Lack of hepatitis B virus reactivation after anti-tumour necrosis factor treatment in potential occult carriers with chronic inflammatory arthropathies.

BACKGROUND: Hepatitis B virus (HBV) reactivation in patients positive for antibody to HB core antigen (anti-HBc), negative for HB surface antigen (HBsAg) and HBV-DNA (potential occult HBV carriers), treated with anti-tumor necrosis factor (TNF)α, is a debated question. The aim of the study was to evaluate the safety of anti-TNFα therapy in anti-HBc positive/HBsAg negative subjects with rheumatoid arthritis (RA) and spondyloarthropathy (SpA). METHODS: All consecutive HBsAg negative RA and SpA outpatients referring to the Immuno-Rheumatology Institute at the S. Andrea hospital, Sapienza, University of Rome who had to undergo anti-TNFα therapy. RESULTS: Among the 169 enrolled subjects, 20 (12%) were potential occult HBV carriers (anti-HBc positive, HBsAg and HBV-DNA negative patients with or without anti-HBs). During the follow-up (mean ± SD 45 ± 22 months), aminotransferases and HBV-DNA, tested every two and six months respectively, did not change. CONCLUSION: This study confirms the substantial safety of anti-TNFα therapy in potential occult HBV carriers RA and SpA patients.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Hepatitis C virus infection among drug addicts in Italy.

There is a lack of updated nationwide records regarding hepatitis C virus (HCV) infection among drug addicts in Italy. The prevalence and characteristics of HCV infection in a national sample of drug addicts in Italy were determined. Five hundred forty-three drug addicts (mean age 35.3 years, 85.1% males), selected from 25 Italian Centers for Substance Dependence were enrolled to be evaluated for anti-HCV, HCV-RNA, HCV genotype, HBV markers, anti-HDV, and anti-HIV during the period of April-November 2009. Anti-HCV prevalence was 63.9%. HCV-RNA was detected in 68.3% of patients positive for anti-HCV. Genotypes 1 and 3 prevailed (49.3% and 39.7%, respectively). However, 9.3% of the subjects had genotype 4, a rate over threefold higher than the one observed in 1996 among drug addicts in central Italy. Needle sharing was the strongest independent predictor of the likelihood to contract an HCV infection (OR 8.9; 95% CI: 5.0-16.0). Only 19.3% of subjects received antiviral treatment for HCV. The prevalence of HBsAg and HIV positivity was 2.8% and 3.1%, respectively. The pattern of HBV markers showed that nearly one-third of subjects had been vaccinated, while 42.3% were negative for any marker of HCV. The prevalence of HCV infection is high among drug addicts in Italy. The incidence of Genotype 4 is increasing and this may lead to the spreading of the disease to the general population in the near future. Efforts should be made to improve the rate of antiviral treatment for drug addicts with HCV infection and vaccination against hepatitis B.

Current practice of chronic hepatitis B treatment in Southern Italy.

BACKGROUND: Treatment choice for chronic HBV infection is a continuously evolving issue, with a wide range of options. We aimed to evaluate the current practice of HBV therapies in the real world in Southern Italy. METHODS: A prospective study enrolling over a six month period (February-July 2010) all consecutive HBsAg positive subjects, never previously treated, referred to 16 liver units in two Southern Italy regions (Calabria and Sicily). RESULTS: Out of 247 subjects evaluated, 116 (46.9%) had HBV-DNA undetectable or lower than 2000 UI/ml. There were 108 (43.7%) inactive carriers, 103 (41.7%) chronic hepatitis, and 36 (14.6%) liver cirrhosis. Antiviral treatment was planned in 94 (38.0%) patients (26 cases with Interferon or Pegylated Interferon and 68 with nucleos(t)ides analogues). As many as 49.5% of subjects with chronic hepatitis did not receive antiviral treatment. DISCUSSION: The majority of chronic HBsAg carrier referring centres for evaluation were not considered suitable for antiviral treatment. Nucleos(t)ides analogues are the preferred first choice for therapy. A long-lasting period of observation may be needed to make appropriate therapeutic decisions in several cases.

Long-term immunogenicity of hepatitis B vaccination in children and adolescents in a southern Italian town.

PURPOSE: Universal anti-hepatitis B vaccination of infants and of 12-year-old children became mandatory in Italy in 1991. The purpose of this study was to evaluate the persistence of anti-hepatitis B surface (HBs) antibodies several years after a primary course of vaccination. METHODS: In 2010, anti-HBs titers were measured in all subjects aged between 5 and 25 years residing in a southern Italian town. Individuals with an anti-hepatitis B antibody concentration of 10 IU/ml or more were considered to be protected. RESULTS: Of the 671 subjects evaluated, 149 (30%) lacked protective antibodies. Fifty-three (29.4%) of the subjects had been vaccinated ≤10 years earlier and 96 (30.3%) more than 10 years earlier (P = not significant). Subjects vaccinated in infancy were more likely to lack protective anti-HBs antibodies than subjects vaccinated at 12 years of age, regardless of the years elapsed since immunization. CONCLUSIONS: Most subjects maintained protective antibodies for a considerable number of years after vaccination. Vaccination in adolescence results in more prolonged immunogenicity than vaccination in infancy.

Unawareness of HBV infection among inpatients in a Southern Italian hospital.

Hepatitis B virus (HBV) infection may run undetected. Unawareness of an ongoing infection delays the diagnosis of HBV-related liver disease and favours the spread of the virus. We have evaluated among hepatitis B surface antigen-positive (HBsAg) inpatients admitted to a Southern Italian hospital the proportion of those aware of their carrier status and correlated the status to signs of liver disease. All patients admitted to the San Giovanni Rotondo Hospital from March 2008 to July 2009 were tested for HBV and hepatitis C virus (HCV) markers, and those positive for HBsAg were interviewed and underwent examinations for liver function and abdominal ultrasound. Overall, of 25,000 patients admitted during the observation period 311 (1.2%) were positive for HBsAg, most of them (98%) being anti-HBe positive. HCV and HDV co-infections were ascertained in 2.9% and 0.6% of cases, respectively. Two hundred and fifty-three subjects (81%) agreed to undergo further investigation, 132 of them (52%) were HBV-DNA positive. One hundred and two patients (40.3%) were unaware of their infection; this was encountered among 29% of HBV-DNA-positive and 52% of HBV-DNA-negative subjects (P < 0.01). Subjects already aware of their infection were more likely to present with abnormal alanine aminotransferase (ALT) levels (27%vs 15%), serological presence of HBV-DNA (63.6% vs. 36%) and liver cirrhosis (30%vs. 13%). A high proportion of HBsAg-positive patients (40.3%) were unaware of their infection, which had evolved to the stage of liver cirrhosis in a consistent percentage of them.

Retrospective, observational, multicentre study on an Italian population affected by chronic hepatitis C who failed to clear HCV-RNA after the combined therapy (PEG-IFN and ribavirin): NADIR study.

There is a lack of information on the characteristics of patients with chronic hepatitis C virus infection (HCV) who fail to respond to antiviral treatment. We studied HCV-positive subjects with chronic liver diseases treated with pegylated-interferon (PEG-IFN) and ribavirin (RBV) who failed to clear HCV in routine clinical practice. A total of 2150 consecutive adult patients treated with PEG-IFN plus RBV therapy in 46 Italian centres between 1 July 2004, and 30 June 2005, were studied. Of the 2150 patients, 923 (42.9%) (M/F 585/335, mean age 54.8 years) failed to achieve a serum HCV-RNA clearance. Of these 923 patients, 429 (46.5%) were nonresponders, 298 (32.3%) relapsers, 168 (18.2%) drop-outs for noncompliance or adverse events and 28 (3.0%) were lost during follow-up. Overall, 642 (70.6%) patients received adequate therapy (defined as more than 80% of the drug doses for >80% of the time). Genotypes 1-4 were observed in 76.9% of cases; genotypes 2-3 in 21.2% and mixed in 1.9%, respectively. Multiple logistic regression analysis identified genotypes 1 and 4 as the sole independent predictors of the likelihood of nonresponse to therapy compared with relapse (OR: 4.38; 95% CI = 2.28-8.4). Age older than 65 years was the sole independent factor associated with no adherence to therapy (OR: 2.22; 95% CI = 1.36-3.62). Patients who fail to respond to treatment are a nonhomogeneous population with different features, and the sole factor that discriminates nonresponse from relapse is the distribution of genotypes 1-4. Co-morbidities are unable to determine the type of treatment failure and inadequate adherence to therapy mostly affects patients older than 65 years of age.

Increasing hepatitis B vaccination coverage among healthcare workers in Italy 10 years apart.

BACKGROUND: In Italy, vaccination against hepatitis B virus infection was strongly recommended for healthcare workers since 1985. Update findings on vaccination coverage are lacking. AIM: To assess current vaccination coverage against hepatitis B in this job category. METHODS: In 2006, 1,632 healthcare workers randomly selected in 15 Italian public hospitals completed a self-administered precoded questionnaire. RESULTS: The overall vaccination coverage was 85.3%, a figure higher than the 64.5% observed in 1996. Vaccine coverage showed a significant downtrend (p<0.01) from the Northern (93.1%) to the Southern (77.7%) areas. Logistic regression analysis showed that residence in the North (Odds ratio 4.2; 95% confidence interval 2.6-6.7) and youngest age (Odds ratio 4.5; 95% confidence interval 2.6-7.8), both were independent predictors of vaccine acceptance. CONCLUSIONS: Ten years apart, vaccine coverage has markedly increased, closely paralleling the downtrend in the incidence of acute B hepatitis among healthcare workers in Italy.

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.

Drinking habits and risk of altered liver enzymes in the general population of a rural area in Southern Italy.

PURPOSE: To assess the overall drinking habits (amount and duration of alcohol intake, as well as type of alcoholic drinks consumed) and their potential for alteration of liver enzymes in a random sample of the general population aged > or =18 years of a rural area in Southern Italy. MATERIALS AND METHODS: Of the 4000 subjects selected, 3306 (82.7%) agreed to take part in the study. Of these, 41% were teetotallers (54.4% females, 26.1% males; p<0.01). A very small proportion of subjects reported > or =4 drinks/day (11.9% males, 0.8% females; p<0.01). RESULTS: Increased aspartate aminotransferase and/or alanine aminotransferase values were observed in 148 (4.5%) subjects. Hepatitis C virus positivity alone, excessive body mass index alone and alcohol intake alone were observed in 28.6, 23.8 and 18.4% of cases, respectively. After exclusion of subjects with chronic viral hepatitis infections (hepatitis B virus and/or hepatitis C virus) and adjustment for the confounding effect of age (>50 years) and body mass index (> or =25) by multiple logistic regression analysis, subjects who reported consuming >4 drinks/day were 2.4-fold (95%CI=1.1-5.2) more likely than teetotallers to have altered liver enzyme values; subjects reporting intake below this threshold were not at risk of alterations in aspartate aminotransferase/alanine aminotransferase (OR 1.4; 95%CI=0.7-2.6). CONCLUSIONS: These findings indicate that only a small proportion of the rural population studied (particularly females) can be considered as alcohol misusers. Moreover, a mild alcohol intake (< or =4 drinks/day) is not associated with alterations in aspartate aminotransferase/alanine aminotransferase levels in the absence of other factors such as hepatitis viruses and impaired body mass index.

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy.

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment.

Characteristics of HCV positive subjects referring to hospitals in Italy: a multicentre prevalence study on 6,999 cases.

In 2001, 6,999 anti-HCV positive subjects referred to 79 Italian hospital in a 6 months enrollment period were evaluated. Of them, 5,632 (80.5%) tested anti-HCV positive alone, 1,163 (16.6%) reported also an excessive alcohol intake, and 204 (2.9%) were also HBsAg positive. Normal biochemistry was observed in 7.8% of cases, chronic hepatitis in 67.9% of cases, liver cirrhosis in 18.9% of cases, and hepatocellular carcinoma in 3.6% cases. HCV positive subjects with excessive alcohol intake were statistically significantly younger, of male sex, and having more severe liver disease than those without excessive alcohol intake. Adjusting for the confounding effect of age and sex by multiple logistic regression analysis, HCV positive chronic hepatitis cases drinking more than four alcoholic drinks daily were 2.2-fold (CI 95% = 1.3-4.0) more likely to progress to liver cirrhosis than teetotallers. These findings indicate that nearly a quarter of HCV positive subjects referred to hospitals in Italy have a severe liver disease causing a remarkable impact on the national health system. Excessive alcohol intake in HCV chronic hepatitis cases increases the risk of progression to liver cirrhosis.

Exposure to HAV infection in patients with chronic liver disease in Italy, a multicentre study.

We carried out a multicentre study on 2830 patients with chronic liver disease from 79 liver units (25 in northern, 24 in central and 30 in southern Italy) to evaluate naturally acquired immunity against hepatitis A virus (HAV) in relation to age, sex, geographical area of origin and entity of liver disease, and to define the strategy for specific vaccination. Antibody to HAV (anti-HAV) was detected in 1514 (53.5%) of the 2830 patients tested; the prevalence was 50.4% in males and 59.1% in females. Both in central and southern Italy the prevalence of anti-HAV positive subjects increased with increasing age from 43.3 and 44.7%, respectively, in the 0-30-year-old subjects to 80.1 and 68.3%, respectively, in those aged over 60 years. The overall prevalence was much lower in northern Italy, as were the variations from one age group to another, from 28.4% in the 0-30-year-old subjects to 38% in those aged over 60 years. 40.6% of patients with cirrhosis lacked naturally acquired protection against HAV; this percentage was higher in northern (60.5%) than in central (34.9%, P < 0.0001) and southern Italy (27.6%, P < 0.0001). The high prevalence of patients in Italy with chronic hepatitis or cirrhosis who lack naturally acquired immunity to HAV warrants the implementation of vaccination programmes against hepatitis A in such patients.

The changing pattern of hepatitis B virus infection over the past three decades in Italy.

By the end of 1970s, Italy was a country at medium endemic level of hepatitis B virus infection, with wide geographical differences; intrafamily transmission was the major mode by which infection spread; hepatitis B e antigen positivity and hepatitis Delta positivity were frequently detected in hepatitis B surface antigen chronic carriers; a high proportion of subjects with chronic liver disease resulted as hepatitis B surface antigen positive. Three decades apart, the picture was completely changed, as documented by several surveys. Nowadays, Italy is a country at very low endemic level of hepatitis B, without geographical differences; the infection is mostly sexually transmitted; hepatitis B e antigen positivity and hepatitis Delta positivity are rarely detected in hepatitis B surfaces antigen chronic carriers; a low proportion of subjects with chronic liver disease result hepatitis B surface antigen positive. These important changes may be due to both non-specific (i.e. improvement in socio-demographic features) and specific (i.e. a comprehensive vaccination program against hepatitis B) preventive measures.

Etiological factor of hepatocellular carcinoma in Italy.

Cirrhosis from any cause is present in the majority (93.1%) of hepatocellular carcinoma (HCC) cases in Italy, it seems to be the common pathway by which several risk factors extent their carcinogenic effect. The mortality rate of HCC in Italy has progressively increased during the period 1969-1994, reflecting the rising number of persons living with cirrhosis as consequence of the remarkable advances in medical management of such patients. Most HCC develops in cirrhosis caused by known and preventable risk factors (hepatitis B virus, HBV, hepatitis C virus, HCV, alcohol and possibly non-alcoholic steatohepatitis, NASH). Unlike alcohol and NASH, HBV and HCV chronic infections act as a risk factors for HCC both because they induce cirrhosis and because they increase the risk in patients with cirrhosis. Moreover, case-control and prospective studies have shown a synergistic effect on HCC risk, when both viral infections occur. Currently, HCV infection is detected in the majority (76.4%) of HCC cases in Italy, reflecting the large cohort of subjects infected with this virus via the iatrogenic route during the 1950s and 1960s. The low rate of HCV infection in the younger Italian generations may generate a downward trend in the HCC mortality rate in the years to come.

Reported risk factors are useless in detecting HCV-positive subjects in the general population.

BACKGROUND: Chronic hepatitis C virus infection is mostly asymptomatic, so it will not be identified if specific diagnostic tests are not performed. AIMS: To evaluate the positive predictive value of some risk factors in detecting anti-hepatitis C virus-positive subjects in the general population. SUBJECTS: Two-thousand five hundred and sixty-one subjects randomly selected from the list of the census in three population-based surveys performed in hepatitis C virus endemic areas in Southern Italy. METHODS: The sensitivity, specificity and positive predictive value of blood transfusion, past use of glass syringes and surgical intervention in detecting hepatitis C virus positivity were assessed. Data were collected using a precoded questionnaire administered by an interviewer. RESULTS: All risk factors showed a poor positive predictive value (ranging from 21.0% for surgical intervention to 29.0% for blood transfusion). The positive predictive value was extremely low (ranging from 2.9 to 4.3%) in subjects younger than 46 years of age, who mostly could benefit from antiviral treatment. The combination of the simultaneous presence of more than one risk factor does not improve the detection of hepatitis C virus infection. CONCLUSIONS: Reported risk factors are useless in detecting hepatitis C virus-positive subjects in the general population.