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Dialysis patients remain at risk of acquiring hepatitis B virus (HBV) infection. The issue of the natural history of HBV among patients undergoing long-term dialysis remains unclear. Assessing the natural history of hepatitis B in patients on maintenance dialysis is problematic because of the unique characteristics of this population: serum aminotransferase activity is lower in dialysis patients compared with patients without renal disease; also, chronic hepatitis B has an insidious and prolonged natural history, and the competing mortality from complications of end-stage renal disease may obscure the long-term consequences of hepatitis B. HBV-related liver disease frequently runs an asymptomatic course in dialysis patients and the liver-related mortality in this population is very low; thus, the prognosis for chronic HBV infection in dialysis patients has been reported as benign. However, the frequency of liver cancer in dialysis patients appears higher than that observed in the general population, this has been related to a greater exposure to HBV/HCV. Cirrhosis is not a frequent comorbid condition in the dialysis population of industrialised countries, but the death rate for dialysis patients with cirrhosis is 35% higher than for those without it. In addition, it has been observed that liver disease remains a significant cause of mortality among HbsAg-positive carriers on dialysis in developing countries. The low viral load measured in dialysis patients with persistent HBsAg carriage could be accounted for by the relatively benign course of HBV-related liver disease in this population. Prospective clinical trials are under way to better define the virological features of HBV in the dialysis population.

Twenty-three patients with hepatitis B were treated with recombinant interferon-alpha-2a. Twelve patients were given 6 MU three times a week for 6 months (Group A); eleven patients were given 9 MU three times a week for an initial 4-month course and subsequently for a further 3-month course after 6 months of no therapy (group B). Eight patients in the group A (66.7%) and seven patients in the group B became negative for HBV-DNA and normalized their ALT, compared to 31% of controls. Relapses were noticed in 75% of the responders in the group A and in 71.4% of the responders in the group B within 12 months after interferon discontinuation. The Authors are consequently of opinion that it is appropriate to try longer treatments with moderate doses of interferon in order to maintain the response as long as possible.

Object: To assess the prevalence and the incidence of the anti-HCV and HBV markers in extracorporeal dialysis patients., Method: From 1990 to 1993, every six months, anti-HCV and anti-HBV markers were determined in 88 dialyzed patients, in 24 health workers from the Nephrology and Dialysis Departments and checked with 4143 blood donors. ALT values were also checked monthly., Results: A 13.6 prevalence of anti-HCV was found while no new anti-HCV case was seen in the three-year observation period. Data referring to HBV infection were affected by vaccination. Statistical survey has shown a significant relation between anti-HCV and blood transfusions and between anti-HBV infection and duration of dialysis. The incidence of HCV infection was 4.1% among health workers who were all HBV vaccinated in the year before the research., Comment: We strongly recommend the observance of such rules as hygiene and prophylaxis, disinfection, sterilization and the use of disposable material. Also, a reduction of the number of transfusions seems to cut down the incidence of hematic infections.

From 1985 through 1992 the following hepatitis B markers HBsAg, anti-HBs and anti-HBc were evaluated in 1797 injecting drug users (IDUs) attending 8 Centers for drug addicts in the Veneto region (north-east Italy). Among all IDUs, 1004 (56%) proved to be positive for at least one of the above markers. In particular our aim was to study the carriers of only anti-HBc. At entry, among these 1004 IDUs, 294 (29%) showed only the anti-HBc; 141 IDUs of them have been followed for a period of time: 77% remained without any marker change and 23% showed the appearance of anti-HBs. Subsequently, other 75 IDUs became carrier only of the anti HBc, for the following reasons: loss of anti-HBs (57%) or HBsAg (15%) appearance only of anti-HBc (28%). No carrier of only anti-HBc seroconverted for HBsAg. The evaluation of our data supports the hypothesis that the carrier status of the only anti-HBc prevents from reinfection by HBV and therefore these subjects do not need vaccination.

An anonymous unlinked seroprevalence study of HIV, HBV and HCV infections has been conducted on 485 sera consecutively submitted to the virology laboratory to be tested for HBsAg; sera came from patients attending general surgery at San Camillo Hospital in Rome. Carriers of HBsAg were 12 (2.5%); antibodies against HIV have been identified in 4 sera (0.8%) and against HCV in 35 (7.2) by ELISA (first generation assay); 25/35 of anti HCV ELISA positive sera were reactive also by RIBA (first generation assay). The observed prevalences of potentially infectious patients represent a risk of occupational transmission for health care workers. Vaccination against HBV, adherence with universal precautions and development of safer surgical devices and techniques are needed to prevent the risk of exposure and, consequently, of occupational acquired infections.

Hepatitis B virus (HBV) is one of the most important causes of chronic liver disease. HBV is a DNA virus with an external glycoprotein surface and an internal nucleocapsid which contains the viral genome. HBV infection is revealed by the appearance of specific markers. Some of these markers are well known and their presence in serum is important to understand the behaviour of the disease. Among them HBsAg, HBeAg, anti-HBs and anti-HBe are found in serum, so as anti-Core; the HBcAg may be found in hepatic tissue and marks infectivity and virus replication. In the few last years some new antigens and antibodies have been studied and their importance in diagnosis and follow-up of hepatitis has been recognized. HBxAg, Pre-S and DNA-Polymerase (Pol) seem to be specific and early signals of viral replication. More studies showed the trans-activating properties of HBxAg; actually the X protein seems to be involved in replicative cycle of HBV. Many Authors also demonstrated a relationship between the presence of X in serum and/or liver and the progression of disease to cirrhosis and hepatocellular carcinoma. The Pol antigen and its antibody seem to be very common markers of HBV infection in serum of patients with hepatitis. Moreover their presence is the only signal of viral infection in some patients which have no other marker of HBV. More studies are of course needed to exactly establish the significance of these new markers and their importance for diagnosis and prognosis of HBV infection.

Knowledge of hepatitis B immunopathogenesis has greatly improved in the last few years thanks to the development of new methods of lymphocyte culture and the introduction of molecular techniques in the study of the cell-mediated antiviral immune responses. Some of the immune mechanisms likely responsible for liver cell injury and viral clearance during hepatitis B have recently been characterized. By using synthetic peptides and high efficiency recombinant expression vectors. HLA class I restricted cytotoxic T cells specifically able to recognize the nucleocapsid antigen of the hepatitis B virus (HBV) have been isolated from the blood of patients with acute self-limited hepatitis B. The observation that this cytotoxic response is lacking or very weak in chronic patients who do not succeed in clearing the virus suggests a major role for cytotoxic T cells in terminating virus infection. Similar behaviour is shown by HLA class II restricted CD4+ T cells which express much stronger levels of response to HBV nucleocapsid antigens in acute than in chronic HBV infection. Whether these defective responses in chronic patients are due to an actual lesion of the host's immune system or to viral mutations affecting immune surveillance and thereby allowing virus escape, still remain open issues. A definitive answer to these questions will, we hope, provide the appropriate tools to devise effective immune therapies against chronic HBV infection.

We report the results of a study carried out to evaluate the extent of hepatitis A virus (HAV) and hepatitis B virus (HBV) circulation in Somalia. Serum samples were collected from 593 subjects (age range 0-83 years) and tested for anti-hepatitis A (HAV) and anti-HAV IgM. Serum samples taken from 1272 individuals (age range 0-83 years) were tested for HBsAg, anti-HBsAg, anti-HBcAg, HBeAg and anti-HBeAg. We confirmed a very high rate of HAV exposure (about 90% of the subjects tested had circulating anti-HAV) as is typical of fecal-orally transmitted infectious agents. The age-specific anti-HAV IgM prevalence suggests that HAV infection is acquired very early in life. Our data also indicate a high rate of HBsAg carriers (range: 10.5%-27.4%) in the Somalian population. When all markers are considered, 60% of the adult population showed evidence of HBV exposure. HBV spreads very subtly: in fact, it is generally transmitted via non-overtly percutaneous routes. In Somalia, hepatitis A virus infection is highly endemic and occurs very early in life. Hepatitis B virus infection is also widespread in this country.

Personal experience of sero-vaccino-prophylaxis for the purposes of vertical interruption of hepatitis B transmitted by mother carriers of HBsAG to their children is reported. Special attention is paid to the problem of the failure of such immunitary strategy in high-risk newborns (children of HBsAg, HBeAg and HBV-DNA positive mothers) and some suggestions are made to reduce the risk of this infection.

The significance of obstetric anamnesis in neonatal risk identification and efficiency of a vaccinal schedule were investigated in order to verify the condition which limited the efficiency of immunoprophylaxis in the prevention of perinatal hepatitis B virus transmission. The data suggested that the lack of obstetric screening is the highest limitative factors in the realization of hepatitis B neonatal prevention. The immunoprophylaxis is surely a substantial method in the prevention of hepatitis B virus perinatal transmission, but the vaccinal schedule and follow-up should be improved.

The efficacy of thymopentin as adjuvant therapy was assessed in 13 people who did not respond to standard anti-hepatitis B vaccination with Pasteur HEVAC or Merck HV-VAX. Thymopentin (Sindtomodulina, Italfarmaco)--was given in doses of 50 mg 3 times a week for 3 consecutive weeks, a booster dose of the vaccine (40 mcg HB VAX injected into the deltoid muscle, or 10 mcg HEVAC subcutaneous) being given at the start of the second week. In 69.23% of the patients whose anamnesis revealed no immune deficiency, the Merrieux Multitest showed defective cell-mediated immunity. The adjuvant treatment produced an adequate immune response to the vaccine (anti ABc antibody titre 10 mU/ml) in 76.9% of cases and normalised cell-mediated immunity in 66.6% of those found to be hypoanergic at basal screening.

Several patients with both Basedow-Graves' hyperthyroidism and viral hepatitis were observed and it was hypothesised that this association could be explained by the individual genetic pattern in which an immunological fragility conditioned a predisposition to autoimmune diseases. This paper reports on the cases observed, the patients' histocompatibility antigen profile and the experimental data found in the literature on autoimmune involvement in the two diseases, whose association may not be coincidental.

An immunohistological survey was made of cryostat liver sections from 30 patients: 17 adults and 13 children affected by chronic hepatitis were studied. Immunofluorescent techniques were used to determine the following: HBsAg, HBcAg, HDV, IgG, serum antibodies, B lymphocytes and CD4+, CD8+ and activated T lymphocytes. The tissue antibody response and the inflammatory infiltrate was more evident in CAH than in CPH. The prevalent cell subpopulation in HBV hepatitis is represented by CD8+ while in non-A non-B and autoimmune forms by CD4+. Furthermore, in histologically more serious forms 75% of the T cells were activated with respect to 25% in non active forms. The difference was statistically significant.

Ten children with chronic hepatitis B have been followed for at least 3 years. All patients received 2 liver biopsies, the first after 1 year of continuous liver disfunction and HBsAg positivity, and the second 2 years after, that showed a mild improvement of the histologic lesions in 4 cases of chronic persistent hepatitis (CPH) and in 1 case of chronic lobular hepatitis (CLH). Three children out of 5 with chronic active hepatitis (CAN) changed to CPH and the other 2 remained unchanged without any evidence of cirrhosis. No patient received any drug for the treatment of hepatitis.

The results of some clinical trials performed with levamisole on 12 HBsAg-positive subjects, including 5 patients with aggressive chronic hepatitis, (ACH) 2 patients with persistent chronic hepatitis (PCH) and 5 healthy carriers are reported. Levamisole was administered in 2.5 mg/Kg/day doses for three consecutive days. During treatment prothrombin activity normalized in ACH and PCH as well as transaminases, the latter starting from the 4th week, even though a two-fourfold increase of the starting values was observed in the first weeks of disease. HBsAg, anti-HBs titres and immunocomplexes values did not show any significant variations, but for 1 case, while some immunological parameters (E, EA rosettes) normalized in those cases showing base- values lower than the norm.

What is known about HBsAg and its usefulness in the prevention of post-transfusion hepatitis is briefly discussed. Personal data concerning its presence in the population of Umbria by application of electrosyneresis and inverse haemagglutination techniques are presented. As usual, the latter technique proved more reliable.

The authors have looked for the markers of HBV by R.I.A. method (HBsAg, anti HBsAg, HBeAg, anti HBeAg, anti HBcAg), of HAV (by measurement on two samples of HAVab or by measurement of HAVab IgM), the immune-complexes (I.C.C.) by C1q solid-phase binding assay method with E.L.I.S.A. with determination after division I.C.C. of HBsAg by R.I.A. method in 33 cases of HBsAg negative acute viral hepatitis. The 9% (3 cases) were HAV acute hepatitis, the 42,4% (14 cases) no A no B acute hepatitis, the 36,3% (12 case) were HBV acute hepatitis, in 9 anti HBcAg positive cases the I.C.C. with HBsAg positive after division resulted positive, the 12,3% (4 cases) had a positivity for HAVab by stereoconversion (2 cases) or HAVab IgM (2 cases) with HBsAg positivity after division I.C.C. This result puts a nosologic problem about the 4 cases of acute viral hepatitis, which, from epidemiological and clinical point of the view are HAV acute hepatitis.

"In vivo" and "in vitro" action of 2 MPG on lymphocytotoxic activity was evaluated in 22 patients with CAH, 14 were HBsAg positive and 8 were negative. The test was performed with and without 2 MPG in the colture medium, and before and after treatment. HBsAg+ patients received 2 MPG treatment, while HBsAg- ones received immunosoppressive therapy and 4 of these were on 2 MPG treatment as well. Cytotoxic Index was reduced non-significantly by addition of 2 MPG in colture medium in both groups. 2 MPG treatment does not modify cytotoxic activity which is reduced by immunosoppressive therapy. These findings suggest a positive effect of 2 MPG on liver-cell metabolism with an increased resistence of the epatocyte to the "in vitro" lymphocytes aggression. Hence it may be suggested an association treatment with immunosoppressive agents and 2 MPG.

Examination was made of 300 serum specimens taken from patients with latent syphilis, in order to study the incidence of HBsAg antigen as compared with the normal population. Examination was by means of counter immunoelectrophoresis, radioimmunoassay and electron microscope with negative staining. The incidence as shown by counter immunoelectrophoresis is 2.33%, by RIA 10% with 86.6% of sub-type AY and 13.3% of sub-type AD, which is significantly higher than the incidence in the normal population. These data would therefore seem to confirm the possibility of sexual transmission of hepatitis B.

Sera of thirty-five hepatitis B surface antigen (HBsAg) positive hemodialysis patients and fifty-three asymptomatic HBsAg chronic carrier were studied to assess the relationship between markers of virus activity (hepatitis B e antigen and core-associated DNA polymerase activity) and titers of HBsAg and of antibody to hepatitis B core antigen (anti-HBc). All sera were tested by solid-phase radioimmunoassay methods. HBeAg was detected in 20 (51%) hemodialysis patients and in 14 (26%) asymptomatic carriers, whereas DNA P activity was present in sera of 21 (60%) and 17 (32%) respectively. The highest titers of HBsAg and anti-HBc expressed as P/N ratio between positive and negative controls, were detected in the majority of hemodialysis patients, whereas asymptomatic carriers showed low titers of these markers. These data suggest that in HBsAg positive hemodialysis patients a more active viral replication occurs and further underline the difference between these patients and other categories of HBsAg carriers in terms of infectivity.

Antibodies against HBsAg were immobilized by covalent linkage on nylon beads to be used in solid phase enzyme-linked immunoassays. The covalent bond between the protein and the partially hydrolyzed support was obtained via glutaraldehyde or succinylester methods. These particular solid phases were compared, in a conventional enzyme-linked immunosorbent assay for hepatitis B antigen, with polystyrene beads coated by simple adsorption of IgG on plastic surface. The analytical response was more satisfactory when the polystyrene beads were used as immunoextractive support even if more IgG molecules could be immobilized on nylon beads.

In 21 subjects HBsAg positive affected by different forms of chronic hepatitis and in one carrier we compared the presence in the liver of HBsAg, HBcAg and delta studied by means of I.F. and the presence of serological markers of hepatitis B virus infection. By the I.F. test, HBsAg was present in all cases, HBcAg in 15 cases (71%), delta in 8 cases (38%). These percentages are almost the same as those of other researches in chronic hepatitis in immunodepressive treatment. About the serological markers, HBsAg and HBcAb were present in 100% of cases, while, regarding the e-anti e system, HBeAg was present in 12 cases (57%) and HBeAb in 7 (33%). In the work effected there is no relation between delta and HBeAg because in 50% of the positive delta subjects there was HBeAb. On the contrary HBcAg and HBeAg are strictly correlated. Therefore the antigens core and delta are not interdependent. We wanted to verify the existence of relation between HBcAg and HBeAg and came to the conclusion that this relation exists in 17 out of 21 subjects (81%). In our researches is clear the long persistence of the hepatic antigens without any connection with the time of treatment and the course of the various chronic hepatitis. The change in the serum from HBeAg to HBeAb occurred in many improved cases but not in all of them. We presume that the long immunodepressive treatment (about 4 years) has influenced our results.

The spread of "A" and "B" hepatitis virus in a limited working environment has been evaluated and the main serum "markers" of this infection (HBsAg, anti-HBs, anti-HBc, anti-HAV) have been researched in 187 subjects (males and females) after being taken on by a large company in Northern Italy. This research, carried out again after 8--10 months from hiring, showed a moderate spread of "B"virus in 6,4% of the subjects observed. This finding is probably due to deficient personal hygiene rather than to environmental factors related to work (these may on the contrary condition the spread of "A" virus which, in the cases observed showed insignificant diffusion).

Unlabelled: Ninety-six chronic asymptomatic HBsAg carriers underwent liver biopsy. Liver histology was normal in 5 cases, showed nonspecific changes in 67, chronic persistent hepatitis in 18, and chronic-active hepatitis in 6. Seventy-four patients were followed for up to 105 months (mean 80 months) in order to evaluate the occurrence of clinical, biochemical, serological or histological changes. Only two patients cleared the HBsAg, respectively 10 and 96 months after undergoing liver biopsy; the latter patient became anti-HBs positive 6 months after he cleared HBsAg. All 10 patients who initially were negative for both HBeAg and anti-HBe became anti-HBe positive during follow-up. All 4 patients who were HBeAg positive at the time of liver biopsy cleared HBeAg 6 to 39 months thereafter. Two of them became anti-HBe positive. None of the patients initially HBeAg negative became positive for this antigen during follow-up. Significant increases of serum transaminases were observed in 5 patients; in one superinfection by delta agent was documented, the other 4 being constantly anti-delta negative. Three of the latter patients underwent repeat liver biopsy, which showed progression from minimal changes to chronic persistent hepatitis in one, and from minimal changes to chronic active hepatitis in another. In the third patient, repeat biopsy showed persistence of chronic persistent hepatitis., In Conclusion: chronic hepatitis occurs in about 25% of chronic asymptomatic HBsAg carriers; clearance of HBsAg is a rare event among these patients; the HBe system has little diagnostic or prognostic value; delta superinfection is rare; however, deterioration of liver histology may occur even in the absence of delta superinfection.