丁型肝炎病毒感染的血清流行病学观察

1987年4月至1988年10月间,本文应用酶联吸附法(EIA)对石家庄地区Ml例乙型肝炎病毒感染者进行了抗-HD的检测,共发现35例阳性,阳性率12.92%,其中男性阳性率14.06%(27/102),女性为10.13%(8/79),男女间差异无统计学意义(P>0.05),提示石家庄地区可能为丁型肝炎病毒感染的高发区.在这些人群中,慢性活动性肝炎、慢性迁延性肝炎和肝硬化的抗-HD阳性率明显高于HBsAg携带者,但三者相互间差异无统计学意义,表明合并或重香感染HDV对乙肝慢性化及肝硬化的形成具有重要的意义。本研究证明在乙型肝炎病毒感染人群中丁型肝炎病毐与年龄、性别、职业等因素关系不密切。     

乙型和丙型病毒性肝炎及相关肝细胞癌的流行现况

乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染是全球主要的健康问题。全球约有3.5亿人（5%）为HBV慢性感染者,其中75%为亚洲人,而HCV的慢性感染者为1.5亿人（2%）。乙型和丙型肝炎是肝硬化和肝细胞癌（HCC）的主要危险因素,肝硬化中的57%和原发性肝癌中的78%为HBV或HCV感染引起。作者将中国、亚洲和美国的HBV、HCV和HCC的流行病学资料进行综述比较,并分析当前危险因素等。在中国和全球其他国家,HBV和HCV仍是HCC的主要危险因素,HBV疫苗的使用显著降低了HBV感染率,进而降低了HCC的患病率,而将来HCV可能取代HBV成为主要危险因素;乙醇作为肝硬化和肝癌的危险因素影响较小。     

Hepatitis B prevention, diagnosis, treatment and care: a review

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B (CHB) infection is associated with an increased risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). The likelihood of developing CHB is related to the age at which infection is acquired; the risk being lowest in adults and >90% in neonates whose mothers are hepatitis B e antigen positive. Treatment of CHB infection aims to clear HBV DNA and prevent the development of complications. There are currently seven drugs available for the treatment of CHB: five nucleos(t)ide analogues and two interferon-based therapies. Long-term treatment is often required, and the decision to treat is based on clinical assessment including the phase of CHB infection and the presence and extent of liver damage. A safe and effective HBV vaccine has been available since the early 1980s. Vaccination plays a central role in HBV prevention strategies worldwide, and a decline in the incidence and prevalence of HBV infection following the introduction of universal HBV vaccination programmes has been observed in many countries including the USA and parts of South East Asia and Europe. Post-exposure prophylaxis (PEP) with HBV vaccine +/- hepatitis B immunoglobulin is highly effective in preventing mother to child transmission and in preventing transmission following sharps injuries, sexual contact and other exposures to infected blood and body fluids. Transmission of HBV in the health care setting has become an increasingly rare event in developed nations. However, it remains a significant risk in developing countries reflecting the higher prevalence of CHB, limited access to HBV vaccination and PEP and a lack of adherence to standard infection control precautions.     

乙型肝炎病毒基因变异及其临床意义

乙型肝炎病毒（hepatitis B vius,HBV）感染是导致慢性乙型肝炎（chronic hepatitis B,CHB）、肝硬化（liver cirrhosis,LC）和肝细胞癌（hepatocellular carcinoma,HCC）的重要原因,全球每年由于HBV慢性感染引起的肝硬化、肝细胞癌死亡患者超过47万人。本文主要对乙肝病毒的相关变异及与临床治疗和预后的关系作一介绍。     

The global impact of vaccination against hepatitis B: a historical overview

Hepatitis B virus (HBV) infection is a world wide public health problem of major concern. HBV infection may lead to chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Vaccination is the most effective measure to control and prevent hepatitis B and its long-term serious sequelae on global scale, both in terms of cost-effectiveness and benefit-cost ratios. According to the WHO recommendations, universal vaccination has been currently implemented in 168 countries world wide with an outstanding record of safety and efficacy. The effective implementation of such programmes of vaccination has resulted in a substantial decrease in disease burden, in the carrier rate and in hepatitis B-related morbidity and mortality. A future challenge is to overcome the social and economic hurdles which still hamper the introduction of hepatitis B vaccination on a global scale.     

免疫系统在乙型、丙型病毒性肝炎发病过程中作用研究进展

乙型病毒性肝炎和丙型病毒性肝炎分别由乙型肝炎病毒和丙型肝炎病毒感染所致。乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）感染呈全球分布,我国是高流行地区,由于HBV、HCV基因的高变性,容易逃避机体免疫系统的清除。HBV、HCV感染免疫系统细胞,造成机体对HBV、HCV感染的免疫应答异常,并引起组织的损伤,导致肝细胞的慢性持续性感染,并可进一步发展成肝硬化,甚至肝细胞肝癌。HBV、HCV主要经血液传播,包括输血与血制品传播、静脉吸毒、针刺、医源性传播、性接触和母婴垂直传播。     

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.     

乙型肝炎病毒感染血清学标志与慢性感染自然史研究进展

乙型肝炎（乙肝）病毒（Hepatitis B Virus,HBV）感染的血清学标志主要有乙肝病毒表面抗原、乙肝病毒表面抗体、乙肝病毒e抗原（Hepatitis B e Antigen,HBeAg）、乙肝病毒e抗体和乙肝病毒核心抗体。慢性HBV感染自然史复杂、多样,与初次感染年龄、HBV载量、基因型、突变位点、HBeAg状态、丙氨酸氨基转移酶（Alanine Aminotransferase,ALT）水平、丙型肝炎病毒和／或丁型肝炎病毒合并感染及宿主免疫状态等有关。慢性HBV感染过程可分免疫耐受期、免疫清除期、低或无病毒复制期和病毒恢复活性期。部分HBeAg阴性、ALT高水平和HBV脱氧核糖核酸高滴度（〉10^5拷贝／ml）患者,可出现肝硬化、肝细胞癌和肝功能衰竭等肝脏相关综合征。现有证据表明,合理使用抗HBV药物可减少后遗症发生率和病死率。     

High prevalence of anti-hepatitis delta virus antibody in chronic liver disease in Somalia.

We have assessed the prevalence of hepatitis delta virus (HDV) infection in people with histologically proven chronic liver disease living in Somalia. Among 104 patients studied (14 with chronic persistent hepatitis, 74 with chronic active hepatitis, and 16 with active cirrhosis), 52 were positive for hepatitis B surface antigen; of these, 26 (50%) carried anti-delta antibodies. HDV infection was detected more frequently in sera from hepatitis B e antigen (HBeAg) negative patients (60.9%) than in HBeAg positive patients (9.1%). Using the dot-blot hybridization technique, serum hepatitis B virus deoxyribonucleic acid was revealed in 73.1% of patients without HDV infection, while it was detected in only 7.7% of anti-delta positive patients. It is concluded that HDV is strongly associated with chronic liver disease in Somalia.     

Epidemiology and clinical outcome of hepatitis D virus infection in Turkey

The prevalence, the epidemiology, the clinical and biochemical characteristics of hepatitis delta virus (HDV) infection were studied in patients with HBsAg-positive acute hepatitis, in those with chronic liver disease, and in apparently healthy carriers in Turkey.Fifty-eight of the 242 carriers of HBsAg (23.9%) and 31 of the 237 (13.1%) patients with acute HBsAg-positive hepatitis had serological evidence of HDV infection. Eleven of these individuals were HBsAg carriers with acute HDV superinfection. The prevalence of HDV infection was significantly (p < 0.001) higher in patients with chronic liver disease (54/165; 32.7%) than in asymptomatic carriers of HBsAg (4/77; 5.2%). The highest prevalence (26/57; 45.6%) of HDV infection was found in patients at high risk of acquiring hepatitis virus infection (health care workers, hemodialysis patients, polytransfused patients) with chronic liver disease.Whereas the frequency of severe or fulminant hepatitis was similar in HBV infected patients (7.8%) and in HBV/HDV coinfected individuals (10%), the frequency of biphasic hepatitis was significantly (p < 0.005) higher in the latter patients (30%) than in those with classical hepatitis B (7.8%). Chronic evolution of the disease was observed in 3.9% of the patients with classical hepatitis B and in 5% of those who had evidence of simultaneous HBV/HDV infection. The 10 carriers of HBsAg who survived the acute HDV superinfection developed chronic delta hepatitis.These findings indicate that HDV is endemic in Turkey and that its prevalence is highest among chronic HBsAg-positive hepatitis patients, implicating HDV as a major cause of liver disease among urban Turkis.Corresponding author.     

Hepatitis B,C, and D Virus Infections and AFP Tumor Marker Prevalence Among the Elderly Population in Mongolia: A Nationwide Survey

ObjectivesInfections with hepatitis B, C, and D virus (HBV, HCV, and HDV) are a major public health problem and lead to serious complications such as cirrhosis and hepatocellular carcinoma. We aimed to determine the seroprevalence of hepatitis B surface antigen (HBsAg), anti-HCV, anti-HDV immunoglobulin G, alpha-fetoprotein (AFP), and dual and triple hepatitis virus infections in Mongolia.MethodsA total of 2313 participants from urban and rural regions were randomly recruited for this cross-sectional study. A questionnaire was used to identify the risk factors for hepatitis virus infections, and the seromarkers were measured using immunoassay kits.ResultsAmong all participants, the prevalence of HBV, HCV, and HDV was 15.6%, 36.6%, and 14.3%, respectively. The infection rates were significantly higher in females and participants with a lower education level, rural residence, older age, and a history of blood transfusion. HBV and HCV co-infection was found in 120 (5.2%) participants and HBV, HCV, and HDV triple infection was detected in 67 (2.9%) participants. The prevalence of elevated AFP was 2.7%, 5.5%, and 2.6% higher in participants who were seropositive for HBsAg (p=0.01), anti-HCV (p<0.001), and anti-HDV (p=0.022), respectively. Elevated AFP was more prevalent in participants co-infected with HBV and HCV (5.8%, p=0.023), HBV and HDV (6.0%, p<0.001), and triple-infected with HBV, HCV, and HDV (7.5%) than in uninfected individuals.ConclusionsNearly half (49.8%) of the study population aged ≥40 years were infected with HBV, HCV, or HDV, and 22.4% had dual or triple infections.     

Endemic hepatitis B virus infection and chronic liver disease mortality in the Republic of Palau, 1990-2002

In the Republic of Palau, a Pacific island nation, approximately 20% of the population is chronically infected with hepatitis B virus (HBV) and is at risk of developing chronic liver disease (CLD), including cirrhosis and hepatocellular carcinoma (HCC). To examine the consequences of HBV infection, we sought to quantify HBV-related CLD mortality in this population. The cause of death was abstracted from death certificates of all persons who died in Palau during 1990-2002. CLD deaths were categorised as cirrhosis or HCC. HBV serological status was determined by review of a hospital database. The cause of death was determined for 1,366 (85%) of 1,608 deaths. CLD was the fifth most common cause of death, accounting for 102 (7%) deaths with a known cause. Of deaths due to CLD, 55 (54%) were from cirrhosis and 47 (46%) were from HCC. Sixty-five percent of CLD decedents and 19% of non-CLD decedents were chronically infected with HBV (P<0.01). The attributable fraction of HBV-related CLD was 54% (58% for cirrhosis and 53% for HCC). CLD mortality rates were approximately twice the worldwide CLD rate. HBV-related CLD is a common cause of death in the Republic of Palau, highlighting the importance of routine infant hepatitis B vaccination, especially in countries with high endemicity.     

HTLV-1, HIV-1, hepatitis B and hepatitis delta in the Pacific and South-East Asia: a serological survey

Blood samples from 13 locations in the Pacific and South-East Asia were tested for evidence of infection with human T-cell lymphotropic virus type-1 (HTLV-1), human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) and hepatitis delta virus (HDV). No samples were positive for antibody to HIV-1. Antibodies to HTLV-1 were found in samples from five locations, the maximum prevalence being 19%, in Vanuatu. Serological markers of HBV infection were found in all locations, the maximal prevalence being 88%, in Majuro, Micronesia. Antibodies to HDV in HBsAg positive sera were found in six locations with a maximum prevalence of 81% in Kiribati.     

Seroprevalence of hepatitis delta virus infection among subjects with underlying hepatic diseases in Chennai, southern India

Four hundred million people are carriers of hepatitis B virus (HBV) worldwide and approximately 5% of these are reportedly positive for hepatitis delta virus (HDV). Several reports indicate a declining trend in the occurrence of HDV infection in the north of tropical India. To our knowledge, no study has been conducted to evaluate whether a similar epidemiological change is occurring in southern India. Therefore we evaluated the seroprevalence of HDV among 153 individuals with HBV-related liver diseases in Chennai, and assessed any change in epidemiological pattern by comparing the results with seroprevalence figures reported previously. Of the 153 patients screened, nine (5.9%) were reactive to anti-delta antibodies, six (3.9%) presented an evidence of past infection (IgG anti-delta positive) and three (2.0%) showed anti-HDV IgM, suggestive of recent HDV infection. Alanine transaminase elevation was not significant in HDV-associated infection compared with HBV alone-infected acute viral hepatitis (AVH) (P=0.82) and chronic liver disease (P=0.77) patients. The anti-HDV positivity in AVH was considerably low (6.6%), compared with previous Indian reports varying from 10.7% to >30%. HDV infection was relatively low and seems to play a minor determining factor of liver diseases in the tropical south Indian population.     

Risk factors associated with hepatocellular carcinoma notified to the Anti–Cancer Council of Victoria in 1991–1992

Abstract: The study aimed to estimate the prevalence of risk factors for liver disease, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, in a population–based series of hepatocellular carcinoma, and to assess the feasibility of retrospective surveys in determining risk factors for hepatocellular carcinoma. A survey of all cases of hepatocellular carcinoma diagnosed in 1991 and 1992 documented the high contribution of alcoholic cirrhosis, particularly in Australian–born men. Low levels of testing for HBV and HCV made their contribution to hepatocellular carcinoma uncertain. No cases of hepatocellular carcinoma due to HBV or HCV were reported in Australian–born subjects. Higher rates of HBV carriage in those tested were found in Asian and Mediterranean immigrants. Testing for HCV was known to have occurred for less than a quarter of subjects, and assessment for multiple aetiological risk factors was rare. The burgeoning epidemic of HCV will require improved surveillance for the sequelae of long–term infection. Satisfactory surveillance will require cooperation from clinicians in regard to the completeness of medical records and adequate resources for cancer registries to supplement their passive reporting system with exposure data. (Aust N Z J Public Health 1997; 21: 626–30)     

Increased hepatitis B virus quasispecies diversity is correlated with liver fibrosis progression

Host immune response and viral factors are involved in disease progression in patients with chronic hepatitis B virus (HBV) infection. However, the relationship between HBV quasispecies and liver fibrosis progression remains unclear. In this study, 447 patients with chronic HBV infection, including 239 with chronic hepatitis B (CHB), 104 with liver cirrhosis (LC) and 104 with hepatocellular carcinoma (HCC) were enrolled. The 239 CHB patients were divided into groups F1, F2, and F3 according to liver fibrosis score. Four fragments of the HBV genome were determined and analyzed using next-generation sequencing. Specific mutations, such as A1762T, G1764A and G1896A, in the BCP/PC region were more common in patients with advanced liver disease and formed the majority of the viral quasispecies pool in patients with LC and HCC. The viral complexity and diversity increased as the fibrosis progressed, especially in patients with CHB who were comparable in age but at different stages of fibrosis. Patients with early-stage fibrosis experienced higher purifying selection pressure in the four sequenced regions, whereas different protein-coding region experienced different negative selection with disease progression. HBV quasispecies diversity may increase fibrosis progression in CHB patients with aging under immune selection.     

Hepatitis B and delta virus infection among "at risk" populations in south east London.

STUDY OBJECTIVE--The hepatitis delta virus (HDV) contributes significantly to the morbidity and mortality of hepatitis B virus (HBV) infection, which is particularly prevalent among intravenous drug users and male homosexuals. A recent report has indicated that HDV first appeared in the South East London intravenous drug using population in 1982. The aim of the present study was to assess the prevalence of HDV in these two groups at risk of HBV infection in South East London. DESIGN--The study was a cohort analysis of HBV and delta virus serum markers, stratified temporally and with respect to intravenous drug use and sexual practice. SETTING--This was a population study of 372 consecutive intravenous drug users attending a local drug rehabilitation centre and 1481 subjects seen at a sexually transmitted disease clinic in the same area, during the years 1979 to 1988. MEASUREMENTS AND MAIN RESULTS--Of 372 intravenous drug users, 195 (52.4%) had evidence of current or past infection with HBV, of whom 17 had chronic HBV infection--a carriage rate of 8.7%. Twelve (70.6%) of these 17 also had chronic HDV infection--the first cases being identified in 1984. By comparison, 406 (27.4%) of the sexually transmitted disease clinic patients had been been exposed to HBV, 32 having chronic HBV--a carriage rate of 7.9% (7.5% v 9.4% among male homosexuals v male heterosexuals). Ten had been exposed to HDV (the first case in 1980) but only two (who did not admit to intravenous drug use) had chronic HDV infections (p less than 0.0005 v the rehabilitation centre patients). CONCLUSIONS--Although the HBV carriage rate is very similar in these two populations, chronic HDV infections were mainly confined to intravenous drug users. However, reports from the USA and France indicate spread of delta virus to the male homosexual community and, since there is clearly a pool of HDV in SE London, vaccination against HBV in these risk groups in likely to be cost-effective and should be actively encouraged.     

Assessment of some risk factors for hepatocellular carcinoma: a case control study

A case-control study of risk for hepatocellular carcinoma (HCC) was carried out in our Department from December 1980 to December 1983. One hundred and twenty consecutive inpatients with HCC were compared with 360 controls pair-matched by sex and age (within years). For each case three different controls were selected from inpatients at the same hospital: one patient with liver cirrhosis; one patient with solid tumor and one patient with chronic illness other than neoplasm or liver disease. We report here the results on alcohol consumption, smoking habit and hepatitis B virus infection. The risk factors investigated are distributed similarly in HCC and cirrhosis. The prevalence of alcohol abuse in HCC is similar to that in cirrhosis and is significantly higher than in other neoplastic or otherwise chronically ill patients (odds ratio 2 X 3 and 3 X 2 respectively). Thus alcohol abuse is probably a risk factor for HCC as a cause of cirrhosis. Smoking habits were similar among the various disease groups and independent of alcohol consumption. The prevalence of heavy smoking was comparable in cases and controls. HbsAg negative-HCC with an ultrasonographic pattern of 'diffuse' alteration was more frequent in heavy smokers.     

Incidence of hepatitis B, C and D infection in chronic liver diseases]

The authors tested hepatitis B (HBsAg, anti-HBs, anti-HBc, IgM anti-HBc, HBe, anti-HBe), C (anti-HCV) and D (anti-HD, IgM anti-HD) virus markers in the sera of 204 patients, who suffered from histologically confirmed chronic liver diseases (age: 18-72, average: 46.8 y) by Sorin Biomedica RIA and Abbott ELISA kits. On the basis of detailed virus serological tests, they obtained data indicating viral etiology in 62% of the cases. 33.3% of the patients were anti-HCV, 52.5% of the patients were HBV marker seropositive and 11.2% of the HBV seropositive cases were anti-HD seropositive. In 2% of the cases seropositivity of all the three viruses was proved. In 26% of the patients seropositivity of two viruses (HBV and HCV, or HBV and HDV) was proved. They observed severe, progressing liver diseases in patients with HBV, HCV and HDV marker seropositivity in a higher ratio than in seronegative patients. In the cases of combined virus marker seropositivity the incidence rate of chronic hepatitis and liver cirrhosis was higher than in only HBV marker seropositive patients, but did not differ significantly from those only anti-HCV seropositive. In the cases of fought-off HBV infection the severity of the liver disease was milder than in the cases of replication and integration stage. Anti-HD seropositivity occurred in all stages of HBV infection, but active HDV infection, in most of the cases, was observed only in cases in the integration stage. Anti-HCV seropositivity was observed mainly in the fought-off HBV infection stage. Their results suggest that HCV infection, like HDV infection, may suppress HBV replication.(ABSTRACT TRUNCATED AT 250 WORDS)