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Background: Daclatasvir (DCV) combinated with Sofosbuvir (SOF) has shown good efficacy and safety profile for HCV patients. The aim was to evaluate the cost-effectiveness of DCV/SOF regimen versus HCV alternative treatments for patients who failed to achieve the SVR12 after a first DAA treatment from Italian perspective (PITER cohort)., Methods: A Markov model of HCV chronically infected patients was used to develop two scenarios: 1) DCV+ SOF versus Ledipasvir (LDV)+ SOF in Genotype (Gt)1 and Gt4; 2) DCV+ SOF versus no retreatment option in Gt1, Gt3, and Gt4. The percentage of patients who failed the first line with SOF/Simeprevir/Ribavirin (RBV) or SOF/RBV and were retreated or not according to evidences from PITER cohort, were used to populate the model. HCV resources consumption and SVR rates were quantified using PITER data. Transition probabilities and utility rates were derived from the literature. The outcomes were expressed in terms of Quality adjusted life years (QALYs). Probabilistic sensitivity analysis (PSA) was performed considering a cost-effectiveness threshold of € 30,000/QALY., Results: In the base-case analysis, DCV+ SOF represents a cost-effectiveness therapy with ICERs lower than the threshold. The PSA showed robust results, ICERs remain below the threshold in 94% and 99% simulations in Scenario 1 and 2, respectively.

Purpose: The prevalence of anti-hepatitis E virus (HEV) and anti-hepatitis A virus (HAV), as well as the possible links with socio-demographic and other viral risks factors, were evaluated in an inmates population., Methods: The study population consisted of 973 consecutively recruited inmates of eight Italian prisons., Results: The anti-HEV prevalence was 11.6 % (113/973). It increased significantly by age (χ(2) for linear trend: p = 0.001) and was significantly higher among non-Italian compared to Italian inmates (15.3 vs. 10.7 %, respectively). Age >40 years [odds ratio (OR) 2.1; 95 % confidence interval (CI) 1.4-3.1], non-Italian citizenship (OR 1.8; 95 % CI 1.1-2.9) and anti-HIV seropositivity (OR 2.2; 95 % CI 1.2-4.2) were the only factors independently associated to anti-HEV positivity by logistic regression analysis. The overall anti-HAV prevalence was 86.4 %, and was significantly higher in non-Italian compared to Italian prisoners (92.6 vs. 84.9 %, respectively; p = 0.02). Age older than 40 years (OR 3.6; 95 % CI 2.2-5.9), <5 years formal education (OR 2.1; 95 % CI 1.3-3.2) and non-Italian nationality (OR 2.7; 95 % CI 1.5-4.8) were factors independently associated to anti-HAV positivity by the logistic regression analysis., Conclusions: Compared to the general population, significantly higher anti-HEV and anti-HAV prevalences were observed in an inmates population in Italy. Old age and non-Italian nationality were factors independently related to both HEV and HAV exposures. This data suggest the important role of low socio-economic factors in the transmission of both infections in high-risk populations. The possible epidemiological and/or pathogenetic links between HEV and HIV exposures need to be studied further.

Background and Aim: Acute hepatitis B course may be significantly modified by underlying chronic hepatitis C. The aim of this study was to compare clinical and virological characteristics of acute hepatitis B in patients with or without chronic hepatitis C virus (HCV) infection., Materials and Methods: Twenty-seven patients with symptomatic acute hepatitis B were enrolled: 14 with underlying chronic HCV (Group A) and 13, matched by age and gender, with single hepatitis B (Group B). All patients were followed-up until HBsAg negativization., Results: Group A patients were HCV-RNA-negative on hospital admission and all but one remained negative during follow-up. HBeAg tested positive in 92.9% and 84.6% of Groups A and B patients, respectively. ALT, bilirubin, prothrombin time values and HBsAg titer were similar in both groups. Nevertheless, lower mean HBV-DNA levels (p=0.03), a shorter duration of HBsAg positivity (p<0.01) and of symptoms before ALT peak (p=0.014), and significantly lower peak ALT values (p=0.03) were observed in Group A compared to Group B patients., Conclusions: Acute HBV infection suppressed HCV replication. Conversely, the underlying HCV infection exerted a modulatory effect on HBV replication which influenced the course, though not the outcome, of the acute disease. Although acute hepatitis B showed a mild clinical course in both groups of patients, HBV vaccination should be suggested to risk subjects.

Background: Albania is a Mediterranean, South-East European developing country where epidemiological data on infectious diseases are scarce. In this study, the seroprevalence of Helicobacter pylori infection in 1,088 Albanian healthy volunteers (472 females followed-up to a prenatal clinic, 173 recruits, 443 health care workers) was evaluated., Materials and Methods: Sera were tested for immunoglobulin-G (IgG) antibodies against H. pylori using a quantitative enzyme immunosorbent assay., Results: The overall H. pylori seroprevalence was 70.7%. The H. pylori seroprevalence increased by age, from 60.4% in individuals younger than 20 years to 81% among those > or = 50 years of age with a significant trend of increase by age. The overall seroprevalence was 73.9% for females and 59.5% for males. In addition the seroprevalence was 55.3% for people living in rural areas and 72.3% for people living in urban areas. No significant differences were found according to level of education except for individuals with elementary level of education. Nurses and hospital auxiliaries have significantly higher H. pylori seroprevalence when compared to other health care workers (physicians and office workers). When each variable (age, gender, area of residence, occupation, and education level) was adjusted for the confounding effect of the other variables by stepwise logistic analysis, we observed that age greater than 40 years and female gender remain the only variables independently associated with the presence of H. pylori IgG antibodies., Conclusions: H. pylori is highly prevalent among the Albanian population. Improving living conditions, education in hygiene, and the supply of running water are measures to prevent the transmission of H. pylori infection and other infections spread by the fecal-oral route in Albania.

Aim: To evaluate the risk of recurrence of hepatocellular cancer (HCC) after liver transplantation (LT)., Methods: The clinical records of 104 patients with HCC in the explanted liver were examined., Results: HCC recurrence occurred in 12 patients. Recurrence was observed in all patients with a single nodule greater than 5 cm. Among the 5 patients with more than 3 tumours with a maximum diameter of 4.5 cm, no recurrence occurred. The survival rates were 81% and 64% at 1 and 5 years, respectively; the recurrence-free survival at 1 and 5 years was, respectively, 93% and 82%. Pre-LT alpha-fetoprotein (AFP) increased at a greater magnitude in patients who experienced recurrence, compared to those who did not. Tumour diameter, differentiation, satellitosis, AFP and the magnitude of AFP increase were predictive of recurrence. The 1- and 5-year recurrence-free survival for the 68 patients who had a single nodule up to 5 cm, or up to 3 nodules all less than 4.5 cm and with a maximum cumulative diameter of 8 cm, or more than 3 nodules all less than 2.5 cm, were 95% and 92%, respectively. For the 13 patients not meeting these criteria, the 1- and 5-year recurrence-free survival was, respectively, 75% and 54% (log Rank test p=0.019)., Conclusions: Patients with more than 3 small HCC nodules before LT could still have a good outcome without recurrence. A rapid increase in AFP could be useful in identifying patients with a greater risk of post-LT HCC recurrence.

Background: Health care workers (HCW) have an elevated risk of acquiring and transmitting parenteral infections. The aim of this study was to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers with the final goal to encourage HBV vaccination of the non-immune Albanian HCW., Methods: Among 480 HCW enrolled, 92 were physicians, 246 were nurses/techniques, 120 were auxiliary workers and 22 were office workers., Results: The HBsAg, anti-HBc and anti-HCV prevalence were 8.1%, 70% and 0.6%, respectively. The highest (11.4%) HBsAg prevalence was observed in the youngest age group (20-30 years of age). High HBsAg prevalence (7.2-7.5%) was detected also in age groups above 30 years. The highest HBsAg prevalence (12.6%) was found in the auxiliaries. The anti-HBc prevalence increased significantly with age from 59% in HCWs younger than 39 years to 87% among those older than 50 years. After adjustments for different job categories, age older than 40 years remained independently associated with anti-HBc positivity (OR = 2.9; 95% CI 1.9-4.6) and inversely associated with the lack of HBV immunity or infection markers (OR = 0.4; 95% CI 0.2-0.7). Of 142 HBsAg negative and/or anti-HBc Ab negative sera, 28 (20%) tested positive for anti-HBs. The 114 remaining individuals with no HBV infection or immunity markers were vaccinated against HBV infection., Conclusions: A high HBV infection rate and low HBV vaccination coverage were found in Albanian HCW. Albania is a Mediterranean country still highly endemic for HBV infection and new strategies to promote HBV vaccination are to be adopted.

Reported here are details of a simultaneous outbreak of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections that occurred in a hemodialysis centre in northern Italy, with three patients seroconverting for HBsAg and four patients seroconverting for HCV antibodies. Phylogenetic analysis of the E2 region of the isolates from HCV-seroconverted patients showed the sequences were grouped in the same distinct branch as in a chronically HCV-infected patient, suggesting that the chronically infected patient was the index case. For the patients with HBV infection, phylogenetic analysis showed strong clustering among the sequences of the three patients who seroconverted to HBsAg and no relatedness between them and the sequences of patients chronically infected with HBV. For one of the patients who seroconverted to HBsAg, the last test with negative results for HBV markers had been performed 18 months prior to HBsAg seroconversion. This patient may have been previously infected with HBV and is presumed to be the source of the outbreak. This report emphasizes the importance of using universal precaution measures and HBV vaccination to prevent the transmission of viral hepatitis among chronic hemodialysis patients.

A case-control study involving 109 in-patients with chronic liver disease and 190 in-patients with no apparent liver disease was conducted to evaluate the seroprevalence of anti-HEV antibodies and the possible association with chronic liver disease. Among cases, the anti-HEV prevalence was 36.6% which increased significantly by age; among controls, the prevalence was 12.1% (P<0.05) and was similar among age groups <60 years. Among cases, aged >50 years (OR 4.0, 95% CI 1.4-11) and the presence of end stage liver disease (ESLD) (OR 4.3, 95% CI 1.4-12.8) were associated independently with anti-HEV positivity. The mean optical density, determined by anti-HEV immunoenzymatic test, was significantly higher among patients with ESLD, compared to the other patients. These results indicate that there is a high seroprevalence of anti-HEV in patients with chronic liver disease and a possible association between HEV infection and/or anti-HEV production and advanced stage chronic liver disease.

Albania is a Mediterranean country, still with a high endemicity level of hepatitis B virus (HBV) infection. The chronic hepatitis B profile was characterized in this geographical area and used as a model to investigate the impact of endemicity level on the prevalence of the two major forms of chronic hepatitis B (HBeAg-positive and HBeAg-negative chronic hepatitis B). A cross-sectional study was conducted among 62 chronic hepatitis B patients consecutively admitted to the most important tertiary health care center for the diagnosis and treatment of liver disease in Albania. HBV-DNA was measured with an in-house PCR with a sensitivity of 10(4) copies/ml which uses primers encompassing the pre-core/core region. PCR products were subjected to sequencing and oligohybridization assay. Of the 62 patients, 75.8% had HBeAg-negative chronic hepatitis B. Genotype D was found in all 39 patients with detectable HBV viremia, for whom the heterogeneity of the region modulating HBeAg expression was assessed. Basic core promoter (BCP) mutations (1762/1764) were observed more often in anti-HBe-positive and older patients. In more than 90% of the HBeAg-negative chronic hepatitis B patients with detectable viremia, HBV that carries the G to A pre-core mutation at nucleotide 1896 was found. Patients with HBeAg-positive chronic hepatitis B were younger than HBeAg-negative chronic hepatitis B patients, and for symptomatic and asymptomatic liver-disease patients, the age of peak prevalence was at least 10 years lower for HBeAg-positive chronic hepatitis B patients. In conclusion, the virological and clinical pattern of chronic hepatitis B in Albania is similar to that observed in other Mediterranean countries; it seems to be independent of the HBV endemicity level., (Copyright 2005 Wiley-Liss, Inc.)

There are limited data on the use of lamivudine for patients with severe forms of acute hepatitis B. We report our experience with the use of lamivudine in six patients with acute HBV infection. Lamivudine was justified by disease severity for four patients and by concerns about risk of chronicity for two patients. The diagnoses of the treated patients were: fulminant liver failure (two patients), severe acute hepatitis B, protracted acute hepatitis B, and new HBV infection in the renal dialysis setting (two patients, one with severe liver injury). Serum HBV DNA titres ranged from 10(5) to 10(7) copies/mL prior to commencement of lamivudine. Lamivudine treatment was associated with a decline in serum HBV DNA and serum transaminases in all patients. All but one patient survived. A 58-year-old man with fulminant hepatitis and multiple organ failure died despite antiviral treatment. When possible, HBeAg and HBsAg seroconversion was documented during follow-up. In the absence of a randomized, prospective study of lamivudine in patients with severe acute hepatitis B, our data encourage the use of this safe and well tolerated drug.

The presence of SENV and TTV infections among 50 patients who had undergone liver transplantation was evaluated. UTR amplification showed that 46 (92%) sera were positive. ORF-1 amplification showed that 25 (50%) patients were positive for either SENV (51.3%), TTV (10.8%), or both (37.8%) all confirmed by sequencing and phylogenetic analysis. SENV-D and SENV-H were the most prevalent viruses. The phylogenetic analysis of isolates showed that whereas SENV-D and SENV-G viruses showed sequence stability and strain persistence, SENV-H had cleared or mutated. Biological differences seem to exist among different genotypes in terms of viral replication and their persistence.

The woodchuck hepatitis virus (WHV)/woodchuck system is studied as animal model of human hepatocellular carcinoma (HCC) induced by chronic hepatitis B virus infection. The aim of the present study was the evaluation of ultrasound (US) liver examination in woodchuck as a routine method to detect HCC nodules and to follow their growth. Sixteen woodchucks were included in the study. US liver examination was carried out in all animals using a 5 MHz convex scanner. Macroscopic and microscopic examinations were performed to evaluate the US findings. The lower limit of nodule detection by US examination was a diameter of 5 mm. Macroscopic and microscopic examinations confirmed US findings in 14 of 16 animals (86.6%). No false negative results were obtained. Increase of nodule size was faster in the early phase of tumour growth. Small nodules (16 +/- 5 mm) appeared as hypoechoic lesions with well-defined margins and homogeneous structure. Large nodules (42 +/- 19 mm) appeared as hyperechoic lesions with irregular margins, heterogeneous or of mixed pattern; microscopical examination showed different degrees of necrosis, inflammation and fibrosis inside these latter neoplasms. The hepatitis reaction was conspicuously more severe around HCC nodules. No fibrosis and/or cirrhosis were found in normal liver parenchyma surrounding tumour nodules. On the whole, US appears to be helpful in the diagnosis of woodchuck HCC even at an early stage. Serial US evaluation can be used to study the growth rate of tumour nodules during natural history or experimental HCC treatments in woodchuck.

Background: Hepatitis C virus (HCV) infection is common worldwide but there are different prevalence rates in different countries. Data on the incidence of HCV in the general population are scarce. Spontaneous viral clearance occurs in 10-25% of infected individuals after acute infection yet controversy exists regarding the frequency of spontaneous clearance during the natural course of HCV infection in the general population., Aims: Anti-HCV prevalence, HCV infection rate, and the kinetics of anti-HCV were studied in a cross section of the general population of central Italy., Study Population and Methods: Anti-HCV prevalence (EIA-3 Ortho, RIBA-3 Ortho Chiron) was estimated in 3884 randomly selected individuals. Infection rate and antibody kinetics were estimated in 2032 participants for whom a second blood sample was taken after a median follow up of seven years. HCV-RNA determination by polymerase chain reaction was performed on follow up sera., Results: The overall confirmed anti-HCV prevalence was 2.4%. Two participants seroconverted for anti-HCV, giving an overall infection rate of 1.4 cases per 10 000 person years (95% confidence interval 0.2-5.2 per 10 000 person years). Of the 36 individuals confirmed as anti-HCV positive at enrollment, seven (19.4%) showed complete seroreversion. Seven (87%) of the eight individuals with indeterminate results at enrollment were serologically non-reactive at the end of follow up. Of the 25 participants confirmed to be anti-HCV positive at both enrollment and follow up, 23 (92.0%) with stable serological profiles tested positive for HCV-RNA at the end of follow up., Conclusions: There is still a permanent risk, although low, of HCV spread in the general population in an area of low level endemicity. In this setting, a wide spectrum of modifications of viral and antibody patterns can be observed in HCV infected patients.

Background: The recently discovered TT virus (TTV) has been shown to be highly prevalent in patients with cryptogenetic chronic liver disease and fulminant hepatitis. To study the frequency of TTV and to evaluate the possible association with liver disease, 37 pediatric and young adult patients with thalassemia, and 36 healthy children were included in the study. The sera of 100 blood donors selected randomly in the same period were also tested for TTV DNA., Methods: The TTV amplification by polymerase chain reaction (PCR) was performed using a first set of primers that recognize an internal sequence into N22 and a second set of primers amplifying a sequence within 5;NCR (5; noncoding region)., Results: The first set of primers revealed TTV DNA in 73% of thalassemic patients, in 8% of healthy children, and in 5% of healthy blood donors. With the second set of primers, the prevalence of TTV DNA was, respectively, 100% in thalassemic patients, 44.5% in healthy pediatric patients, and 87% in healthy blood donors. All individuals who tested positive for TTV by the first set of primers were also positive by the second primer set. The TTV infection seemed not to be the cause of altered transaminase levels. Sequencing of TTV clones from thalassemic patients showed the presence of different TTV variants in the same serum., Conclusion: The prevalence of TTV in polytransfused children is similar to that detected in blood donors. Moreover, TTV can be detected in healthy children of all ages. The presence of TTV seems to have no clinical significance.

Background: The aim was to estimate the prevalence and the persistence of GB virus C/hepatitis G virus (GBV-C/HGV) exposure markers in a group at high risk for transfusion-transmitted agents., Patients and Methods: Serum samples from 37 thalassemic patients were screened for GBV-C/HGV RNA by reverse transcription PCR (RT-PCR) and for antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2)., Results and Discussion: GBV-C/HGV RNA and anti-E2 were detected in 13 (35%) and 12 (32%) sera, respectively. Contemporary presence of both markers was found in one patient. GBV-C/HGV exposure was found in 24 patients (64.8%). Mean levels of liver enzymes were similar in both exposed and unexposed GBV-C/HGV groups. 33 out of 35 patients showed no change in GBV-C/HGV RNA and anti-E2 status in sera taken 6 months apart. The rate of persistent infection was 92.3% and the anti-E2 seroconversion rate was 23% for sera taken at least 6 months apart. The temporal overlap between anti-E2 seroconversion and loss of detectable GBV-C/HGV RNA may last more than 6 months.

Background/aim: The aim of the study was to estimate the prevalence, risk factors and genotype distribution of hepatitis C virus (HCV) in the general population older than 5 years of age in a southern Italian town. The positive predictive value of alanine transaminase (ALT) screening in identifying HCV positive subjects was also assessed., Methods: Cluster random sampling from the census of the general population was used. ELISA and RIBA tests assessed the presence of anti-HCV; nested reverse transcription polymerase chain reaction (RT-PCR) was used to identify HCV-RNA; genotyping was performed by INNO-LIPA III. The association linking anti-HCV seropositivity with potential risk factors was assessed by multiple logistic regression analysis., Results: Among the 488 subjects enrolled, 79 (16.2%) were anti-HCV positive. The prevalence increased from 1.2% in subjects 6-29 years of age to 42.1% in those > or = 60 years. Forty percent of these positive subjects also had abnormal ALT level and 54.4% were HCV RNA positive by PCR. The positive predictive value of the ALT test in identifying anti-HCV positive subjects was 65%; however, it was 46.7% in subjects younger than 60 years of age and 90.5% in those 60 or older. Genotype 1b was detected in 74% of subjects, type 2c in 23.3%, and type 1a in 2.3%. The only two variables significantly associated with HCV seropositivity in multivariate analysis were age older than 45 years (O.R. 8.5; CI 95%=3.0-24.1) and past use of glass syringes (O.R. 3.4; CI 95%=1.5-7.6)., Conclusions: These findings confirm that HCV infection is endemic in southern Italy, particularly among the elderly. Percutaneous exposure, such as injections with nondisposable, multiple-use, glass syringes used in the past for medical purposes may have played a major role in the spread of HCV infection. ALT screening is not useful in detecting HCV positive subjects in the general population, particularly among subjects who could benefit from antiviral therapy.

We conducted an analytical review of 194 full papers on interferon (IFN) therapy for chronic hepatitis C to evaluate current methodology (i.e. study design, criteria for evaluating the efficacy of therapy and predictors of response). Of the papers evaluated, 64 were randomized controlled trials (RCT), 40 were non-randomized controlled trials (NRCT) and 90 were observational studies (OS). The methodological analysis was focused mainly on clinical trials. The number of patients enrolled in RCT was higher compared with the number enrolled in NRCT. Uniform enrolment criteria were used in less than 50% of the trials. Only 20% of RCT and 2.5% of NRCT used criteria for defining sample size. The response rate was calculated on an intention-to-treat basis in 36 of the RCT and in 14 of the NRCT. The outcome of treatment and the criteria employed to define the response to treatment were found to be far from standardized. In 51.5% of the RCT and 42.5% of the NRCT, normalization of alanine aminotransferase (ALT) level at the end of follow-up was the only marker of response studied. Only 57.6% of the trials considered histological evidence as an important outcome. Among the clinical trials, 71.1% evaluated predictors of good response to IFN therapy. In 51% of the OS, ALT normalization by the end of follow-up was the only criterion for defining response. In conclusion, to ensure a high level of reliability in comparing or combining the results of different studies, some basic general requirements must be followed when planning trials on antiviral therapy.

The prevalence of anti-HEV was assessed in 2,233 subjects aged 20-79 years in the Republic of San Marino in the years 1990-1991. The sera were tested by ELISA and further confirmed by Western blot (WB) analysis. The overall anti-HEV prevalence was 1.5%. A significant trend by age was observed. Anti-HEV prevalence was 0.6% in subjects <30 years and 3.3% in those older than 70 years of age. Family size larger than four persons (OR = 3.8; 95% CI = 1.8-13.2) was the sole independent predictor of anti-HEV positivity in the multivariate analysis. Anti-HAV and anti-HEV prevalences did not show a parallel trend by age. No association was found either between hepatitis E virus (HEV) or hepatitis C virus (HCV) infections. Follow-up samples 5 years apart were available for 38 out of 54 (70%) anti-HEV ELISA-positive subjects. Eight out of 22 (37%) WB-confirmed anti-HEV-positive subjects were still anti-HEV-positive after 5 years. However, anti-HEV remained positive in all but two (75%) of the subjects with WB-confirmed ELISA positivity value of S/CO > or = 2 (cutoff 1.2), but in only 2 out of the 14 subjects (14%) with a WB-confirmed ELISA positivity value of S/CO < 2 (P < 0.005). None of the 16 subjects ELISA-positive but not WB-confirmed was anti-HEV-positive 5 years apart. Therefore, only a relative proportion of subjects once infected with HEV maintain for at least 5 years anti-HEV antibodies.

The present study examined the effect of hepatitis B virus (HBV) and alcohol intake, and the role of hepatitis delta virus (HDV) and hepatitis C virus (HCV) in the aetiology of chronic liver disease in Albania. A total of 106 cases of liver cirrhosis or chronic hepatitis were compared to 195 control patients without these or other liver diseases. Adjusted odds ratios were 52.7 (95% CI 22.7-122) for HBV surface antigen, 26.9 (95% CI 4.9-147) for anti-HCV, 26.2 (95% CI 3-1-221) for anti-HDV, 2.4 (95% CI 1.3-4.4) for lifetime alcohol intake and 2.3 (95% CI 1-5.5) for duration of alcohol intake. Although not significant, an interaction was suggested between HBsAg and anti-HCV and between HBsAg and alcohol intake. Our study underlines the role of hepatitis viruses in the development of chronic liver diseases. Additionally, it suggests that heavy alcohol intake may magnify the effect of HBV on these diseases. HBV vaccination and alcohol abstention appear to be important strategies to reduce the risk of liver cirrhosis and chronic hepatitis in Albania.

A revision of the polymerase chain reaction (PCR) core procedure was performed for genotyping hepatitis C virus (HCV) in 139 patients from Italy. This procedure, developed prior to the identification of new genotypes, may be inadequate in several geographical areas. We proposed a new typing mixture in which primers for types 2c and 4, that are reported to be circulating in Italy, were added and a primer for type 2b was substituted. Using the modified procedure, 139 HCV-positive patients were analysed. The HCV genotype was identified in 96.4% of the cases. We observed double infections and unclassified genotypes in 5 (3.6%) and 5 (3.6%) patients, respectively. The classification of isolates into genotypes and subtypes 2b, 2c and 4 was confirmed by sequence analysis. Furthermore, the efficiency and accuracy of the modified core procedure were evaluated by parallel testing of 107 out of 139 samples using the line probe assay, and demonstrated a 98.9% degree of concordance. The results demonstrated the specificity of the selected primers for type 2c, 2b and 4 and confirmed the circulation of types 2c and 4 in Italy. In conclusion, the proposed modified PCR procedure is the only primer-specific PCR genotyping method available for identification of the 2c and 4 genotypes reported to be circulated in Italy and other European countries.

Background: There are limited data on the use of high interferon (IFN) dosage for treatment of children and young adults with hepatitis C virus infection and in those affected by thalassemia major (TM)., Objectives: To assess the response of children and young adults with chronic hepatitis C disease, including those affected by TM, to high dose natural alpha-interferon (IFN-alpha). To evaluate the effect of iron overload in response to high dose IFN-alpha in young chronic hepatitis C virus thalassemia patients., Methods: We conducted a therapeutic trial of natural IFN-alpha, using 10 million units/m2 three times a week for 6 months in 14 chronic hepatitis C patients ages 5 to 28 years; 7 also had TM. The follow-up period lasted 12 months., Results: Ten patients (73%) showed normal or nearly normal alanine aminotransferase values at the end of follow-up (biochemical response), but only five (35%) were negative for serum hepatitis C virus-RNA (complete responders). Four of the patients (57%) with TM were sustained complete responders. No correlation was found between the initial serum concentration of ferritin and response to IFN therapy. Patients infected with genotype 1b showed a poor response although high dose of natural IFN was used., Conclusions: These results indicate that IFN-alpha can be used in children and young patients with chronic hepatitis C disease as well as in those affected by TM. Treatment with high dosage natural IFN-alpha in children and young adults with hepatitis C infection does not appear to be more effective than dosages previously used.

In 1996 the prevalence, risk factors, and genotype distribution of hepatitis C virus (HCV) infection were assessed in the general population of a town in southern Italy. The sample was selected from the census by a systematic 1:4 sampling procedure. The participation rate was 96.6%. Among the 1,352 subjects enrolled, 195 (14.4%) tested reactive to antibody to HCV (anti-HCV) with enzyme immunoassay (EIA 3). When further tested with recombinant immunoblot assay (RIBA 3), 170 subjects (87.2%) tested positive, 23 subjects (11.8%) had indeterminate results, and 2 subjects (1%) tested negative. Thus, the overall anti-HCV EIA-positive RIBA-confirmed prevalence was 12.6% (170 of 1,352 subjects) and increased from 1.3% in subjects younger than 30 years to 33.1% in those > or =60 years of age. This latter age group accounted for 72.3% of all anti-HCV-positive subjects. Females tested positive more frequently than males (14.1% vs. 10.5%; P < .05). Alanine transaminase (ALT) concentrations were abnormal in only 4.1% (7/170) of anti-HCV EIA-positive RIBA-confirmed subjects. This suggests that ALT screening is not useful in the detection of anti-HCV-positive subjects in a general population. The results of multiple logistic regression analysis showed that an age of less than 45 years, the use of glass syringes, and dental therapy were all independent predictors of anti-HCV positivity. HCV RNA was detected by polymerase chain reaction in 75.9% of the 195 anti-HCV EIA-positive subjects: in 84.7% (144/170) of the RIBA-confirmed subjects; in 17.4% (4/23) tested as RIBA indeterminate; and in neither of the two subjects who tested RIBA negative. HCV type 1b was detected in 75 subjects (50.7%), type 2b in 1 subject (0.7%), type 2c in 66 subjects (44.6%), type 3a in 4 subjects (2.7%), and type 4 in two subjects (1.3%). These figures differ from those of Italian patients with chronic liver disease in whom genotype 2 is more rare. None of the individuals was infected with more than one genotype. The distribution of the two most common HCV viral types (1b and 2c) was not statistically different in terms of mean age, sex, or risk factors and suggests that they may have had a parallel spread in this community. These findings provide one of the highest overall anti-HCV prevalence rates in a general population with a likely cohort effect, i.e., decreased risk of infection along generations. These observations may indicate an epidemic or focus of hepatitis C that occurred several years earlier. The majority of anti-HCV-positive subjects in the oldest age group and with no clinical evidence suggests that HCV infection is a very prolonged and indolent disease.