急性重型肝炎患者肝组织中庚型肝炎病毒的检测

检测急性重量型肝炎患者肝组织中庚型肝炎病毒（ＨＧＶ）的存在状况及探讨与发病的关系,采用免疫组化方法以抗－ＨＣＶＮＳ５单克隆抗体对２６例急性重型肝炎患者尸检肝组织中的ＨＧＶ等抗原进行了检测,结果显示２６例肝组织中检测出ＨＧＶ阳性６例（２３．１％）ＨＧＶＮＳ５Ａｇ阳性着色颗粒表达于残存的肝细胞浆内,阳性细胞呈片簇状分布于汇管区周围,６例中４例重叠有ＨＢＶ或／和ＨＣＶ感染,肝组织中ＨＢｓＡｇ或／和ＨＣＶ     

Detection and viral nucleotide sequence analysis of transfusion-transmitted virus infection in acute fulminant and non-fulminant hepatitis

The impact of transfusion-transmitted virus (TTV) infection on acute fulminant and non-fulminant hepatitis is unclear. In this study, serum samples from 164 patients with acute hepatitis of various aetiologies, from 34 asymptomatic hepatitis B virus carriers and from 202 healthy adults were tested for TTV DNA by the semiconserved nested polymerase chain reaction. TTV viraemia was prevalent in patients with acute hepatitis C, in patients with acute hepatitis D virus superinfection and in patients with non-A–E hepatitis (27–30%) but the incidence was not significantly different from that of healthy controls (31 of 202, 15.3%). There were no significant differences in gender, age, presence of hepatitis G virus, the occurrence of fulminant hepatitis, or in serum albumin, bilirubin or alanine aminotransferase levels (9/30 vs 35/134) between patients with or without TTV viraemia. Seven of the nine TTV-positive patients with fulminant hepatitis were co-infected with hepatitis C, D or E. TTV clones from 18 subjects, with or without fulminant hepatitis, were sequenced and analysed phylogenetically. Eleven (61.1%) belonged to TTV group 1, six (33.3%) to TTV group 2 and one to TTV group 3. No particular strain of TTV was associated with fulminant hepatitis. In summary, in Taiwan, TTV is prevalent in the general population as well as in patients with liver diseases. TTV plays an insignificant role in acute fulminant and non-fulminant hepatitis. Its influence on outcome requires a longitudinal study.     

Variations of hepatitis B virus precore/core gene sequence in acute and fulminant hepatitis B

Variations of the hepatitis B virus (HBV) precore/core sequence has been shown to play a role in the development of active liver disease in chronic hepatitis B. Whether this is also an important viral factor in the pathogenesis of acute and fulminant hepatitis B is unknown. To determine the precore/core gene sequence in patients with acute and fulminant hepatitis B, 11 patients with fulminant hepatitis B and seven patients with acute hepatitis B were studied. The sequences of precore/core gene were determined by direct sequencing of the polymerase chain reaction amplicons generated from the HBV isolated from patients' serum. For the 11 patients with fulminant hepatitis B, the precore/core regions were successfully amplified in 10 patients. Eight patients exhibited precore stop codon mutations. In addition, nine of the 10 fulminant hepatitis B patients had frequent nucleotide substitutions with corresponding changes in the predicted amino acid sequences in the mid-core and the 5 terminus region of the core gene. In contrast, precore stop codon mutants were not detected, and variations of the HBV core gene were minimal in patients with acute hepatitis B. The association of HBV precore mutants and HBV core gene variations with fulminant hepatitis B and not acute hepatitis B suggested that these variations may be important in modulating the clinical course of HBV infection.     

Minimal role of GB virus-C/hepatitis G virus in fulminant and subfulminant hepatitis in Taiwan

BACKGROUND: The role of GB virus-C/hepatitis G virus (GBV-C/HGV) in fulminant hepatitis (FH) and subfulminant hepatitis (SFH) remains unclear. METHODS: Thirty-two FH or SFH patients, with adequate clinical information and serum specimens, were studied. Serum samples were tested for hepatitis markers and genomes of hepatitis A-E viruses, as well as GBV-C/HGV. RESULTS: Of the cases of FH/SFH studied, one (3%) was caused by anti-tuberculosis agents, 26 (81%) had hepatotropic virus infection, and five (16%) had no identifiable cause. Of the 26 patients with hepatotropic virus infection, five had acute hepatitis B infection (one with acute hepatitis D virus (HDV) co-infection), one had acute hepatitis C infection, 16 were hepatitis B surface antigen carriers with reactivation or superimposed by unidentified agent(s) (two had triple virus infections), three were hepatitis B carriers with HDV superinfection, and one had GBV-C/HGV infection in addition to exposure to halothane. GBV-C/HGV-RNA was detected in only three of 32 patients (9%) and all had a history of blood transfusion or co-existing causative factors. Of the 26 patients with hepatotropic virus infection, 18 were tested for antibodies against GBV-C/HGV envelope protein and seven were reactive, suggesting past infection. CONCLUSIONS: The role of GBV-C/HGV in causing FH and SFH is minimal in Taiwan and HBV infection remains the major aetiology. These findings also suggest the existence of as yet unrecognized agents, responsible for such catastrophic illnesses.     

Role of transfusion-transmitted virus in acute viral hepatitis and fulminant hepatic failure of unknown etiology

BACKGROUND AND AIM: The role of the newly described transfusion-transmitted virus (TTV), a circular single-stranded DNA virus, has been investigated in acute liver disease, comprising 36 patients with acute viral hepatitis (AVH) and 25 with fulminant hepatic failure (FHF), including 50 volunteer blood donors as controls. METHODS: Detection of TTV DNA sequences was carried out by polymerase chain reaction (PCR) using primers derived from the UTR(A) region of the TTV genome. The clinical course and biochemical profile when infected with TTV alone or coinfected with other classical hepatotropic viruses were analyzed. All patients were first evaluated for liver function profile and for the presence of various hepatotropic viruses using serological tests and PCR in serologically negative patients. RESULTS: Transfusion-transmitted virus DNA was detected in 80.6% (29/36) of the AVH cases and in 76% (19/25) of the FHF cases, which were significantly higher levels (P < 0.05) than the 52% (26/50) observed in volunteer blood donors. No significant difference in symptoms, clinical course, liver function and risk factor profile between TTV-positive and TTV-negative patients could be observed in both AVH and FHF patients. TTV was found to coexist with both parenterally and non-parenterally transmitted hepatotropic viruses in similar frequency in both AVH and FHF patients. Further, there was no significant difference in the mortality rates between TTV-positive and TTV-negative FHF patients. Also, there was no difference between patients coinfected by TTV and other hepatotropic viruses and those with TTV infection alone. CONCLUSION: Thus, it appears that TTV, although it exists in a very high frequency in the Indian population, appears to have no significant etiological role in AVH and FHF.     

Hepatitis G virus RNA and its relation to hepatitis C infection in adult haemophilic patients

The prevalence of hepatitis C virus (HCV) infection and hepatitis G virus (HGV) RNA were studied in 50 adult haemophilic patients who had received commercial clotting factors prior to 1980. HGV RNA was detectable in 6/50 patients (12%); 49/50 (98%) had antibody to HCV and 40/49 (82%) of these were viraemic with detectable HCV RNA; 5/6 patients with detectable HGV RNA had co-existing HCV infection and viraemia. The HGV PCR products from all six patients were directly sequenced and all were shown to be similar to that of HGV but more diverse from that of GB virus C. One patient who had persistent abnormal liver function tests had detectable HGV RNA but no evidence of hepatitis B or C. The presence of HGV RNA in the absence of hepatitis B and C infection indicates that this virus is capable of independent transmission. Independent response to interferon was demonstrated in one patient with co-infection who lost HGV but not HCV after interferon therapy.     

Interferon treatment of two patients with quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV)

Abstract: We administered interferon (IFN) to two patients who had quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV), a recently isolated novel DNA virus. Nine mega-units of natural alpha-IFN were administered daily during the first two weeks and thrice weekly during the following 22 weeks (total dose, 720 mega-units). In both cases, serum alanine aminotransferase (ALT) levels decreased during IFN administration but increased thereafter. The concentrations of HCV, HIV, HGV, and TTV declined with the administration of IFN. However, the concentrations of these 4 viruses increased after the cessation of IFN with the except of TTV in patient 2 which disappeared during treatment and did not subsequently reappear. IFN reduced the concentrations of 4 viruses, in an apparently independent manner.     

Hepatitis G virus infection in patients with bleeding disorders

Eighty-two patients with bleeding disorders registered with our centre were screened for infection with hepatitis G virus (HGV). 80 patients were positive for hepatitis C (HCV) antibodies, 66 of whom (83%) were HCV PCR positive. 11 patients (13%) were HGV RNA-positive, a similar prevalence rate to that of other studies of patients with bleeding disorders who received factor concentrates prior to the introduction of viral inactivation procedures. There was no significant difference in histological activity index (HAI) between the 10 HGV RNA-positive and the 31 HGV RNA-negative patients who underwent liver biopsy for assessment of HCV infection (median HAI scores 5.5, range 2–10 and four, range 0–10 respectively, P  = 0.07). One patient in each group had established cirrhosis. In patients who underwent HCV quantitation there was no significant difference in HCV viral titre between HGV RNA-positive and negative patients (median HCV titre in HGV RNA-positive patients 2.10 × 10⁵ DNA copies /ml ( n  = 8) range 4.17 × 10² to 4.17 × 10⁶, median HCV titre in HGV RNA-negative patients 3.33 × 10⁵ ( n  = 31) range 1.00 × 10³ to 6.67 × 10⁶, P  = 0.68). In this study there was no evidence that individuals co-infected with HGV and HCV have more severe liver disease than those infected with HCV alone.     

各型肝炎病毒单纯及重叠感染的研究

目的 探讨病毒性肝炎患者甲～戊，庚型肝炎病毒(HAV-HEV，HGV)单纯感染及重叠感染情况。方法 采用EIA法检测病毒性肝炎患者血清抗-HAV IgM，HBV标志物、抗-HCV IgM、抗-HDV IgM、抗-HEV IgM、抗-HGV IgM。结果 共检测210例病毒性肝炎患者HAV-HEV、HGV血清标志物，20例未检出(9．5％)，190例患者检出标志物阳性(90．5％)。HBV感染率89，5％(188／210，其中有34例为既往感染，占16．2％，现症感染154例，占73．3％)；HAV感染率29．0％(61／210)，HCV、HDV感染率均为8．1％(17／210)、HEV、HGV感染率依次为10．0％(21／210)、7．1％(15／210)。各临床类型中单纯感染占61．4％(129／210)，二重感染占32．4％(68／210)，以HAV HBV、HBV HDV、HBV HEV感染模式最常见，三重感染占6．2％(13／210)，以HAV HBV HDV感染模式最常见；临床上以肝炎肝硬化、重型肝炎重叠感染常见，急性肝炎最少见。结论 病毒性肝炎中HBV感染最常见，其次为HAV感染；单纯感染、二重感染多见，三重感染少见；重叠感染发生率随病情加重而增加。     

Protective effect of OK-432 (streptococcal preparation) on murine fulminant hepatitis following mouse hepatitis virus infection

The effects of OK-432 (streptococcal preparation) on murine fulminant hepatitis were investigated. Hepatitis was induced by injection of mouse hepatitis virus type 2 (MHV-2) at a strength of either 1 x 10(3) or 1 x 10(4) plaque-forming units (PFU). Mice without OK-432 treatment died within 5 days, whereas mice preinoculated with OK-432 showed survival rates of 50% (1 x 10(3) PFU) or 10% (1 x 10(4) PFU) after 60 days. Survival time was not prolonged if OK-432 was injected after MHV-2. Examined histologically, mice not treated with OK-432 showed severe haemorrhagic necrosis of the liver, often panlobular. Treated mice showed less necrosis; the least necrosis was observed in those injected with OK-432 before MHV-3. In those mice injected first with OK-432 and then with 1 x 10(3) PFU of MHV-2 that survived 7 days, autopsy showed a very slight and focal hepatic necrosis, with follicular infiltration by lymphocytes and macrophages. Mitogenic reaction of spleen cells was remarkably less than normal in mice with MHV-2 injection. However, mice injected with OK-432 before MHV-2 (same treatment as mice showing high survival rates) showed relatively high reactivity in comparison with mice not treated with OK-432.     

Lack of evidence for hepatitis B virus (HBV) infection in fulminant non-A,non-B hepatitis

We studied eight patients who had orthotopic liver transplantation for fulminant hepatic failure in the course of acute non-A, non-B hepatitis. HBV DNA was searched for extensively in the liver tissue by PCR using several sets of primers in conventional and heminested reactions. All patients were negative for HBV DNA in liver tissue by all assays employed; furthermore, they were negative for HEV RNA, HCV RNA, and HBV DNA in serum. Although the causative role of HEV and HCV in fulminant non-A, non-B hepatitis cannot be excluded, our data do not support a causative association between this syndrome and HBV infection.This study was supported by Grant CR20 from the Mayo Clinic and Foundation. D.H.P. is supported by Public Health Service grants AI 32403, AR 41497, and AI 30548 from the National Institutes of Health.     

Evidence of ongoing virus multiplication in type B fulminant hepatitis

The presence of HBeAg- and HBV-specific DNA-polymerase (DNA-P) activity—regarded as markers of HBV multiplication—were studied in 40 patients with fulminant hepatitis B within 1-5 days of the onset of hepatic encephalopathy. HBeAg and DNA-P were detected in three (7 %) and 21 (51%) of the patients respectively. Only three (7%) were positive for anti-HBs. DNA-P activity was present in 38.1 % even 10 days after the appearance of icterus. Present findings confirm an ongoing HBV multiplication in about half of the patients of fulminant hepatitis B.