Prevalence and clinical features of hepatitis delta virus infection in the Miyako Islands, Okinawa, Japan

The aims of this study were twofold: (1) to determine the prevalence and clinical features of hepatitis delta virus (HDV) infection among subjects positive for hepatitis B surface antigen (HBsAg) living in the Miyako Islands, Okinawa Prefecture, Japan, and (2) to clarify the relationship between HDV-RNA level and severity of HDV-related liver disease. One hundred and ninety-nine HBsAg-positive subjects (123 asymptomatic carriers [ASCs], 3 patients with acute hepatitis [AH], 50 patients with chronic hepatitis [CH], 15 patients with liver cirrhosis [LC], and 8 patients with hepatocellular carcinoma [HCC], were tested for antrbody to HDV (anti-HDV) by radioimmunoassay. Anti-HDV-positive individuals were examined to determine semi-quantified HDV-RNA level by polymerase chain reaction (PCR). The overall prevalence of anti-HDV among the 199 subjects was 21.1%. The positivity rate tended to increase with age or the severity of the underlying liver disease: anti-HDV-positive rates were 10.6% (13/123) in ASCs, 32.0% (16/50) in patients with CH, 40.0% (6/15) in patients with LC, and 87.5% (7/8) in patients with HCC. None of the patients with AH were positive for anti-HDV. There was no correlation between semi-quantified serum HDV-RNA levels and the severity of chronic liver disease in patients positive for anti-HDV. The present study showed the local spread of HDV infection in the Miyako Islands, Okinawa, Japan. Although the anti-HDV positivity rate tended to increase with the severity of the underlying liver disease, the severity of HDV-related liver disease did not correlate with the semi-quantified serum HDV-RNA level. (Received Oct. 13, 1997; accepted June 26, 1998)     

Seroepidemiological study of hepatitis E virus infection in Japan using a newly developed antibody assay

PURPOSE: A seroepidemiological study of hepatitis E virus (HEV) infection was conducted in Japan, where HEV infection is not considered endemic. METHODS: IgG and IgM class antibodies to HEV were measured with a newly developed enzyme-linked immunosorbent assay in which recombinant virus-like particles were used as an antigen. A total of 1253 individuals (401 males and 852 females; age range, 6-89 years) were enrolled from two different areas: area 1 (n = 478), in which hepatitis C was endemic; and area 2 (n = 775), in which it was not endemic. RESULTS: The HEV antibody (IgG class) positive rate was 6.7% in area 1 and 4.6% in area 2. Similarly, the HAV antibody (IgG class) positive rates were 65.3% and 72.3%. The age- and sex-specific prevalence of both HAV and HEV antibodies was quite similar in the two areas, and the HAV antibody positive rate clearly increased with age in both males and females. On the other hand, the HEV antibody positive rate showed a slight tendency to increase with age in males, but not in females. None of the 32 individuals with the HEV antibody who were interviewed had a history of visiting countries in which hepatitis E was endemic. In both areas, the mean age, percentage of males, and HAV antibody positive rate were significantly higher in the group of individuals with the HEV antibody than in the group of those without it, according to conventional statistical analyses. Of the three factors age, male sex, presence of HAV antibody, and the area factor, only male sex was statistically significant (P < 0.001) on multivariate logistic regression analysis. Two (0.2%) of the total of 1253 individuals were positive for the IgM class antibody to HEV. CONCLUSIONS: Our results suggest the possibility that HEV infection is circulating in Japan at a low level. HEV infection was associated with male sex, but not with HAV infection.     

Seroepidemiology of hepatitis C virus infection in hemodialysis patients and the general population in Fukuoka and Okinawa,Japan

In 1992, a seroepidemiologic study was carried out among hemodialysis patients and the general population in Fukuoka and Okinawa, Japan to determine the presence of hepatitis C virus (HCV) infection and HCV viremia. The markers used were antibody to HCV, determined by second-generation assay (anti-HCV), and HCV RNA, determined by the polymerase chain reaction. The prevalence of anti-HCV in Fukuoka was 3.3%, 73 per 2237 persons, significantly (P<0.001) higher than the 0.4%, 5 per 1295, in Okinawa. The prevalence of anti-HCV in hemodialysis patients in Fukuoka was 51.9% (161 of 310 patients), significantly (P<0.001) higher than the 9.1% (13 of 143 patients) in Okinawa. The ratio of HCV RNA-positive to anti-HCV-positive persons was significantly higher in hemodialysis patients (147/174, 84.5%) than in the general population (49/78, 62.8%) (P<0.001). Elimination of HCV among hemodialysis patients appears to be difficult, as such patients have lower immune responses than the general population. In Fukuoka, but not in Okinawa, blood used for transfusion was supplied by paid donors at commercial blood banks from 1953 to 1969. This may explain why HCV infection is endemic in Fukuoka and not in Okinawa. Differences between the prevalence of anti-HCV in the hemodialysis patients in Fukuoka and Okinawa reflect differences in the prevalence in the general population in these two areas of Japan.     

Epidemiology of hepatitis D virus (delta) infection in Yugoslavia

ABSTRACT— In 614 HBsAg-positive Yugoslavian patients, radioimmunoassay testing for anti-delta showed the presence of this antibody in serum in 11.2%. Of the patients, 213 belonged to a risk group (i.v. drug users, hemophiliacs, hemodialysed patients and patients with posttransfusion hepatitis); a significant number of these patients (63; 29.6%) were found to have anti-delta. A second group was composed of 401 HBsAg-positive patients from the general population (patients with acute hepatitis B, with fulminant hepatitis B and patients with chronic HBV infection); delta infection was found only in six (1.5%). Immunohistochemical methods failed to demonstrate the delta antigen in the livers of 73 patients with chronic HBV infection. Testing the liver of 36 patients with fulminant hepatitis B for delta antigen demonstrated this reactivity in only one (2.8%) liver sample. Delta antigen was also found in the liver of a female patient who underwent biopsy in 1972. The results of this study suggest the HDV is not endemic in Yugoslavia; however, it is frequently found in patients at risk of blood exposure, primarily i.v. drug users.     

Risk of liver cirrhosis and hepatocellular carcinoma in subjects with hepatitis B and delta virus infection: A study from Kure, Japan

To investigate the effect of hepatitis delta virus (HDV) superinfection on the long-term outcome of Japanese subjects with chronic hepatitis B virus (HBV) infection, we examined the presence of antibodies to hepatitis delta antigen (anti-HD) in serial serum samples collected from 1127 subjects with chronic HBV infection. The subjects were followed for at least 36 months (mean: 121.3 months) between 1973 and 1991. Among 69 cases where anti-HD was detected, eight (12%) developed liver cirrhosis (LC) and six (9%) developed hepatocellular carcinoma (HCC). However, among 1058 cases without anti-HD, there were 43 patients (4%) who developed LC and 29 (3%) who developed HCC. The prevalence of LC and HCC was significantly higher among the cases with anti-HD than those without anti-HD. The proportion of LC and HCC per 1000 person years was 10.46 and 7.84, respectively among cases with anti-HD, and 4.05 and 2.73 among those without anti-HD, respectively. The overall relative risk of LC and HCC was 2.58 and 2.87, respectively; 95% confidence interval (CI): LC, 1.14–5.13; HCC, 1.03–6.23. These results indicate that in the Kure district in Japan, where HDV infection of persons infected with HBV is about 6%, such superinfection increases the risk of LC and HCC.     

Epidemiological study of hepatitis E virus infection in the general population of Okinawa,Kyushu, Japan

Background and Aim: The aim of this study was to investigate the prevalence of hepatitis E virus (HEV) infection in the general population of Japan by determining presence of the antibody to HEV (anti‐HEV). Methods: The prevalence of HEV infection was determined by positivity of serum antibody to HEV (anti‐HEV). Results: On retrospective analysis, a significant decrease in anti‐HEV prevalence was found in Okinawa healthy residents from 1995 (15.8%) to 2005 (5.5%) (P < 0.0001). In 2005, the anti‐HEV prevalence was significantly higher in Okinawa wild boar hunters (25.3%) than in the residents (male 7.7% and female 4.1%) (P < 0.0001). A significant difference was found in the history of consumption of undercooked or raw boar meat between anti‐HEV positive and negative hunters (100% vs 64.3%) (P = 0.0018). Conclusions: In conclusion, the anti‐HEV prevalence has decreased in the residents of this area, but HEV infection has continued at a high rate in the hunters through the custom of eating undercooked or raw boar meat.     

Epidemiology and clinical pattern of hepatitis delta virus infection in Pakistan

BACKGROUND AND AIMS: The global epidemiology of hepatitis delta virus (HDV) infection is changing. This study was performed to determine the epidemiology and clinical impact of hepatitis delta in Pakistan. METHODS: Countrywide data was collected from 1994 to 2001. A total of 8721 patients were tested for hepatitis delta antibody. A subset of 97 hepatitis delta antibody reactive inpatients with chronic liver disease were compared to 97 patients admitted with liver disease due to hepatitis B alone. RESULTS: Of the 8721 patients tested, 1444 (16.6%) were reactive for hepatitis delta antibody. Most were males (87.4%, P < 0.001) and younger (mean age 31 years, P < 0.001) compared to HDV non-reactive patients. Prevalence of delta infection was highest in the rural (range 25-60%) compared to the urban population (range 6.5-11%). Analysis of the inpatient data showed that delta infected patients had significantly less severe clinical liver disease and a trend towards lesser development of hepatocellular carcinoma compared to delta negative patients. CONCLUSIONS: (i) HDV infection is present in 16.6% of hepatitis B infected patients in Pakistan, most commonly in younger males living in rural areas; and (ii) delta virus infected patients have less severe clinical liver disease compared to delta negative, hepatitis B patients.     

我国部分地区鹿、牛群中戊型肝炎病毒血清流行病学调查

目的调查我国部分地区鹿和牛群戊型肝炎病毒（HEV）感染情况。方法采集我国某地区13个鹿场780份鹿血，2个散养鹿群18份血和长春地区牛血80份，分离血清。应用抗HEV抗体酶联免疫试剂盒（双抗原夹心法）对血清样品进行抗HEV抗体检测。用χ^2检验分析不同养殖场鹿血清HEV抗体水平。结果798份鹿血清抗HEV抗体阳性率为43．61％。13个集约化养殖鹿场中有5个鹿场的血清样品抗体呈阳性，阳性率分别为48．02％、47．25％、60．69％、41．94％、40．91％；其余8个鹿场的血清样品均为阴性。两个散养鹿群的抗体阳性率分别为40．00％和46.15％。80份牛血清样品的抗体阳性率为20％。结论我国鹿群尤其是散养鹿群普遍存在HEV感染。牛群也存在较高的HEV感染率。     

HDV重叠感染可增加慢性乙型肝炎患者的肝细胞癌风险

HDV的重叠感染可加速慢性乙型肝炎患者的肝病进程,尤其肝细胞癌(HCC)的发生风险明显增高。但HDV的致癌机制有待进一步探索,治疗方式及效果也亟待突破。综述了HDV相关HCC流行病学新特点、致病机制的新认识和诊疗进展等,对推进研发更精准的HDV检测手段、更有效的治疗药物及减少HDV相关HCC具有重要意义。     

Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States

Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%–5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%–2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09–5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.     

Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients in eastern Turkey: still a serious problem to consider

Summary. Hepatitis delta virus (HDV) is a serious cause of liver‐related morbidity and mortality. Coexistent infection with HDV tends to aggravate the course of hepatitis B virus (HBV)‐associated liver disease. The aim of this study was to determine the prevalence of HDV infection among patients chronically infected with HBV in the Elazig region, which is in eastern Turkey. A group of 282 patients infected with chronic HBV were investigated for the study. Anti‐HDV seropositivity was evaluated in all patients. The anti‐HDV‐positive patients were further tested for HDV RNA. Severity of liver disease was assessed by liver biopsy. Regression analysis was used to determine the relationship between independent variables and HDV positivity. Of 282 chronic HBV patients, 192 were men (68.1%) and 90 were women (31.9%). The mean age was 43.8 ± 12.7 (between 18 and 73 years). Anti‐HDV was positive in 45.5% of the patients (128/282). Among the 128 anti‐HDV‐positive patients, 116 were checked for HDV RNA and 56.9% were found positive (66/116). Chronic HDV infection rate was therefore present in at least 23.4% of the whole study group (66/282). There were 83 patients with cirrhosis (29.4%) in the study group. Anti‐HDV seroprevalence and HDV RNA presence were higher in those with cirrhosis (61.4% and 42.2%, respectively). No significant relationship was found between anti‐HDV seropositivity and demographic factors such as age, sex and operation or transfusion history except family history. HDV‐RNA‐positive patients had significantly higher ALT and lower albumin levels when compared to HDV‐RNA‐negative patients. HDV‐RNA‐positive patients also had a significantly higher fibrosis stage. In conclusion, these findings demonstrated that HDV infection is endemic and still a serious problem in the Elazig region of eastern Turkey. HDV infection is significantly related to the family exposure and increases the risk of severe liver fibrosis in this region.     

Age-specific antibody to hepatitis E virus has remained constant during the past 20 years in Japan

We investigated the presence of antibodies to hepatitis E virus (anti-HEV) and hepatitis A virus (anti-HAV) by enzyme immunoassays in sera from 1015 individuals collected in 1974, 1984 and 1994. Age-specific profiles of anti-HEV remained unchanged with a peak at 40-49 years, while those of anti-HAV started to increase in individuals aged 20-29 years in 1974, 30-39 years in 1984 and 40-49 years in 1994. These results suggest that a silent HEV infection has been taking place in the last 20 years or so in Japan, while HAV infection has been terminated at least since 1974.     

Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

Sero-epidemiologic study of hepatitis C virus infection in Fukuoka, Japan

We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan, to investigate the high mortality rate from liver disease. Antibodies to hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%). Multivariate logistic regression analyses showed that presence of anti-HCV, male gender, and history of liver disease were associated with the presence of liver dysfunction, and that age of more than 40 years and a particular district were associated with the presence of anti-HCV. HCV RNA was more frequently detected in anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05). The incidence of liver dysfunction was significantly higher in HCV RNA-positive men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings suggest that: (1) HCV was correlated with the high mortality rate from liver diseases, (2) there were district-related differences in the incidence of HCV, and (3) the lower frequency of elimination of HCV from men may explain why they showed a high mortality from liver disease. (Received Mar. 4, 1997; accepted Aug. 22, 1997)     

Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta‐analysis

Background: Recent reports suggest a decline of delta hepatitis (DH) in the West as well as in the Far East. Aim: To study the DH seroepidemiology in Turkey. Methods: Statistical power analysis was utilized based on data available in a recent article using prevalence figure estimates. Binominal distribution was applied in order to assess the number of samples required to estimate the prevalence with a given precision. Results: Out of 62 studies in the original study, 32 were eliminated because of insufficient power. A total of 6734 patients (5231 with chronic hepatitis and 1503 with cirrhosis) were analysed. Anti‐HDV seropositivity among patients with chronic hepatitis B (CHB) and hepatitis B‐induced cirrhosis was lowest in the west of the country and highest in the southeast (5 vs. 27%, P<0.0001 and 20 vs. 46%, P<0.0001) respectively. Compared with data obtained before 1995, after 1995, DH prevalence in patients with CHB and cirrhosis decreased from 29 to 12% (P<0.0001) and from 38 to 27% (P=0.03) in central and southeast Turkey and from 38 to 20% (P<0.0001) and from 66 to 46% (P<0.002) in west and southeast Turkey respectively. Conclusion: Despite the decrease of its prevalence in Turkey, DH remains a significant health problem in parts of the country with low socio‐economic level.     

Phylogenetic tree-based epidemiological analysis of hepatitis C virus transmission in a region of Japan with a high prevalence of infection

Local clustering of hepatitis C virus (HCV) infection has been demonstrated in various regions in Japan. HCV genotypes have now been compared between infected individuals from districts of Saga prefecture with either a high (H district) or low (L district) prevalence of HCV-seropositivity. The prevalence of HCV genotype 1b was significantly higher (P<0.001) in the H district (45/50; 90%) than in the L district (19/36; 52.8%). A phylogenetic tree was constructed based on the genomic sequences of viral isolates from 20 patients infected with genotype 1b in the H district. Almost all these HCV strains clustered in the same regions of the tree. With regard to risk factors for HCV transmission, the percentage of patients with a history of surgery was significantly higher in the H district than in the L district (58 versus 33.3%; P<0.05). Of 20 patients infected with similar strains of HCV in the H district, 16 (80%) had at least one parenteral risk factor associated with medical care. These results indicate an increased transmission of similar strains of HCV in the H district as a result of nosocomial infection.