Iwanami E, Yano M, Koga M, Shirahama S, Tsuda T.
Local spread of HDV infection transiently occurring in Japan.
J Gastroenterol Hepatol. 1993 Nov-Dec;8(6):565-8. doi: 10.1111/j.1440-1746.1993.tb01653.x.
Abstract/Text
Hepatitis B virus (HBV) carriers and patients with acute hepatitis B living in the Kamigoto islands, a part of Japan with a high incidence of HBV carriage, were retrospectively tested for serum anti-hepatitis D virus (anti-HDV) and they were compared with the inhabitants of Oita City (an area with an average HBV carriage rate). The prevalence of anti-HDV in HBV-infected individuals was 8.3% (42/507) in Kamigoto and 0% (0/101) in Oita City. With one exception, all of the positive serum samples in Kamigoto were collected before 1986, and the mean age of the positive individuals was significantly younger than that of the negative individuals (P < 0.005). Among the 42 anti-HDV-positive patients, nine (21%) had definite liver disease. The route of infection was uncertain in most cases (i.e. sporadic), but two pairs of mothers and children were detected. Although the prevalence of anti-HDV positivity in Japan has been reported to be very low (about 1% or less), the present investigation showed that the local spread of HDV infection in Kamigoto occurred on a minor scale up to 1986. The infections presumably resulted from the closed environment and the high incidence of HBV carriage in these islands. Accordingly, there could be a considerable risk of the outbreak of HDV infection in the future under similar conditions, even in countries where the disease has never been detected previously.
Rizzetto M.
The delta agent.
Hepatology. 1983 Sep-Oct;3(5):729-37. doi: 10.1002/hep.1840030518.
Abstract/Text
Wong DC, Purcell RH, Sreenivasan MA, Prasad SR, Pavri KM.
Epidemic and endemic hepatitis in India: evidence for a non-A, non-B hepatitis virus aetiology.
Lancet. 1980 Oct 25;2(8200):876-9. doi: 10.1016/s0140-6736(80)92045-0.
Abstract/Text
69 serum pairs from two common-source water-borne outbreaks and one series of endemic cases of hepatitis in three parts of India were tested for hepatitis A and hepatitis B virus infections. None of the patients had evidence of HAV infection and only 10.1% had evidence of HBV infection. A large proportion of hepatitis in India seems to be caused by previously unrecognised agents.
Rizzetto M Rosina FViral Hepatitis third edition SectionVl Hepatitis D virus epidemiology and natural history (ed vby Thomas H) p583-592 Blackwell Science Ltd Massachusetts 2005.
Stockdale AJ, Kreuels B, Henrion MYR, Giorgi E, Kyomuhangi I, de Martel C, Hutin Y, Geretti AM.
The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis.
J Hepatol. 2020 Sep;73(3):523-532. doi: 10.1016/j.jhep.2020.04.008. Epub 2020 Apr 23.
Abstract/Text
BACKGROUND AND AIMS: There are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among HBsAg-positive people.
METHODS: We searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random effects models.
RESULTS: We included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6-5.7) among all HBsAg-positive people and 16.4% (14.6-18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11-0.25) of the general population, totalling 12.0 (8.7-18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10-26) for cirrhosis and 20% (8-33) for HCC.
CONCLUSIONS: An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precision of burden estimates.
LAY SUMMARY: We combined all available studies to estimate how many people with hepatitis B also have hepatitis D, a viral infection that only affects people with hepatitis B. About 1 in 22 people with hepatitis B also have hepatitis D, increasing to 1 in 6 when considering people with liver disease. Hepatitis D may cause about 1 in 6 of the cases of cirrhosis and 1 in 5 of the cases of liver cancer that occur in people with hepatitis B. Hepatitis D is an important contributor to the global burden of liver disease.
Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
矢野右人, 井上長三: δ肝炎の臨床と日本における現況. 日本臨床1989;47（3）:715-720.
Sakugawa H, Nakasone H, Shokita H, Kawakami Y, Nakachi N, Adaniya H, Mizushima T, Nakayoshi T, Kinjo F, Saito A, Taira M, Takaesu H, Onga N.
Seroepidemiological study on hepatitis delta virus infection in the Irabu Islands, Okinawa, Japan.
J Gastroenterol Hepatol. 1997 Apr;12(4):299-304. doi: 10.1111/j.1440-1746.1997.tb00425.x.
Abstract/Text
A seroepidemiological study was performed to clarify the prevalence of hepatitis delta virus (HDV) infection among the general population in the Irabu islands, Okinawa, Japan. Of 2028 healthy people examined who had received their annual health check-up in 1994-95, 195 (9.6%) were positive for hepatitis B surface antigen (HBsAg). Of these 195 HBsAg-positive individuals, 46 (23.6%) showed a positive reaction for antibody to HDV (anti-HDV). The positivity rate of anti-HDV among HBsAg-positive subjects tended to increase with age up to 50-59 years of age. The prevalence of anti-HDV also varied among the seven districts in the islands (0-63.3%). None of the anti-HDV-positive subjects was included in the high risk group for parenterally transmitted diseases. The unusually high prevalence of anti-HDV among HBsAg-positive individuals, particularly in the older age groups, seemed to reflect the natural prevalence or previous HDV infection, rather than a current or imported infection of HDV. Although the great majority of HBsAg-positive subjects with anti-HDV were asymptomatic, abnormally high values of serum transaminases were more frequently seen in these subjects compared with HBsAg-positive subjects without anti-HDV.
小方則夫ほか：デルタ（D型）肝炎ウイルス感染症。疫学、感染様式、臨床病像の概略、日本臨肱 2004;62.suppl8.ウイルス肝炎(下):406-707.
Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, Sagnelli E, Brunetto MR, Rizzetto M.
Chronic hepatitis D: a vanishing Disease? An Italian multicenter study.
Hepatology. 2000 Oct;32(4 Pt 1):824-7. doi: 10.1053/jhep.2000.17711.
Abstract/Text
Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s HDV circulation had substantially declined. We have assessed the prevalence of HDV infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti-HDV positivity were evaluated. Anti-HDV antibodies were found in 69 of 834 (8.3%) HBsAg-positive patients. Cohabitation with an anti-HDV-positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti-HDV antibodies. The overall prevalence of anti-HDV antibodies was lower than those observed in 2 multicenter surveys performed in 1987 and 1992 (23% and 14%, respectively). By 1997, the percentage of anti-HDV-positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti-HDV antibodies (11.7%) was found in patients with cirrhosis. This prevalence was as high as 40% in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5% per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The results anticipate the almost complete control of HDV infection in the near future.
Rizzetto M.
Hepatitis D: the comeback?
Liver Int. 2009 Jan;29 Suppl 1:140-2. doi: 10.1111/j.1478-3231.2008.01937.x.
Abstract/Text
Hepatitis D virus (HDV) infection has considerably diminished in Europe since the 1970-1980s. The prevalence rates of chronic hepatitis D in HBsAg carriers in Italy have declined from 25% at the beginning of the 1980s to 8% in the 1990s. Similar declines in prevalence have been reported in Spain, Taiwan and Turkey. Better public health standards, HBV vaccination and the effect of measures to control the spread of human immunodeficiency virus have brought about a decline in the numbers of HBsAg carriers and therefore a decline in the HBV-dependent HDV. However, HDV has not declined further in Europe in the last decade, as the pool of fresh infections in migrants from HDV-endemic areas is counterbalancing the shrinking cohort of long-standing domestic infections acquired in the epidemic of the 1970-1980s. Hepatitis D remains an important health problem outside Europe, and new foci of infection continue to be identified in developing countries.
Koh C, Heller T, Glenn JS.
Pathogenesis of and New Therapies for Hepatitis D.
Gastroenterology. 2019 Jan;156(2):461-476.e1. doi: 10.1053/j.gastro.2018.09.058. Epub 2018 Oct 18.
Abstract/Text
Hepatitis delta virus (HDV) infection of humans was first reported in 1977, and now it is now estimated that 15-20 million people are infected worldwide. Infection with HDV can be an acute or chronic process that occurs only in patients with an hepatitis B virus infection. Chronic HDV infection commonly results in the most rapidly progressive form of viral hepatitis; it is the chronic viral infection that is most likely to lead to cirrhosis, and it is associated with an increased risk of hepatocellular carcinoma. HDV infection is the only chronic human hepatitis virus infection without a therapy approved by the US Food and Drug Administration. Peginterferon alfa is the only recommended therapy, but it produces unsatisfactory results. We review therapeutic agents in development, designed to disrupt the HDV life cycle, that might benefit patients with this devastating disease.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
阿部敏紀, 相川達也, 赤羽賢浩ほか：本邦に於けるE型肝炎ウイルス感染の統計学的・疫学的・ウイルス学的特徴 全国集計254例に基づく解析. 肝臓 2006;47:384-391.
Mizuo H, Yazaki Y, Sugawara K, Tsuda F, Takahashi M, Nishizawa T, Okamoto H.
Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido, Japan.
J Med Virol. 2005 Jul;76(3):341-9. doi: 10.1002/jmv.20364.
Abstract/Text
Hepatitis E in industrialized countries has not been well studied. To define the possible risk factors for transmission of hepatitis E virus (HEV) and for the severe form of hepatitis E in Japan, we investigated the clinical and virological characteristics of hepatitis E in 32 patients who contracted the mild (n=23) or severe form (n=9) of domestically acquired hepatitis E between 1996 and 2004 in Hokkaido, where hepatitis E is most prevalent in Japan. Nine patients with the severe form of hepatitis E included two patients with fulminant hepatitis E and seven patients who were diagnosed with severe acute hepatitis in which hepatic encephalopathy did not appear during the course of the illness despite low plasma prothrombin activity (or=20 mg/dl). At least 25 patients (78%) had consumed uncooked or undercooked pig liver and/or intestine 1-2 months before the onset of hepatitis E. When compared with the seven patients with HEV genotype 3, the 25 patients with HEV genotype 4 had a higher peak alanine aminotransferase (ALT) level (P=0.0338) and a lower level of lowest prothrombin activity (P=0.0340). The severe form of hepatitis E was associated with the presence of an underlying disease (56% [5/9] vs. 17% [4/23], P=0.0454). The study suggests that zoonotic food-borne transmission of HEV plays an important role in the occurrence of hepatitis E in Hokkaido, Japan, and that the HEV genotype and the presence of an underlying disease influence the severity of hepatitis E.
Copyright (c) 2005 Wiley-Liss, Inc.
Ohnishi S, Kang JH, Maekubo H, Arakawa T, Karino Y, Toyota J, Takahashi K, Mishiro S.
Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan.
Hepatol Res. 2006 Dec;36(4):301-7. doi: 10.1016/j.hepres.2006.08.002. Epub 2006 Sep 12.
Abstract/Text
In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.
Khuroo MS, Teli MR, Skidmore S, Sofi MA, Khuroo MI.
Incidence and severity of viral hepatitis in pregnancy.
Am J Med. 1981 Feb;70(2):252-5. doi: 10.1016/0002-9343(81)90758-0.
Abstract/Text
A prospective field study was carried out during an epidemic of non-A non-B hepatitis for determining the incidence and severity of hepatitis in pregnant women, nonpregnant women of child bearing age and men (15 to 45 years old). In 36 (17.3 percent) of 208 pregnant women viral hepatitis developed, as compared to 71 (2.1 percent) of 3,350 nonpregnant women and 107 (2.8 percent) of 3,822 men. The incidence of disease in pregnant women was higher than in the two control groups. The incidence of viral hepatitis in the first, second and third trimesters was 8.8 percent, 19.4 percent, and 18.6 percent, respectively. The incidence in all three trimesters was higher, when compared to that in nonpregnant women. In eight pregnant women (22.2 percent) with viral hepatitis, fulminant hepatic failure developed, as compared to its occurrence in three men (2.8 percent) and in no nonpregnant women. This significantly increased incidence of fulminant hepatitis in pregnancy was indicative of a greater severity of hepatitis during pregnancy. Increased susceptibility to fulminant hepatitis was observed exclusively in the last trimester. Nonfulminant viral hepatitis did not influence the course of pregnancy or fetal well-being. Fetal loss in fatal fulminant hepatitis was a consequence of maternal death and could not be ascribed to direct effect on the fetus or pregnancy.
Khuroo MS, Kamili S, Jameel S.
Vertical transmission of hepatitis E virus.
Lancet. 1995 Apr 22;345(8956):1025-6. doi: 10.1016/s0140-6736(95)90761-0.
Abstract/Text
Little is known about vertical transmission of hepatitis E virus from infected mothers to their infants. We studied eight babies born to mothers infected with hepatitis E in third trimester. One baby was icteric at birth with elevated transaminases and four babies had anicteric hepatitis. Two babies were born with hypothermia and hypoglycaemia and died within 24 h; one had massive hepatic necrosis. Hepatitis E virus RNA was detected by PCR in cord or birth blood samples of five infants. Six infants had evidence of hepatitis E infection. We conclude that hepatitis E virus is commonly transmitted from infected mothers to their babies with significant perinatal morbidity and mortality.
Singh S, Mohanty A, Joshi YK, Deka D, Mohanty S, Panda SK.
Mother-to-child transmission of hepatitis E virus infection.
Indian J Pediatr. 2003 Jan;70(1):37-9. doi: 10.1007/BF02722743.
Abstract/Text
OBJECTIVES: Water borne or enterically transmitted non-A-non-B hepatitis is a major public health problem in India. Many of these cases carry fatal outcome. The hepatitis E virus (HEV) has been considered to be the most important causative agent of this entity. The severity and fatality rates of HEV infection are reported to be rather more in pregnant women. However, there is meager information from India, on mother to child transmission of this agent.
METHODS: During 1997-98, we studied 60 pregnant women suspected to have acute viral hepatitis to understand the frequency of various viral etiologies, disease course and outcome of the pregnancy. Six cord blood samples were tested for IgG, and IgM antibodies against hepatropic viral agents and also for hepatitis E virus RNA by RT-nested PCR using ORF-1 as target.
RESULTS: Of the 60 pregnant patients hospitalised at All India Institute of Medical Sciences, New Delhi for acute hepatitis, 22 (37%) were positive for IgM anti-HEV antibodies and 10% were infected with hepatitis B virus. Co-infection of HEV with Hepatitis B and C was seen in 1 and 2 patents, respectively. Most (72%) of the HEV infected patients were in third trimester of pregnancy (P<0.05). Of the 6 cord blood samples tested 3 (50%) were positive for HEV RNA. Though, all mothers were RNA positive, half of the babies did not get infected in utero with HEV. Fourteen of the 22 (63.6%) HEV infected mothers developed fulminant hepatic failure and all died.
CONCLUSION: The mortality rate in HEV [corrected] infected mothers was 100%. Mother to child transmission of hepatitis E virus infection was established in 50%.
