Post-transfusion non-A, non-B Hepatitis Research Articles

Non-A, non-B hepatitis: a prospective study of a hemodialysis outbreak with evaluation of a serologic marker in patients and staff.

An outbreak of non-A, non-B hepatitis (NANBH) in a hemodialysis unit was prospectively studied and the clinical, biochemical, and serologic events were correlated with an experimental immunodiffusion assay for serum antigen and antibody. One hundred sixteen subjects (76 dialysis patients and 40 staff members) were studied over an 8-month period. Hepatitis was defined as two consecutive SGPT levels greater than two times the upper limit of normal occurring in two separate samples drawn greater than 7 days apart in the absence of other likely causes of liver disease. Weekly serum specimens were obtained and tested for SGPT, SGOT, alkaline phosphatase, bilirubin HBsAg, anti-HBc, anti-HBs, total anti-HAV, and anti-HAV IgM by commercial reagents, and for antigen and antibody by agar gel diffusion using reference reagents previously obtained from well-documented posttransfusion NANBH patients. Clinical evaluations were performed three times per week. Thirty patients and none of the staff developed NANBH. The NANBH patients were asymptomatic, except for two patients with jaundice. Fifteen of the 30 patients were positive for antigen which was detectable in at least one serum collected during the acute phase. Six patients and 10 staff without clinical NANBH or abnormal serology had antigen. Antigenemia was also observed in three patients with acute hepatitis B, with chronic hepatitis B in one patient and with alcoholic hepatitis in one patient. Thus, an antigen was detected in a high proportion of patients during the acute phase of NANBH, and it was also found in exposed patients who had other liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of hepatitis C virus infection in Australia.

Since the discovery in 1989 of hepatitis C virus (HCV) as the infectious agent responsible for the vast majority of post-transfusion non-A non-B hepatitis the patterns of transmission and clinical consequences of this highly prevalent flavivirus have been widely studied. This paper reviews available evidence on the epidemiology of HCV infection in Australia, including HCV notification data obtained through public health surveillance systems, HCV seroprevalence surveys among high risk populations, and models for estimating and projecting HCV transmission and long-term consequences of chronic HCV infection. Over the period 1990-2000 approximately 160,000 notifications of HCV infection were received by State and Territory health jurisdictions making it the most commonly notified communicable disease in Australia. Approximately 210,000 people are estimated to be living with HCV infection in Australia, with an estimated 80% having acquired their infection through injecting drug use. Less than 500 cases of newly acquired HCV infection are notified each year, however, an estimated 16,000 new infections occur annually. Despite the widespread introduction of needle and syringe programmes in the late 1980s, HCV transmission continues at high levels among current injecting drug users (IDUs) with incidence and prevalence estimates of 10-20/100 person years and 50-55%, respectively. Levels of HCV transmission are particularly high in both younger and incarcerated IDUs. In contrast to HCV infection, prevalence of HIV among current IDUs has remained below 2% since 1995. Although a small minority of people with chronic HCV infection will develop liver failure or hepatocellular carcinoma, the incidence of these advanced disease complications is estimated to double over the next decade. The epidemic of HCV infection continues to escalate in Australia, predominantly through transmission related to injecting drug use. As the population of people with chronic HCV infection and progressive liver disease expands the public health burden of advanced disease complications will be considerable.

Response to interferon alfa-2b therapy in mutitransfused children with beta-thalassemia and chronic hepatitis C.

Hepatitis C virus is responsible for the majority of cases of post-transfusion non-A non-B hepatitis in patients with thalassemia major. Interferon alfa is an effective treatment for patients with chronic hepatitis C. Response to therapy is related to the duration of treatment, the viral load in serum, and the hepatitis C virus genotype. The purpose of this study was to estimate the response of multitransfused children with beta-thalassemia and chronic hepatitis C to interferon alfa-2b therapy. Thirteen patients with beta-thalassemia and chronic hepatitis C, (mean age+/-SD, 14.1 +/- 1.7 years) participated in the study. Liver biopsy, estimation of HCV RNA, and virus genotyping were performed before onset of treatment. All patients were positive for HCV RNA in a low concentration; two patients carried the la genotype, four had genotype 3, and seven had genotype 4. Patients were treated with 3 x 10(6) U of subcutaneous interferon alfa-2b three times weekly. Eleven of 13 patients received therapy for 18 months; the remaining two underwent therapy for 6 months. Six of 13 patients responded completely to therapy, four responded partially, and three did not respond at all. The grade of inflammation and stage of fibrosis was lower in complete responders. Complete responders had lower ferritin values compared with the values for partial and nonresponders before starting therapy. The results suggest that interferon therapy should be recommended for children with beta-thalassemia major complicated by a low viral concentration of hepatitis C.

Hepatitis C Virus Infection in Dialysis and Clinical Nephrology

Hepatitis C Virus (HCV), a single-strand RNA virus, has recently been cloned and sequenced. It causes nearly all cases of non-A non-B post-transfusion hepatitis (NANBH), and is responsible for most of the community-acquired NANBH. Considerable progress has been made in characterizing HCV and understanding the prevalence, transmission, and natural history of HCV infection.

A comparison of hepatitis C virus (HCV) RNA and – antibody as markers of infection and predictors of infectivity

The diagnosis of hepatitis C virus (HCV) infection currently relies on the detection of antibody to HCV (anti-HCV). However, anti-HCV positivity may indicate past infection, current infection or possibly non-specific reactivity. For confirmation of current infection the virus needs to be assayed directly and this is possible by the polymerase chain reaction (PCR). The aims were to compare HCV RNA and anti-HCV as markers of infection in two groups of individuals: (i) a heterogeneous group with suspected HCV infection and (ii) a small group of blood and bone marrow donors, and their respective recipients. Serum samples were tested for alanine aminotransferase (ALT) as part of a liver function screen, for anti-HCV by ELISA II, and HCV RNA was detected by PCR. Single round and nested PCR was performed using primers designed from the sequence of the 5'-untranslated region of the HCV genome. Of the 36 subjects in the heterogeneous group, 19/22 anti-HCV-positive patients with chronic non-A non-B hepatitis (NANBH) were viraemic, and the majority (17/19) demonstrated elevated ALT. However, HCV RNA was undetected in seven anti-HCV-positive patients, four of whom suffered autoimmune hepatitis Type I and three were low risk blood donors. Of the remaining subjects (seven/36) who were anti-HCV-negative, three/seven were HCV-RNA-positive and included two with acute post-transfusion (PT) NANBH and a recent needlestick victim who contracted HCV. In the second group, four individuals (donors), including a mother with a history of drug use, were implicated in transmission to three recipients. ALT levels were normal in all donors but raised in two of the recipients. PCR determined which of two anti-HCV-negative blood donors was infectious, confirmed transmission between a bone marrow donor and recipient, and indicated that anti-HCV detected in a newborn child represented passive transfer of antibody. Anti-HCV detected by ELISA II is a useful marker of chronic HCV infection, particularly in association with raised ALT. However, HCV RNA is a superior marker of acute HCV infection, a more reliable predictor of infectivity and is more specific.

Molecular typing of hepatitis C virus genome from sera and liver tissues of patients with anti-HCV positive chronic liver disease.

The authors investigated the distribution of HCV genotypes in patients with various chronic liver diseases in Korea. Study population was 70 individulals, positive for second generation anti-HCV EIA, consisting of 37 cases with sporadic non-A, non-B (NANB) chronic hepatitis (CH), 12 NANB hepatocellular carcinoma, 16 post-transfusion NANB hepatitis, 4 non-B blood donors and 1 healthy family member of a patient with sporadic CH. Molecular typing was performed by RT-nested PCR with type-specific primer sets deduced from the NS-5 region of HCV. The prevalence of type II was 75.0% and type III was 25.0% in sera. In liver tissues, type II HCV was shown in 63.0%, type III HCV in 3.7% and co-infections with type II and III HCV were observed in 18.5% of 27 samples biopsied. In the sera of patients with chronic hepatitis, typing results were relatively well correlated with those in tissues (75%), but type III could not be observed. Among 12 HCC patients, type III HCV appeared only in tissues, not in sera. These results suggest that type II HCV may be the major HCV type in Korea, and co-infections with type II and-III HCV may not be rare in chronic liver diseases with HCV.

Evaluation of Antibodies to Hepatitis C Virus in a Long‐Term Prospective Study of Posttransfusion Hepatitis Among Thalassemic Children

SummaryDuring an 8‐year prospective study of post‐transfusion hepatitis conducted at the Thalassemic Center of Cagliari (Italy), including 135 newly diagnosed thalassemic children on long‐term transfusion maintenance, 83 children (61%) developed non‐A, non‐B hepatitis (NANBH). Resolution of NANBH was observed in 17 (20%) cases, and chronicity in 57 (69%), whereas the remaining 9 (11%) experienced one or two additional bouts of acute NANBH. Of the 83 children with NANBH, 75 (90%) showed anti‐hepatitis C virus (HCV) seroconversion when tested by second‐generation enzyme‐linked immunosorbent assay (ELISA), whereas first‐generation ELISA showed anti‐HCV in only 59 (71%) cases (p = 0.003). Moreover, the newly developed assay allowed an earlier detection of anti‐HCV response in most of the patients who seroconverted by both assays, reducing significantly the mean onset‐seroconversion interval (5 ± 9.4 weeks vs. 14.5 ± 20.8 weeks, p < 0.05). It was significantly more sensitive for the identification of HCV infection, not only in resolving NANBH, but also in NANBH progressing to chronicity (79 vs. 35%, respectively, p = 0.008; and 93 vs. 79%, p = 0.028). The pattern of antibody response with first‐generation assay was characterized by clearance of anti‐HCV with time, in most of the patients who recovered, and by persistence of anti‐HCV in the majority of those who progressed to chronicity, whereas second‐generation ELISA usually showed persistence of anti‐HCV over time, regardless to the outcome of the disease. The pattern of anti‐HCV observed by first‐generation assay in children who experienced multiple episodes of acute NANBH was generally characterized by clearance of anti‐HCV after recovery, followed by reappearance and rise of the antibody titer concomitant with the new episode of acute hepatitis, whereas second‐generation assay revealed again the persistence of the antibody in most cases. This study shows that HCV is the major cause of NANBH among polytransfused thalassemics. Whether some posttransfusion NANBH without detectable anti‐HCV (10%) may be caused by viruses other than HCV remains to be clarified.

Seroepidemiology of hepatitis C virus in Beijing, China

To investigate the seroprevalence of hepatitis C virus (HCV) in China we tested sera from healthy individuals without hepatitis and no history of parenteral blood exposure and from patients admitted to a hepatitis hospital in Beijing. Sera were tested for anti-HCV by first-generation enzyme immunoassay; selected positives were tested with two second-generation EIAs, one utilizing recombinant antigens and the other synthetic peptides. We found anti-HCV with the following frequencies: 10 of 164 (6%) individuals with no disease; 2 of 36 (5.5%) patients with acute non-A non-B hepatitis (NANBH); 26 of 39 (67%) patients with post-transfusion NANBH; 10 of 34 (29%) patients with chronic hepatitis negative for hepatitis B surface antigen (HBsAg); 3 of 30 (10%) patients with chronic HBsAg-positive hepatitis; 0 of 19 patients with acute HBsAg-positive hepatitis. Of 24 repeat-positive sera, 19 were positive by both and 4 by one second-generation tests. We conclude that hepatitis C infection is common in China, that it contributes substantially to the incidence of post-transfusion hepatitis, and that HCV plays a significant role in both acute and chronic hepatitis. Further studies are needed to extend these observations and to define the predominant routes of transmission of HCV in China.

Etiological investigation of acute post‐transfusion non‐A, non‐B hepatitis in China

The etiology of acute post-transfusion hepatitis (PTH) non-A, non-B (NANB) in China was investigated with the combination of advanced techniques, including a second generation of enzyme immunoassay for detection of the antibodies to hepatitis C virus (anti-HCV), a reverse transcription and nested polymerase chain reaction (RT-nPCR) for HCV RNA, and a PCR for hepatitis B virus DNA. Of the 57 patients who were diagnosed as acute PTH-NANB, 46 (80.7%) were positive for anti-HCV and 41 (71.9%) had HCV RNA. Combining together, 53 (93.0%) were seropositive for anti-HCV and/or HCV RNA. Surprisingly, 18 of these with HCV markers were also positive for HBV DNA, although they were negative for HBsAg, suggesting that a portion of the patients with acute PTH NANB were coinfected by both HCV and HBV. In addition, 4 (7%) of the patients with acute PTH-NANB had no detectable HCV and HBV markers with the use of the above-mentioned techniques. These results indicate that etiologic agents(s) other than HCV and HBV may also cause acute PTH-NANB or that the current techniques may still not be sensitive enough to detect trace levels of HCV and HBV markers.

Predictive Value of Screening Tests for Persistent Hepatitis C Virus Infection Evidenced by Viraemia

In November 1989, Japanese Red Cross Blood Centres started screening for heaptitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the C100-3 viral peptide as the first such nationwide programme in the world. Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61-80%, but this was not as complete a success as our programme to prevent post-transfusion hepatitis B by screening for high titer hepatitis B core antibody, which we began in the same period. In order to acquire more effective control of PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa (Ortho2, Abbott2)and second-generation antigen agglutination (PA, PHA) tests have been employed. Among 16,500 donors in 11 blood centers, 365 were serologically positive by at least one of these tests. Among these, HCV RNA was detected in 138 units and the remaining 227 were HCV RNA negatives. The effectiveness of these serological tests to detect HCV RNA-positive status were analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests were highly effective to predict HCV viraemia among blood donors. Also, these tests can easily determine antibody titre. By either PHA or PA, all units with ^ 212 agglutination titre (120 and 122 units) were HCV RNA positive and all agglutination-positive units with serum alanine aminotransferase level higher than 35 Karmen units were HCV RNA positive. These results have formed the basis for implementing a more effective screening for HCV viraemia in blood donors, where effectiveness is defined as enhancing the protection of patients from post-transfusion hepatitis C and providing higher quality information to achieve more effective donor counselling.

Also with a restrictive transfusion policy, screening with second-generation anti-hepatitis C virus enzyme-linked immunosorbent assay would have reduced post-transfusion hepatitis C after open-heart surgery.

The incidence of post-transfusion hepatitis non-A, non-B (PTH-NANB) was prospectively assessed among open-heart surgery patients from the southeast region of Sweden before the introduction of antihepatitis C virus (HCV) blood donor screening. Blood samples for alanine aminotransferase analysis were drawn before and 2, 3, and 4 months after transfusion. Surgery was performed in four centres. Of 190 transfused and followed-up patients 2 (1.1%) contracted PTH-NANB, both operated on at the centre with significantly fewer transfusions than the other centres. One patient had antibodies to HCV detected by first-generation (C100-3) and later by second-generation anti-HCV enzyme-linked immunosorbent assay (ELISA-2) and by positive second-generation recombinant immunoblot assay (4-RIBA). The other patient, although negative by first-generation anti-HCV ELISA, was positive by second-generation ELISA and by 4-RIBA. Both patients were hepatitis C-viremic by polymerase chain reaction (PCR). All the six donors implicated in the two hepatitis cases were first-generation anti-HCV-negative, but two, one for each patient, were positive by second-generation anti-HCV ELISA. This finding was confirmed by positive 4-RIBA in only 1 donor, the other being 'indeterminate'. However, in both donors hepatitis C viremia was found by PCR. This study shows that the second-generation anti-HCV ELISA will further reduce the risk for PTH-NANB/C and draws attention to the problem of evaluation of confirmatory tests.

Transmission of serologically silent hepatitis B virus along with hepatitis C virus in two cases of posttransfusion hepatitis.

The polymerase chain reaction (PCR) was used to investigate the presence of hepatitis B virus (HBV)-related DNA sequences in blood from three blood donors and two transfusion recipients who developed posttransfusion non-A, non-B hepatitis (NANBH). In the first case, the sole donor was positive for antibody to hepatitis B surface (HBs) and core (HBc) antigens and had elevated alanine aminotransferase (ALT) levels, while the recipient had no HBV serologic markers. Both the donor and the recipient had serologic markers of hepatitis C virus (HCV) and were found positive for HBV DNA and HCV RNA sequences by PCR. The second case involved two donors and one recipient. Serologic tests for conventional HBV markers were negative in all three individuals, but one of the donors had elevated ALT. HBV DNA sequences were detected by PCR in the serum of the recipient and of the donor with high ALT, but not in the serum of the donor with normal ALT. Anti-HCV was detected in the serum of the recipient and of the suspect donor but not in that of the donor with normal ALT. The sequences amplified in the S region and determined after cloning of PCR products for both donor-recipient pairs were indistinguishable from each other and identical to the sequence of the major HBV subtype of adw in the first case and ayw in the second case. Furthermore, for the second case, an identical single-point mutation was found in both the donor and the recipient. These data confirm the transmission of conserved HBV sequences together with HCV in posttransfusion NANBH.(ABSTRACT TRUNCATED AT 250 WORDS)

Seroconversion to hepatitis C virus antibodies in patients with acute posttransfusion non-A, non-B hepatitis in Sweden with a second generation test.

28 patients with posttransfusion non-A, non-B (NANB) hepatitis in Stockholm, Sweden, were studied for seroconversion to hepatitis C virus antibodies (anti-HCV) and time lag to seroconversion by first and second generation tests. 15/28 patients (54%) seroconverted to anti-HCV with a first generation anti-HCV ELISA using C100-3 from the nonstructural (NS) region 4 of the HCV genome and 23 (82%) with a second generation anti-HCV ELISA including also antigens from the core and NS3 regions of the HCV genome. The mean time from onset of hepatitis to seroconversion was 6.1 weeks (0-18 weeks) with the first generation test and 2.3 weeks (0-7 weeks) with the second generation test. Development of chronic hepatitis was noticed in 14/23 (61%) patients who seroconverted to anti-HCV with the second generation ELISA and in none of 5 patients with posttransfusion NANB hepatitis who did not seroconvert. The inclusion of antigens from the core and NS3 regions of the HCV genome has increased the sensitivity of the second generation anti-HCV ELISA as compared to the first generation ELISA and also shortened the time lag to seroconversion in patients with posttransfusion hepatitis C. Patients with posttransfusion NANB hepatitis seroconverting seem more prone to develop chronic disease than patients not seroconverting.

Anti-hepatitis C virus screening will reduce the incidence of post-transfusion hepatitis C also in low-risk areas.

The incidence of post-transfusion hepatitis non-A, non-B (PTH-NANB) was prospectively assessed in two areas in the southeast region of Sweden. Patients undergoing hip arthroplasty were studied with blood sampling for alanine aminotransferase analysis before and at 2, 3, and 4 months after transfusion. Of the patients 97% and 82% were transfused and received a mean of 5.5 and 3.4 units in Linköping and Oskarshamn, respectively. None of 38 patients in Oskarshamn but 4 of 144 patients (2.8%) in Linköping contracted PTH-NANB. Two of these four patients developed antibodies against hepatitis C virus (HCV) by the first-generation anti-HCV enzyme-linked immunosorbent assay (ELISA) (C100). The other two patients remained negative by this test. HCV infection was, however, indicated in all four patients by positive second-generation anti-HCV ELISA confirmed by positive second-generation recombinant immunoblot assay (4-RIBA). Three of the patients were positive by polymerase chain reaction (PCR). Serum from one blood donor to the four hepatitis patients (altogether three donors) was found positive by first- and second-generation anti-HCV ELISA and 4-RIBA and was also PCR-positive. Three other blood donors, who did not transmit hepatitis, were anti-HCV ELISA (C100)-positive. This study shows that if anti-HCV ELISA had been available at the start of the trial, all cases of PTH would have been avoided at the expense of only 0.7% transfusion units discarded. Routine anti-HCV ELISA testing of all transfusion units will reduce the incidence of PTH-C even in low-risk areas.

Hepatitis C virus antibody response in acute and chronic non-A, non-B hepatitis.

Patients with post-transfusion, community-acquired or hemodialysis-acquired non-A, non-B hepatitis (NANBH) were tested for antibody to hepatitis C virus (HCV) during acute-phase and resolving or chronicized illness. HCV appears to be involved in most cases of post-transfusion and hemodialysis-acquired NANBH, but only in 40% of community-acquired NANBH. Second generation HCV antibody assays are more specific and sensitive, favoring early detection of HCV seroconversion and identification of HCV-antibody-positive individuals years after exposure to the virus.

Serodiagnosis of hepatitis C virus infection by ELISA for antibodies against the putative core protein (p20 c) expressed in Escherichia coli

The putative core gene of hepatitis C virus (HCV) was incorporated into a plasmid vector (pCC5-J4), and expressed in Escherichia coli. The product of 180 amino acids (p20 c) was purified by gel electrophoresis in the presence of sodium dodecyl sulfate, and used in enzyme-linked immunosorbent assay for antibodies against the putative core protein of HCV (anti-p20 c). Anti-p20 c was detected in 13 (1.5%) of 873 apparently healthy blood donors. It was detected in 205 (86.5%) of 237 patients with acute or chronic non-A, non-B (NANB) hepatic disease, significantly more frequently ( p < 0.01) than antibodies against the C100-3 protein encoded by nonstructural regions of HCV (anti-C100-3) that was found in 178 (75.1%). Anti-p20 c developed in the circulation of a patient with acute NANB hepatitis much earlier than anti-C100-3. HCV RNA was detected by polymerase chain reaction in serum samples from blood donors positive for anti-p20 c in high titers, one of which was negative for anti-C100-3. These results indicated that anti-p20 c would be useful in complementing anti-C100-3 for the diagnosis of NANB hepatitis and further decreasing the incidence of posttransfusion NANB hepatitis.

Post-transfusion NANBH in the light of a test for anti-HCV

The incidence of post-transfusion hepatitis (PTH) varies over an order of magnitude in different parts of the world. For example, prospective studies from Spain and the UK reveal rates of PTH of approximately 10 and 0.5% respectively. Similarly the association of a history of transfusion in patients with chronic liver disease varies widely; in Japan, with high rates of PTH, the association appears obvious whereas in the UK less obvious. These factors must be taken into account when assessing the cost-effectiveness of pre-transfusion screening for anti-HCV. A useful approach to assessing the value of screening donors for anti-HCV is to study prospectively the correlation of anti-HCV and PTH. In carefully selected cases of PTH, the correlation of anti-HCV and PTH in donor-recipient sets of samples may be very high. However, the predictive value of ‘first-generation’ assays for anti-HCV in routine studies of unselected cases of PTH may be less than 20% in countries with low rates of transfusion-transmitted non-A, non-B hepatitis (NANBH). The anti-HCV screening tests and supplementary assays are continually evolving. More recent assays incorporate structural as well as non-structural antigens in both types of ELISA use for screening and in the supplementary tests such as the recombinant based immunoblots. The polymerase chain reaction (PCR) is also valuable for confirmation of viraemia but a negative result does not rule out the possibility of the presence of antibody in the absence of virus; nor can it rule out the presence of virus in very low levels in the blood stream, although virus may be present at a higher level in the liver or other tissues. However, these highly sophisticated supplementary assays are very expensive and their value as components of mass screening programmes must be assessed for each individual country before they are implemented.

Hepatitis C: Improving the diagnostic armamentarium

A new four-antigen recombinant immunoblot assay (4-RIBA) for confirmation of hepatitis C virus (HCV) C-100 enzyme-linked immunosorbent assay (ELISA) reactivity was tested in stored serum samples (1984–86) of blood donors and recipients and compared with results from polymerase chain reaction (PCR) analysis of fresh (1990) plasma samples in donors and recipients from the original study. Of 37 HCV C-100 ELISA-positive blood products, 8 were 4-RIBA positive, of which 7 were implicated in post-transfusion non-A, non-B hepatitis (PT-NANBH) and/or PCR confirmed recipient HCV infection. Of 9 recipients with PTNANBH, 8 were reactive in 4-RIBA (6 positive and 2 indeterminate). With fresh plasma samples, 3 donors and 6 recipients who were 4-RIBA positive were also PCR positive. 4 4-RIBA indeterminate and 78 4-RIBA negative samples of donors and recipients were PCR negative. Of 6 4-RIBA positive recipients, 5 were PCR positive four to six years later. 1.6% of the 383 recipients became chronically infected with HCV. The new 4-RIBA represents a candidate confirmation test to discriminate between infective and non-infective HCV C-100 ELISA-positive blood donors.

Hepatitis C virus infection in Japan

Because of the high incidence of non-A non-B post transfusion hepatitis and its relation to hepatocellular carcinoma, HCV antibody screening for blood transfusion was begun in November 1989. Seroepidemiological studies revealed the great magnitude of HCV infection in acute hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in Japan. Approximately 1.6 million HCV antibody-positive persons are now in Japan. Major routes of infection are considered to be horizontal blood borne infection in the past and blood transfusion.

Immunological abnormalities in acute posttransfusion hepatitis non‐A non‐B

A variety of immunological parameters has been serially examined in the blood of 12 patients with acute post-transfusion hepatitis non-A non-B (PTHNANB). Several alterations of these tests were transiently detected when comparing with healthy, extensively transfused subjects as well as with normal volunteers: 1. Low proportions of CD8+ T lymphocytes were observed at the disease onset, and these returned to normal after 1 month; 2. A diminution of the proliferative response of blood lymphocytes to mitogens was detected during the same period of time; 3. By the third month of disease, an enhanced spontaneous IgG secretion by cultured lymphocytes was found, and this observation was restricted to those patients who had not recovered. These alterations suggest that the immune system might be involved in the course of hepatitis C virus infection.