Viral hepatitis comparative epidemiology

The epidemiology of HAV, HBV, HCV, HDV and HEV is compared. Spread of HAV and HEV is by the faecal/oral route whereas HBV, HCV and HDV are spread by blood or blood products. HEV is more likely to produce large epidemics than HAV but sporadic cases also occur. HBV, HCV and HDV all occur after blood transfusion, in haemophiliacs and intravenous drug abusers but they differ in their geographical distribution and in the frequency of perinatal transmission which is only common with HBV. Superinfection and interaction between these viruses is discussed.     

Viral hepatitis and haemophilia

Modern therapy with clotting factor concentrates has been dramatically successful in preventing and alleviating the worst effects of haemophilia. Before the mid to late 1980s, when effective methods of concentrate sterilization were introduced, such therapy was associated with a virtual certainty of transmission of viral hepatitis. Many patients who received intensive therapy before this time now have evidence of chronic and progressive liver disease, in which non-A, non-B agents are thought to be of dominant pathogenetic importance. Complex viral interactions involving both hepatotropic agents and HIV may occur in haemophiliacs, whose responses to infection may show atypical patterns. Interferon seems promising as a therapeutic agent. Vaccination against hepatitis B virus infection remains mandatory in patients without serological evidence of immunity.     

Viral hepatitis among practising dentists.

A survey among Auckland dentists has shown a high experience of viral hepatitis occuring during practising years. The prevalence of dentists affected is higher than for similar groups of American dentists, and the incidence of viral hepatitis among dentists practising in Auckland appears to be rising. This study supports the view that infection with viral hepatitis should be regarded as a occupational health risk for practising dentists.     

Viral hepatitis in the Christchurch community.

AIM: To determine the relative frequency of known causes of viral hepatitis in the Christchurch community. METHODS: Serum samples were collected at a private laboratory from patients aged 15-75 years who had an elevated transaminase of at least twice normal. RESULTS: One hundred and thirty-three subjects entered the study of whom 32 were positive for Epstein Barr virus, three for cytomegalovirus, nine for hepatitis A virus, and eight for hepatitis B virus. Paired convalescent samples were obtained from 64 of the remaining 81 subjects (17 lost or declined) and seven of these were positive for hepatitis C. Assuming a similar percentage in the lost/declined group this corrects to nine. CONCLUSION: The relative frequency of viral agents causing hepatitis was Epstein Barr virus 52%, cytomegalovirus 5%, hepatitis A virus 15%, hepatitis B virus 13% and hepatitis C virus 15%. Hepatitis C virus is a common cause of viral hepatitis in the Christchurch community.     

Viral hepatitis B: established and emerging therapies

Chronic hepatitis B virus (HBV) infection has a variable course leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis and clinical outcome of HBV infection are strictly dependent on both viral factors, such as life cycle and genotypic variants, and host immune response (i.e. viral persistence). Although therapy of hepatitis B is evolving, which between single and/or combined agents are most effective, how long therapy should last, which criteria should be used to start or continue and switch or stop therapy are to be defined. Two major groups of therapies are currently utilized for chronic hepatitis: immunomodulatory (interferons) and antivirals (nucleoside and nucleotide analogues), all with their own advantages and limitations. In fact, the development of specific antiviral therapies has provoked the appearance of a relevant problem: drug resistances. The emerged antiviral drug-resistant strains of HBV leads to a poor prognosis for infected patients. Thus, many basic and clinical research challenges remain in defining optimal means of management of viral hepatitis B and its related liver diseases. This paper provides a review of new available and developing treatment options for HBV associated liver diseases. In the near future the most realistic therapeutic option for the majority of patients with HBV infection will be combination and/or long-term use of new and stronger antiviral drugs, if they maintain good safety profiles, achieve low resistance rates and will be available at lower prices.     

Viral hepatitis in international travellers: risks and prevention

Viral hepatitis is caused by a number of unrelated hepatotrophic viruses, known and unknown. Five hepatitis viruses namely HAV, HBV, HCV, HDV and HEV have been well characterized and the epidemiology and disease pattern of each agent has been defined. In the West, HAV, HBV and HCV are major causes of viral hepatitis. In the East, HEV is the most common cause of viral hepatitis. HAV is ubiquitous in childhood in such countries and accounts for less than 4% of disease in adults. Viral hepatitis becomes a problem to an international traveller when he envisages a journey from low endemic to high endemic area and is susceptible to the infection endemic at his destination. Millions of such potentially susceptible travellers from Europe, the USA, Canada, Japan, Australia, and New Zealand visit endemic areas every year for various reasons. Viral hepatitis is the most common reported immunization-preventable disease among travellers to developing countries. Imported viral hepatitis incapacitates the incumbents for an average of 4-10 weeks. Considering the magnitude of the travel, the number of cases of viral hepatitis and case fatality of around 2%, the disease causes significant morbidity and mortality in such communities. It has been estimated that viral hepatitis occurs 100 times more frequently than typhoid fever and 1,000 times more often than cholera in travellers to developing countries. Hepatitis A is the most common form of viral hepatitis in travellers and cumulative data have shown a risk of 3-6 cases/1,000 persons/month of stay whereas the risk of acquiring hepatitis B is 10 times lower.     

Viral nucleotide changes in asymptomatic hepatitis B carriers undergoing interferon treatment

Background: Interferon might induce mutation in regions of hepatitis B virus DNA that encode for immunologic target of cytotoxic T lymphocytes.
Aim: To investigate the short-term effect of steroid priming and interferon therapy on hepatitis B virus, we followed the nucleotide changes in the precore and core region of hepatitis B virus DNA in seven healthy asymptomatic carriers who underwent steroid priming followed by recombinant alpha interferon for 3 months.
Methods: Hepatitis B virus DNA from serial sera of the patients were polymerase chain reaction-amplified, and the precore and core region directly sequenced and analysed.
Results: Analysis revealed no serial changes in the hepatitis B virus nucleotide sequence in any of the patients.
Conclusions: Steroid priming and short-term treatment with interferon in healthy asymptomatic patients does not select for hepatitis B virus with mutations in the precore and core region.     

Viral protein complexed liposomes for intranasal delivery of hepatitis B surface antigen

Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases. Lipid core nanocapsules (LNCs), 50 nm in size, were shown to pass though the round window membrane (RWM) and reached the spiral ganglion cells and nerve fibers, among other cell types in the inner ear. The present study aimed to evaluate the toxicity of the LNCs in vitro and in vivo, utilizing intact round window membrane delivery in rats. The primary cochlear cells and mouse fibroblast cells treated with LNCs displayed dosage dependant toxicity. In vivo study showed that administration of LNCs did not cause hearing loss, nanoparticle application-related cell death, or morphological changes in the inner ear, at up to 28 days of observation. The cochlear neural elements, such as synaptophysin, ribbon synapses, and S-100, were not affected by the administration of LNCs. However, expression of neurofilament-200 decreased in SGCs and in cochlear nerve in osseous spiral lamina canal after LNC delivery, a phenomenon that requires further investigation. LNCs are potential vectors for the delivery of drugs to the inner ear.     

Viral hepatitis in elderly haemodialysis patients: current prevention and management strategies

Viral hepatitis continues to be a relevant topic for haemodialysis centres, although the number of infected dialysis patients is declining in most countries. Chronic hepatitis B and C lead to detrimental complications such as liver cirrhosis and hepatocellular carcinoma. These complications can be avoided by successful antiviral treatment. In individuals with normal renal function, drug therapy of chronic hepatitis B is evolving quickly. Today there are several options but no agreed standard therapy. In the absence of renal failure, chronic hepatitis C should be treated with a combination of pegylated interferon-alpha and ribavirin. For both infections, there is no general indication to treat all patients; several criteria can be used to predict benefits and downsides.Chronic renal failure severely alters immune function, particularly activation of T lymphocytes and cytokine production by mononuclear cells. Aging further influences the immune system with deviation of T-lymphocyte differentiation. Both effects seem to act additively, leaving the elderly haemodialysis patient with extensive immune dysfunction. While these effects do not put the patient at risk of opportunistic infection, they do have a relevant effect on the clinical course of viral hepatitis.Haemodialysis patients infected with hepatitis B manifest a subclinical, often anicteric disease, and at least 60% of the infections become chronic. These patients usually do not fulfil the criteria for successful antiviral treatment, since they have normal or slightly elevated liver enzyme levels and few histological signs of liver inflammation. In addition, the prognosis in terms of cirrhosis and hepatocellular carcinoma might be more favourable than in individuals with normal renal function. The former standard treatment of chronic hepatitis B with interferon-alpha or its derivate pegylated interferon was badly tolerated in dialysis patients and associated with low efficacy. Indeed, prior to the advent of nucleoside analogues there was a clear recommendation not to treat chronic hepatitis B infection in all except a few dialysis patients. However, the newer treatment options appear to work well. In particular, there is growing evidence for the effectiveness and tolerability of lamivudine in dialysis patients, including the elderly. Use of adefovir and entecavir has also been reported in a few cases. At present, while we still do not recommend treatment, therapy with nucleoside analogues might be an option in selected patients, for example, those planning renal transplantation. The major effort against hepatitis B should be directed at vaccination and hygienic precautions to prevent the infection.Treatment of hepatitis C in patients undergoing haemodialysis is also limited by the poor tolerability of interferons. Ribavirin is contraindicated because of severe haemolytic anaemia, although a few studies have attempted to manage this with administration of high doses of erythropoetin. Those patients who complete the full course of interferon therapy may expect sustained viral responses comparable with healthy individuals, but in most trials, 30-50% of patients were forced to interrupt treatment because of adverse effects. There is no general indication to treat chronic hepatitis C in haemodialysis patients. Arguments in favour of treatment include elevated liver enzymes, histological signs of relevant liver inflammation, younger age, a virus genotype other than 1 and planned renal transplantation.