HCV antiviral therapy in injection drug users: difficult to treat or easy to cure?

UNLABELLED: Background and rationale of the study. Hepatitis C infection is very common among injection drug users(IDUs). In clinical practice there is reluctance to treat IDUs, because considered difficult-to-treat. Aim of this study was to evaluate the response to antiviral treatment in IDUs compared to non-IDUs. MAIN RESULTS: In this observational retrospective study, 204 non cirrhotic patients(112 IDUs, 92 non-IDUs) with chronic hepatitis C, treated with PEG-IFN and ribavirin in a tertiary centre for IDUs of Southern Italy from 2008 to 2011 were analyzed. Age, sex, genotype, steatosis, response to previous therapy, rapid(RVR), early(EVR), end-of-treatment(ETR), sustained(SVR) virological response were evaluated. IDUs were mainly young and males, with prevalence of genotype 3. A higher SVR rate in IDUs group compared to non-IDUs only in PerProtocol(PP) analysis (90% vs. 78,9% ;p = 0.04). On the contrary, in IntentionToTreat(ITT) analysis, no significant difference was relieved. A higher SVR rate at ITT analyses in naïve non-IDUs patients was found (76,13% vs. 90%, p = 0.021), but at PP analysis wasn't confirmed. Treatment was well tolerated; a higher dropout rate was reported in IDUs (24 patients) compared to non-IDUs (2 patients). In order to exclude the effect of viral genotypes on SVR a genotype matched statistical analysis was done and no difference was found. CONCLUSIONS: IDUs naïve patients, due to young age and high prevalence of genotype 3, appear good candidates to dual antiviral therapy with high SVR rates. Dropout is the main non-response cause among these subjects, but through an optimal monitoring program with a multidisciplinary setting, their "difficult to treat" characteristics can be overcome.

Distribution pattern of hepatitis C virus genotypes and correlation with viral load and risk factors in chronic positive patients.

OBJECTIVE: Hepatitis C virus (HCV) has emerged as a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The purpose of this study was to describe the distribution pattern of HCV genotypes in chronic hepatitis patients in the Campania region of southern Italy and estimate their association with risk factors and viral load. MATERIALS AND METHODS: 404 consecutive HCV ribonucleic acid-positive patients were included in the study. HCV genotyping was carried out by the HCV line probe assay test and viral load estimation by the TaqMan real-time PCR system. RESULTS: The predominant genotype was 1 (63.6%), followed by genotype 2 (29.4%), 3 (6.2%) and 4 (0.8%). Subtype 1b was more frequent in females than in males. Conversely, genotype 3 was more frequent in males. No significant difference was observed in age distribution of HCV genotypes. Surgery and dental therapy were the most frequent risk factors for genotype 1 and intravenous drug abuse and tattooing for genotype 3. Patients with genotype 1 more frequently showed high HCV viral load when compared to those with genotypes 2 and 3. CONCLUSION: The present study revealed that HCV genotypes 1 and 2 accounted for over 95% of all HCV infections in the Campania region, and genotype 1 was more frequently associated with a higher viral load when compared to genotypes 2 and 3.

Clinical presentation, outcome, and response to therapy among patients with acute exacerbation of chronic hepatitis C.

BACKGROUND & AIMS: The slow asymptomatic progression of chronic hepatitis C (CHC) can be interrupted by an acute exacerbation, characterized by increased serum levels of alanine aminotransferase (ALT) and bilirubin and other symptoms of acute hepatitis. We aimed to provide more information about the clinical presentation of acute exacerbation of CHC. METHODS: We identified 82 consecutive patients, from 2 locations in Italy, who had an acute exacerbation of CHC from January 2005 through June 2010; we followed them up for a median period of 36 months. These cases were hepatitis C virus (HCV) RNA positive, hepatitis B surface antigen-negative, and had not received anti-HCV therapy. They were matched with 82 subjects with hepatitis C without reactivation for age, sex, and HCV genotype (controls). Sixty-nine cases and 73 controls were followed up for at least 2 years. Liver biopsy specimens had been taken from 23 cases and 31 controls-once before enrollment in the study and once during the follow-up period. RESULTS: HCV genotype 2 was detected in 46.4% of cases, and HCV genotype 1 was detected in 43.9%. Among cases, the mean ALT level was 1063 ± 1038 IU/dL, and the mean total bilirubin level was 15.87 ± 7.15 mg/dL. A higher percentage of cases carried the interleukin-28B CC genotype than controls (40.2% vs 24.4%; P < .05). Among cases, 43.5% had a steady increase in ALT level (>2-fold baseline value); for 56.5% of these patients, ALT levels returned to baseline values before the acute exacerbation of chronic hepatitis. Based on comparisons of biopsy specimens, 18 cases (78.3%) and 11 controls (35.5%) had increasing fibrosis, with Ishak scores increasing by more than 2 (P < .005); 14 cases (60.9%) and 3 controls (9.6%) had increases in necroinflammation of more than 2 points (P < .005). Thirty-two cases (46.4%) and 38 controls (52%) received treatment with pegylated interferon and ribavirin; a sustained virologic response was achieved in 26 cases (81.2%) and 23 controls (60.5%). CONCLUSIONS: Although an acute exacerbation of chronic hepatitis is a serious medical condition, most patients achieve a sustained virologic response after treatment with pegylated interferon and ribavirin.

Efficacy of Pegylated interferon α-2a and α-2b in patients with genotype 1 chronic hepatitis C: a meta-analysis.

BACKGROUND: Two formulations of Pegylated interferon (Peg-IFN) are on the market for treatment of chronic hepatitis C virus (HCV) infection. The purpose of this meta-analysis was to assess the efficacy of Peg-IFN α-2a versus Peg-IFN α-2b in combination with ribavirin in anti-human immunodeficiency virus (HIV)-negative patients with genotype 1 chronic HCV infection. METHODS: The following criteria were to be met for inclusion in the meta-analysis: (a) original data from randomized and non-randomized clinical trials; (b) study on the efficacy of conventional doses of Peg-IFN α-2a (180 µg/week) versus Peg-IFN α-2b (1.5 µg/kg of body weight/week), both in combination with ribavirin, in antiviral therapy-naïve HCV-genotype 1 subjects; (c) at least one of these primary outcomes: Rapid Virological Response (RVR); Early Complete Virological Response (EVR); End of Treatment Response (ETR); Sustained Virological Response (SVR); (d) odds ratio estimates of relative risk (RR) and associated 95% confidence intervals (CIs) or at least data enabling them to be computed; (e) English language; and (f) published as a full paper up to December 2011. RESULTS: Seven published studies met the inclusion criteria, allowing a meta-analysis on 3,026 patients. Peg-IFN α-2a and Peg-IFN α-2b showed similar rate of RVR (RR = 1.05; 95% CI = 0.87-1.27, p = 0.62) and SVR (RR = 1.08; 95% CI = 0.99-1.18, p = 0.098). Peg-IFN α-2a more frequently than Peg-IFN α-2b achieved EVR (RR = 1.11; 95% CI = 1.02-1.21, p = 0.013) and ETR (RR = 1.22; 95% CI = 1.14-1.31, p < 0.0001). CONCLUSION: The standard schedules of Peg-IFN α-2a and Peg-IFN α-2b, both in combination with ribavirin, can be used indifferently for patients with chronic HCV genotype 1 who are anti- to eliminate HIV-negative and antiviral treatment-naïve.

Virological pattern in plasma, peripheral blood mononuclear cells and liver tissue and clinical outcome in chronic hepatitis B and C virus coinfection.

BACKGROUND: We aim to evaluate in chronic hepatitis B virus-hepatitis C virus (HBV-HCV) coinfection the interplay of these viruses in liver tissue, peripheral blood mononuclear cells (PBMC), and plasma and to analyze the effect on disease course and response to treatment. METHODS: We enrolled 19 patients with chronic HBV-HCV coinfection, 20 with chronic HCV and 20 with chronic HBV infection at their first liver biopsy, all were naive for antiviral therapy. The patients' plasma, PBMC and liver biopsy samples were tested for HBV DNA and/or HCV RNA by real-time PCR, according to the presence/absence of hepatitis B surface antigen and antibodies against HCV in the serum. RESULTS: Contemporary presence of HBV DNA and HCV RNA was rare in plasma (5.3% of cases) and PBMC (10.6%), but frequent in liver tissue (52.6%). Of 10 cases circulating only HCV RNA and treated with pegylated interferon (PEG-IFN) plus ribavirin for 12 months, two showed a sustained response, and eight cleared HCV RNA but became HBV-DNA-positive in plasma; these eight had detectable HBV DNA in liver at baseline. One patient, who was plasma HBV-DNA-positive/HCV-RNA-negative at baseline, showed a sustained response after 18 months of PEG-IFN treatment; another, who was plasma HBV-DNA/HCV-RNA-positive at baseline, cleared only HCV RNA during 12 months of PEG-IFN plus ribavirin treatment. Seven cases remained untreated. CONCLUSION: Despite a reciprocal inhibition in plasma, HBV and HCV frequently coexist in liver tissue, a condition to be taken into consideration when deciding therapy.

Prevalence and associated risk factors of latent tuberculosis infection among undergraduate and postgraduate dental students: A retrospective study.

To estimate the prevalence of latent tuberculosis (TB) infection (LTBI) in Italian dental students exposed to the same occupational risks as dental health care personnel and to evaluate potential risk factors, a cross-sectional study was conducted on undergraduate and postgraduate students. After clinical evaluation, students were given a tuberculin skin test; in those found positive, an interferon-γ release assay (IGRA) was conducted. Of the 281 students enrolled, 10 were only TST positive; 8 were TST or/and IGRA positive. We found that participants testing positive at TST and/or IGRA, a group in which the risk of false LTBI positives is minimal, were older and had been studying longer. Although the prevalence of LTBI among dental students in our study was low, a risk of acquiring a work-related infection exists even in a country with a low incidence of TB. Thus, dental students should be screened to catch LTBI early on.

Hepatitis B virus and hepatitis C virus infection in healthcare workers.

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus (HBV) and 1000000 to hepatitis C virus (HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.

Role of ITPA and IL28B variants in the management of chronic hepatitis C treatment.

The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been associated to protection of anemia and sustained virological response, respectively, in patients with chronic hepatitis C (CHC) during antiviral therapy. Aim of this study was to evaluate the single and combined role of both polymorphisms in the management of peg-interferon-ribavirin treatment in CHC patients. We studied 79 Italian patients with histology proven CHC treated with pegylated interferon plus ribavirin for 6-12 months on the base of HCV genotype. Patients were carefully followed-up for anemia development which was classified as mild, moderate or severe in relation to levels of haemoglobin decreasing; ribavirin dosage reduction and/or epoietin administration were carried out, where needed. Sustained virological response (SVR) was considered for HCV-RNA clearance after 6 months of treatment stop. Decay of haemoglobin at month 1 of treatment significantly correlated with ITPA activity (p 0.0004) and at multivariate analysis ITPA activity was the only parameter associate with anemia (R - 0.4; p 0.0004). SVR was obtained in 47% of patients. IL28B CC variant was associated with SVR (p 0.01), but IL28B polymorphisms had no influence on the ITPA polymorphism. This study confirms the role of ITPA variants in the prediction of development of severe anemia during antiviral treatment for CHC and demonstrates the absence of influence of IL28B variant on ITPA polymorphisms. These two polymorphisms can be useful in the management of patients that need antiviral therapy for HCV chronic infection.

Vaccination against hepatitis b virus: are Italian medical students sufficiently protected after the public vaccination programme?

BACKGROUND: The development of a vaccine against hepatitis B virus (HBV) has been a major achievement in terms of prevention of HBV infection. For the present study, we analysed the long-term immunogenicity and effectiveness of HBV vaccination among healthcare students with different working seniorities. METHODS: A cross-sectional study of undergraduate and postgraduate students attending the Medical School of the Second University of Naples was conducted between September 2012 and December 2014. HBV serum markers were determined and multivariate logistic regression analysis was used to identify factors associated with the level of long-term immunogenicity. RESULTS: Of the 2,932 subjects evaluated, only 33 (1.1 %) declared no history of vaccination. All vaccinated subjects were HBsAg/anti-HBc negative, 459 of which had an anti-HBs titre <10 IU/L. The latter were younger, more likely to be attending a healthcare profession school (i.e., dental hygienists, nursing, paediatric nursing, radiography and midwifery) than a medical school (at either undergraduate or postgraduate level) and more likely to have been vaccinated in infancy. CONCLUSION: The results of this study suggest that assessment of HBV serum markers in workers potentially exposed to hospital infections is useful to identify small numbers of unvaccinated subjects or vaccinated subjects with low antibody titre, all of whom should be referred to a booster series of vaccinations.

Peg-interferon plus ribavirin with or without boceprevir or telaprevir for HCV genotype 1: a meta-analysis on the role of response predictors.

BACKGROUND & AIM: To compare the efficacy of pegylated-interferon (Peg-IFN) α-2a or α-2b and ribavirin given as dual therapy versus triple therapy (Peg-IFN and ribavirin plus boceprevir or telaprevir) in patients with HCV-1 chronic hepatitis naïve for anti-HCV therapy or relapsers to dual therapy in relation to the presence of constitutional, clinical and virological predictors of treatment response. METHODS: Included in the meta-analysis were studies meeting these criteria: original data from randomized trials on the efficacy of dual versus triple therapy in therapy-naïve patients or relapsers; at least one primary outcome clearly defined: sustained virological response in patients with or without rapid virological response (RVR), with genotype 1a or 1b, low or high HCV load, IL28-B CC or non-CC genotype, mild or severe fibrosis; odds ratio estimates of relative risk (RR) and 95% confidence intervals; English language; and published up to the end of June 2013. RESULTS: Seven original studies met the inclusion criteria, allowing a meta-analysis on 3,652 patients. Triple therapy was more effective than dual, regardless of IL-28B genotype, HCV sub-genotype, liver fibrosis, and baseline HCV load. In 1,045 patients who achieved RVR, SVR was more frequently achieved with dual therapy (RR = 1.11; p = 0.002) than triple. The same results were achieved when only the therapy-naïve patients were considered. CONCLUSIONS: Triple therapy provides a significantly higher SVR rate than dual therapy, but dual therapy obtains a significantly higher SVR rate in patients with RVR. The data stress the clinical importance of a 4-week lead-in phase in direct-acting antiviral-based treatment.

Liver biopsy in chronic hepatitis C: the experience of 15 Italian wards of infectious diseases.

To evaluate the impact of liver histology on the management of HCV-related chronic hepatitis, 281 patients with chronic HCV infection who consecutively underwent percutaneous liver biopsy (LB) at one of the 15 participating Italian Units of Infectious Diseases were investigated in 2005. Demographic, aetiological, laboratory and clinical data and information on methods applied to perform ultrasonography (US) and LB were recorded. Males predominated (61.6%), mean age was 47.5 years and the mean BMI 22.3. In each case LB was US-guided or US-assisted. An 18-gauge Menghini-type needle was used in 203 (72.2%) cases. The length of the specimen ranged between 1.5 and 5 cm in 279 (99.3%) cases, it was smaller in two cases, but the diagnosis was still possible. Haemoperitoneum was the only (0.4%) major unpredictable complication; minor complications were also infrequent (4%). Using both clinical and laboratory data and US examination the physician misdiagnosed liver histology in 25% of cases. After LB the physicians changed their opinion on whether to treat with PEG-INF plus ribavirin in 43 (15.5%) cases. Liver histology allows more accurate diagnosis and enables physicians to make the most appropriate choic.

Antiviral treatment of HCV-related cirrhosis.

The primary aim of antiviral therapy in HCV liver cirrhosis is to stop viral replication and, consequently, to prevent the clinical progression of fibrosis, liver decompensation and the onset of hepatocellular carcinoma. However, the results of therapy are different according to the different clinical stages of cirrhosis. In patients with bridging fibrosis or histological cirrhosis international trials have demonstrated that the sustained virological response to the highly active combination of pegylated interferon plus ribavirin was substantially similar to that observed in subjects with chronic hepatitis C without cirrhosis. Few data are available as to the efficacy and tolerability of antiviral treatment in patients with fully developed clinical cirrhosis, with or without decompensation, and all studies to date underscore the difficulties in the management of the more frequent and severe side effects in these patients. In patients with a more severe disease who do not achieve a sustained virological response, an alternative option is to reduce or suppress inflammation and fibrosis progression with long-term suppressive therapy in the hope to prevent clinical deterioration and the onset of hepatocellular carcinoma. Three international trials are currently evaluating the use of antiviral treatment as a maintenance antiviral therapy.