Transmission of and liver injury by TT virus in patients on maintenance hemodialysis

To study the prevalence and clinical significance of TT virus (TTV) infection in hemodialysis patients, we tested for TTV DNA in serum, using the nested polymerase chain reaction. The prevalence of TTV DNA in 352 hemodialysis patients was 32%, significantly higher than that in 50 healthy blood donors (12%). The prevalence increased with age (P = 0.0098); it was 20% (22/110) in patients aged less than 49 years, 37% (69/188) in those aged 50–69 years, and 41% (22/54) in those aged over 70 years. Other clinical features and the prevalence of other hepatitis viral markers tested did not differ between patients with TTV DNA and those without it. The detection rate of hepatitis C virus (HCV) and hepatitis G virus (HGV) viremias increased with duration of hemodialysis and with the number of blood transfusion units, but the prevalence of TTV viremia did not. Twenty-nine of 91 patients followed for 5 years were initially positive for TTV DNA. Of these 29 patients, 17 (59%) carried this viremia for at least 5 years. Fourteen of the 62 patients (23%) who were initially negative for TTV DNA acquired TTV viremia. Serum alanine aminotransferase (ALT) levels were elevated in patients with HCV viremia but not in patients with HGV or TTV viremia. However, the mean ALT level in patients with all three viremias (HCV, HGV, and TTV) was significantly higher than that in patients with one or two of the viremias. More than 30% of the hemodialysis patients had TTV viremia and the carrier state was maintained for years. The hemodialysis procedures, including blood transfusion, did not seem to be crucial for the transmission of TTV. The pathogenic effects of TTV on hepatitis appear to be limited. (Received July 21, 1998; accepted Sept. 25, 1998)     

Incidence of Post-Transfusion Hepatitis before and after Screening for Hepatitis C Virus Antibody

To evaluate the effectiveness of screening test for antibody to hepatitis C virus (anti-HCV), the incidence of acute post-transfusion HCV infection in patients who underwent cardiovascular surgery and received blood transfusion was studied. All patients were followed prospectively with serum biochemistry tests and viral hepatitis markers before and periodically for at least 6 months after cardiovascular surgery. None of them had history of liver disease and none tested positive for anti-HCV prior to blood transfusion. Before blood donors were screened for anti-HCV with a second-generation HCV diagnostic kit, 28 (12.4%) of 226 patients or 0.49% of 5,690 unit transfusion had seroconverted to anti-HCV during a 6-month follow-up. The incidence of post-transfusion hepatitis (PTH) C in 91 patients who had received 1–12 units transfusion was significantly lower than in 135 patients who had received more than 12 units transfusion (6.6 vs. 16.3%, p<0.05). However, none of the 87 transfused patients, since anti-HCV screening in July 1992, developed PTH C (p<0.05). The result demonstrates that screening for anti-HCV by a more sensitive second-generation HCV diagnostic assay may protect the patients studied from PTH C. It further provides a firm argument for the necessity of a nation-wide blood donor screening.     

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.     

Transfusion-Associated Hepatitis in a Tertiary Referral Hospital in India

Background and Objectives: In Indian blood banks, screening for hepatitis B virus (HBV) is currently done by the EIA method, but no routine screening is done for hepatitis C virus (HCV). Materials and Methods: To determine the incidence of transfusion-associated HCV hepatitis, and of any residual transfusion-associated hepatitis (TAH) after HBsAg screening, we prospectively studied 182 patients who underwent surgery and received blood transfusion. These recipients had normal alanine aminotransferase (ALT) and were negative for HBsAg (monoclonal EIA), and anti-HCV (third-generation EIA) before receiving transfusion. Results: Of the 818 blood units transfused after routine screening (average 4.49±3.3 U/patient, range 1–14), 14 (1.7% of units) were found to be infected. Of the 182 recipients, 14 (7.69%) developed TAH during a follow-up of 6 months, 3 (21.4%) from HBV, 10 (71.5%) from HCV, and 1 (1.7%) from a coinfection of HBV and HCV. All patients with TAH due to HCV were asymptomatic. One patient with TAH due to HBV (33%) and 5 with TAH due to HCV (50%) developed chronic infection with persistently elevated ALT at 6 months. Conclusions: With the current screening practices, the incidence of TAH remains high in India and is mainly due to HCV infection. Furthermore, the screening methods for HBV also need to be improved.     

Clinical and laboratory characteristics of acute hepatitis C in patients with end-stage renal disease on hemodialysis

BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing hemodialysis are a risk group for hepatitis C virus (HCV) infection. The characteristics of acute hepatitis C infection in this population are not well known. GOALS: To evaluate the clinical and laboratory characteristics of acute hepatitis C in ESRD patients treated with hemodialysis. STUDY: ESRD patients on hemodialysis with acute hepatitis C, characterized by elevated alanine aminotransferase (ALT) followed by anti-HCV seroconversion were studied. RESULTS: Thirty-six patients (58% females, 44+/-12 y), with a mean time on hemodialysis of 2 years, were included. Only 2 (6%) patients had jaundice. ALT elevation was observed in all patients. Median peak ALT was 4.7 x upper limit of normal. The median interval between ALT elevation and anti-HCV seroconversion was 1 month (0 to 8). None of the patients with detectable HCV-RNA showed spontaneous clearance of viremia within 12 weeks of follow-up. Three (8%) patients presented ALT elevation followed by anti-HCV seroconversion with undetectable HCV-RNA. CONCLUSIONS: Acute hepatitis C is frequently asymptomatic in ESRD patients on hemodialysis and should be suspected in all patients presenting elevated ALT. Determination of HCV-RNA is important for the confirmation of infection. Anti-HCV seroconversion seems to occur early and spontaneous clearance of HCV-RNA is uncommon.     

Prevalence of antibodies to hepatitis C virus in HBsAg negative hemodialysis patients.

The prevalence of hepatitis C virus (HCV) infection was estimated in a 14-month study using anti-C100-3 antibody assay in 31 HBsAg negative patients on maintenance hemodialysis (MHD) for > or = 3 months. One and three patients respectively had ALT elevation and anti-HCV positivity at entry. During MHD (mean period of follow up 9.9 mo), 11 (35.5%) patients had, on fortnightly estimation, ALT elevation which lasted for < or = 6 months in seven patients and for > 6 months in four. Fourteen (45.2%) patients had anti-HCV (including the three positive at entry). There was no significant difference in frequency of anti-HCV positivity in patients with normal and elevated ALT (57.1% and 42.9% respectively). The number of blood transfusions and duration of MHD were similar in anti-HCV positive and anti-HCV negative patients. We conclude that our MHD patients have a high frequency of hepatitis and anti-HCV positivity, and these may not be related to blood transfusions.     

The epidemiology of TT virus (TTV) infection in a hepatitis C and B virus hyperendemic area of southern Taiwan

TT virus (TTV) is a newly isolated DNA virus from the serum of a patient with posttransfusion hepatitis of unknown etiology in 1997. To evaluate the clinical and molecular characteristics of TT virus (TTV) in a hepatitis C virus (HCV) and B (HBV) hyperendemic area (Masago), 200 residents were enrolled in the study. The sera were tested for alanine aminotransferase (ALT), HCV RNA and GB virus C/Hepatitis G virus (HGV) RNA, TTV DNA, HBsAg, anti-HCV and antibodies to HGV E2-protein (anti-E2). TTV DNA was positive in 99 of the 200 sera with a prevalence rate of 49.5%. The prevalence of HBsAg, anti-HCV, HCV RNA, HGV RNA, anti-E2 and HGV exposure (defined as positive for serum HGV RNA and/or anti-E2) was 38.9%, 69.5%, 64.5%, 17.0%, 25.5% and 39.5%, respectively. Neither clinical nor virological factors were associated with TTV viremia. The rate of ALT abnormality was significantly elevated in HCV RNA-positive (34.9%) than -negative (7.0%) residents (p < 0.001). HCV viremia was the only factor significantly associated with ALT elevation by multiple logistic regression (odds ratio: 6.96; 95% C.I.: 2.60-18.7). We concluded that in this HCV/HBV hyperendemic area, the prevalence of TTV DNA was high. No significant clinical factor was observed to be associated with TTV infection. TTV infection is not related to abnormal ALT levels and ALT abnormality was mainly attributable to HCV but not TTV, HBV or HGV infection.     

Studies on hepatitis C virus infection in haemodialysis patients]

To examine the prevalence of hepatitis C virus (HCV) in haemodialysis patients without blood transfusion in Hiroshima Prefecture, antibody to HCV (anti-HCV) was studied by the Ortho ELISA Kit in sera from 393 consecutive haemodialysis patients and in sera from 510 age and sex matched healthy members of the general population (control). An additional confirmatory test was done by a recombinant immunoblot assay. 1) Anti-HCV was detected in 70 of the 393 dialysis patients and 3 of the 510 healthy controls (17.8% vs 0.6%, p less than 0.01). Prevalence of anti-HCV in haemodialysis patients sera was increased by the volume of blood transfusion, and even in dialysis patients who had no blood transfusion, the frequency of anti-HCV positivity (9.2%) was greater than the healthy controls (p less than 0.01). Thus, the major route of HCV transmission in haemodialysis patients without blood transfusion may be via the haemodialysis treatment. 2) The prevalence of anti-HCV increased significantly with the ALT level and abnormal ALT activity of the anti-HCV positive group were significantly greater than that of the negative group. Thus, it is suggested that HCV infection may be an etiologic factor of liver dysfunction in haemodialysis patients.     

Hepatitis C virus antibodies, viral RNA and genotypes in sera from patients on maintenance haemodialysis

SUMMARY. Patients on maintenance haemodialysis in four dialysis centres were tested for markers of hepatitis C virus (HCV) infection. Antibody to HCV (anti-HCV) was detected by the second-generation enzyme immunoassay in 142 (26%) of the 543 patients and HCV RNA in 117 (22%) of whom four were without detectable anti-HCV in serum. Seventy-seven (66%) were infected with HCV of genotype II/1b, 31 (27%) with genotype III/2a and eight (7%) with genotype IV/2b. in a distribution similar to that in blood donors who carried HCV asymptomatically. Haemodialysis patients had high HCV RNA titres comparable to those of patients with chronic hepatitis C. HCV RNA was detected in 96 (26%) of the 365 patients with a history of transfusion more frequently than in 21 (12%) of the 178 without previous transfusion ( P <0.001). In transfused patients, frequencies of anti-HCV and HCV RNA increased in parallel with the duration of haemodialysis. The frequency of anti-HCV in non-transfused patients, however, did not change appreciably with the duration of haemodialysis up to 22 years. The patients with anti-HCV had a higher frequency of HCV RNA in serum than symptom-free blood donors with anti-HCV (113/142 or 80% vs 109/166 or 66% P <0.01) and the patients with HCV RNA had a lower frequency of elevated aminotransferase levels than blood donors with HCV RNA (5/113 or 4% vs 27/109 or 25%, P <0.00l). These results indicate that transfusion is a significant cause of HCV infection in patients on maintenance haemodialysis, and that these patients are prone to establish the HCV carrier state after infection.     

Serum hepatitis C virus sequences in posttransfusion non-A, non-B hepatitis.

We investigated 17 patients (12 males and 5 females, ages 2 to 57 years old) with posttransfusion non-A, non-B hepatitis to determine relationships between clinical courses and hepatitis C virus (HCV) markers. The patients were grouped according to time course of abnormal serum alanine aminotransferase (ALT) levels into three categories (chronic biochemical disease, biochemically resolved chronic disease, and acute disease). Latest serum samples (1.3 to 10.8 years after blood transfusion) were used to detect antibodies against C100-3 antigen (anti-HCV) by enzyme-linked immunosorbent assay and HCV sequences by polymerase chain reaction (PCR) assay. Of the 17 patients, 13 patients (76.5%) were anti-HCV positive and 8 patients (47.1%), including one anti-HCV negative case, were positive for HCV RNA. In total, 14 patients (82.4%) were positive for either HCV markers. With respect to clinical course, HCV RNA was detected in six of eight patients (75%) with chronic biochemical disease, and in two of five patients (40%) with biochemically resolved chronic disease. HCV RNA was not detectable in convalescent sera from four patients with acute disease. These results show that there is a relationship between clinical status and HCV viremia, but that normal liver function tests do not always represent the clearance of the virus. Viremia in two patients with normal ALT level suggests that hepatitis is not only caused by viral cytopathic effects, but also by immunologic reactions against virus-infected cells. Thus, PCR is useful in determining the persistence of HCV infection as well as to diagnose anti-HCV negative HCV infection.