Association of antiviral therapy with reduced disease progression in chronic Hepatitis B patients: Results from a nation-wide cohort study.

BACKGROUND AND AIMS: Although effective treatment in terms of inducing virological and biochemical response for chronic hepatitis B (CHB) is available, its effect on the clinical course of the disease has not yet been accurately estimated. Objective of this study was to evaluate the effect of antiviral therapy and its type [interferon +/- nucleos(t)ide analogs (NAs) vs. NAs] on the occurrence of a clinical event (liver decompensation, liver transplant, hepatocellular carcinoma and death from a liver-related cause) in CHB patients. METHODS: The study population was derived from the HEPNET-Greece, a nationwide cohort study aimed to evaluate the current epidemiological course of viral hepatitis. To account for time-dependent confounding, Cox marginal structural models were used to analyze data. RESULTS: Thirty out of 2,125 eligible patients experienced a clinical event during their follow-up. When comparing treated to untreated individuals, the hazard ratio (HR) for a clinical event was 0.39 (95% CI: 0.16-0.98; p =0.044) in the whole sample, whereas there were indications of a more intense effect in the subgroup of patients with cirrhosis at presentation (HR =0.16, 95% CI: 0.02-1.21; p =0.075). The effect of Interferon initiated treatment was not significantly different of that of NAs. There was some evidence, albeit not statistically significant, of a protective treatment effect on hepatocellular carcinoma development (HCC). CONCLUSIONS: Data from observational studies can provide useful inference, provided they are analyzed appropriately. The current study has shown that the available treatment options for CHB offer a significant clinical benefit to CHB infected individuals. Hippokratia 2016, 20(3): 214-221.

Hepatocellular carcinoma risk in HBeAg-negative chronic hepatitis B patients with or without cirrhosis treated with entecavir: HepNet.Greece cohort.

Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients treated with lamivudine. Whether HCC rates are comparable in patients treated with the current first-line antivirals remains uncertain. We estimated the incidence and evaluated predictors of HCC in a large nationwide prospective cohort (HepNet.Greece) of HBeAg-negative CHB patients treated with entecavir. HBeAg-negative CHB patients from the same cohort who were initially treated with lamivudine were used as controls. We included 321 patients treated with entecavir for a median of 40 months and 818 patients treated initially with lamivudine for a median of 60 months. In the entecavir group, HCC developed in 4 of 321 (1.2%) patients at a median of 1.5 (range: 1.0-4.5) years, while the cumulative HCC incidence was significantly higher in cirrhotics than noncirrhotics (1, 3, 5 years: 0%, 3%, 9% vs 1%, 1%, 1%; P = 0.024) and in older patients (P = 0.026). Entecavir compared with lamivudine group patients had lower HCC incidence (1, 3, 5 years: 0.3%, 1.2%, 2.8% vs 0.7%, 3.8%, 5.6%; P = 0.024). However, in multivariable Cox regression analysis, the HCC risk was independently associated with older age (P < 0.001), male gender (P = 0.011) and cirrhosis (P = 0.025), but not with the initial agent. In conclusion, our large nationwide study indicates that the HCC risk remains increased in entecavir-treated HBeAg-negative CHB patients with cirrhosis, particularly of older age, at least for the first 5 years. The HCC risk does not seem to be significantly reduced with entecavir compared with antiviral therapy starting with lamivudine.

Significant epidemiological changes in chronic hepatitis C infection: results of the nationwide HEPNET-GREECE cohort study.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is an important health problem worldwide. The aim of the study is to describe the baseline characteristics and possible epidemiological changes of the patients with chronic HCV infection included in a nationwide Greek study. PATIENTS AND METHODS: two thousand eight hundred seventeen (2817) patients, followed-up at 20 hepatology centres throughout Greece between the years 1997 and 2006 were enrolled in the study. RESULTS: Intravenous drug use (IDU) and history of blood transfusion prior to 1992 was reported in 30.7% and 22.6% of our patients, respectively. In 1865 (66.2%) patients with known genotypes, the distribution for genotype 1, 2, 3 and 4 was 45.1%, 7%, 34% and 13.9% respectively. Genotype 1 was more common in older people, in women (55.9% p<0.001) and patients with transfusion-related hepatitis (61.6% p<0.001). Genotype 3 was more common in younger patients, in men (43% p<0.001) and in IDUs (63.3% p<0.001). A significant reduction of transfusion-related hepatitis C incidence (p<0.001) in conjunction with the proportion of genotype 1 (p<0.001) was observed during the last three decades while an increase in IDU infected patients and genotype 3 was detected. CONCLUSIONS: Our study showed a significant change in HCV genotype distribution and source of HCV infection during the last three decades and under that scope, urgent actions are needed in order to control the spread of HCV infection.

Epidemiology, course and disease burden of chronic hepatitis B virus infection. HEPNET study for chronic hepatitis B: a multicentre Greek study.

SUMMARY: Hepatitis B virus infection (HBV) has been recognized as a major health problem worldwide. Greece belongs to the intermediate endemicity countries with a trend of decreasing prevalence of HBV infection during the last decade. However, the recent massive immigration to our country may have led to alterations of HBV epidemiology. In this study, we evaluated the epidemiological features of HBV infection in a sample of 3480 patients followed up during the years 1997-2006. Immigrants mainly from Albania represented the 18.6% of the total study population and 56.6% of children. The majority of the patients had no family history of HBV infection (67.3%) or of acute hepatitis (95.4%), no known source of infection (64.6%), with intrafamilial spread accounting for 16.9% of the HBV transmission in adults and 33.9% in children. HBeAg(-) hepatitis B was the predominant form of hepatitis (92.1%) among the Greek patients in contrast to the immigrants where 16.6% were HBeAg(+). Liver cirrhosis was diagnosed in 8.8% of the total population and 0.9% had hepatocellular carcinoma. A high proportion of children were HBeAg(+) (62%), 55% from immigrant families, 25.2% were infected in the perinatal period and had no evidence of disease complications. In conclusion our results showed (a) a changing pattern in the epidemiology of HBV infection in Greece due to the significant number of HBeAg(+) patients, especially among children and (b) a considerable number of patients although aware of their infection, present with advanced disease.