Giorgio Fiore

Epidemiology of hepatitis C Virus infection in an area of Southern Italy

BACKGROUND/AIMS Hepatitis C virus (HCV) has been recognized as a major cause of liver disease, but little is known about its diffusion at population level. To estimate the prevalence and incidence of HCV infection and to explore potential risk factors at population level, an epidemiologic study was carried out. METHODS A cohort was built up in 1985, on a random sample of the population of Castellana, a small town in southern Italy (Bari province), and followed up until 1993. HCV ELISA II and RIBA HCV 2.0 were used as screening and confirmatory tests, respectively. RESULTS The overall anti-HCV prevalence was 26.0% (511/1969) at enrollment. The HCV infection incidence rate was 34.2x100,000 person-years (3 cases/8766 persons-years). A secular trend (referent born before 1930; born 1930-39 Odds Ratio (OR) 0.72, 95% Confidence Interval (95% CI) 0.56-0.94; born 1940-49, OR 0.33, 95% CI 0.25-0.44; born 1950 or after, OR 0.15, 95% CI 0.09-0.23) and geographical pattern (referent born outside Bari province; born in Bari province, OR 1.71, 95% CI 0.93-3.16; born in Castellana G, OR 2.29, 95% CI 1.29-4.05) were found by logistic regression analysis after controlling for several confounding factors. CONCLUSIONS The high prevalence, moderate incidence, and marked decrease in HCV infection in the cohort of birth in a population without known risk factors suggest that an epidemiological transition has been operating at population level since the 1950s.

In-situ immunophenotyping study of hepatic-infiltrating cytotoxic cells in chronic active hepatitis C

Objective: Beside the hypothesis of a direct viral cytopathy, several lines of evidence argue in favour of hepatic damage triggered by immune‐mediated mechanisms in hepatitis C virus (HCV) infection. The intrahepatic localization of HCV antigen‐specific cytotoxic T‐lymphocytes (CTLs) to disease sites has been described; however, very few data are available about the degree and the role of hepatic‐infiltrating natural killer (NK) cells in chronically HCV‐infected subjects. Design: In a series of percutaneous needle liver biopsies obtained from 35 consecutive untreated patients with chronic active hepatitis C, we performed an in‐situ immunophenotyping study to evaluate the degree of cytotoxic NK cell infiltration as compared to CTLs, the hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA‐I and HLA‐II), and cell adhesion molecules (CAM) in the context of liver inflammatory infiltrates. The data were correlated with the histological activity index (HAI) of disease. Results: In‐situ immunophenotyping analysis of CAM provided evidence for the intrahepatic expression of leucocyte adhesion molecules (CD11a and CD2) and their corresponding ligands on hepatocytes (CD54 and CD58) in all cases. A significant parallel expression of CD11a and CD54 as well as CD2 and CD58 structures, restricted to hepatic lobules within the disease sites, was also observed, even if their induction exhibited different degrees of correlation with biological and/or histological activities. A membranous pattern of HLA‐I and HLA‐II antigen expression on hepatocyte clusters was found in all tissue samples, although HLA‐I expression was significantly higher than HLA‐II. Moreover, lymphocyte subset analysis displayed a CD8+ T‐cell lobular infiltration within inflammatory and/or spotty necrosis areas in all cases, while CD4+ T‐cells were confined to the portal and periportal levels. A few scattered CD56+ and CD16+ NK cells, mainly distributed at periportal areas within inflammatory and/or necrotic foci, were detected in 7/35 (20%) and in 5/35 (14.2%) cases, respectively. On the other hand, CD8+ T‐cell lobular expression exhibited a linear correlation with HAI (r: 0.698, P<0.01). Finally, cytotoxic cell infiltration degree did not correlate with HCV serotypes. Conclusion: Our findings suggest a limited role for NK cells in the immune mechanism of liver injury in chronic active hepatitis C, while providing further support for the involvement of CD8+ T‐cells at disease sites.

Prevalence of antibodies to hepatitis C virus among family members of patients with chronic hepatitis C

In this study, 108 family members of 40 chronically HCV-infected patients (19 post-transfusion and 21 sporadic), and 45 families of 16 anti-HCV-negative index cases (control group) were tested for anti-HCV antibodies. Anti-HCV antibodies were found in 16 (14.8%) families of anti-HCV positive index cases (15% males and 14.6% females; p = NS), with no difference between families of index cases with post-transfusion and those with sporadic HCV infection. Out of the 16 anti-HCV positive family members, 12 (75%) had clinical and/or serological evidence of chronic liver damage. None of the control group subjects were anti-HCV-positive (p < 0.01). The rate of anti-HCV positivity was 34.4% among spouses, 14.3% among siblings, 16.7% among cohabitants and 2.3% among children; anti-HCV antibodies were not detected among parents. We found a positive correlation between the prevalence of anti-HCV antibodies among families and the severity of the HCV-related chronic liver damage of the index cases (p < 0.00005). In addition, to confirm that HCV infection and HCV-related chronic hepatitis may be transmitted intrafamiliarly, our findings also indicate that horizontal, especially sexual contact, is a more important route of HCV infection than vertical/perinatal transmission. Finally, the risk of acquiring HCV infection among families appears to be the highest when index cases are suffering from severe HCV-related chronic hepatitis.

Correlation between Hepatitis B Virus Deoxyribonucleic Acid and Receptors for Polymerized Human Albumin in HBV Chronic Infection

This study indicates that hepatitis B virus deoxyribonucleic acid (HBV DNA) is actually the most sensitive marker for the identification of HBV-related pathologies in active replication phase and does not correlate with serum receptor activity for polymerized human serum albumin which can be found in absence of either HBV DNA or HBeAg in HBV chronic infection.

Immunoresponsiveness in chronic hepatitis C patients : Correlation between tissue and serum findings

In the present study, intrahepatic CD8+ lymphocyte infiltrates as well as HLA class I and CD54 (ICAM-1) antigen expression at both tissue and serum levels were evaluated in 54 untreated patients with chronic hepatitis C stratified on the basis of histological diagnosis (Chronic Persistent Hepatitis/Chronic Lobular Hepatitis -CPH/CLH- and Chronic Active Hepatitis -CAH-: 22 and 32 subjects, respectively). The relationships between soluble HLA-I (sHLA-I) and ICAM-1 (sICAM-1) serum levels and their membrane-bound counterparts, CD8+ liver infiltration and serum alanine aminotransferase (ALT) were also studied. A strong HLA-I and CD54 tissue expression, associated to the presence of CD8+ cell infiltrates in necro-inflammatory areas, and elevated sHLA-I and sICAM-1 serum amounts were observed in all patients. At the same time, no difference was found at tissue level between the two groups of patients with respect to the mean scores of HLA-I and CD54 expression, while CAH subjects displayed a significantly higher CD8 periportal and lobular reactivity in comparison to the other subset. Serological assays outlined higher values of circulating HLA-I molecules in CPH/CLH patients and higher sICAM-1 levels in the CAH group. Finally, a negative correlation was found between sHLA-I and ALT in CAH subjects while, in all patients, sICAM-1 positively correlated with both CD8 tissue infiltration and ALT. Our findings confirm the occurrence of an immune activation status during chronic hepatitis C and suggest that sHLA-I molecules might play a down-modulating role on immunoresponsiveness of these patients.