Clinical features and progression of perinatally acquired hepatitis C virus infection

The purpose of this prospective-retrospective study was to provide information about the clinical features and progression of hepatitis C virus (HCV) infection transmitted perinatally. Seventy children born to HCV infected woman were enrolled consecutively in five European centers between 1990 and 1999, provided they had HCV RNA in the serum during the first year of life and/or were still anti-HCV positive at 18 months. Sixty-two infants were followed up to 24 months of age or more (range, 24 months-11 years; average, 4.8 +/- 2.3 years). A wide range of ALT elevation was observed in 93% of the infants in the first year of life. During the follow-up, a sustained ALT normalization with loss of HCV RNA was seen in 12/62 (19%) of the children within 30 months of life; 66% of the infants had developed an ALT peak greater than 5x normal at onset (vs. 28% of children with persistent viremia; P < 0.05), and 50% had HCV genotype 3 (vs. 17% of viremic children). Conversely the cumulative probability of chronic progression was 81%. Chronic infection was asymptomatic and liver disease was mild in all 11 children who underwent a biopsy. In conclusion the early stage of acquired perinatally HCV infection is characterized by a wide range of ALT abnormalities, suggesting the interaction of multiple host and virus factors. The chronic progression rate of infection is high, but the associated liver disease is usually mild. High ALT levels at onset seem to offer greater opportunity of biochemical remission and loss of viremia during follow-up.     

Evolution of hepatitis G in children with vertically transmitted HGV

Background A new hepatitis-associated RNA virus, belonging to the Flaviviridae, has been recently discovered and called HGV (GBV-C). This virus has been shown to be transmitted parenterally. In this study we examined a group of children born to HCV infected women. Methods Between September 1994 and December 1998, we studied a cohort of 53 pregnant women, aged between 20 and 43 years. They were all HCV Ab and HCV RNA positive, with a diagnosis of chronic hepatitis. One patient was HbsAg positive and 4 patients (pts.) (7.5%) were HIV Ab positive. Anamnestic information revealed that: 28 pts. (52.8%) were IVDUs, 11 pts. (20.8%) had been haemotransfused and 14 pts. (26.4%) had no risk factors. We examined HGV RNA by RT nested PCR, using primers from the 5'UTR of HGV. Anti-HGV antibodies (anti-E2) were detected with an ELISA test using recombinant E2 protein. Ten of the 53 pregnant women (18.9%) were HGV RNA positive (32 other pts., 60.4%, were positive for anti-E2 antibodies). We monitored their children for 18-24 months (with clinicai and haematological controls), looking for HGV RNA, anti-E2 antibodies, HCV RNA and for ALT serum levels. Results Seven (70%) new-bom children proved HGV RNA positive at follow-up; all babies were HCV RNA negative at controls. Four of them were born vaginally; none of them was breast-fed. HGV RNA was first detectable at the 3rd month of life in 3 babies, and all babies were HGV RNA positive at the 6th month of life. Six babies (85.7%) remained positive during the observation period. One baby (14.3%) seroconverted at 10 months, developing anti E-2 antibodies and becoming HGV RNA negative. Four babies (57.1%) maintained normal ALT serum levels during the whole follow-up period, while 3 patients showed a low increase in ALT serum levels. The ALT values normalised at later controls. Conclusions HGV infection shows a very high (70%) rate of vertical transmission but a low and doubtful pathogenicity with asymptomatic evolution in babies. Patients who did not develop anti-E2 antibodies at the 12th month of life remained infected without persistent signs of hepatic failure.     

Mother to infant transmission of hepatitis C virus infection

Eight women with chronic hepatitis C virus (HCV) infection during pregnancy gave birth to 11 children. Five of these children had elevated ALT, but only two had increased levels in more than one sample. All children tested before 6 months of age were positive for anti-HCV at most up to 7 months of age and then became negative. One child with a maximum ALT level of 8.4 mukat/l however, regained anti-HCV positivity at 12 months of age, and a liver biopsy at 21 months of age showed resolving hepatitis. Passively acquired HCV antibodies are obviously found in newborns of anti-HCV-positive mothers with chronic hepatitis. In 1 of 11 children, active anti-HCV production and concomitant liver disease suggested mother to infant transmission of hepatitis C virus infection.     

Multicenter trial on mother-to-infant transmission of GBV-C virus

Evidence indicates that the GBV-C or hepatitis G virus can cause persistent infection in humans, but little is known on the importance of vertical transmission. To assess the risk of mother-to-infant transmission and the clinical outcome of infected babies, we investigated 175 anti-HCV positive mothers and followed-up their children for 3–33 months. GBV-C RNA was detected by RT-PCR and anti-E2 antibody was assayed by EIA. Thirty-four (19.4%) women were GBV-C RNA positive and transmission occurred to 21 (61.8%) babies; 20 (95.2%) acquired GBV-C alone, and one (4.8%) GBV-C and HCV. Maternal factors such as intravenous drug use, HIV coinfection, HCV-RNA positivity, and type of feeding were not correlated with GBV-C transmission. GBV-C RNA remained persistently positive in all infected babies but one baby who seroconverted to anti-E2. Seven (35%) babies with GBV-C alone developed marginally elevated ALT; the baby with HCV and GBV-C co-infection had the highest ALT peak value (664 IU/l). Seven of the 141 (5%) babies born to the GBV-C RNA negative mothers acquired HCV and six (85.7%) had abnormal ALT. The mean ALT peak value was significantly higher (P < 0.05) for babies with HCV than for those with GBV- C. None of the children with GBV-C or with HCV became icteric. GBV-C is frequently present in anti-HCV positive women. The infection is transmitted efficiently from mother to baby and rate of transmission is much higher than that for HCV. GBV-C can cause persistent infection in babies but usually without clear evidence of liver disease. J. Med. Virol. 54: 107–112, 1998. © 1998 Wiley-Liss,Inc.     

Accuracy of HCV-RNA PCR tests for diagnosis or exclusion of vertically acquired HCV infection

The aim of the study was to estimate the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and likelihood ratios for HCV-RNA PCR tests for the early diagnosis or exclusion of HCV infection in vertically exposed children. Data were included for children with confirmed HCV infection status from a European multi-center study. Confirmation was dependent on antibody status at or beyond 18 months, the 'gold standard' measure of infection status against which the use of qualitative HCV-RNA PCR tests was assessed. Of the 547 children included in this analysis, 193 were HCV-infected and 354 were not. Sensitivity of the HCV-RNA PCR test was low at birth (22%), but increased to 85% by 6 months. Specificity of RNA PCR was constant over age at 98%. The PPV of the PCR test rose from 33% at birth to 78% at 9 months of age, while NPV ranged from 96% to 99%. The high positive likelihood ratios from 1 month of age indicate strong evidence to diagnose infection but the negative likelihood ratios were consistent with weak evidence to exclude infection. The results suggest that the first qualitative HCV-RNA PCR test should be delayed until after the first month of life given the low sensitivity in the first few weeks. Although a negative test result after this time indicates probable absence of infection, this should be confirmed with a negative anti-HCV antibody test between 9 and 15 months of age as negative PCR results can be observed in infected children with fluctuations in viremia.     

聚合酶链反应鉴定丙型肝炎病毒母婴传播的状态及其…

采用多种方法,动态检测了１１例丙型肝炎病毒感的孕妇所生的婴儿血抗－ＨＣＶ和ＨＣＶＲＮＡ。发现用合成肽酶联免疫吸附试验检测婴儿抗－ＨＣＶ阳性率显著低于第二低重组抗原ＥＬＩＳＡ;用２ｎｄＥＬＩＳＡ检测,６例婴儿脐血和静脉血抗－ＨＣＶ阳性,５例持续１－５月阴转,１例阳性持续１３个月。     

Impaired response to alpha interferon in patients with an inapparent hepatitis B and hepatitis C virus coinfection

Summary.  The possibility of hepatitis B virus (HBV) infection in HBsAg-negative patients has been shown. However, an “inapparent” coinfection by HBV in hepatitis C virus (HCV)-positive patients generally is not taken into account in clinical practice. Mechanisms responsible for resistance to interferon (IFN) have not been completely clarified. The aim of this study was to investigate whether an “inapparent” coinfection by HBV in anti-HCV-positive chronic liver disease patients may influence IFN response. Fourteen anti-HCV positive, HBsAg-negative but serum HBV DNA-positive patients by PCR and 111 anti-HCV-positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis were treated with 3 MU of recombinant α-2a IFN 3 times weekly for 12 months. Serum HBV DNA and HCV RNA were determined before treatment, after 6–12 months and in coincidence with ALT flare-up by PCR. HBV PCR was performed using primers specific for the S region of the HBV genome and HCV PCR with primers localised in the 5′NC region of HCV genome. IgM anti-HBc was tested using IMx Core-M Abbott assay. By the end of treatment, ALT values had become normal in 4/14 HBV DNA-positive patients (28%), but all “responders” (4/4) relapsed between 2 and 5 months after therapy. All but one patient were HCV RNA-positive before treatment, 6 were also both HBV DNA and HCV RNA-positive during ALT flare-ups. In 5 patients, only HBV DNA and in 3 patients, only HCV RNA was detected when transaminase values increased. All patients remained HBsAg-negative and anti-HCV-positive. IgM anti-HBc was detected both before treatment and during ALT elevation in 3 patients and only during ALT relapse in 3 others. Of the 111 anti-HCV positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis, a biochemical response to IFN treatment was observed in 54% of the cases. Relapse of ALT values was observed in 47% of the cases during a follow-up of 1 year after treatment. “Inapparent” HBV/HCV coinfection may be implicated in cases of resistance to IFN treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by IFN treatment. The pathogenic role of HBV in liver disease was confirmed by detection of IgM anti-HBc in some cases; the appearance of these antibodies only after IFN treatment suggests that IFN may exert a selective role in favour of HBV. Further studies will show the effect of different treatment schedules. HBV DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding interviral relationships and mechanisms involved in multiple hepatitis virus infections.     

Twenty-four mini-pool HCV RNA screening outside a blood transfusion setting: results of a 2-year prospective study

The usefulness of 24 mini-pool hepatitis C virus (HCV) RNA screening was evaluated in a 2-year prospective study carried out on a total of 6432 consecutive anti-HCV negative specimens in a routine diagnostic laboratory setting. A total of 268 mini-pools were tested using an automated commercial PCR assay for qualitative detection of HCV RNA, with a lower limit of detection of 50 IU/ml. Eighteen (0.28%) anti-HCV negative/HCV RNA positive serum samples obtained from 12 patients (all intravenous drug users), were detected. Ten patients responded to an invitation for follow-up testing. Five, three and one patient seroconverted in the first, second and third follow-up sample, respectively. One patient had not seroconverted by the end of the study period. The interval between the first HCV RNA positive sample and the first anti-HCV positive samples was 24–192 days. The costs of detecting a single anti-HCV negative/HCV RNA positive sample and a single anti-HCV negative/HCV RNA positive patient using the 24 mini-pool HCV RNA screening strategy were estimated to be around €643 and 965, respectively. It was shown that screening for HCV infection using the 24 mini-pool HCV RNA screening strategy can also be both useful and cost effective outside a blood transfusion setting.     

肝病产妇丙型肝炎病毒母婴传播的可能性调查

对１９９１～１９９３年在南京市钟阜医院肝病产科住院的１０４７例肝病产妇中１２例丙型肝炎病毒抗体和／或丙型肝炎病毒核糖核酸阳性者，追踪观察了所生１２名婴儿的丙型肝炎病毒感染情况，发现１例抗－ＨＣＶ和ＨＣＶＲＮＡ均阳性的孕妇所生的婴儿，０、１、６和１２个月时抗－ＨＣＶ和ＨＣＶＲＮＡ均阳性，且该婴儿ＨＣＶ的血清型与母亲一致。结果提示，肝病产妇丙型肝炎病毒母婴传播是可能的，但不是主要的传播途径。     

GB virus C (GBV-C) infection in patients with chronic hepatitis C. Influence on liver disease and on hepatitis virus behaviour: Effect of interferon alfa therapy

The aim of this study was to evaluate, in patients with chronic hepatitis C, 1) the prevalence and the epidemiological characteristics of GB virus C (GBV-C) infection, 2) the influence of GBV-C on hepatitis C virus (HCV) infection, 3) the pathogenicity of GBV-C in the absence of treatment and under interferon therapy, and 4) the effect of interferon alfa on GBV-C and HCV replications. One hundred fifteen patients with chronic hepatitis C were studied. Before treatment, they were tested for GBV-C RNA by PCR and GBV-C genotype was determined for positive samples. Pretreatment information was collected, including age, gender, source of HCV, estimated duration of HCV infection, alanine aminotransferase and gamma-glutamyl transpeptidase activities, cirrhosis and Knodell's score on liver biopsy, HCV genotype, HCV viral burden and anti-HCV core IgM antibodies. The genetic complexity of the hypervariable region 1 (HVR1) of HCV was studied by PCR-Single Strand Conformation Polymorphism. All patients were treated with 3 to 9 mega units of interferon alfa-2a three times per week for 3 to 6 months. The influence of GBV-C on the evolution of ALT and HCV replication during and after treatment was studied, and GBV-C and HCV RNA were monitored monthly by PCR during this period. Eighteen patients (16%) were GBV-C RNA-positive. Among 11 samples studied, GBV-C genotype 2a was present in 9 cases, 2b in one case and type 3 in one case. GBV-C RNA-positive patients were significantly younger than GBV-C RNA-negative ones (38.4 ± 11.5 vs. 47.4 ± 14.0, P = 0.012), a result independent of the route of transmission and the disease duration. No difference between GBV-C RNA-positive and -negative patients was found for other epidemiological parameters (e.g. gender, risk factor for parenteral viral infections, disease duration and HCV genotypes), or for the characteristics of HCV infection and related liver disease (e.g. HCV RNA level, genetic complexity of the HVR1, anti-HCV core IgM, alanine aminotransferase and gamma-glutamyl transpeptidase activities, cirrhosis and Knodell's score). GBV-C did not influence the rates of ALT normalization at months 3, 6 and 12 and of sustained hepatitis C virological response at month 12 of treatment follow-up. During treatment, GBV-C viremia became undetectable in 12 patients (67%) but relapse occurred after treatment withdrawal in all the nine patients with sufficient follow-up. In the remaining six patients (33%), GBV-C resisted interferon. Whatever the effect of interferon on GBV-C replication, the ALT levels correlated with the presence of HCV RNA. In conclusion, GBV-C infection is frequent in patients with chronic hepatitis C, who are mainly, but not exclusively, infected by GBV-C genotype 2a. GBV-C positive patients are significantly younger than GBV-C negative ones. GBV-C does not seem to affect HCV replication, liver disease and responses of HCV infection and liver disease to interferon therapy. GBV-C is sensitive to 3 mega units of interferon alfa administered three times per week in two-thirds of the patients, but relapse is constant with this dosage after treatment withdrawal. J. Med. Virol. 54:26–37, 1998. © 1998 Wiley-Liss, Inc.     

Predicting factors of present hepatitis C virus infection among patients positive for the hepatitis C virus antibody

Background/Aims

To identify the predicting factors of present hepatitis C virus (HCV) infection among patients with positivity for antibodies to HCV (anti-HCV).

Methods

We analyzed patients who showed positive enzyme immunoassay (EIA) results and performed an HCV RNA test as a confirmatory test at Kyung Hee University Hospital at Gangdong from June 2006 to July 2012. The features distinguishing the groups with positive and negative HCV RNA results were reviewed.

Results

In total, 490 patients were included. The results of the HCV RNA test were positive and negative in 228 and 262 patients, respectively. The index value of anti-HCV, mean age, platelet counts, total bilirubin, prothrombin time international normalized ratio, albumin and alanine transaminase (ALT) levels differed significantly between the two groups. On multivariable analysis, an index value of anti-HCV >10 [odds ratio (OR)=397.27, P<0.001), ALT >40 IU/L (OR=3.64, P=0.001), and albumin <3.8 g/dL (OR=2.66, P=0.014) were related to present HCV infection.

Conclusions

Although EIA is not a quantitative test, considering the anti-HCV titer with ALT and albumin levels may be helpful in predicting present of HCV infection.     

Simultaneous detection of hepatitis C virus (HCV) core antigen and anti-HCV antibodies improves the early detection of HCV infection

To evaluate whether a new enzyme immunoassay developed for the simultaneous detection of hepatitis C virus (HCV) core antigen (Ag) and anti-HCV antibodies (anti-HCV Ab) (Monolisa HCV Ag/Ab ULTRA; Bio-Rad) could improve the early detection of HCV infection, we compared its sensitivity to that of anti-HCV, HCV core Ag, and HCV RNA assays. The populations studied included 12 blood donor samples positive for HCV RNA and HCV core Ag but negative for anti-HCV antibodies and 23 hemodialysis patients who developed anti-HCV Ab (seroconversion) during the follow-up. From these 23 individuals, 83 samples sequentially collected prior to seroconversion and 108 samples collected after seroconversion were tested. Six of 12 blood donations were positive by the HCV Ag/Ab assay. In the hemodialysis cohort, the 24 HCV RNA-negative samples were negative by the HCV Ag/Ab assay and 23 of the 59 HCV RNA-positive samples (39%) were positive. The HCV Ag/Ab assay detected HCV infection on average 21.6 days before the most sensitive antibody assay. The HCV Ag/Ab assay did not detect HCV infection as early as the HCV RNA assay (mean delay, 30.3 days) or HCV Ag assay (mean delays, 27.9, and 16.3 days by the HCV core Ag quantification assay and the HCV Ag blood screening assay, respectively). This new assay provides a notable improvement for the early detection of HCV infection during the so-called window period compared with anti-HCV Ab assays and could be a useful alternative to HCV RNA detection or HCV core Ag assays for diagnosis or blood screening when nucleic acid technologies or HCV core Ag detection are not implemented.     

Human parechovirus 1 infections in young children--no association with type 1 diabetes

The epidemiology, transmission and clinical symptoms of human parechoviruses [HPeV, classified earlier as enteroviruses; echovirus 22 (HPeV1) and echovirus 23 (HPeV2)] remain poorly characterized. Enteroviruses and one parechovirus species, the Ljungan virus, have been associated with type 1 diabetes in humans and rodents. The occurrence of human parechovirus 1 (HPeV1) infections in young children and their possible association with type 1 diabetes was evaluated. The prospective birth cohort study comprised 221 Finnish children carrying genetic type 1 diabetes susceptibility and who were observed from birth. Thirty-four children developed multiple diabetes-associated autoantibodies, and 18 children progressed to clinical type 1 diabetes during the follow-up. HPeV1 infections were diagnosed by measuring neutralizing antibodies from the follow-up sera taken every 3-12 months. In addition, viral RNA was analysed by RT-PCR from stool samples taken every month from six of the participants. HPeV1 infections were found to occur early in childhood. The median age of infection was 18 months and 20% of the children had had an infection by the age of 1 year. The number of infections started to increase from the age of 6 months and most children had their first infection by 36 months. Nearly all (99%) mothers were HPeV1 antibody positive. No difference was found in infection frequency between boys and girls, nor between prediabetic, diabetic and control subjects. Most infections (87%) occurred during autumn, winter and spring.     

Prevalence of anti-HCV and HCV viremia in hemodialysis patients in Taiwan.

Hepatitis C viral infection in 125 hemodialysis patients from Taiwan was studied using a second-generation anti-HCV immunoassay (EIA II) (Abbott HCV 2.0 EIA) and the polymerase chain reaction (PCR) to detect the HCV RNA in the serum. A total of 59 patients (47.2%) were positive by EIA II. In comparison, the conventional C100-3 anti-HCV assay was positive in 40 (32.0%). HCV RNA was found in 47 patients (37.6%). Patients with elevated serum transaminase level had a higher positive rate of anti-HCV and HCV RNA. The dialysis time was longer for those patients positive for anti-HCV than for those who were negative. A total of 57 of the 59 EIA II-positive cases had a history of blood transfusion. The HBsAg status did not influence the anti-HCV positivity. Among the 59 EIA II-positive patients, 66.1% were also positive for HCV RNA, and of the 47 HCV RNA-positive cases 83.0% were positive for EIA II. It is concluded that the high prevalence of specific HCV infection and HCV viremia was present in these patients. Prevention of cross-contamination during dialysis and blood screening before transfusion are important for the control of HCV infection in these patients.     

Hepatitis C virus infection among pregnant women in Yaounde,Cameroon: prevalence,viremia, and genotypes

Central Africa is considered to be an area of high endemic hepatitis C infection. To determine the prevalence of anti-HCV antibodies, HCV RNA, and the genotype distribution in Cameroon, 1,494 pregnant women attending antenatal care units in Yaounde, Cameroon were screened for HCV infection. Anti-HCV antibodies were detected with a 3rd generation ELISA (Monolisa anti-HCV plus version 2, BioRad, Richmond, CA). All anti-HCV antibody-positive sera were then tested with another 3rd generation ELISA (AxSYM) HCV version 3, Abbott Laboratories, Abbott Park, IL) and subsequently for HCV RNA (Amplicor HCV, Roche Diagnostics, Basel, Switzerland). Genotype was determined by phylogenetic analysis of the NS5b gene. Seventy-three pregnant women were found to be anti-HCV antibody positive by the first ELISA, but only 28 were anti-HCV positive by both ELISA. The prevalence of anti-HCV antibodies was thus 1.9% (28/1,494) (95% CI: 1.3-2.7%). 21/28 (75%) of the positive samples by both ELISA were HCV RNA positive. The 45 samples that were HCV antibody negative by the second ELISA were also HCV RNA negative. The HCV subtypes identified were 1a (24%), 2f (38%) and 4f (38%). In contrast to previous studies, anti-HCV antibodies were rare among pregnant women in Cameroon. The percentage of HCV seropositive pregnant women who had circulating HCV RNA was similar to that observed in Europe. Several HCV genotypes were found in Cameroon.     

Mother-to-infant transmission of hepatitis C virus: rate of infection and assessment of viral load and IgM anti-HCV as risk factors

One hundred twenty-six mother-infant couples were studied and 105 exposed babies were monitored for at least 12 months to define the risk of mother-to-infant HCV transmission. Infection occurred in 5 out of 76 infants (6.6%) born to 69 viraemic mothers and in none of 29 born to 26 non-viraemic mothers. Only one child was HCV RNA positive one month after birth, while the remaining children became positive at the 3rd to 4th month. HCV genotypes of the babies matched those of their mothers. No difference was found between women who transmitted the virus and those who did not with regard to age, history of drug abuse, HIV infection, ALT abnormal values, HCV genotype, type of delivery, and breast-feeding. Four out of 5 infected infants were born to mothers with IgM anti-HCV (P = 0.04). The mean viral titre in transmitting women (10(7.2)) was higher than in non-transmitting (10(6.5)), and the proportion of mothers with viral load > or = 10(7) was statistically higher in transmitting than non-transmitting women (P = 0.03). These data show that HCV perinatal infection is a rare event and suggest that IgM positivity and high viral load (> or = 10(7)) in the mother are independent variables correlated with HCV transmission (O.R. = 14.5; 95% CI: 1.3-160.7 and O.R. = 16.3; 95% CI: 1.5-179.9, respectively).     

Occult hepatitis C virus infection during an outbreak in a hemodialysis unit in Thailand

Control of hepatitis C virus (HCV) in hemodialysis populations is a major public health priority, but the preferred methods to prevent and rapidly detect HCV outbreaks in these populations remains subject to debate. We enrolled 231 hemodialysis patients at three dialysis centers in Chiang Mai, Thailand. Patients were followed every 6 months for 3 years and tested for the presence of serum HCV antibody and HCV RNA at each visit. We additionally isolated and tested peripheral blood mononuclear cells (PBMCs) for HCV RNA collected at the 30-month follow-up visit. Fifty-one study participants negative for anti-HCV at the baseline enrollment visit seroconverted over the course of the 3-year follow-up period. Of 11 individuals who transiently lost detectable serum HCV viremia, we were able to detect HCV RNA from the PBMCs of two individuals. Our results suggest that occult HCV infection may be common among hemodialysis patients, and serum HCV RNA testing may be supplemented with PBMC testing to maximize diagnostic sensitivity and aid in outbreak containment. Further work on the diagnostic implications of HCV compartmentalization in hemodialysis and other settings is urgently needed.     

Coxsackie B virus infections in women with miscarriage

Serum samples from 1,765 consecutive Sardinian blood donors, negative for hepatitis B surface antigen (HBsAg) and for antibodies to human immunodeficiency virus (HIV) (anti-HIV), were evaluated for the presence of antibodies to hepatitis C virus (anti-HCV) by second-generation ELISA. Anti-HCV was detected in 25 (1.45%) of the 1,765 donors examined. Anti-HCV was found in 15 of the 1,690 (0.9%) donors with normal alanine aminotransferase (ALT) and in 10 of the 75 (13%) donors with elevated ALT (P < 0.0001). Of the 15 anti-HCV-positive donors with normal ALT, only five (33%) were confirmed to be positive by second-generation RIBA, six (40%) were indeterminate, while four (27%) were RIBA negative. HCV RNA, as detected by polymerase chain reaction (PCR) using a set of primers from the 5′-noncoding region, was found in six of the 15 (40%) donors with normal ALT, including five RIBA, positive and one indeterminant. Of the 10 anti-HCV-positive donors with elevated ALT, all were RIBA positive and eight (80%) had detectable HCV RNA. Thus, among ELISA-reactive donors, those with elevated ALT had a significantly higher probability of being positive for secondgeneration RIBA and HCV RNA compared to those with normal ALT levels (P = 0.028). None of the 65 donors with elevated ALT but negative for anti-HCV by ELISA had detectable serum HCV RNA, as compared to eight of 10 anti-HCV ELISApositive donors (P < 0.0001). However, although negative for HBsAg, 12 of the 65 (18%) had serum HBV DNA by PCR. This study demonstrates that the combined use of second-generation ELISA and RIBA anti-HCV assays is highly effective in identifying HCV infection, whereas the specificity of ELISA alone for the screening of blood donors with normal ALT values appears to be limited. In contrast, in donors with elevated ALT levels, there is a positive correlation between second-generation assays (ELISA and RIBA) and HCV viremia. The high proportion of inapparent HBV infection in blood donors with elevated ALT levels underlines the importance of this test for the prevention of transfusion-associated viral hepatitis.     

Immunosuppressive therapy and hepatitis C virus infection: the clinical course of liver disease

In a retrospective long-term follow-up study the clinical course of liver disease was examined in renal allograft recipients with hepatitis C virus (HCV) infection and negative hepatitis B surface antigen under immunosuppressive therapy. We compared 42 anti-HCV antibody (anti-HCV) positive patients (study group) to 213 anti-HCV negative patients (control group). All patients received immunosuppressive therapy. Measurements were made of the following: aminotransferases, bilirubin, albumin, gammaglobulins, ascites, spleen diameter, HCV RNA, and anti-HCV antibody. We found all but four anti-HCV positive patients to be HCV RNA positive prior to transplantation. There were no differences in overall mortality or mortality secondary to liver disease or sepsis. Normal liver enzymes were found in 13 (31%) anti-HCV positive and in 137 (64%) anti-HCV negative patients during the whole mean observation period of 65 months (range 10–215). Aminotransferase activity decreased in anti-HCV positive and negative patients during the observation period. Liver function with regard to synthesis and excretion was normal in anti-HCV negative and anti-HCV positive patients. No signs of portal hypertension were observed in the anti-HCV positive group. Neither the different immunosuppressive regimens nor the antirejection therapy led to differences between anti-HCV positive and negative groups with respect to liver function and did not alter the clinical course. We conclude that HCV infection in patients under immunosuppressive therapy causes only a mild liver disease, as determined by clinicochemical and clinical parameters, and that mortality rate is not increased.Abbreviations ALT Alanine aminotransferase - AST Aspartate aminotransferase - CMV Cytomegalovirus - EBV Epstein-Barr virus - ELISA Enzyme-linked immunosorbent assay - HBsAg Hepatitis B surface antigen - HCV Hepatitis C virus