Hepatitis D virus infection: Progress on the path toward disease control and cure.

This article discusses the impact of Hepatitis D virus (HDV) infection as a major cause of liver-related morbidity and mortality in people with Hepatitis B virus (HBV) infection. The article reviews the current knowledge and unanswered questions about the epidemiology, pathogenesis, and natural history of HDV infection. Although effective treatments for HDV infection have been elusive, interferon alfa is recommended for at least 48 weeks. However, response rates with standard-of-care peginterferon alfa are suboptimal, leading to few patients with a sustained virologic response. The article proposes novel approaches to treating HDV and HBV, including targeting reduction or loss of hepatitis B surface antigen (HBsAg) reduction, and discusses potential strategies for achieving HBsAg loss in patients with chronic HBV infection. Finally, the article discusses the landmark decision of accepting viral and biochemical surrogates by regulatory authorities, opening the door for the clinical development of drugs for patients with HDV infection.

Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign.

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come.

Discontinuation of Passive Immunization Is Safe after Liver Transplantation for Combined HBV/HDV Infection.

Patients after LT due to combined HBV/HDV infection are considered to be high-risk patients for recurrence of hepatitis B and D. To date, life-long prophylaxis with hepatitis B immunoglobulin (HBIG) and replication control with nucleos(t)ide analogs (NA) remains standard. We examined the course of 36 patients that underwent liver transplantation from 1989 to 2020 for combined HBV/HDV-associated end-stage liver disease in this retrospective study. Seventeen patients eventually discontinued HBIG therapy for various reasons. Their graft function, histopathological findings from routine liver biopsies and overall survival were compared with those that received an unaltered NA-based standard regimen combined with HBIG. The median follow-up was 204 and 227 months, respectively. The recurrence of HBV was 25% and did not differ between the groups of standard reinfection prophylaxis NA/HBIG (21.1%) and HBIG discontinuation (29.4%); (p = 0.56). No significant differences were found regarding the clinical course or histopathological aspects of liver tissue damage (inflammation, fibrosis, steatosis) between these two groups. Overall, and adjusted survival did not differ between the groups. Discontinuation of HBIG in stable patients after LT for combined HBV/HDV did not lead to impaired overall survival or higher recurrence rate of HBV/HDV infection in this long-term follow-up. Therefore, the recommendation of the duration of HBG administration must be questioned. The earliest time of discontinuation remains unclear.

[Reduction of HBV and HDV infection in two indigenousmpeoples of Peruvian Amazon after the vaccination against hepatitis B]. / Reducción en la infección por VHB y VHD en dos poblaciones indígenas de la Amazonia peruana después de la vacunación contra la hepatitis B.

OBJECTIVE: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. MATERIALS AND METHODS: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. RESULTS: The prevalence rates of HBsAg, anti-HBc total, anti- HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). CONCLUSIONS: These findings show the elimination of HBVmcarriers in children <11 years, eight years following introduction of the vaccination against HBV.

OBJETIVO: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. MATERIAL Y MÉTODOS: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. RESULTADOS: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. CONCLUSIONES: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.

Reducción en la infección por VHB y VHD en dos poblaciones indígenas de la Amazonia peruana después de la vacunación contra la hepatitis B / Reduction of HBV and HDV infection in two indigenous peoples of Peruvian Amazon after the vaccination against hepatitis B

Resumen: Objetivo: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. Material y métodos: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. Resultados: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. Conclusiones: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.

Abstract: Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. Materials and methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. Results: The prevalence rates of HBsAg, anti-HBc total, anti-HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). Conclusions: These findings show the elimination of HBV carriers in children <11 years, eight years following introduction of the vaccination against HBV.

Role of Sodium Taurocholate Cotransporting Polypeptide as a New Reporter and Drug-Screening Platform: Implications for Preventing Hepatitis B Virus Infections.

PURPOSE: Sodium taurocholate cotransporting polypeptide (NTCP) is a transmembrane protein responsible for delivering indocyanine green (ICG), an ideal infrared fluorescent dye, from extracellular space into the cytoplasm. Additionally, NTCP located in the hepatocyte membrane is the portal for hepatitis B and D virus (HBV/HDV) infections. This study verified the feasibility of NTCP as a reporter and further established a drug-screening platform for HBV/HDV infections. PROCEDURES: NTCP was transduced into HT-29, a colorectal cancer cell line. To examine the use of NTCP as a reporter, NTCP-expressing cells were treated with ICG and examined through flow cytometry, an in vivo imaging system (IVIS), and confocal microscopy. Furthermore, ICG was administrated to NTCP-expressing tumor-bearing nude mice and examined using the IVIS. To study the drug-screening platform, NTCP-expressing cells were treated with cyclosporin A, an NTCP inhibitor, and ICG, and examined using a multimode detection platform. Moreover, nude mice were injected with NTCP inhibitors and ICG, and subsequently, their ICG signal was examined in vivo and in the blood. RESULTS: In the reporter study, the ICG signal was higher in NTCP-expressing cells/tumors than in control cells/tumors after ICG treatment. In the drug-screening platform study, NTCP-expressing cells had decreased ICG intensity after treatment with NTCP inhibitors and ICG. Nude mice that were administered cyclosporin A had lower ICG intensity in the liver and higher intensity in the peripheral tissue and blood. CONCLUSIONS: NTCP and ICG form an ideal reporter system with extensive applications in cancer biology, robust drug-drug interactions, and drug screening in HBV/HDV infections.

Hepatotropic viruses (hepatitis A, B, C, D and E) in a rural Brazilian population: prevalence, genotypes, risk factors and vaccination.

BACKGROUND: People living in settlement projects represent an emergent rural population in Brazil. Data on their health is scarce and there are no data on viral hepatitis in this population. This study investigated the epidemiology of viral hepatitis A-E in residents of settlement projects in central Brazil. METHODS: During 2011 and 2012, 923 people living in rural settlements in central Brazil were interviewed and tested to estimate the prevalence of exposure to viral hepatitis A-E, to identify the circulating hepatitis B virus (HBV)/hepatitis C virus (HCV) genotypes and risk factors for HBV exposure and to evaluate adherence to the hepatitis B vaccination series. RESULTS: Overall, 85.9, 3.9, 0.4 and 17.3% of individuals showed evidence of exposure to hepatitis A virus (HAV), hepatitis E virus, HCV and HBV, respectively. Among HBV-DNA positive samples (n=8), subgenotypes A1 (n=3) and A2 (n=1) and genotype D/subgenotype D3 (n=4) were identified. Hepatitis D virus superinfection was detected in 0/16 HBsAg-positive participants. A total of 229 individuals showed serological evidence of HBV vaccination. In total, 442 settlers were eligible for vaccination, but only 150 individuals completed the vaccine series. All anti-HCV-positive samples (n=4) were also HCV-RNA positive and identified as subtype 1a. CONCLUSIONS: The intermediate endemicity of HAV, the higher prevalence of HBV exposure compared with urban areas and the low compliance with HBV vaccination requires preventive measures focused on rural populations, emphasizing the need for HAV and HBV vaccination.

AMSSM Position Statement Update: Blood-Borne Pathogens in the Context of Sports Participation.

This AMSSM position statement update is directed toward health care providers of patients involved in sport and exercise. There have been significant advances in clinical and scientific research in the understanding of blood-borne pathogens (BBPs), and this update incorporates these advancements. This document is intended as a general guide to clinical practice based on the current state of evidence, while acknowledging the need for modification as new knowledge becomes available. Confirmed transmission of BBPs during sport is exceedingly rare. There are no well-documented reports of HIV, hepatitis C virus, or hepatitis D virus transmission during sport. There is also no evidence for universal testing for BBPs as a specific requirement for participation in sports. Competitive athletes and nonathletes should follow appropriate general public health agency recommendations for screening for BBPs, considering their individual risk factors and exposures. Standard (universal) precautions must be followed by those providing care to athletes. Exercise and athletic participation can help promote a healthy lifestyle for persons living with BBPs. Those with acute symptomatic BBP infection should limit exercise intensity based on their current health status. Education is the key tool for preventing BBP transmission. Research gaps include evaluation of the prevalence of BBP infections in competitive athletes, the effects of long-term, intense training on infected athletes, and the effects of BBP treatment therapies on performance.

Hepatitis delta virus and hepatocellular carcinoma: an update.

Hepatitis delta virus (HDV) is a defective RNA virus that depends on the presence of hepatitis B virus (HBV) for the creation of new virions and propagation of the infection to hepatocytes. Chronic infection with HDV is usually associated with a worsening of HBV infection, leading more frequently to cirrhosis, increased risk of liver decompensation and hepatocellular carcinoma (HCC) occurrence. In spite of a progressive declining prevalence of both acute and chronic HDV infection observed over several years, mainly due to increased global health policies and mass vaccination against HBV, several European countries have more recently observed stable HDV prevalence mainly due to migrants from non-European countries. Persistent HDV replication has been widely demonstrated as associated with cirrhosis development and, as a consequence, development of liver decompensation and occurrence of HCC. Several treatment options have been attempted with poor results in terms of HDV eradication and improvement of long-term prognosis. A global effort is deemed urgent to enhance the models already existing as well as to learn more about HDV infection and correlated tumourigenesis mechanisms.

Virus entry and its inhibition to prevent and treat hepatitis B and hepatitis D virus infections.

While chronic infection with the human hepatitis B virus (HBV) and hepatitis delta virus (HDV) inflict major health burdens worldwide, current therapies cannot cure patients. One possible novel approach is blocking virus entry to prevent the establishment of infection in naïve hepatocytes. As HBV and HDV use identical viral envelope proteins and the same entry mechanisms, such a strategy would target both viruses. Entry inhibitors (e.g. neutralizing antibodies) have been relegated to the limited role of prophylaxis. However, recent clinical data and infection studies show that new viral entry inhibitors could play a major role in eliminating intrahepatic HBV/HDV genomes. We highlight the consequences on viral persistence after preventing virus entry and the therapeutic benefits entry inhibitors could achieve.

Hepatitis B Virus and Hepatitis D Virus Recurrence in Patients Undergoing Liver Transplantation for Hepatitis B Virus and Hepatitis B Virus Plus Hepatitis D Virus.

BACKGROUND: In this study, we retrospectively analyzed the recurrence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection after liver transplantation for HBV and HBV+HDV co-infection. METHODS: Data from patients infected with HBV and HBV+HDV who underwent liver transplantation between March 2003 and June 2013 at the Liver Transplantation Institute of Inonu University were analyzed retrospectively. A total of 255 patients were included in the study. Group 1 (n = 127) comprised patients who underwent liver transplantation because of HBV, and group 2 (n = 128) comprised patients who underwent liver transplantation because of HBV+HDV. A positive HDV antibody serologic test result was taken to indicate liver disease caused by HBV+HDV. RESULTS: Thirteen of 255 were positive for the HBs Ag (5.1%). Nine (7.1%) and 4 (3.1%) patients were positive for the HBs Ag in groups 1 and 2, respectively (7.1%); the difference was not significant (P = .150). No HDV recurrence was detected in either group. The average time to HBs Ag seroconversion in 13 patients was 7.8 months after surgery (6.34 months in group 1 and 11.1 months in group 2). CONCLUSIONS: In our study, recurrence rate of HBV after liver transplantation is not statistically different than the recurrence rate of HBV+HDV co-infection. A low recurrence rate was achieved by the prophylaxis protocol in use at our center. There is no standard protocol for prevention of HBV and HDV recurrence; therefore, we need new studies.

Sodium taurocholate cotransporting polypeptide acts as a receptor for hepatitis B and D virus.

Infection of hepatitis B virus (HBV) remains a major public health problem worldwide. Understanding the viral infection and developing antivirals against HBV have been hampered by the lack of convenient culture systems and animal models for the infection. Sodium taurocholate cotransporting polypeptide (NTCP), a key bile acid transporter expressed in liver, was recently identified as a critical receptor for viral entry of HBV and its satellite virus hepatitis D virus (HDV). This finding enabled a reliable cell culture system for the viruses. Detailed studies have shown that NTCP is the major determinant for the species specificity of HBV and HDV at entry level. NTCP is responsible for most sodium-dependent bile salt uptake in liver. The molecular determinant critical for HBV/HDV infection overlaps with that for bile acids transporting on NTCP. We evaluated bile acids as potential antivirals for HBV and HDV infection, and developed bile acid derivatives that effectively block taurocholate transporting as well as viral infections. The discovery that NTCP acts as a receptor for HBV has opens a new door for future studies towards the ultimate goal of curative treatment of HBV infection.

Hepatitis B, C y D

Infográfico acerca de hepatitis B, C y D, como se propagan y las medidas para protegerte Infographic on hepatitis B, C y D, what symptoms, transmission, and measures to protect

Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy.

The spread of hepatitis B virus (HBV) infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B, from 10/100000 inhabitants in 1984 to 0.85/100000 in 2012, and by the reduced prevalence of hepatitis B surface antigen (HBsAg)-positive cases among chronic hepatitis patients with different etiologies, from 60% in 1975 to about 10% in 2001. The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3% in the 1980s to 1% in 2010. Linked to HBV by its characteristics of defective virus, the hepatitis delta virus (HDV) has shown a similar epidemiological impact on the Italian population over time. The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from 24% in 1990 to 8.5% in 2006. Before the beneficial effects of HBV mass vaccination introduced in 1991, the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations, the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size. A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.

Hepatitis delta: the rediscovery.

Hepatitis D is returning to western Europe through immigration. The clinical presentation recapitulates the typical features of a florid hepatitis D. Hepatitis D is also being rediscovered in the developing world and in the United States. Hepatitis D virus (HDV) remains endemic in many countries and efforts are underway to map the infection at local levels and improve the medical alert to hepatitis D. In the United States it is generally thought that HDV has gone and hepatitis D is no longer a problem. Awareness of hepatitis D in the country has recently been revived.

Epidemiological update of hepatitis B, C and delta in Latin America.

Viral hepatitis B, C and delta still remain a serious problem in Latin America. Data from the 1980s indicated that HBV and HDV infection are the main causes of chronic hepatitis. However, the spread of HBV infection could be controlled through the implementation of immunization programmes. Different countries from Mexico to Argentina display marked differences in terms of HBV genotype distribution. HBV genotype F has been identified as the most frequent in most Latin America countries, except for Mexico and Brazil, where genotypes H and A are the most frequent, respectively. In Latin America, the overall prevalence of HCV antibody is estimated to be 1.5%. Latin American countries have been very proactive in screening their blood supplies, thus minimizing risk of HCV transmission through transfusion. The number of diagnosed and treated patients is still low, thereby increasing the burden of complications such as liver cirrhosis or hepatocellular carcinoma. The most prevalent HCV genotype is 1, which is the genotype with the greatest worldwide spread, but it is a different genotype from other regions like Africa and Asia. HDV is present worldwide but its distribution pattern is not uniform. HDV was recently detected in novel geographic regions, reinforcing that it is a very serious health threat in under-developed countries. The main prevalence areas are the Mediterranean basin, the Middle East, central and northern Asia, western and central Africa, the Amazonian basin (Brazil, Peru, Venezuela and Colombia) and the Pacific islands. Novel strategies to increase HBV immunization in the Latin American population are needed to warrant thorough coverage in the rural areas.

Prime/boost immunization with DNA and adenoviral vectors protects from hepatitis D virus (HDV) infection after simultaneous infection with HDV and woodchuck hepatitis virus.

Hepatitis D virus (HDV) superinfection of hepatitis B virus (HBV) carriers causes severe liver disease and a high rate of chronicity. Therefore, a vaccine protecting HBV carriers from HDV superinfection is needed. To protect from HDV infection an induction of virus-specific T cells is required, as antibodies to the two proteins of HDV, p24 and p27, do not neutralize the HBV-derived envelope of HDV. In mice, HDV-specific CD8(+) and CD4(+) T cell responses were induced by a DNA vaccine expressing HDV p27. In subsequent experiments, seven naive woodchucks were immunized with a DNA prime and adenoviral boost regimen prior to simultaneous woodchuck hepatitis virus (WHV) and HDV infection. Five of seven HDV-immunized woodchucks were protected against HDV infection, while acute self-limiting WHV infection occurred as expected. The two animals with the breakthrough had a shorter HDV viremia than the unvaccinated controls. The DNA prime and adenoviral vector boost vaccination protected woodchucks against HDV infection in the setting of simultaneous infection with WHV and HDV. In future experiments, the efficacy of this protocol to protect from HDV infection in the setting of HDV superinfection will need to be proven.

[Epidemiology of viral hepatitis]. / Epidemiologija virusnih hepatitisa.

Understanding the country-specific epidemiology of disease, which may vary greatly among countries, is crucial for identifying the most appropriate preventive and control measures. An overview of the local epidemiology of viral hepatitis in Croatia is given in this paper. The overall prevalence of hepatitis B in Croatia is low (less than 2% HBsAg carriers in the general population). Hepatitis B incidence and prevalence began to decline significantly following the introduction of universal hepatitis B vaccination in 1999. Information on HBsAg seroprevalence is derived from routine testing of certain subpopulations (pregnant women, blood donors) and seroprevalence studies mostly targeted at high-risk populations. Universal childhood vaccination against hepatitis B remains the main preventive measure. We recommend testing for immunity one to two months after the third dose of hepatitis B vaccine for health-care workers. The incidence and prevalence of hepatitis C have also been declining in the general population. The main preventive measures are ensuring safety of blood products, prevention of drug abuse, and harm reduction programs for intravenous drug users. Hepatitis A incidence has declined dramatically since fifty years ago, when thousands of cases were reported annually. In the last five years, an average of twenty cases have been reported per year. The reduction of hepatitis A is a consequence of improved personal and community hygiene and sanitation. Hepatitis D has not been reported in Croatia. The risk of hepatitis D will get to be even smaller as the proportion of population vaccinated against hepatitis B builds up. Hepatitis E is reported only sporadically in Croatia, mostly in persons occupationally in contact with pigs and in travelers to endemic countries. In conclusion, Croatia is a low prevalence country for hepatitides A, B and C. Hepatitis D has not been reported to occur in Croatia and there are only sporadic cases of hepatitis E. Since hepatitis A is a rare disease occurring sporadically, which is a consequence of improved sanitation and hygiene, hepatitides B and C are the main causes of viral hepatitis in Croatia. The introduction of universal mandatory hepatitis B vaccination of schoolchildren in 1999 resulted in a decrease in the incidence of hepatitis B, which is most pronounced in adolescents and young adults, and further decrease in the incidence and prevalence is expected as the pool of susceptible individuals decreases through vaccination. The incidence of hepatitis C is decreasing as well. In spite of a relatively favorable epidemiological situation, hepatitis B and C are still a significant public health burden with an estimated 25,000 persons chronically infected with HBV and about 40,000 persons chronically infected with HCV in Croatia.

Epidemiology of hepatitis D.

Hepatitis D occurs worldwide. The major victims of the hepatitis D virus (HDV) are individuals carrying the hepatitis B surface antigen (HBsAg); around 5% of the HBsAg carriers in the world are infected also by HDV. With the implementation of a hepatitis B virus (HBV) vaccination since the 1990s, the incidence of hepatitis D has consistently declined in the developed world, particularly in Southern Europe; however, immigrants from areas where HDV remains endemic are reintroducing the infection.Hepatitis D continues to ravage populations of developing and poor countries where HBV remains unchecked; action is needed to enforce HBV vaccination as effective prophylaxis not only against HBV, but against HDV as well.