decrease HCC risk and for vigilant adherence to HCC surveillance.
Risk Factors for Progressing To Chronic Liver Disease in HCV
2022
Introduction: Chronic hepatitis C virus (HCV) infection is one of the major causes of cirrhosis of liver and leads to significant morbidity and mortality. Thus, has become an important indication for liver transplantation all over the world which can be decreased by early detection and timely treatment. Aim: To study the risk factors associated with development of chronic liver disease in patients of chronic hepatitis C. Materials & Methods: It was a retrorospective study done at Medical Gastroenterology Department, PGIMS, Rohtak in which six years data i.e.from 01.01.2015 to 31.12.2020, pertainining to Ninety two (92) chronic hepatitis C patients who had already developed chronic liver disease (CLD) at time of presentation, was analyzed. Observations: Out of the total 92 patients, there was clear cut male predominance i.e. 69 (75%) with rural background (villages) i.e. 68 (73.91%). The age distribution in these 92 patients varied between 30-90 yrs of age and characterstically peak was seen in 50-60 yrs age group i.e. 39 patients (42.39%). The majority of patients had high baseline HCV viral load (> 4 lakhs I.U. /ml) i.e. 56 patients (60.86%). Out of total 92 patients, 38 patients (41.30%) were smokers, 36 patients (39.13%) were alcoholic, 22 patients (23.91%) had past history of surgical intervention, 11 patients (11.95%) were diabetic, 9 patients (9.78%) had got tattoo,7 patients (7.60%) had history of previous blood transfusion and 11 patients (11.95%) gave history of use of alternative medications. Results: The risk factors associated with development of chronic liver disease in chronic hepatitis C patients are high baseline HCV RNA viral load, older age, male gender, rural background, history of smoking, alcohol and Diabetes Mellitus.
Cohort effect of HCV infection in liver cirrhosis assessed by a 25 year study
Journal of Clinical Virology, 2000
Background: The role of HCV infection in the development of chronic liver disease is still unclear. Objecti6es: Assess the presence of HCV infection in patients with liver cirrhosis. Study design: 123 cases of cirrhotic liver randomly selected over a 25 years period from the autopsy archives of the Pathology Department of the University of Trieste, Italy, were analyzed for the presence of HCV viral genome. Methods: Total RNA was extracted from formalin-fixed paraffin-embedded tissues of the cirrhotic liver. Genotype analysis for HCV was performed after RT-PCR by dot-blot hybridization with the three major genotype-specific probes (G1, G2 and G3). Results: The overall HCV genome frequency was 50.4% (62/123). The positivity was quite constant in the 1969 -1979 period (35-38%), rose to 65% in 1984, peaked to 77% in 1989 (PB 0.005 vs. the previous decade), and decreased to 50% in 1994. HCV genotype G1 was found in 89% of the 62 positive samples. The mean age of death of HCV-positive and HCV-negative patients was comparable (69 9 12 vs. 67 9 16 years, NS). Conclusions: These data show an increasing frequency of HCV infection in cirrhotic liver tissues from 1969 to 1994, which peaked in 1989. The genotype G1 was the almost uniquely associated with cirrhosis. These findings indicate that the HCV infection occurred around the late 1950s-early 1960s, thus supporting the hypothesis of a cohort effect. HCV infection seems not to alter the natural history of liver cirrhosis as indicated by the comparable age at death of HCV positive and HCV negative patients.
Clinical Gastroenterology and Hepatology, 2017
Background & Aims-Few studies have examined factors associated with disease progression in hepatitis C virus (HCV) infection. We examined the association of 11 risk factors with adverse outcomes in a population-based prospective cohort observational study of Alaska Native/American Indian persons with chronic HCV infection. Methods-We collected data from a population-based cohort study of liver-related adverse outcomes of infection in American Indian/Alaska Native persons with chronic HCV living in Alaska, recruited from 1995 through 2012. We calculated adjusted hazard ratios (aHR) and 95% CIs for end-stage liver disease (ESLD; presence of ascites, esophageal varices, hepatic encephalopathy, or coagulopathy), hepatocellular carcinoma (HCC), and liver-related death using a Cox proportional hazards model. Results-We enrolled 1080 participants followed for 11,171 person-years (mean, 10.3 years); 66%, 19%, and 14% were infected with HCV genotypes 1, 2, and 3, respectively. On multivariate analysis, persons infected with HCV genotype 3 had a significantly increased risk of developing