Clinical epidemiology of chronic viral hepatitis B: A Tuscany real-word large-scale cohort study

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)- infected patients in the Tuscan public health care system. METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-na\uefve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/\u3bcL [interquartile range (IQR) 169\u2013521 cells/\u3bcL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1\u20135.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93\u20134.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75\u20130.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40\u20130.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91\u20130.99; P = 0.02). Conclusions: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy

Impact of the M184V resistance mutation on virological efficacy and durability of lamivudine-based dual antiretroviral regimens as maintenance therapy in individuals with suppressed HIV-1 RNA: A cohort study

Background. Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. Methods. We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. Results. Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (P = .016). Conclusions. Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips

The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy

The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load 100,000 copies/ml, virologic success was only associated with the use of integrase inhibitors in the first cART regimen. Independent predictors of immunological success were baseline CD4+ cell count and wGSS <3. High baseline HIV-1 RNA, predicted activity of the first-line regimen based on genotypic resistance testing, gender, and use of new agents were found to predict time to achieve virological success. The type of initial nucleoside analog backbone was not found to predict virological response

HCV infection is a risk factor for gallstone disease in liver cirrhosis: an Italian epidemiological survey. J Viral Hepat

We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality. © 2007 The Authors

The aetiology of chronic hepatitis in Italy: results from a multicentre national study

Background: No recent national-level data on the aetiology of chronic hepatitis are available in Italy. Aim: To evaluate the current aetiology of chronic hepatitis in Italy. Patients: A total of 6210 chronic hepatitis patients (both prevalence and incident cases) consecutively admitted to 79 hospitals located throughout Italy were enrolled over a 6-month period in 2001. The hospitals were randomly selected through systematic cluster sampling. Results: The main agent associated with chronic hepatitis was hepatitis C virus, which was found in 76.5% of the patients (in 62.6% it was the only aetiologic factor). Hepatitis B surface antigen was present in the serum of 12.2% of the cases (in 9.2% it was the only aetiologic factor). Hepatitis B e antigen and hepatitis Delta were detected in 16.6% and 7.0%, respectively, of hepatitis B surface antigen-positive patients. A history of alcohol abuse was found in 19.2% of the cases (5.5% without viral infection). Autoimmune hepatitis and inborn metabolic disorders were extremely rare. The prevalence of hepatitis C virus-related cases was significantly lower in incident cases, compared to prevalent cases (55.1% versus 65.0%; p < 0.01). The mean alanine aminotransferase level was significantly higher in hepatitis B surface antigen-positive patients, compared to hepatitis B surface antigen-negative patients. The histology was less severe in non-viral-related cases. Conclusions: Hepatitis C virus is the most important pathogenic factor for chronic hepatitis in Italy; however, the comparison between prevalent and incident cases suggests that this infection will play a less important role in the future. A comparison with previous reports shows that both hepatitis B virus-related and hepatitis Delta virus-related cases are decreasing

HCV infection is a risk factor for gallstone disease in liver cirrhosis: An Italian epidemiological survey

We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality. \uc2\ua9 2007 The Authors