Persistence of immunity 18-19 years after vaccination against hepatitis B in 2 cohorts of vaccinees primed as infants or as adolescents in Italy.

This study was aimed at assessing the anti-HBs persistence and immune memory 18-19 y after vaccination against hepatitis B in healthy individuals primed as infants or adolescents. We enrolled 405 teenagers (Group A) vaccinated as infants, and 409 young adults (Group B) vaccinated as adolescents. All vaccinees were tested for anti-HBs and anti-HBc antibodies; those found anti-HBc positive were further tested for HBsAg and HBV DNA. Eight individuals belonging to Group B were positive for anti-HBc alone, and were excluded from analysis. Individuals with anti-HBs concentration ≥ 10 mIU/ml were considered protected while those with anti-HBs concentration <10 mIU/ml were offered a booster dose and re-tested 2 weeks later. Overall, 67.9% individuals showed anti-HBs concentrations ≥ 10 mIU/ml (48.9% in Group A vs 87.0% in Group B, p < 0.001). The antibody geometric mean concentration (GMC) was higher in Group B than in Group A (102.5 mIU/ml vs 6.9 mIU/ml; p < 0.001). When boosted, 94.2% of vaccinees with anti-HBs <10 mIU/ml belonging to Group A and 94.7% to Group B showed an anamnestic response. Post-booster GMCs were similar in both groups (477.9 mIU/ml for Group A vs 710.0 mIU/ml for Group B, p = n.s.). Strong immunological memory persists for at least 18-19 y after immunization of infants or adolescents with a primary course of vaccination. Thus, booster doses are not needed at this time, but additional follow up is required to assess the long-life longevity of protection.

Acute Hepatitis B After the Implementation of Universal Vaccination in Italy: Results From 22 Years of Surveillance (1993-2014).

BACKGROUND: Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. METHODS: We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. RESULTS: A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. CONCLUSIONS: Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection.

Key Role of Sequencing to Trace Hepatitis A Viruses Circulating in Italy During a Large Multi-Country European Foodborne Outbreak in 2013.

BACKGROUND: Foodborne Hepatitis A Virus (HAV) outbreaks are being recognized as an emerging public health problem in industrialized countries. In 2013 three foodborne HAV outbreaks occurred in Europe and one in USA. During the largest of the three European outbreaks, most cases occurred in Italy (>1,200 cases as of March 31, 2014). A national Task Force was established at the beginning of the outbreak by the Ministry of Health. Mixed frozen berries were early demonstrated to be the source of infection by the identity of viral sequences in patients and in food. In the present study the molecular characterization of HAV isolates from 355 Italian cases is reported. METHODS: Molecular characterization was carried out by PCR/sequencing (VP1/2A region), comparison with reference strains and phylogenetic analysis. RESULTS: A unique strain was responsible for most characterized cases (235/355, 66.1%). Molecular data had a key role in tracing this outbreak, allowing 110 out of the 235 outbreak cases (46.8%) to be recognized in absence of any other link. The data also showed background circulation of further unrelated strains, both autochthonous and travel related, whose sequence comparison highlighted minor outbreaks and small clusters, most of them unrecognized on the basis of epidemiological data. Phylogenetic analysis showed most isolates from travel related cases clustering with reference strains originating from the same geographical area of travel. CONCLUSIONS: In conclusion, the study documents, in a real outbreak context, the crucial role of molecular analysis in investigating an old but re-emerging pathogen. Improving the molecular knowledge of HAV strains, both autochthonous and circulating in countries from which potentially contaminated foods are imported, will become increasingly important to control outbreaks by supporting trace back activities, aiming to identify the geographical source(s) of contaminated food, as well as public health interventions.

Reconstruction of the Evolutionary Dynamics of A(H3N2) Influenza Viruses Circulating in Italy from 2004 to 2012.

BACKGROUND: Influenza A viruses are characterised by their rapid evolution, and the appearance of point mutations in the viral hemagglutinin (HA) domain causes seasonal epidemics. The A(H3N2) virus has higher mutation rate than the A(H1N1) virus. The aim of this study was to reconstruct the evolutionary dynamics of the A(H3N2) viruses circulating in Italy between 2004 and 2012 in the light of the forces driving viral evolution. METHODS: Phylodinamic analyses were made using a Bayesian method, and codon-specific positive selection acting on the HA coding sequence was evaluated. RESULTS: Global and local phylogenetic analyses showed that the Italian strains collected between 2004 and 2012 grouped into five significant Italian clades that included viral sequences circulating in different epidemic seasons. The time of the most recent common ancestor (tMRCA) of the tree root was between May and December 2003. The tMRCA estimates of the major clades suggest that the origin of a new viral strain precedes the effective circulation of the strain in the Italian population by 6-31 months, thus supporting a central role of global migration in seeding the epidemics in Italy. The study of selection pressure showed that four codons were under positive selection, three of which were located in antigenic sites. Analysis of population dynamics showed the alternation of periods of exponential growth followed by a decrease in the effective number of infections corresponding to epidemic and inter-epidemic seasons. CONCLUSIONS: Our analyses suggest that a complex interaction between the immune status of the population, migrations, and a few selective sweeps drive the influenza A(H3N2) virus evolution. Our findings suggest the possibility of the year-round survival of local strains even in temperate zones, a hypothesis that warrants further investigation.

Clinical, epidemiological and virological features of acute hepatitis B in Italy.

PURPOSE: To evaluate the association of hepatitis B virus (HBV) genotypes, basal core promoter (BCP)/precore (PC) and S gene mutations with the clinical-epidemiological characteristics of acute hepatitis B (AHB) in Italy. METHODS: During July 2005-January 2007, 103 symptomatic AHB patients were enrolled and prospectively followed up at 15 national hospitals. HBV genotypes, BCP/PC and S gene variants were determined by nested-PCR and direct sequence analysis. RESULTS: Genotype D, A and F were detected in 49, 45 and 6% of patients, respectively. BCP, PC, and BCP plus PC variants were found in 3.1, 11.3 and 7.2% of patients, respectively. At enrollment, 68.3% of patients were hepatitis B e antigen (HBeAg)-positive and 31.7% HBeAg-negative. BCP/PC mutations were more common in HBeAg-negative than in HBeAg-positive patients (p < 0.0001). Compared to genotype D patients, those harboring non-D genotypes were more frequently males (p = 0.023), HBeAg-positive (p < 0.001), had higher bilirubin (p = 0.014) and viremia (p = 0.034) levels and less frequently carried BCP/PC mutations (p < 0.001). Non-D genotype patients more often were from Central Italy (p = 0.001) and reported risky sexual exposure (p = 0.021). Two patients had received vaccination before AHB: one harbored genotype F; the other showed a S gene mutation. Four patients developed fulminant AHB; mutations were found in 2 of 3 patients who underwent BCP/PC sequencing. After a 6-month follow-up, only 2 (2.8%) patients developed persistent infection. CONCLUSION: AHB by non-D genotypes is increasing in Italy and is associated with risky sexual exposure. The ability of some genotypes to cause persistent and/or severe infection in Italy warrants larger studies for clarification.

Surveillance of hepatitis A virus in urban sewages and comparison with cases notified in the course of an outbreak, Italy 2013.

BACKGROUND: Over the past 20 years, Hepatitis A notifications in Italy have been in decline. Since the beginning of 2013 however, Italy has been experiencing a foodborne hepatitis A outbreak caused by genotype IA, involving hundreds of cases. Consumption of frozen mixed berries was deemed the potential vehicle of infection.We aimed to investigate the spread of hepatitis A virus (HAV) in Italy through the monitoring of urban sewages collected at Wastewater Treatment Plants (WTPs) and a subsequent comparison of environmental surveillance data with data from the clinical surveillance performed during the epidemic. METHODS: The study covered 15 months, from July 2012 to September 2013, comprising the outbreak and the preceding six months. Environmental surveillance consisted of the analysis of urban sewage samples collected at 19 WTPs in seven of the Italian regions most affected by the epidemic. HAV isolates were detected and typed using a nested RT-PCR targeting the VP1/2A junction. Parallel clinical surveillance was performed by the sentinel surveillance system for acute viral hepatitis (SEIEVA) and by the ministerial Central Task Force on Hepatitis A, established with the purpose of determining the source of the outbreak and adopting appropriate outbreak control strategies. RESULTS: A total of 38/157 wastewater samples (24.2%) were positive for HAV, 16 collected in 2012 and 22 in 2013. Several HAV strains were detected, including the IA variant implicated in the outbreak and isolated from clinical cases over the same period. The vast majority of sequences belonged to genotype IB. Interestingly however, although these included variants related to strains that had been involved in past Italian epidemics, none were detected in recent clinical samples, probably due to underreporting or asymptomatic circulation. Conversely, a number of sequences were identified in clinical samples that were not found in wastewaters. CONCLUSIONS: The percentage of sewage samples detected as HAV-positive in this study are consistent with the classification of Italy as a country with low/intermediate endemicity. A combined environmental/clinical surveillance is able to provide a more complete picture of the spread of HAV and of the genotypes circulating in the population, allowing a better understanding of changes in disease trends.

Hepatitis B virus infection among first-time blood donors in Italy: prevalence and correlates between serological patterns and occult infection.

BACKGROUND: A prospective, 1-year study was performed among Italian first-time, volunteer blood donors, who account for 12% of all donations, in order to assess the frequency and serological patterns of hepatitis B virus infection and the presence of occult infection. MATERIALS AND METHODS: Consecutive donors (n=31,190) from 21 blood transfusion centres, from age classes not subjected to universal HBV vaccination, were tested for HBsAg and anti-HBc by commercial immunoassays. Other HBV serological markers were searched for and qualitative and quantitative assessments of HBV-DNA were made in HBsAg and/or anti-HBc-positive individuals. RESULTS: Of the 31,190 donors studied, 100 (0.32%) were positive for both HBsAg and anti-HBc, 2 for HBsAg (0.01%) alone, and 2,593 (8.3%) for anti-HBc. Of these last, 86.7% were also positive for anti-HBs (with or without anti-HBe), 2.9% were positive for anti-HBe without anti-HBs and 10.4% had no other HBV markers (anti-HBc alone). A general north-south increasing gradient of HBV prevalence was observed. Circulating HBV-DNA was found in 96.8% of HBsAg-positive subjects as compared to 0.55% (12/2,186) of anti-HBc-positive/HBsAg-negative subjects, with higher frequencies among anti-HBs-negative than among anti-HBs-positive ones (1.68% vs. 0.37%; p <0.01) and among the 57 cases positive for both anti-HBc and anti-HBe (7%). HBV-DNA levels were significantly higher in HBsAg-positive subjects than in HBsAg-negative ones (median: 456 IU/mL vs. 38 IU/mL). CONCLUSIONS: The prevalence of HBV infection among Italian first-time blood donors is much lower than in the past. The presence of occult infections in this group was confirmed (frequency: 1 in 2,599), supporting the hypothesis of long-term persistence of HBV infection after clearance of HBsAg. HBsAg and nucleic acid amplification testing for blood screening and vaccination against HBV are crucial in order to further reduce the risk of transfusion-transmitted HBV towards zero.

Reconstruction of the evolutionary dynamics of the A(H1N1)pdm09 influenza virus in Italy during the pandemic and post-pandemic phases.

The aim of this study was to reconstruct the evolutionary dynamics of the A(H1N1)pdm09 influenza virus in Italy during two epidemic seasons (2009/2010 and 2010/2011) in the light of the forces driving the evolution of the virus. Nearly six thousands respiratory specimens were collected from patients with influenza-like illness within the framework of the Italian Influenza Surveillance Network, and the A(H1N1)pdm09 hemagglutinin (HA) gene was amplified and directly sequenced from 227 of these. Phylodynamic and phylogeographical analyses were made using a Bayesian Markov Chain Monte Carlo method, and codon-specific positive selection acting on the HA coding sequence was evaluated. The global and local phylogenetic analyses showed that all of the Italian sequences sampled in the post-pandemic (2010/2011) season grouped into at least four highly significant Italian clades, whereas those of the pandemic season (2009/2010) were interspersed with isolates from other countries at the tree root. The time of the most recent common ancestor of the strains circulating in the pandemic season in Italy was estimated to be between the spring and summer of 2009, whereas the Italian clades of the post-pandemic season originated in the spring of 2010 and showed radiation in the summer/autumn of the same year; this was confirmed by a Bayesian skyline plot showing the biphasic growth of the effective number of infections. The local phylogeography analysis showed that the first season of infection originated in Northern Italian localities with high density populations, whereas the second involved less densely populated localities, in line with a gravity-like model of geographical dispersion. Two HA sites, codons 97 and 222, were under positive selection. In conclusion, the A(H1N1)pdm09 virus was introduced into Italy in the spring of 2009 by means of multiple importations. This was followed by repeated founder effects in the post-pandemic period that originated specific Italian clades.

Hepatitis E in Italy: a long-term prospective study.

BACKGROUND & AIMS: In developed countries, hepatitis E is usually associated with travelling to endemic areas, but a growing number of sporadic cases are also seen in patients with no travel history. The aim of this study was to assess the impact and the molecular epidemiology of hepatitis E in Italy. METHODS: Between January 1994 and October 2009, we analyzed 651 patients with acute non-A-C hepatitis. Diagnosis of hepatitis E was based on the presence of IgM anti-HEV and/or the detection of HEV RNA by RT-PCR. Viral isolates were sequenced and phylogenetically characterized. RESULTS: A total of 134 out of 651 (20.6%) patients tested had acute hepatitis E. All were anti-HEV IgM and IgG positive and 96 (71.6%) were also positive for HEV RNA. Moreover, 39 (6%) patients were anti-HEV IgG positive but negative for both IgM anti-HEV and HEV RNA. A total of 109 (81.3%) patients developed hepatitis E travelling to endemic areas, 3 (2.3%) acquired intra-familial infection from relatives who developed travel-related disease, while 22 (16.4%) patients denied having travelled abroad. In all patients, acute disease had a self-limited course with ALT normalization within 3-6 weeks. Phylogenetic analysis of 39 isolates from patients with a travel-related disease showed that they belonged to genotype 1, while sequences from five patients with autochthonous hepatitis E belonged to genotype 3. CONCLUSIONS: In Italy, most cases of hepatitis E are travel related, caused by viral genotype 1, while autochthonous cases are caused by genotype 3. The prevalence of genotype 3 among pigs and boars suggests that HEV infection may have zoonotic origins in non-endemic countries.

Hepatitis B immune memory in children primed with hexavalent vaccines and given monovalent booster vaccines: an open-label, randomised, controlled, multicentre study.

BACKGROUND: In 2000, hexavac and infanrix hexa were licensed in Europe for primary immunisation of children against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive infections caused by Haemophilus influenzae b. In 2005, hexavac was suspended because of concerns about the long-term immunogenicity of its hepatitis B component. We aimed to assess the duration of immunity and need for booster injections in children primed with these vaccines. METHODS: In an open-label, randomised, controlled, multicentre study in six local health units and at the Bambino Gesù Paediatric Research Hospital in Italy, antibody concentrations were measured 5 years after immunisation of infants with hexavac or infanrix hexa. Children with concentrations of antibodies to hepatitis B surface antigen (anti-HBs) lower than 10 mIU/mL were randomly assigned by simple randomisation to receive a booster of HBVaxPro or engerix B monovalent hepatitis B vaccine and tested 2 weeks later. Primary endpoints were the proportion of children with anti-HBs concentrations of at least 10 mIU/mL, geometric mean concentrations (GMCs) of antibody 5 years after vaccination, and the proportion of children with anti-HBs concentrations lower than 10 mIU/mL who had anamnestic response to booster. The study is registered with Agenzia Italiana del Farmaco, code FARM67NFPN. FINDINGS: 1543 children were enrolled, 833 had received hexavac and 710 infanrix hexa. 831 children who received hexavac and 709 who received infanrix hexa were included in the analysis. 319 children who received hexavac (38.4%, 95% CI 35.1-41.7) had anti-HBs concentrations of at least 10 mIU/mL compared with 590 who received infanrix hexa (83.2%, 80.5-86.0; p<0.0001). GMCs before booster were 4.5 mIU/mL in the hexavac group compared with 61.3 mIU/mL in the infanrix hexa group (p<0.0001). After booster 409 (92.1%, 89.6-94.6) of 444 children primed with hexavac and 99 (94.3%, 89.8-98.7) of 105 primed with infanrix hexa had anti-HBs concentrations of at least 10 mIU/mL (p=0.4); GMCs were 448.7 mIU/mL and 484.9 mIU/mL (p=0·6). The two booster vaccine groups did not differ in number of side-effects; no serious adverse events were reported. INTERPRETATION: 5 years after immunisation with hexavalent vaccines, immunological memory seems to persist in children with anti-HBs concentrations lower than 10 mIU/mL, suggesting that booster doses are not needed. Additional follow-up is needed. FUNDING: Agenzia Italiana del Farmaco.

The changing face of the epidemiology of type A, B, and D viral hepatitis in Italy, following the implementation of vaccination.

The morbidity and mortality rates of viral hepatitis A, B and Delta have dramatically dropped in Italy during the last decades. Thanks to the general improvements in hygiene and sanitation, hepatitis A has shifted from a high to an intermediate/low endemicity status. Vaccination against hepatitis A is recommended to people at increased risk, including travellers to endemic areas, military personnel and individuals at occupational risk. The implementation of universal anti-hepatitis B vaccination of infants and adolescents has resulted in a dramatic decline in disease burden and in the carrier rate. An additional benefit of hepatitis B vaccination is that hepatitis Delta has also substantially declined.

Impact of nucleic acid testing for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus on the safety of blood supply in Italy: a 6-year survey.

BACKGROUND: Nucleic acid testing (NAT) for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been implemented in several European countries and in the United States, while hepatitis B virus (HBV) NAT is still being questioned by opinions both in favor and against such an option, depending on the HBV endemicity, health care resources, and expected benefits. STUDY DESIGN AND METHODS: This survey was aimed to assess the NAT impact in improving the safety of blood supply in Italy, 6 years after implementation. The study involved 93 Italian transfusion centers and was carried out in 2001 through 2006. A total of 10,776,288 units were tested for the presence of HCV RNA, 7,932,430 for HIV RNA, and 3,405,497 for HBV DNA, respectively. RESULTS: Twenty-seven donations or 2.5 per million tested were HCV RNA-positive/anti-HCV-negative; 14 or 1.8 per million units tested were HIV RNA-positive/anti-HIV-negative; and 197 or 57.8 per million donations tested were HBV DNA-positive/hepatitis B surface antigen-negative. Of the latter, 8 (2.3/10(6)) were collected from donors in the window phase of infection and 189 (55.5/10(6)) from donors with occult HBV. Sixty-eight percent of the latter donors had hepatitis B surface antibody, 74.5 percent of whom with concentrations considered protective (>or=10 mIU/mL). CONCLUSION: NAT implementation has improved blood safety by reducing the risk of entering 2.5 HCV and 1.8 HIV infectious units per million donations into the blood supply. The yield of NAT in detecting infectious blood before transfusion was higher for HBV than for HCV or HIV. However, the benefit of HBV NAT in terms of avoided HBV-related morbidity and mortality in blood recipients needs to be further evaluated.

Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study.

BACKGROUND: Universal anti-hepatitis-B vaccination of infants and adolescents was implemented in Italy in 1991. We undertook a multicentre study in previously vaccinated individuals to assess the duration of immunity and need for booster, over 10 years after vaccination. METHODS: In 1212 children and 446 Italian Air Force recruits vaccinated as infants and adolescents, respectively, we measured the concentrations of antibodies to hepatitis-B surface antigen (anti-HBs) and the presence of antibodies to hepatitis-B core antigen (anti-HBc) at enrollment; postimmunisation values were not available. Individuals positive for anti-HBc were tested for hepatitis B surface antigen (HBsAg) and hepatitis B viral DNA. Individuals with anti-HBs concentrations at 10 IU/L or more were regarded as protected; those with antibody less than 10 IU/L were given a booster dose and retested 2 weeks later. Individuals showing postbooster anti-HBs concentrations of less than 10 IU/L were offered two additional vaccine doses and retested 1 month after the third dose. FINDINGS: Protective anti-HBs concentrations were retained in 779 (64%, 95% CI 61.6-67) children and 398 (89%, 86.4-92.1) recruits. We recorded antibody amounts of less than 10 IU/L in 433 children (36%, 33-38.4) and 48 (11%, 7.9-13.6) recruits. One child and four recruits were positive for anti-HBc, but negative for HBsAg and hepatitis B viral DNA. Antibody concentrations were higher in recruits than in children (geometric mean titre 234.8 IU/L vs 32.1 IU/L, p=0.0001). 332 (97%) of 342 children and 46 (96%) of 48 recruits who received a booster showed an anamnestic response, whereas ten (3%) children and two (4%) recruits remained negative for anti-HBs or had antibody concentrations of less than 10 IU/L. Prebooster and postbooster antibody titres were strongly correlated with each other in both groups. All individuals given two additional vaccine doses (eight children and two recruits) showed anti-HBs amounts of more than 10 IU/L at 1 month after vaccination. INTERPRETATION: Strong immunological memory persists more than 10 years after immunisation of infants and adolescents with a primary course of vaccination. Booster doses of vaccine do not seem necessary to ensure long-term protection.

Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth.

Long-term follow up studies of hepatitis C virus (HCV) infection rarely exceed 20-25 yr. We studied the outcome of HCV infection in 35-yr-old adults infected at birth (1968) through mini transfusions of blood. A retrospective-prospective study was carried out. The cohort included 31 individuals who were given mini blood transfusions (21-30 ml) collected from a donor subsequently revealed to be HCV infected. At enrollment (1998), 18 of 31 (58.1%) recipients had anti-HCV antibody and 16 (88.9%) of them were HCV-RNA positive. All viremic recipients and the infectious donor had the same genotype 1b. Sequence analysis of E1/E2 and NS5b regions, coupled with phylogenetic analysis, indicated that HCV isolates from donor/recipients were linked. Eleven of the 16 viremic recipients gave consent to liver biopsy. Nine had no fibrosis or mild portal fibrosis and 2 had either discrete (Ishak's staging 3) or marked (Ishak's staging 4) fibrosis. During the prospective follow-up period (1998-2003), 2 patients were given therapy, one of whom achieved sustained clinical and virologic response. A second biopsy, performed in 5 patients at a 5 yr interval, revealed no substantial modifications in 4 cases and progression from absence of fibrosis to mild portal fibrosis in the fifth. In conclusion, taking into account the limited study sample, these findings suggest that HCV infection acquired early in life shows a slow progression and mild outcome during the first 35 yr of infection.

Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studies.

We identified 15 patients with acute hepatitis C (AHC) among 29 healthy volunteers participating in 2 consecutive pharmacokinetics studies. Molecular techniques were used to determine the relatedness of viral strains, whereas clinical and virologic follow-up was started to establish the course and outcome of the acute infection. After presentation, serum liver enzymes and HCV RNA were monitored weekly for 4 months, then monthly for at least 12 months. Liver biopsy was performed 6 to 12 months after AHC diagnosis. Phylogenetic analysis of coding regions for the envelope glycoproteins E1 and E2 was performed. At presentation, all 15 patients tested HCV RNA-positive and had HCV genotype 2c. Phylogenetic analysis indicated a common source of infection. Fourteen patients agreed to be followed prospectively. Infection resolved spontaneously in 8 patients, HCV RNA becoming undetectable by 4 to 5 months after the presumed time of infection in 5 of them and by 8, 13, and 24 months in the remaining 3. Six patients developed chronic infection. Liver biopsies performed in 9 subjects who were HCV RNA-positive 6 months after AHC diagnosis revealed that the prevalent histologic finding was lobular inflammation. In conclusion, our homogeneous cohort showed a wide spectrum of clinical, virologic and histologic features, and, more importantly, short-term outcome differed noticeably despite the common source of infection.