Aplastic anemia and viral hepatitis. Non-A, Non-B, Non-C?

OBJECTIVE--To test the hypothesis that the rare, often fatal, syndrome of hepatitis-associated aplasia is associated with hepatitis C virus infection. DESIGN--Case series. SETTING--Tertiary referral centers in the United States, Japan, Italy, and Germany. PATIENTS--Twenty-eight patients with onset of aplastic anemia within 90 days after seeking medical attention for jaundice, or having serum transaminase levels 150% or more of normal (hepatitis-associated aplasia patients) and three patients who developed aplastic anemia following liver transplantation for non-A, non-B hepatitis. OUTCOME MEASURES--Presence of hepatitis C in serum, bone marrow, and liver samples, detected by the polymerase chain reaction; antibody testing; and percentage of activated peripheral cytotoxic T lymphocytes determined by immunophenotyping. RESULTS--Hepatitis ribonucleic acid was present in the serum samples of 10 (36%) patients with hepatitis-associated aplasia. However, hepatitis C virus viremia was associated with transfusions received after the onset of aplasia: seven (58%) of 12 patients with hepatitis-associated aplasia who had received 21 or more units of blood products at the time of serum sampling were viremic, compared with only three (19%) of 16 patients with hepatitis-associated aplasia who had received 20 or less units of blood products (P less than .05). Hepatitis C virus was not found in blood and bone marrow samples of three National Institutes of Health case patients tested at the time of diagnosis. None of three livers from non-A, non-B hepatitis patients who developed aplastic anemia after liver transplantation contained hepatitis C virus ribonucleic acid. Activated CD8+ T lymphocytes were elevated three- to 20-fold early in the course of hepatitis-associated aplasia. CONCLUSIONS--Our results implicate a novel, non-A, non-B, and non-C agent in both hepatitis-associated aplasia and fulminant hepatitis.     

急性起病的非甲非乙型病毒性肝炎的病原分析

对HBsAg(一)、IgM抗HAV(一)临床诊断为急性非甲非乙肝炎63例,进行了病原学鉴定。以聚合酶链反应(PCR)检测HBV DNA,HCV RNA,并检测了IgM抗HBc和抗HCV血清抗体。诊断为急性丙型肝炎15例(23.8％),急性乙型肝炎20例(31.7％),慢性HBV携带者急性活动19例(30.2％),乙、丙型混合肝炎2例(3.2％),病原不明7例(11.1％)。结果表明在临床所谓的急性非甲非乙肝炎中,急性和慢性乙型肝炎仍占多数。     

Epidemiology of hepatitis C virus. A preliminary study in volunteer blood donors

In a survey carried out from 1985 through 1986, volunteer blood donors to The Greater New York Blood Program were tested for two surrogate markers for non-A, non-B hepatitis--elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen. Stored serum samples from selected donors were also recently tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 0.9% to 1.4% of donors and was higher in black and Hispanic donors than in white donors. Anti-HCV prevalence increased with increasing age through the fourth decade of life, but decreased thereafter, possibly reflecting the disappearance of detectable antibody with time. Anti-HCV correlated with both alanine aminotransferase level and the presence or absence of antibody to hepatitis B core antigen. These associations suggest that donor screening for elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen was, as expected, at least partially effective in preventing transfusion-associated non-A, non-B hepatitis. The detection of anti-HCV in donors who have neither an elevation of alanine aminotransferase level nor presence of antibody to hepatitis B core antigen suggests that donor screening for anti-HCV will further reduce the risk of transfusion-associated hepatitis.     

The development of hepatitis C antibody shortly after acute icteric non-A non-B hepatitis.

OBJECTIVE: To determine the relationship between the development of hepatitis C antibody (anti-HCV) and the clinical symptoms in acute hepatitis C. DESIGN: Retrospective analysis of sera from patients with acute non-A non-B hepatitis. SETTING AND PATIENTS: Patients admitted to Fairfield Hospital with the diagnosis of acute non-A non-B hepatitis between 1979 and 1989. Inclusion criteria included a typical clinical illness, accompanied by an alanine aminotransferase level of more than 2.5 times the upper limit of normal (normal, less than or equal to 40 U/L) and negative serological test results for acute hepatitis A and B. MAIN OUTCOME MEASURE: Time to develop anti-HCV after the onset of symptoms in patients with acute hepatitis C. RESULTS: Seroconversion was demonstrated in 26 of the 128 patients who fulfilled the inclusion criteria. In these patients, antibody was detected between one week and 32 weeks after the onset of dark urine; more than half the patients (54%) had seroconverted by four weeks and a third (34%) developed antibodies within two weeks. Of 20 patients who had sera collected within four weeks of the onset of dark urine, 14 (70%) had developed antibody. CONCLUSION: These results suggest that in patients with community-acquired hepatitis C, seroconversion occurs significantly earlier than is observed in patients who have been infected by blood transfusion. Sera taken shortly after the onset of symptomatic hepatitis C may be useful in the diagnosis of this condition.     

Prevalence of antibodies to hepatitis C virus after blood transfusion in heart surgery.

We studied the frequency and time of appearance of antibodies to the hepatitis C virus (HCV) retrospectively in the sera of 127 patients who underwent heart surgery between 1983 and 1986. They received blood from volunteer donors hepatitis B surface antigen (HBsAg) negative with normal serum alanine-aminotransferase levels. A prospective follow-up was carried out every 15 days for at least 6 months from the moment of the transfusion. Of the ten patients who developed biochemical criteria of post-transfusional non-A non-B hepatitis, six seroconverted to anti-HCV (60%). Of the other 117, two were already positive before transfusion (1.51%), one patient showed antibodies only in the first post-transfusional serum (passive transfer), and another two patients with no evidence of post-transfusional hepatitis developed HCV antibodies on the 90th day, remaining indefinitely (afterwards seroconversion without hepatitis); both patients'' earlier sera were anti-HCV negative. Four (40%) of the ten patients with post-transfusional hepatitis did not develop any serum markers to known hepatotropic agents. Although these findings do not exclude a viral infection by these viruses, they are consistent with the involvement of an unidentified non-A, non-B, non-C agent.     

Epidemiology and hepatitis C virus in Victoria

Parenterally transmitted non-A, non-B (NANB) hepatitis virus or hepatitis C virus is a common cause of both acute and chronic hepatitis. Using a recently developed enzyme-linked immunosorbent assay we looked at the prevalence of antibodies to hepatis C virus (anti-HCV) in a number of groups. People with haemophilia (75.6%) and intravenous drug users (61.9%) had the highest prevalence, while homosexual men attending a sauna (34.1%) and prisoners (30.8%) had a moderately high prevalence of anti-HCV. A lower prevalence of antibody was detected in female prostitutes (10.4%), institutionalised mentally retarded subjects (9.5%), homosexual men requesting human immunodeficiency virus (HIV) testing through their local doctor (8.8%), dialysis patients (5.9%), renal transplant patients (6.9%), and patients referred from a sexually transmitted diseases clinic (6.2%). The lowest prevalence of anti-HCV was recorded in women attending a provincial hospital for antenatal care (0.4%). The predominance of anti-HCV in groups of people exposed to blood-borne and sexually transmitted infections suggests that these routes may be primarily involved in the spread of hepatitis C virus infection.     

Prospective study of post-transfusion hepatitis after cardiac surgery in a British centre

A series of 248 consecutive patients undergoing cardiac surgery were examined in a prospective study of post-transfusion hepatitis in a single British centre. Patients received a total of 1796 units of blood or blood products (mean blood transfusion 6.28 units per patient). During five to 30 days after operation 38 of the patients showed an increase in serum transaminase activities. There was no serological evidence for fresh infection by hepatitis A or B virus, cytomegalovirus, Epstein-Barr virus, or herpes virus in any of these patients. The increase in transaminase activities was unexplained and reached over 100 IU/l (normal less than 40 IU/l) in six patients. The incidence of acute short incubation post-transfusion non-A, non-B hepatitis was therefore thought to be 2.4%. These six patients had normal liver function six months after transfusion but a further two of the surviving 228 patients had raised serum transaminase activities at six months. In one of these, liver biopsy disclosed chronic persistent hepatitis; in the other, alcoholic liver disease was suspected. The incidence of significant chronic liver disease after blood transfusion possibly attributable to a non-A, non-B hepatitis agent was therefore only 0.4%.     

Lower prevalence of anti-hepatitis C antibody in dialysis and renal transplant patients in Ireland

It is well recognised that haemodialysis and renal transplant patients are at increased risk of developing non-A, non-B hepatitis. Recently the genome of hepatitis C virus (HCV), the major causative agent for non-A, non-B hepatitis, has been isolated. Anti-HCV seroprevalence was assessed in all haemodialysis patients (266) in Ireland who in March 1990 had been dialysed for at least 6 months. For comparative purposes, 272 patients who had functioning renal transplants for greater than 6 months were also studied. Potential risk factors such as age, number of blood transfusions and time on dialysis were evaluated.     

急性散发非甲非乙型肝炎的病源学

本文对河南省8个医疗单位,在1985年3月至1986年9月期间,所提供的94例急性病毒性肝炎病人的104份血清样品,进行了HAV,HBV、CMV及EBV感染的血清学标志物实验。结果68.4%的病例是HBV,20.2%是非甲非乙型肝炎(HNANB)及8.9%是HAV。实验中由于采用了HBV-DNA探针和IgM抗体诊断试剂,相应地提高了实验质量。