丙型肝炎病毒感染的自然演变规律分析

目的　了解我国人群丙型肝炎病毒 (HCV)感染的自然演变规律。方法　 2 0 0 1- 12～ 2 0 0 2 - 0 7对河北省固安县和赵县 2 83例因单采血浆而感染丙型肝炎者进行调查分析 ,男性 137例 ,女性 14 6例。行腹部超声检查及丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、谷氨酰转肽酶 (GGT)采用速率法检测 ,HCVRNA的测定采用荧光定量PCR方法。转化生长因子 - β1(TGF - β1)、组织金属蛋白酶抑制因子 - 1(TIMP - 1)、三型前胶原肽(PⅢP)、四型胶原 (PC -Ⅳ )、透明质酸 (HA) ,采用ELISA方法。结果　 (1)非侵入性诊断 (包括临床诊断、超声诊断、血清学诊断 )为慢性肝炎轻度者 14 6例 ,占 5 1 .6 % ;中度 97例 ,占 34. 3% ;重度 15例 ,占 5 . 3% ;肝硬化 4例 ,占1 .4 % ;脂肪肝 2 1例 ,占 7 .4 %。(2 ) 2 83例感染者中 2 5 8例测定了HCVRNA ,阴性率 2 3. 3% ,表明该组人群感染HCV后 12～ 2 5年有较高的HCV自发阴转率。 (3)慢性肝炎重度和肝硬化组的ALT、AST、GGT均值明显高于其他组 ,慢性肝炎重度组ALT值异常率为 5 3 .3% (8/ 15 ) ,AST值异常率为 5 3 .3% (8/ 15 )。肝硬化组ALT值异常率为10. 0 % (4/ 4 ) ,AST值异常率为 10. 0 % (4/ 4 ) ,差异有显著性。 (4)慢性肝炎重度和肝硬化组肝纤维化血清学诊断指     

Mode of hepatitis C virus infection,epidemiology, and chronicity rate in the general population and risk groups

Since the discovery of the hepatitis C virus (HCV), it has become evident that this infectious agent is a primary cause of posttransfusion and sporadic non-A, non-B hepatitis. Identification and introduction of surrogate markers for posttransfusion hepatitis and later introduction of anti-HCV screening has decreased the incidence of posttransfusion hepatitis. Community-acquired HCV infection is less common than posttransfusion HCV hepatitis. HCV infection may lead to liver cirrhosis without prior evidence of laboratory or histologic infection. Populations at risk for HCV infection include patients receiving organ transplants, health care workers, infants born to HCV-infected mothers, and hemodialysis patients. Intravenous drug abusers and their sexual partners also demonstrate a high rate of HCV infection. Nosocomial HCV transmission may occur despite the observance of universal precautions. Dental or surgical intervention, salivary inoculation, family members infected with HCV, cocaine abuse, HIV infection, and lower socioeconomic status also each correlate with an increased risk of infection. HCV infection is associated with many immune-mediated diseases. There may also be some relationship between human leukocyte antigens and HCV infection. Since there currently is no HCV vaccine, prevention of exposure remains the only possibility for reducing HCV transmission and prevalence.     

Prevalence of hepatitis C virus infection in the general population of northern Spain

OBJECTIVES: To estimate the prevalence of hepatitis C in a population of northern Spain and describe (i) the risk factors associated with infection and (ii) the distribution of genotypes. DESIGN: Randomized cross-sectional study. METHODS: A random sample of 1,170 people participated in the study. Sociodemographic data were obtained. Antibodies against hepatitis C virus (anti-HCV) and hepatitis C virus (HCV) genotypes were determined. RESULTS: Nineteen of 1,170 (1.6%) subjects were anti-HCV positive (95% CI 1.0-2.6%). In 12 cases (63%), viraemia was present, and the predominant genotype was 1 b (80%). Anti-HCV positive subjects were older than anti-HCV negative subjects (55.8 +/- 15.3 v. 44.8 +/- 20.9; P = 0.02). Two peaks of maximum frequency were found (in the fourth decade and in those over 60 years). Parenteral drug addiction predominates among those of the fourth decade, while transfusion and surgery predominate in people over 60 years. Three (16%) subjects knew they were carriers of HCV. Only three variables remained significant in the multivariate model (illegal drug use, P< 0.0001; previous hepatitis, P< 0.0001; and age, P< 0.02). CONCLUSIONS: Our study emphasizes the need to develop health policies that can cope with the foreseeable increases in the problems associated with HCV infection in the near future.     

Role of hepatitis C virus infection in spontaneous hepatitis B surface antigen clearance during chronic hepatitis B virus infection.

To examine the role of hepatitis C virus (HCV) infection in spontaneous hepatitis B surface antigen (HBsAg) clearance during the course of chronic hepatitis B virus (HBV) infection, serum specimens from 32 asymptomatic HBsAg carriers and 22 patients with chronic hepatitis type B who underwent spontaneous HBsAg clearance were studied for antibody to HCV (anti-HCV) using commercial EIAs. The results were compared with those of control groups matched for age, sex, hepatitis B e antigen, antibody to hepatitis delta virus, and cirrhosis. Eight (25%) of the asymptomatic carriers and 9 (41%) of the patients with chronic hepatitis were seropositive for anti-HCV in contrast to 1.6% and 9.1% of their respective control groups (P less than .01). Serum alanine aminotransferase level was persistently abnormal after HBsAg clearance in one asymptomatic carrier and in four patients with chronic hepatitis. These patients were seropositive for anti-HCV and at least one of them was negative for HBV-DNA by polymerase chain reaction. The data suggest that HCV superinfection may not only suppress HBV or terminate the HBsAg carrier state but may also assume the role of HBV as the cause of persistent hepatitis or transaminase elevation.     

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.     

Transmission, natural history, and treatment of hepatitis C virus infection in the pediatric population

Compared with the adult population, hepatitis C virus infection may differ in the pediatric age group with respect to transmission, course, and response to treatment. The prevalence of hepatitis C in children is between 0.05% and 0.4%. The major mode of acquisition has shifted from parenteral transmission to maternal-infant transmission. However, the actual rate of maternal-infant transmission is low. The natural history of hepatitis C in children is not well characterized, although the available information suggests a milder disease than in adults. In the eight studies of treatment with interferon for hepatitis C in children, the incidence of a complete sustained response varied from 0 to 45%. No pediatric studies have evaluated quality of life or the effect of treatment on the development of cirrhosis and hepatocellular carcinoma. Children may respond better to treatment than adults. We recommend that children with hepatitis C are considered for treatment only as part of a controlled clinical trial.     

Epidemiology and natural history of hepatitis C virus infection

Hepatitis C virus (HCV) affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma. Globally, at least one third of hepatocellular carcinoma cases are attributed to HCV infection, and 350000 people died from HCV related diseases per year. There is a great geographical variation of HCV infection globally, with risk factors for the HCV infection differing in various countries. The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations. A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma, and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma. However, prospective cohorts comprising individuals with HCV infection are still uncommon. The risk evaluation of viral load elevation and associated liver disease/cancer in HCV (REVEAL-HCV) study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years. Most of them have acquired HCV infection through iatrogenic transmission routes. As the participants in the REVEAL-HCV study rarely receive antiviral therapies, it provides a unique opportunity to study the natural history of chronic HCV infection. In this review, the prevalence, risk factors and natural history of HCV infection are comprehensively reviewed. The study cohort, data collection, and findings on liver disease progression of the REVEAL-HCV study are described.     

特殊人群丙型肝炎病毒感染特征分析

目的 了解近年来就诊我院各科患者丙型肝炎病毒（HCV）的感染情况,以及抗-HCV阳性者一般临床特征。方法对2007年1月至12月我院门诊、急诊、病房等就诊患者抗-HCV检测的结果和阳性分布状况进行分析。同时,对2006年1月至2007年12月的全部抗-HCV阳性者分析其临床及病毒学特征。结果在2007年22146例无重复检测人群中,498人（2．25％）抗-HCV阳性。其中,手术前筛查人群的阳性率为0．72％,感染科和肾脏疾病相关科室阳性率分别为8．80％和7．43％。0～20岁组及21～40岁组中男性的阳性率显著高于女性。此外,抗-HCV阳性人群中近30％伴抗-HBc阳性,14％伴HBsAg阳性。HCV1b型是最主要的基因型（60．98％）,其次是2a（19．51％）和3a型（9．76％）。结论近年来因非肝功能异常而就诊我院的患者HCV感染率处于较低水平,现阶段通过输血传播HCV的概率已较低,可能存在其他感染途径。     

Seroprevalence of hepatitis C virus in the general population of northwest Tanzania

Sera from 516 participants enrolled in a population-based cross-sectional study in northwest Tanzania were tested for antibodies to hepatitis C virus (HCV). The mean age of study subjects was 29 years (range = 16-49 years); 43% were men, 6% reported a history of blood transfusion, and 4% were infected with human immunodeficiency virus-1 (HIV-1). Although 53 of 516 sera (10.3%, 95% confidence interval [CI] = 7.8-13.2%) were repeatedly reactive by a third-generation enzyme immunoassay (EIA-3), only 6 of the 53 were positive when tested with a third-generation recombinant immunoblot assay (confirmed HCV seroprevalence = 1.2%, 95% CI = 0.4-2.5%). The positive predictive value of the HCV EIA-3 in this population was 18.8% (95% CI = 7.0-36.4%). False positivity was not correlated with EIA-3 optical density values, age, sex, infection with HIV-1, or a history of blood transfusion, but it was marginally associated with increased serum IgG levels. We conclude that the prevalence of HCV is low in this region and that the HCV EIA-3 has a higher false-positivity rate in this population than has been reported among U.S. blood donors.     

The natural history of chronic hepatitis C virus infection

In conclusion, the natural history of chronic HCV infection has not yet been fully defined. Current data suggest that the process runs an indolent course during the first two decades after initial infection, accounting for modest morbidity and mortality. Serious sequelae are more likely to emerge as the disease process enters the third and fourth decades after infection. These sequelae will presumably be concentrated among those whose liver biopsies display features of cirrhosis, but seem less likely to effect those with liver biopsy evidence of chronic hepatitis alone unless their disease advances to cirrhosis. The frequency of progression from chronic hepatitis to cirrhosis as the disease process enters the third decade remains to be determined. Associated chronic alcoholism appears to be an important additive factor, but other factors that might promote disease progression need to be defined. It seems probable that end-stage liver disease will result in only a proportion of infected individuals. If so, the challenge is to learn how to determine for each individual during the course of their chronic illness what outcome can be expected.     

The natural history of hepatitis C virus infection.

The natural history of HCV infection remains ill-defined. The knowledge accumulated on the progression of HCV to date is important, however. It is now abundantly clear that the progression of disease is generally slow, and the development of cirrhosis and its complications is a possibility, not a probability as hitherto thought. Predicting the outcome remains a quandary for clinicians. Ultimately it will be possible to define the natural history of hepatitis C infection through a combination of research in the fields of virology, immunology, and molecular biology and by monitoring the biochemical and histologic progress of the disease. Only then will it be possible to intervene appropriately and develop new therapies to prevent the progression to cirrhosis and hepatocellular carcinoma.     

TT virus infection during chronic hepatitis C

OBJECTIVE: The pathogenic role of TT virus (TTV) is not well known, especially during chronic hepatitis C virus (HCV) infection. We retrospectively investigated the presence of TTV DNA in the plasma of patients with chronic HCV infection and compared the characteristics of TTV-DNA-positive and -negative groups. METHODS: Between November 1996 and November 1998, 234 patients were included. Inclusion criteria were persistently elevated serum alanine aminotransferase (ALT) levels, anti-HCV and HCV-RNA positivity, and seronegativity for hepatitis B virus and human immunodeficiency virus markers. TTV DNA was amplified in nested polymerase chain reaction with TTV-specific primers, and products were analyzed by agarose-gel electrophoresis. Data were analyzed using the chi2, Fisher's exact test, or Mann-Whitney test, as appropriate. RESULTS: TTV DNA was detected in 19 (8.1%; 95% confidence interval: 4.6-11.6%) patients. TTV-DNA-positive and TTV-DNA-negative patients did not differ statistically for age, gender ratio, source of HCV infection, HCV disease duration, biological parameters, histological grade, HCV-RNA load, or HCV genotype. Although nonsignificant (p = 0.21), there was a trend for a higher prevalence of TTV DNA in patients with an unknown cause of HCV infection (4/22, 18.2%) than in intravenous drug users (4/84; 4.8%), in those exposed to potential risk factors (4/49; 8.2%), or in those having received blood transfusion (7/79; 8.9%). CONCLUSIONS: Because the rates of HCV replication and the severity of liver lesions in TTV-DNA-negative and -positive patients were similar, the hepatic pathogenicity of TTV in chronic hepatitis C patients is questionable.     

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.     

Hepatitis C virus RNA and antibody response in the clinical course of acute hepatitis C virus infection.

Hepatitis C virus RNA, anti-hepatitis C virus immune response and biochemical markers of liver injury were investigated in 17 patients with acute non-A, non-B hepatitis. At the first observation, 1 to 3 wk from the clinical onset, all patients had hepatitis C virus RNA in their serum, and most (15 of 17) were positive for second-generation anti-hepatitis C virus enzyme immunoassay. Follow-up serum samples were available for 10 patients. The rate of recombinant immunoblot assay-confirmed anti-hepatitis C virus enzyme immunoassay reactivities increased from 67% in the first 3 wk to 86% after 21 wk. Elevated ALT levels were associated with hepatitis C virus RNA positivity in most of cases, but the viral nucleic acid was also detected in sera with normal or slightly increased enzyme values. None of the single antibodies tested were related to hepatitis C virus RNA positivity or to the clinical phase of the infection. Therefore hepatitis C virus RNA determination might provide important additional information as compared with anti-hepatitis C virus markers, allowing earlier diagnosis, discrimination of active infection and, possibly, prognostic evaluation.     

Clinical course of pregnant women with chronic hepatitis C virus infection and risk of mother-to-child hepatitis C virus transmission

As far as concerns chronic hepatitis C virus infection in pregnant women, different points remain to be elucidated, such as the clinical course, the rate of mother-to-child hepatitis C virus transmission and, in particular, its route and the possible risk factors. This review aimed to analyse current data on the prevalence of chronic hepatitis C virus infection in pregnant women and its relationship with risk factors, the rate of mother-to-child hepatitis C virus transmission and the factors possibly involved, particularly the maternal hepatitis C virus viral load and the human immunodeficiency virus coinfection, and the type of delivery and feeding. Finally, the appropriate timing for HCV-RNA testing in newborns has been reviewed.     

Antiviral treatment responses in patients with chronic hepatitis C virus infection evaluated by a third generation anti-hepatitis C virus assay

summary . Antibodies to hepatitis C virus (HCV) may decrease or disappear after viral clearance in treated or spontaneously resolved infection. We evaluated the usefulness of serial antibody assays in predicting the antiviral treatment responses. One hundred and four chronic hepatitis C patients who received 24 weeks of interferon and ribavirin combination therapy were assayed with a third generation enzyme immunoassay anti-HCV. The mean titre of anti-HCV decreased by more than 50% (from 89.5 ± 10.8 to 43.6 ± 17.5) at 48 weeks post-treatment in patients with a sustained virological response, while in nonsustained virological responders and nonresponders, the titres remained over 85% of the pretreatment level at 48 weeks post-treatment. There was a divergence of anti-HCV titres between sustained and nonsustained virological responders during 6–9 months. By using the ratio of 9-month to 6-month titres as an index and receiver operator characteristic curve analysis with the cut-off point set at 90%, we could differentiate sustained virological responders from nonsustained virological responders with a sensitivity and specificity of 91.7% and 90.9%, respectively, 3 months after treatment. The titre of this third generation anti-HCV decreased progressively in sustained virological responders and this assay may be used to monitor and predict antiviral treatment responses.