The epidemiology of hepatitis delta virus infection in Cameroon.

OBJECTIVE: To investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon. DESIGN: We tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies. RESULTS: Overall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15-49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude <4°N) while having rural/outdoor work (OR=15.2; 95% CI: 8.35 to 27.6, when compared with living on latitude ≥4°N and not having rural/outdoor work). CONCLUSION: We found evidence for effective intra-household transmission of HDV in Cameroon. We also identified large differences in prevalence between regions, with cases concentrated in forested areas close to the Equator, as described in other tropical areas. The reasons underlying these geographical variations in HDV prevalence deserve further investigation.

Hepatitis D reactivation in a patient with metastatic renal cell carcinoma receiving sunitinib therapy.

BACKGROUND: Cytotoxic and immunosuppressive therapies for cancer treatment may allow hepatitis reactivation. Hepatitis due to viral hepatitis reactivation is detected in 14%-25% of hepatitis B surface antigen (HBsAg)-positive cancer patients undergoing anticancer treatments. Drug toxicity may be confused with hepatitis reactivation, which may cause a delay in diagnosis. CASE REPORT: A 60-year-old man with metastatic renal cell carcinoma was treated with sunitinib. Sixteen months after sunitinib inception, liver enzymes were elevated and viral hepatitis reactivation was detected as hepatitis delta virus infection in the HBsAg-positive patient. CONCLUSION: Cancer patients should be screened for viral hepatitis prior to immunosuppressive therapy or chemotherapy.

Delta hepatitis within the Veterans Affairs medical system in the United States: Prevalence, risk factors, and outcomes.

BACKGROUND & AIMS: Low hepatitis delta prevalence estimates in the United States are likely biased due to low testing rates. The objectives of this study were to quantify the prevalence of testing and identify factors associated with hepatitis D positive status among chronic hepatitis B patients in the Veterans Health Administration. METHODS: We performed a nationwide retrospective study of all veterans who tested positive for HBsAg from October 1999 to December 2013. Hepatitis D antibody testing results were used to stratify patients into three groups: HDV-positive, HDV-negative, and HDV-not tested. Demographics, comorbidities, additional laboratory data and clinical outcomes were compared across these groups of patients using standard statistical approaches. RESULTS: Among 25,603 patients with a positive hepatitis B surface antigen, 2175 (8.5%) were tested for HDV; 73 (3.4%) patients tested positive. Receiving HDV testing was associated with receipt of testing for HBV, HIV, and HCV. Predictors of positive HDV results included substance abuse and cirrhosis. Fitting a predefined high-risk profile (abnormal ALT with suppressed HBV DNA titers) was strongly associated with testing positive for HDV (OR 3.2, 95%CI 1.4-7.5). Most (59%) of HDV-positive patients were HCV co-infected. HDV-positive subjects had higher risks of all-cause mortality. Incidence rates of HCC were 2.9 fold higher in HDV-positive relative to HDV-negative individuals (p=0.002). In adjusted analyses, HDV was independently associated with HCC (OR 2.1, 95%CI 1.1-3.9). CONCLUSIONS: Testing rates for hepatitis delta in chronic hepatitis B patients in the United States are inappropriately low. Approaches to increase testing for HDV particularly in high-risk subsets should be explored.

Hepatitis D virus coinfection and superinfection.

HDV is a defective RNA pathogen requiring the simultaneous presence of HBV to complete its life cycle. Two major specific patterns of infection have been described: the coinfection with HDV and HBV of a susceptible, anti-HBs-negative individual, or the HDV superinfection of a chronic HBV carrier. Coinfection mostly leads to the eradication of both agents, whereas the majority of patients with HDV superinfection evolve to chronic HDV infection and hepatitis. Chronic HDV infection worsens the preexisting HBV-related liver damage. HDV-associated chronic liver disease (chronic hepatitis D) is characterized by necroinflammation and the relentless deposition of collagen culminating, within a few decades, into the development of cirrhosis and hepatocellular carcinoma.

[Current concepts of pathogenesis, clinical course and treatment of hepatitis delta (35 years since its discovery)].

Chronic HDV infection is a most serious and rapidly progressing hepatic disease with high risk of liver cirrhosis and hepato cellular carcinoma (HCC). Many aspects of its pathogenesis, virus biology and treatment remain unknown 35 years after the discovery of the disease. HDV is significantly different from HCV and HBV despite common route of infection. HDV as a satellite pathogen realizes its pathological action in an organism with compromised immune system that proved unable to eliminate HBEV. Hepatic lesions induced by HBV create favourable conditions for HDV propagation that causes rapid development of cirrhosis and its complications. The low efficacy of IFN-alpha therapy is due to the properties of HDV that inhibits the immune response. In most cases, decompensation and hepatic insufficiency determine prognosis of and mortality from HDV infection rather than HCC as in HBV and HCV.

Hepatites virais: B, C e D: atualização / Viral hepatitis: B, C and D: an update

JUSTIFICATIVA E OBJETIVOS: As hepatites causadas pelos vírus da hepatite B (VHB), vírus da hepatite C (VHC) e vírus da hepatite (VHD) têm como aspecto comum a transmissão por via parenteral e a possibilidade de cronificação. Revisar os aspectos clínico-epidemiológicos, diagnósticos, terapêuticos e profiláticos das infecções virais por tais agentes é o escopo do presente artigo. Realizou-se pesquisa bibliográfica nas bases de dados Scielo e Pubmed empregando-se os descritores hepatite B (hepatitis B); hepatite C (hepatitis C); hepatite D (hepatitis D) e hepatite G (hepatitis G), assim como livros texto, consensos e diretrizes relacionadas ao tema.CONTEÚDO: As formas agudas das hepatites B, C e D são usualmente benignas, podendo, sem embargo, ocorrerem quadros de hepatite fulminante. Em situações nas quais o sistema imunológico não é capaz de depurar o VHB e/ou VHC, há cronificação da infecção, com risco de desenvolvimento de cirrose e consequente insuficiência hepática crônica, bem como carcinoma hepatocelular. As hepatites B e D são imunopreveníveis, graças à vacina parao vírus B, mas, até o momento, não há imunoprofilaxia disponível para o vírus C.CONCLUSÃO: As hepatites pelos VHB e VHC constituem importantes desafios para a medicina atual, especialmente pela prevalência das infecções no planeta e pelo risco de desenvolvimento das complicações crônicas. Neste contexto, destaque-se a importância da avaliação diagnóstica, da instituição da terapêutica adequada e do emprego das medidas preventivas para tais infecções, elementos que devem ser solidamente conhecidas pelo clínico.

BACKGROUND AND OBJECTIVES: Hepatitis caused by hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) have in common the transmission by parenteral route and the possibility of chronification. Reviewing the clinic, epidemiology, diagnose, therapeutics and prophylaxis of viral infections by these agents is the scope of this work. Bibliographic research was conducted both at databases Scielo and Pubmed through the chosen descriptors: hepatitis B, hepatitis C, hepatitis D and hepatitis G, and text books, consensus and guidelines related to the subject.CONTENTS: The acute viral B, C and D hepatitis are usually benign, though acute liver failure, fulminant hepatitis, may occur. In the cases when the immune system is unable to debug HBV and HCV the infection becomes chronic, cirrhosis with consequent chronic liver insufficiency and hepatocellular carcinomamay develop. HBV and HDV are immunopreventable, thanks to the hepatitis B virus vaccine, but at this point there's no immunoprophylaxis available for hepatitis C virus. CONCLUSION: HBV and HCV hepatitis are great challenges for medicine, particularly due to the prevalence of infections worldwide and the risk of chronic complications. In this context, diagnostic evaluation, adequate therapeutic care, and preventive measures must be soundly known by the physician.

Hepatitis delta in Switzerland: a silent epidemic.

OBJECTIVES: The sero-prevalence of co-infection with the hepatitis B virus (HBV) and the hepatitis D virus (HDV) is well known in many European countries, starting from 6.8% in Germany to more than 27% in some Turkish areas. To gain a better description of this infection in Switzerland, and to characterise those affected, a questionnaire was sent to all Swiss gastroenterologists, hepatologists and infectologists. METHODS: A questionnaire was received by 349 physicians which asked them to report on all HBV- and HDV-infected patients seen at their units/offices. RESULTS: A total of 101 HDV-positive patients seen by 78 specialists were analysed. The physicians were in charge of 1'699 patients with chronic hepatitis B, giving a 5.9% prevalence of HDV infection in HBV-positive patients. A predominance of males (75%) from Switzerland (39%), and of African origin (21%) was recorded. Most had been contaminated by intravenous drug use (62%), followed by vertical transmission (15%), sexual contact (13%) or transfusion with blood or blood products (2%). The majority (74%) had a very low (<103 UI/ml) HBV viral load and 75% were HBeAg-negative. A total of 76% percent of those who had a liver biopsy had significant fibrosis (≥F2), and only 21% had received standard therapy (interferon or pegylated interferon-α). Overall, 10% recovered spontaneously (anti-HBs-positive). CONCLUSION: With a prevalence of 5.9% of hepatitis D in HBsAg-positive patients, Switzerland seems less affected than most other European countries, however, it is possible that this infection is under-diagnosed. Intravenous drug use was the main risk factor. Associated advanced liver disease was also very common.

HDV: thirty years later.

The hepatitis D virus (HDV) was discovered in Italy in the mid-1970s during a major outbreak of hepatitis D in the Mediterranean basin. The outbreak has been brought under control in Europe and throughout the industrialized world in the last twenty years; in parallel, the clinical pattern of HDV disease has consistently changed. Though the decline of hepatitis D has diminished attention to this problem and at present testing for HDV is not seldom neglected, hepatitis D is not eradicated in Europe and its circulation did not decline further in the last decade. Fresh new cases are cumulating in migrants from HDV endemic areas of the developing world. Hepatitis D remains a major health problem in many developing areas with outbreaks of the disease continuing to be reported from Asia, Africa and South Africa.

Management of acute hepatitis B.

Acute hepatitis B virus (HBV) is a common cause of acute icteric hepatitis in adults. The vast majority of these patients resolve this acute infection and develop long-lasting immunity. In contrast, the vast majority of patients who develop chronic HBV have minimal symptoms and do not develop jaundice after becoming infected with HBV. These patients will frequently remain undiagnosed for years or decades. Approximately 1% of persons with acute HBV develop acute liver failure. Preventing acute HBV with vaccination is the best treatment. Although universal vaccination is now administered to newborns in many countries, the majority of adults have not been vaccinated and remain at risk. Because the majority of patients with acute HBV resolve this infection spontaneously, treatment with an oral anti-HBV agent is not necessary. However, the use of an oral anti-HBV agent is not unreasonable to use in a patient who is developing acute liver failure from severe acute HBV.

The frequency of hepatitis D virus in patients with hepatitis B in Iran: an increasing rate?

This study sought to determine the seroprevalence of the hepatitis D virus (HDV), the risk factors and its association with the severity of liver disease. Continuous patients at Tabriz and Tehran Hepatitis Clinics were enrolled during 2007-2008 in a cross-sectional study. Demographic data and possible risk factors for infection were recorded for all hepatitis B surface antigen positive patients. The blood samples of 847 patients infected with the hepatitis B virus were evaluated. The seroprevalence of HDV was 9.3%. This rate was significantly higher after reaching 40 years of age. The rate was 12.7% in patients with chronic hepatitis B and 4.7% in patients with in-active hepatitis B; the difference was statistically significant. A history of dental interventions and several trips abroad were good predictors of HDV infection in logistic regression. No significant difference in liver function tests was found. The seroprevalence of HDV was higher than in some other studies from Iran but a decrease was noted in younger age.

[Recent etiology and clinical features of acute viral hepatitis in a single center of Korea].

BACKGROUND AND AIMS: The etiology of acute viral hepatitis in Korea has been dynamically changing during the recent years. The aim of this study was to investigate the recent etiology and the clinical features of acute viral hepatitis in a single center of Korea. METHODS: We performed a retrospective analysis of a prospective cohort of 55 patients who were diagnosed with acute viral hepatitis A to E during the period from May 2005 to August 2006. In addition to the clinically acute manifestations, the confirmatory serological tests were performed for the diagnosis of acute hepatitis A, B, C and E. RESULTS: The proportion of patients with acute viral hepatitis A, B, C, E and others were 56.4% (n=31), 12.7% (n=7), 18.2% (n=10), 9.1% (n=5) and 3.6% (n=2), respectively. The mean age of the patients with acute hepatitis A, B, C and E were 29.1+/-4.38, 38.7+/-11.72, 45.3+/-17.62 and 32.4+/-6.58 years, respectively. There was no fatal case. All cases of acute hepatitis B and six out of ten cases of acute hepatitis C recovered spontaneously. Four out of the five patients with acute hepatitis E had no history of travel to endemic area. CONCLUSIONS: The most common etiology of acute viral hepatitis in Korea is hepatitis A virus, and hepatitis C and B virus were the next most common causes. The sporadic cases of acute hepatitis E were not rare, and coinfection of HAV and HEV was observed. A multicenter, prospective study is warranted in the future.

Immunology of HDV infection.

Hepatitis delta virus (HDV) infection may occur as coinfection with hepatitis B virus (HBV) or as superinfection of a chronically HBV-infected patient. A strong antibody response is mounted, which persists for many years; however, it is not able to modulate the course of infection. In most cases the superinfection takes a chronic course. In patients with inactive disease (HDV PCR negative) an oligospecific T-helper cell immune response and a cytotoxic T-cell response were found, which were absent in patients with persistent viremia. The role of the cellular immune response in liver injury during acute infection has not been investigated. Vaccination strategies tested in the woodchuck model induced specific B- and T-cell responses but failed to protect from HDV infection.

The woodchuck model of HDV infection.

The Eastern woodchuck, Marmota monax, has been a useful model system for the study of the natural history of hepadnavirus infection and for the development and preclinical testing of antiviral therapies. The model has also been used for hepatitis delta virus (HDV). In this chapter several new applications of the woodchuck model of HDV infection are presented and discussed. The development of a woodchuck HDV inoculum derived from a molecular clone has facilitated the analysis of viral genetic changes occurring during acute and chronic infection. This analysis has provided insights into one of the more important aspects of the natural history of HDV infection-whether a superinfection becomes chronic. These results could renew interest in further vaccine development. An effective therapy for chronic HDV infection remains an important clinical goal for this agent, particularly because of the severity of the disease and the inability of current hepadnaviral therapies to ameliorate it. The recent application of the woodchuck model of chronic HDV infection to therapeutic development has yielded promising results which indicate that targeting the hepadnavirus surface protein may be a successful therapeutic strategy for HDV.

Risk factors for hepatitis B in an outbreak of hepatitis B and D among injection drug users.

During January-April, 2000, 12 cases of acute hepatitis B were reported in Pierce County, Washington, compared with seven in all of 1999. Seven (58.3%) case patients were injection drug users (IDUs), three of whom were coinfected with hepatitis D virus (HDV) and died of fulminant hepatitis. Vaccination clinics were implemented at the local health department and needle exchange program to control the outbreak. We investigated this outbreak to determine risk factors for hepatitis B virus (HBV) transmission among IDUs. Hepatitis B cases were ascertained through routine surveillance and prevaccination testing at vaccination clinics. We conducted a case-control study comparing IDU case patients with HBV-susceptible IDUs identified at the vaccination clinics. Fifty-eight case patients were identified during January-December, 2000, 20 (34.5%) of whom were coinfected with HDV. Thirty-eight case patients (65.5%) reported current IDU. In the case-control study, the 17 case patients were more likely than the 141 controls to report having more than one sex partner [odds ratio (OR) =4.8, 95% confidence interval (CI) =1.5-15.0], injecting more than four times a day (OR = 4.5, 95% CI =1.2-15.6) and sharing drug cookers with more than two people (58.8% vs. 14.0%, OR =14.0, 95% CI =2.4-81.5). Results were similar after controlling for syringe sharing in multivariable analysis. IDUs should be vaccinated against hepatitis B and should be advised against sharing drug injection equipment.

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.

Latest discoveries on the infection and coinfection with hepatitis D virus.

HDV is an incomplete virus that has HBV infection as a prerequisite. Superinfection by HDV leads to acute hepatitis and causes progression to liver cirrhosis in a significant proportion of HBsAg carriers. The traditional methods for the diagnosis of HDV infection, such as detection of serum anti-HD antibodies, are sufficient for the clinical diagnosis of delta infection. However, such techniques lack the sensitivity and specificity required to more accurately characterize the nature of HDV infection and to assess the efficacy of therapies. Recent improvements in molecular techniques, such as HDV RNA hybridization and RT-PCR, have provided increased diagnostic precision and a more thorough understanding of the natural course of HDV infection. These advances have enhanced the clinician's ability to accurately evaluate the stage of HDV infection, response to therapy, and occurrence of reinfection after orthotopic liver transplant.

Acute and chronic viral hepatitis.

Viral hepatitis is the most common cause of acute and chronic hepatitis. The term viral hepatitis generally refers to infections resulting from one of the hepatotrophic viruses: hepatitis A, B, C, D, and E. The last 10 years have brought many important advances in understanding the epidemiology, pathogenesis, molecular biology, and immunoprophylaxis of infections caused by hepatotrophic viruses. Development of sensitive and specific immunoassays has enabled detection of specific agents. This has allowed for identification of infected patients and monitoring response to therapy. Additionally, serologic markers have allowed for isolation of contaminated blood products and a reduction in the spread of disease. The remaining challenge is the application of this knowledge to the treatment and prevention of viral hepatitis. This article explores the risk factors, epidemiology, microbiology, clinical and laboratory diagnosis, treatment, and prevention of the hepatotrophic viral infections.

Hepatitis delta virus.

The purpose of this article is to give a concise update on our understanding of hepatitis delta virus (HDV). For more extensive background information the reader is directed to published reviews [1-5].