Understanding viral hepatitis B

Epidemic jaundice, known today as viral hepatitis, was described by Hippocrates nearly 2500 years ago. Yet only in the past 20 years or so have the main viruses that cause hepatitis been elucidated. During this short interval, the main modes of transmission and effective methods of prevention also have been described.     

Management of chronic viral hepatitis

Chronic viral hepatitis is a leading cause of death worldwide. Four of the six identifiable hepatitis viruses are associated with chronic disease. Until recently, the only accepted treatment has been injected interferon alfa. New antiviral medications currently hold promise in the treatment of hepatitis B. Hepatitis C remains more difficult to treat than hepatitis B, but involving the patient in selecting the treatment and identifying patients with better responses to interferon may help the physician direct the management of such patients more successfully.     

Treatment of chronic viral hepatitis

Recent advances have been made in the treatment of chronic viral hepatitis, mainly with recombinant interferon (IFN) alpha. However, the present treatment of chronic viral hepatitis is not entirely satisfactory because the efficacy is inconstant and/or incomplete. In chronic hepatitis B IFN-alpha induces a sustained interruption of hepatitis B virus (HBV) replication, with a HBeAg to anti-HBe seroconversion in about 30% of patients. Patients most likely to respond are those with no immunosuppression, HBV infection acquired during adulthood or active liver disease with low HBV replication. Responders usually show a significant decrease in serum HBV DNA levels during the first 2 months of therapy, followed by a significant increase in the level of aminotransferases. New nucleoside analogues might be useful in combination with IFN-alpha in the treatment of those who do not respond to IFN therapy. In chronic hepatitis B-D, the rate of sustained response to IFN-alpha therapy is low. To be effective, IFN-alpha must be used at a high dosage (9-10 mega units) with a long duration (1 year). In chronic hepatitis C, IFN-alpha at a dosage of 3 mega units over 6 months, induces a sustained response in about 20% of patients. A higher dosage of IFN (5-10 mega units) and a longer duration of treatment increases the rate of sustained response but is associated with poor tolerance. Non-responders to a first course of IFN do not respond to a second course of treatment. In patients who respond but relapse after treatment, the rate of sustained response after a second course of IFN needs to be assessed. Ribavirin, which has a significant antiviral effect on hepatitis C virus, might be useful in combination with IFN-alpha. At the dosage (3-6 mega units) usually used, IFN-alpha is relatively well tolerated. In about 10% of the patients therapy is interrupted, mainly because of severe fatigue, thyroid dysfunction or depression.     

Fecal-oral transmission of viral hepatitis

The cumulative, subchronic and chronic toxicity of B-193 were studied on the rats and mice. It was found that this compound exerted weak tendency to cumulation in the body. Only the highest doses of B-193 (70, 40 mg/kg po for 12 weeks) caused the increase of animals mortality. Studies on subchronic and chronic toxicity have demonstrated, that B-193 administrated po or ip for 3 weeks, and po for 12 weeks, in general, neither affects the body weight gain nor the mass and morphology of heart, liver and kidneys, as well as spontaneous locomotor activity of animals. The weak depressant effect of B-193 on peripheral blood morphology was seen only after 3 weeks po or ip treatment with this compound. The moderate effect of B-193 on activity of alanine and aspartate transaminases (A1At and AspAt) and serum protein level found after 3 weeks of treatment, was no longer observed after 12 weeks of treatment. This could indicate that above effects of B-193 are reversible.     

Treatment of chronic viral hepatitis

The initial appearance of tyrosine hydroxylase (TH)-, serotonin (5-HT)-, gamma-aminobutyric acid (GABA)-, calcitonin gene-related peptide- (CGRP), substance P-, and synaptophysin-immunoreactivity in the rat pituitary gland, and in the related brain regions was investigated. Several groups of TH-immunoreactive neurons were first detected in the brain stem on day E17, and in the hypothalamus on day E18, followed by TH-immunoreactivity in the median eminence and infundibulum on E19-E20. TH-positive fibers appeared in the posterior lobe on day E20 and in the intermediate lobe on day P0. 5-HT-immunoreactivity was first detected on day E17 in neurons and nerve fibers in the brain stem and in the median eminence, respectively. On day E18, a few 5-HT-immunoreactive fibers were detected in the posterior lobe of the pituitary, although they were consistently seen in the infundibulum from day E19. In newborn rats, some 5-HT-immunoreactive fibers, but no neurons, were seen in the hypothalamus. GABA immunoreactivity appeared on day E17 in several nerve fibers of the infundibulum and the posterior lobe. Some neurons in the cortex and ventral hypothalamus transiently expressed GABA-immunoreactivity on day E17. In newborn rats, a plexus of GABA-immunoreactive fibers was detected for the first time in the intermediate lobe. No CGRP-immunoreactive fibers could be detected in the prenatal pituitary. On day P10, CGRP-immunoreactive fibers were first observed in the anterior lobe. Later their number considerably increased, while only sporadic fibers could be found in the intermediate or posterior lobes. No substance P-immunoreactivity could be detected in any of the lobes in the embryonic or developing postnatal rat pituitary, instead the adult anterior lobe occasionally showed some substance P-immunoreactive fibers. Synaptophysin-immunoreactivity was first detected in the posterior lobe on day E20, followed shortly by its expression in the intermediate lobe in newborn rats. The time course of GABA and 5-HT expression revealed in the present study suggests that these transmitters, which are initially expressed in the developing pituitary clearly before synaptic maturation, may act as trophic molecules during the prenatal period.     

Therapy of hepatitis C

The purpose of this review is an update of the therapy of hepatitis C especially with Interferon-alpha. From the large number of publications on this topic the established facts were worked out. Taking these facts as a base guidelines for the therapy in practical use were defined. In addition the aspects of therapeutic strategies of chronic hepatitis C which until now can not definitely be judged are discussed. In the relatively few patients in whom hepatitis C is diagnosed already in the acute phase, Interferon-alpha-treatment (3 x 3 million units 3 times a week) for 3 to 4 months increases the percentage of patients in whom HCV-RNA in the serum is eliminated. In patients with chronic hepatitis C, after decision finding for treatment, a standard scheme is recommended which consists of a monotherapy with recombinant Interferon-alpha. The dosage of Interferon-alpha is in the first 12 to 16 weeks 5 up to 6 million units given 3 times a week. For the further therapy 3 million units 3 times a week seems to be appropriate. The recommended duration of Interferon-alpha-therapy is 12 months. A long-term benefit of about 20% can be achieved in unselected groups of patients when judged on the permanent normalisation of serum transaminases and elimination of HCV-RNA in the serum. Important factors which may influence the probability of a sustained response, like HCV genotype, virus titer in serum, duration of the disease, high hepatic iron content and the presence of cirrhosis, are discussed. Up to now there exist no reliable guidelines in the case of a "no change" situation and for patients with a flare-up of inflammatory activity during or after therapy. Combination therapy of Interferon-alpha with other drugs like analogous of nucleotides (for example ribavarin), non steroidal antirheumatic drugs and ursodesoxycholic acid (UDCA) have still to be evaluated in controlled clinical trials.     

Decimeter-wave physiotherapy in viral hepatitis

Effectiveness was evaluated of magnetotherapy, inductothermy, UNF electric field and electromagnetic waves of decimetric wave band (460 MHz) on the projection of the liver, adrenals and thyroid gland in controlled trials enrolling a total of 835 patients with viral hepatitis (type A, B, associated forms). A conclusion is reached that optimum effectiveness of decimetric field on the projection of the adrenals and thyroid gland can be achieved through the application of minimum power and everyday alternation of exposures. It has been estimated that as many as 69 percent of the patients derive benefit from the above treatment.     

Preventive vaccination for viral hepatitis

Viral hepatitis A-E belong to the most important infectious diseases worldwide. Viral hepatitis is highly endemic in most developing countries in Africa, South East Asia, and southern America; however also in industrialized countries as Germany hepatitis A, B and C represent a thread which should not be underestimated. In Germany, there are about 20,000 to 40,000 hepatitis A infections every year, most of them acquired abroad; about 50,000 new hepatitis B infections and about 5,000 to 8,000 infections with hepatitis C virus occur every year. About 500,000 individuals are chronic carriers of hepatitis B virus and roughly the same number is supposed to be chronically infected with hepatitis C virus. As possibilities for therapeutic intervention in chronic hepatitis B and C are still limited, immunoprophylactic measures are of particular importance. Passive and active immunization is available for hepatitis A and B but so far not for hepatitis C. Passive immunization by application of specific immunoglobulins gives protection which is effective within a few hours but is limited according to the amount of immunoglobulin to six to twelve months. Active immunization on the other hand induces a specific immune response starting after a delay of usually days or sometimes weeks but nevertheless lasting for at least several years. The combination of both methods, passive-active immunization, has the advantage of immediate protection due to the immunoglobulin which lasts until the active immunization induces an endogenous antibody production.     

Chronic viral hepatitis in childhood

In endemic areas infection with hepatitis B virus is a common cause of chronic liver disease in childhood. High levels of viral replication and mild ALT abnormalities are the rule in children infected perinatally and many of them are likely to maintain viral replication through their youth. Conversely about 90% of children infected later in life clear HBeAg and achieve sustained remission of liver disease before reaching adulthood. The eventual outcome of infection and disease in these patients remains unpredictable as reactivation of liver damage and viral replication may occur after several years of sustained remission. Cirrhosis is a rare and early complication of chronic HBV infection in children, and a risk factor for hepatocellular carcinoma. IFN therapy can accelerate HBV DNA clearance, improving the spontaneous anti-HBe seroconversion rate in Caucasian children by two to three times. Hepatitis delta is the most severe form of chronic viral hepatitis in childhood. Cirrhosis can be diagnosed in up to 26% of patients at presentation, and few cases respond to IFN therapy. Hepatitis C is relatively rare in children. Before the discovery of HCV, blood transfusions were the most common source of infection. Hepatitis C is usually a mild, asymptomatic disease in otherwise healthy children, but has a poor propensity to spontaneous remission over the years. For this reason, and based on the experience in adults, IFN treatment is now being evaluated.     

Health personnel and viral hepatitis

The cytotoxicity of restorative dental materials must be investigated to ensure a safe biological response. The MTS assay, a valid and reliable measure of cell viability based on the mitochondrial activity of cultured cells, was used to evaluate the affects on human periodontal ligament (PDL) cells of two resin-modified glass ionomer cements (R-M GICs) (Fuji Duet and Fuji II LC, GC America, Chicago, IL) and one dental amalgam (Contour, Caulk, York, PA)-all suggested materials for root perforation repair. Twelve 4 x 6 mm cylinders of each material were fabricated and placed in 5 ml of alpha-minimum essential medium supplemented with 100 micrograms/ml of penicillin, 50 micrograms/ml of gentamicin, and 5% fetal bovine serum for 24, 48, and 72 h (n = 3). One hundred microliters of eluate was transferred to triplicate wells containing PDL cells previously plated at a density of 10,000 cells/well in a 96-well plate, and incubated for 24 h at 37 degrees C with 5% carbon dioxide. alpha-Minimum essential medium with supplements provided baseline data. Optical density at 490 nm, directly proportional to the number of viable cells, was determined according to manufacturer instructions. Analysis of variance was used to detect differences between treatments and Tukey's HSD (p < 0.05) to detect for differences between group means. Results demonstrated that both material and time affected cell viability (p < 0.0001), with amalgam eluate significantly inhibitory on cell viability at 24 h, compared with control and the two other tested materials. At 48 and 72 h, all three materials exhibited a similar slightly inhibitory effect on the cell viability. Use of resin-modified glass ionomer cement as a root perforation repair material initially (< 24 h) may result in a more favorable response by PDL cells than the tested dental amalgam.     

Vaccines for prevention of viral hepatitis

A 17-item competency questionnaire, modified for use with children and adolescents (CQ-ChP), was used to evaluate competency to consent to hospitalization and treatment in child psychiatric inpatients. A total of 25 consecutive English-speaking psychiatric child inpatient admissions were studied. Demographic data were statistically analyzed using chi 2, and there were no significant statistical differences between the competent and incompetent groups (using CQ-ChP scores and cut-offs). The various demographic/clinical variables and scores on the questionnaire were also statistically evaluated using chi 2. The only statistical significance was the association between reading level and competency with a value of p < .05. Therefore, by achieving a reading level at the fifth-grade standard, subjects were found to be competent as measured by the CQ-ChP.     

The immunological diagnosis of chronic viral hepatitis

Chronic viral diseases of the liver are associated with changes in immune reactions mediated by T and B lymphocytes and dependent in severity on etiological factor (virus of hepatitis B, delta, C, their combination), the disease stage (hepatitis, cirrhosis), the process activity, kind of immune correction. HBsAg, viral hepatitis B marker, was detected in 21.2% of 1400 cases with chronic active hepatitis and liver cirrhosis. 32% of HbsAg-seropositive patients had antibodies to delta-antigen. Antibodies to HBsAg, HCV were found in 27.7 and 14.9% of the above patients. Chronic viral diseases of the liver with persistence of HBV, HDV and HCV markers are characterized by a complex of immune disorders, including a moderate rise in peripheral blood of IgM, IgG, IgA, IgE, Ig kappa, lambda, immune complexes, cryoglobulins, autoantibodies to subcellular structures as well as changes in regulatory (suppressor, helper) and effector (lymphokine-producing) functions of T lymphocytes, inhibition of phagocytosing capacity. The above shifts in immune status, clinical and biochemical activity of the disease are more pronounced in chronic active hepatitis with HCV markers compared to BHV. Of maximal intensity they were in combined viral infection HBV+HDV or HBV+HCV.