Demographics and outcomes of hepatitis B and D: A 10-year retrospective analysis in a Swiss tertiary referral center.

BACKGROUND: Hepatitis B virus (HBV) is a major global health challenge with approximately 250-350 million chronically infected individuals. An improved understanding of the demographic features and outcomes of chronic HBV infection and hepatitis D virus (HDV) infection in low-endemic areas may improve prevention, early identification and management both at individual and community levels. Here, we retrospectively analyzed the demographic and clinical characteristics, treatment rates and outcomes of adult patients with chronic HBV infection with or without HDV coinfection examined at Lausanne University Hospital, Switzerland over a 10-year period. METHODS: We analyzed the medical records of all adult patients with chronic HBV and HDV infection examined in our center between 2007 and 2016. Liver-related outcome was defined as the occurrence of cirrhosis, hepatocellular carcinoma, liver transplantation or liver-related death. Analyses were performed using logistic regression and results were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: Of 672 consecutive patients, 421 (62.6%) were male, median age was 36 years (interquartile range, 28-46 years), and 233 (34.7%) were of African origin. The prevalence of HDV coinfection was 7.1% and the proportion of anti-HDV-positive patients with detectable HDV RNA was 70.0%. In multivariate analysis, HDV coinfection was the strongest predictor for liver-related outcome (OR 6.06, 95% CI 2.93-12.54, p<0.001), followed by HBeAg positivity (OR 2.47, 95% CI 1.30-4.69, p = 0.006), age (OR per 10-year increase 2.03, 95% CI 1.63-2.52, p<0.001) and sex (OR for female 0.39, 95% CI 0.22-0.71, p = 0.002). The predictive accuracy of the multivariate model was high (receiver operator characteristic area under the curve 0.81). CONCLUSION: This retrospective study underscores the importance of migration in the epidemiology of chronic hepatitis B in low-endemic areas. HDV coinfection, HBeAg positivity and age predicted liver-related outcomes while female sex had a protective effect.

Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia.

BACKGROUND & AIMS: Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. METHODS: In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. RESULTS: Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024). CONCLUSIONS: HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis.

Hepatitis delta-associated mortality in HIV/HBV-coinfected patients.

BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes. METHODS: All HIV-infected patients with a positive hepatitis B surface antigen test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC). RESULTS: Of 818 patients with a positive hepatitis B surface antigen tests, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% CI: 12.9-18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (60.6% vs. 9.1%) and to have a positive hepatitis C virus (HCV) serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41-3.84), liver-related death (7.71, 3.13-18.97) and with the occurrence of HCC (9.30, 3.03-28.61). Results were similar when persons who inject drugs or HCV-coinfected patients were excluded from the analyses. CONCLUSIONS: The prevalence of HDV in hepatitis B surface antigen-positive patients in the Swiss HIV Cohort Study (SHCS) is high and HDV infection is independently associated with mortality and liver-related events, including HCC. LAY SUMMARY: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, eight times more likely to die from a liver-related cause and nine times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection.

Antiviral treatment and liver-related complications in hepatitis delta.

Hepatitis delta virus (HDV) is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG-IFNα) is effective in only 25%-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow-up, 5.2 years; range, 0.6-18.8). Liver cirrhosis was already present in 62 patients at first presentation. Twenty-nine percent of patients did not receive any antiviral treatment, 38% were treated with interferon alfa (IFNα)-based therapies, and 33% received nucleos(t)ide analogues (NAs) only. Clinical endpoints defined as hepatic decompensation (ascites, encephalopathy, and variceal bleeding), hepatocellular carcinoma, liver transplantation, and liver-related death developed in 55 patients (40%). Patients who received IFNα-based therapies developed clinical endpoints less frequently than those treated with NA (P = 0.02; HR, 4.0) or untreated patients (P = 0.05; HR, 2.2; 17%, 64%, and 44%), respectively, which was significant in both chi-square and Kaplan-Meier analysis. In addition, considering various clinical and virological parameters, IFNα therapy was independently associated with a more benign clinical long-term outcome in multivariate logistic regression analysis (P = 0.04; odds ratio, 0.25; 95% confidence interval, 0.07-0.9). Loss of HDV RNA during follow-up was more frequent in IFNα-treated patients and strongly linked with a lower likelihood to experience liver-related complications. CONCLUSION: IFNα-based antiviral therapy of hepatitis delta was independently associated with a lower likelihood for clinical disease progression. Durable undetectability of HDV RNA is a valid surrogate endpoint in the treatment of hepatitis delta. (Hepatology 2017;65:414-425).

Anti-HDV IgM as a marker of disease activity in hepatitis delta.

BACKGROUND: Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker. METHODS: Samples of 120 HDV-infected patients recruited in an international multicenter treatment trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA-IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and angiogenetic factors were measured using multiplex technology (Bio-Plex System). A second independent cohort of 78 patients was studied for the development of liver-related clinical endpoints (decompensation, HCC, liver transplantation or death; median follow up of 3.0 years, range 0.6-12). RESULTS: Anti-HDV IgM serum levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%) patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels, various other antiviral cytokines were negatively associated with anti-HDV IgM. Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05). CONCLUSIONS: Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap marker to determine disease activity in hepatitis delta which has prognostic implications. High anti-HDV IgM levels may indicate an activated interferon system but exhausted antiviral immunity.

Case fatality rate of acute viral hepatitis in Italy: 1995-2000. An update.

BACKGROUND: Fulminant hepatic failure is the most serious complication of viral hepatitis. Although this event occurs rarely, it may be fatal. AIMS: To evaluate the case fatality rate (several deaths divided by number of cases x 100) for each viral hepatitis type in Italy from 1995 to 2000. PATIENTS: Acute hepatitis cases identified by the surveillance system for acute viral hepatitis, which covers approximately 58% of the Italian population. RESULTS: Twenty-five deaths (0.1%) occurred among the 18 460 acute viral hepatitis cases observed from 1995 to 2000, a rate threefold lower than the 0.3% reported during the period 1985-1994. The highest case fatality rate (0.4%) was seen for acute hepatitis B (18 deaths among 4257 cases). Only one death (0.01%) occurred among the 11 063 acute hepatitis A cases and two deaths (0.1%) among the 1536 acute hepatitis C cases. No deaths were observed among the 309 acute hepatitis A cases superimposed on chronic HBsAg carriers and the 166 superimposed on chronic HCV carriers. Intravenous drug use (22.2% of cases) and other parenteral exposures (22.2% of cases) were the most frequent non-mutually exclusive sources of infection reported by subjects who died of acute hepatitis B. CONCLUSIONS: Analysis of surveillance system data from 1995 to 2000 indicates that, in Italy, deaths due to acute viral hepatitis are rare, but most commonly observed with acute hepatitis B. There is no evidence that acute hepatitis A may be fatal in chronic HBsAg or HCV carriers. The overall better survival rate may probably reflect improvements in the treatment of fulminant hepatitis in the last few years in Italy.

Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep).

BACKGROUND: The effect of hepatitis delta virus (HDV) infection on the clinical course of cirrhosis type B is poorly defined. AIMS: To investigate the impact of HDV status on morbidity and mortality in cirrhosis type B. PATIENTS/METHODS: Retrospective cohort study of 200 Western European patients with compensated cirrhosis type B followed for a median period of 6.6 years. RESULTS: At diagnosis, 20% of patients had antibodies to HDV (anti-HDV); median age was lower in anti-HDV positive cirrhotics (34 v 48 years respectively). Kaplan-Meier five year probability of hepatocellular carcinoma (HCC) was 6, 10, and 9% in anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 22, 16, and 19% and for survival they were 92, 89, and 83% respectively. Cox regression analysis identified age, albumin concentration, gamma-globulin concentration, and HDV status as significant independent prognostic variables. After adjustment for clinical and serological differences at baseline, the risk (95% confidence interval) for HCC, decompensation, and mortality was increased by a factor of 3.2 (1.0 to 10), 2.2 (0.8 to 5.7), and 2.0 (0.7 to 5.7) respectively in anti-HDV positive relative to HDV negative cirrhotic patients. The adjusted estimated five year risk for HCC was 13, 4, and 2% for anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 18, 8, and 14% and for survival 90, 95, and 93% respectively. CONCLUSIONS: HDV infection increases the risk for HCC threefold and for mortality twofold in patients with cirrhosis type B.

Survival and complications in a cohort of patients with anti-delta positive liver disease presenting in a tertiary referral clinic.

BACKGROUND/AIMS: Our aim was to evaluate the clinical outcome and survival of patients with anti-Delta positive liver disease in The Netherlands. METHODS: We evaluated those patients visiting our hospital between 1978 and 1993 with respect to clinical, virological and histological parameters. During the follow-up period the occurrence of complications of the liver disease and survival was determined. Thirty patients with a median age of 34 years (range 21-52) were included. RESULTS: During an average follow up of 4.8 years, nine patients died. The overall 5-year survival as estimated by Kaplan-Meyer analysis was 71%, which was comparable to hepatitis B cirrhosis patients. However, in the group without active hepatitis B replication (HBeAg-negative) a clear trend towards a worse survival was identified in Delta cirrhosis patients. Complications and deaths occurred exclusively in the patient group with cirrhotic liver disease. The complications (ascites, elevated bilirubin >34 micro mol/l), variceal bleeding and spontaneous bacterial peritonitis) occurred in 52% of the patients with a follow up of more than 6 months (n=27). Fifty-seven percent of those patients died. In our population anti-Delta positive liver disease affects predominantly young patients and is related to advanced liver disease. CONCLUSIONS: In view of the high death rate, liver transplantation should be considered when signs or symptoms of decompensated liver disease occur.

Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. The Investigators of the European Concerted Action on Viral Hepatitis (EUROHEP).

A multicenter longitudinal study was performed to assess the survival of hepatitis B surface antigen positive compensated cirrhosis, primarily in relation to hepatitis B virus replication and hepatitis delta virus infection, and to construct a prognostic index based on entry characteristics. This cohort study involved nine university medical centers in Europe. Three hundred and sixty-six Caucasian HBsAg positive patients with cirrhosis who had never had clinical manifestations of hepatic decompensation were enrolled and followed for a mean period of 72 months (6 to 202 months). Inclusion criteria were biopsy-proven cirrhosis, information on serum hepatitis B e antigen and antibody to hepatitis D virus at the time of diagnosis and absence of complications of cirrhosis. At entry 35% of the patients were HBeAg positive, 48% of the patients tested were HBV-DNA positive and 20% anti-HDV positive. Death occurred in 84 (23%) patients, mainly due to liver failure (45 cases) or hepatocellular carcinoma (23 cases). The cumulative probability of survival was 84% and 68% at 5 and 10 years, respectively. Cox's regression analysis identified six variables that independently correlated with survival: age, albumin, platelets, splenomegaly, bilirubin and HBeAg positivity at time of diagnosis. According to the contribution of each of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. No difference in survival of hepatitis D virus infected and uninfected patients was observed. Termination of hepatitis B virus replication and/or biochemical remission during follow up correlated with a highly significant better survival. These data show that in compensated cirrhosis B, hepatitis B virus replication, age and indirect indicators of poor hepatic reserve and established portal hypertension significantly worsen the clinical course of the disease, whereas hepatitis D virus infection does not influence the prognosis. The highly significant improvement in life expectancy following cessation of hepatitis B virus replication and biochemical remission favors antiviral therapy in those patients with a guarded prognosis, as estimated by a prognostic index.

Impact of immunoprophylaxis and patient selection on outcome of transplantation for HBsAg-positive liver recipients.

We have studied the roles of immunoprophylaxis, patient selection policy and coexistent hepatitis D virus infection in the outcome of 56 HBsAg-positive elective liver transplant recipients. Twenty-nine unselected patients not treated with immunoprophylaxis formed group 1 and were compared to a recent consecutive series of 27 patients (group 2) in whom pre-transplant serological status was determined and who received immunoprophylaxis. One-year actuarial HBsAg serological recurrence rates were 48% in group 2 and 90% in group 1 with particular improvement in recipients who were either HBV DNA-negative or who had co-existent hepatitis delta virus infection. One-year patient survival has improved from 62% in group 1 to 86% in group 2 with improvements in hepatitis delta virus-negative and replicating recipients. Patients who have either co-existent hepatitis delta virus infection or are in group 2 have 1-year survival rates comparable to elective HBsAg-negative recipients (19/21 (90%), 22/27 (86%) vs 87%, respectively). In the event of recurrence, severe graft injury is diminished in recent patients and in those with coexistent delta infection who also have lower levels of circulating HBV DNA. Retransplantation for associated graft injury has a poor prognosis irrespective of administration of immunoprophylaxis. In elective liver recipients, immunoprophylaxis and/or hepatitis delta virus infection modulate hepatitis B virus recurrence and associated graft injury with consequent improvement in patient survival.

Liver transplantation in cirrhosis due to hepatitis D virus infection.

In a series of 49 patients transplanted for cirrhosis due to hepatitis D virus (HDV) infection and receiving anti-HBs immunoglobulins, the 2-year actuarial rate of hepatitis B virus (HBV) reinfection was only 13%, a prevalence much lower than the 29% rate in patients transplanted for HBV-DNA-negative cirrhosis and the 96% rate in patients transplanted for HBV-DNA-positive cirrhosis. HBV reinfection after transplantation in patients with cirrhosis due to HDV infection was invariably associated with HDV reinfection. In a few patients, in the absence of HBV reinfection, transient replication of HDV took place and was not associated with liver lesions of hepatitis. In conclusion, patients with cirrhosis due to HDV infection are good candidates for liver transplantation.

Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela.

To define better the epidemiology and clinical impact of hepatitis delta virus (HDV) infection among hepatitis B virus (HBV) carriers in less developed countries, the authors prospectively studied a cohort of 216 Yucpa Indian HBV carriers in Venezuela. HBV carriers were followed regularly between 1983 and 1988 by physical examination, laboratory testing for liver enzymes and HBV and HDV markers, and epidemiologic history. Among the cohort, 74 (34%) were initially positive for HDV infection, and 35 additional persons became infected during the study. Risk factors for new HDV infection included living in southern Yucpa villages; being young adults (15-19 years) or young children (1-9 years), and living in a household with a person with acute HDV infection. Persons with HDV infection were at high risk of developing chronic liver disease; 56% of HDV-infected persons had moderate-to-severe chronic liver disease at the end of the study compared with none of the HBV carriers without HDV infection. Mortality rates were 6.9% and 8.8% per year, respectively, among initially HDV-positive HBV carriers and those with new HDV infection, because of rapidly progressive chronic liver disease and fulminant hepatitis; mortality was significantly lower in HBV carriers without HDV infection and in non-HBV carriers. HDV superinfection is a devastating disease in HBV carriers in tropical South America. Prevention of HBV infection with hepatitis B vaccine is the best available tool to reduce the impact of this problem.

Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation.

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function.

[The clinical picture and outcome of acute delta infection]. / Klinika i iskhody ostrogo del'ta-gepatita.

A total of 60 patients were observed with acute hepatitis delta defined at examination of 200 adult subjects with acute HBsAg-positive hepatitis. Moderate and severe forms of the disease occurred more frequently, lethality reached 13.3%. An unfavorable prognosis was related to a short-term prejaundice period with intoxication (high body temperature, head ache, vertigo, recurrent vomiting, IgM antibodies presence in the serum at the height of the disease). No patients achieved cure within 9 months following the discharge from hospital. The process acquired the form of long-term convalescence with transformation into chronic hepatitis delta.

Hepatitis B and delta viruses in fulminant hepatitis.

From June 1985 to 1989, we studied 39 cases with fulminant viral hepatitis. These included 32 cases due to hepatitis B, of whom 27 died. Twenty of the 32 cases were positive for delta antibody, and all of them died. Four cases who died were negative for IgM anti-HAV, HBsAg and IgM anti-HBc and were classified as NANB. Thus, a total of 31 patients died. Hepatitis B and delta virus infection were the major risk factors for fulminant hepatitis and eventual death.

[Viral hepatitis in pregnant women--the relationship of the severity of the disease to the etiology of the infection]. / Virusnye gepatity u beremennykh--zavisimost' tiazhesti bolezni ot étiologii infektsii.

The author summarizes the experience of many years (1956-1989) gained with studies into the relationship between the gravity of viral hepatitides in the pregnant and etiology of disease. Virus A hepatitis runs a favourable course in the pregnant, i.e. without severe and fulminant forms. In virus B hepatitis, the pregnant women are threatened with the development of hepatic coma associated with a high maternal lethality. The latter one has noticeably been decreasing over the recent years (from 1.79% in 1956-1965 to 0.29% in 1966-1980 and to 0.21% in 1981-1989, which is not so much related to the perfection of the treatment methods as to the diminution of the share of virus B hepatitis. Virus E hepatitis may be of the greatest mortal danger for mothers in conditions of water epidemic. In that case the lethality among pregnant women may reach 12.1% (in the Turkmenian SSR) and 15.6% (in the Kirghiz SSR). The aggravating influences of virus C and D hepatitides on the pregnancy outcomes and maternal lethality have not been studied much. Estimation of etiological factors in viral hepatitis occurring in the pregnant is an important prerequisite for organization of the rational preventive and treatment measures.

Delta virus infection in Jerusalem.

The role of hepatitis delta virus (HDV) infection was analyzed retrospectively in a highly selected population of 76 patients who were hospitalized in Jerusalem for hepatitis B surface antigen positive for chronic active hepatitis and cirrhosis. Of 25 patients in whom serum and liver tissue were available, 5 patients (20%) showed evidence for HDV infection using a serum anti-HDV IgG radioimmunoassay; in one of them, HDV was also detected in nuclei of infected hepatocytes by immunofluorescence (IF). When only serum was tested, 12 of 45 patients (27%) were anti-HDV IgG positive. The use of IF alone had a very low yield of HDV detection. All HDV-positive patients with available serum had superinfection with the delta agent as confirmed by a negative anti-HBc IgM assay. The majority of HDV-positive patients were immigrants from Rumanian or Middle Eastern and Mediterranean origin. The mean age of delta-positive patients was 10 years lower at clinical presentation as compared with HDV-negative patients. HDV-positive patients had a higher mortality as compared with the HDV-negative group. In conclusion, HDV infection is prevalent among Israeli patients with chronic liver disease and persistent hepatitis B virus infection and leads to a significant morbidity and mortality.