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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.

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 34.2×100 000 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 1950's.

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 CDT16+ 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

Based on the observation of steatosis in the majority of liver biopsy specimens from hepatitis C virus (HCV) infected patients, it has been suggested that HCV may be pathogenetically implicated. We aimed to determine the influence of possible underlying metabolic disorders on this association.In a series of 148 consecutive patients with chronic hepatitis, with and without HCV infection, we evaluated by logistic regression analysis the association between steatosis and HCV, controlling for diabetes, obesity, hyperlipidaemia and alcohol. These are all known to be factors associated with a fatty liver, and also with the histological degree of liver disease.Antibodies to HCV were detected in 121 of 148 (81.8%) patients. Steatosis, distributed in different histological patterns, was found in 73 of 121 (60%) HCV-positive and in 14 of 27 (52%) HCV-negative patients (P = NS). Using simple logistic regression, the association Of HCV to steatosis was weak and not statistically significant (OR, 1.14; 95% CI, 0.61-3.27). The same was true for hyperlipidaemia (OR, 4.45; 95% CI, 0.52-37.9). A strong and statistically significant association was found, however, between obesity and steatosis (OR, 4.18) and between steatosis and the highest degree of histological severity (Liver cirrhosis vs chronic persistent hepatitis: OR, 12.8). Using multivariate analysis, the association between steatosis and HCV was shown to be not significant. Hyperlipidaemia, among all the independent variables tested, was shown to be co-linear with obesity.Our findings seem to suggest that HCV is irrelevant as a risk factor for a fatty liver. The results indicated that there is a 'confounding' role of obesity and hyperlipidaemia, and that the severity of liver disease is associated with steatosis and HCV.

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.

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.

Clinical course, morphologic changes, immunohistochemical localization of HBV-associated markers (HBsAg, HBcAg), and serum HBV-DNA production are described in 2 chronic HBsAg carriers superinfected with HAV and hepatitis non-A, non-B virus. Our data suggest that the superinfections do not cause more severe disease and do not influence the clinical course of the HBsAg chronic carriers. Our observations indicate that a careful diagnosis of hepatocytolysis is necessary in HBV chronic infection, in order to discriminate causes that are able to induce severe damage in underlying disease.

Routine use of commercially available antisera against hepatitis B core antigen (HBcAg) obtained from Escherichia coli transfected with HBV-DNA, has permitted a re-evaluation of the histochemical distribution of the antigen in liver tissue. HBcAg, classically described almost exclusively in the nucleus, was found with a very high frequency in the cytoplasm of liver cells. Our data indicate, however, that formalin fixation and paraffin embedding destroy part of HBcAg antigenicity and eliminate most of its cytoplasmic expression. HBcAg was found in 6/7 (85.7%) of HBsAg/HBeAg positive subjects, and in 2/12 (16/6%) of HBsAg/anti-HBe positive subjects; in both subgroups the cytoplasmic expression of the antigen correlated with the presence of circulating hepatitis B virus-deoxyribonucleic acid (HBV-DNA).

Serum patterns of preS gene encoded proteins during the chronic phase of hepatitis B virus infection and their relationship with hepatitis B virus deoxyribonucleic acid and hepatitis B 'e' antigen were investigated. The results indicate that the presence of preS1 and/or preS2 antigens in serum does not correlate with circulating hepatitis B virus deoxyribonucleic acid and hepatitis B 'e' antigen. It is, therefore, suggested that preS antigens cannot be regarded as specific markers of active viral replication in chronically hepatitis B virus infected patients.

In this review, we analyzed the role played by central and peripheral chemoreceptors (CHRs) in vasopressin (AVP) secretion control. Central neural pathways subserving osmotic and non-osmotic control of AVP secretion are strictly correlated to brain areas participating in chemoreception mechanisms. Among the different brain areas involved in central chemoreception, the most important site has been localized in the retrotrapezoid nucleus of the rostral ventrolateral medulla. These central CHRs are able to detect very small pH/CO2 fluctuations, participating in brain blood flow regulation, acid-base balance and blood pressure control. Decreases in arterial pH and increases in arterial pCO2 stimulate AVP release by the Supraoptic and Paraventricular Nuclei. Carotid CHRs transduce low arterial O2 tension into increased action potential activity, leading to bradycardia and coronary vasodilatation via vagal stimulation, and systemic vasoconstriction via catecholaminergic stimulation. Stimulation of carotid CHRs by hypoxia increases neurohypophyseal blood flow and AVP release, an effect inhibited by CHRs denervation. Two renal CHRs have been identified: Type R1 CHRs do not have a resting discharge but are activated by renal ischemia and hypotension; Type R2 CHRs have a resting discharge and respond to backflow of urine into the renal pelvis. Signals arising from renal CHRs modulate the activity of hypothalamic AVPergic neurons: activation of R1 and R2 CHRs, following increased intrapelvic pressure with solutions of mannitol, NaCl and KCl, produces a significant increase of AVP secretion and the same effect has been obtained by the intrarenal infusion of bradykinin, which excites afferent renal nerves, as well as by the electrical stimulation of these nerves.