Infection with TT virus, a novel transfusion-transmissible DNA virus, in haemophiliacs and in blood products

We evaluated the characteristics and rate of infection with TT virus (TTV), a novel DNA virus, in Japanese haemophiliacs. TTV DNA was measured in 60 haemophiliacs by semi-nested polymerase chain reaction. Co-infection with hepatitis C virus (HCV), hepatitis G virus (HGV) and human immunodeficiency virus (HIV) was also evaluated. In addition, the rate of detection of TTV DNA in blood products was evaluated. TTV DNA was detected in 35/60 haemophiliacs (58.3%). There were no differences in the backgrounds or characteristics between haemophiliacs with and without TTV infection, except for higher levels of IgG and IgM in patients with TTV infection. In patients infected with TTV of types other than type 1, which are rarely detected in Japan, the rate of co-infection with HCV of imported types was high; TTV of types other than type 1 in Japanese haemophiliacs were probably transmitted by imported blood products. TTV DNA was detected in over half of the blood products tested, but TTV DNA concentrations in these products were lower than in the serum of haemophiliacs.     

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.     

A prospective study of transfusion-transmitted virus transmission by blood transfusion

Recently, a new single-stranded DNA virus (TT virus, TTV) has been isolated and related to post-transfusion hepatitis. The aim of this study was to investigate the prevalence of TTV in blood donors and blood recipients, and the incidence of TTV transmission by blood transfusion. TTV DNA and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV), were examined in 130 blood recipients, and the presence of TTV was studied in their 340 corresponding blood donors. The prevalence of TTV infection was 10.6% (36/340) in donors and 8.5% (11/130) in blood recipients, before transfusion. Eighteen subjects (15.1%) were found to be TTV positive, after transfusion, in the 119 blood recipients without TTV before transfusion; at least one of the corresponding donors was TTV positive. There were 46 subjects with post-transfusion hepatitis virus infection, 45 with HCV infection (including seven co-infected with TTV) and two with HBV infection (including one co-infected with HCV and one co-infected with TTV). The recipient with TTV and HBV co-infection and three of the seven patients with TTV and HCV infection had alanine aminotransferase (ALT) levels higher than 90Ul^–1, but only two of the 10 isolated TTV infections had a mild ALT elevation. These results show that prevalence of TTV was high in blood donors and hospitalized patients, and isolated TTV infection is not related to significant ALT elevation.     

Natural history of the TT virus infection through follow-up of TTV DNA-positive multiple-transfused patients

Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA-positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA-positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)     

High rate of TTV infection in multitransfused patients with pediatric malignancy and hematological disorders

The prevalence of transfusion-transmitted virus (TTV) infection has not been known in patients suffering from pediatric malignancies and hematological disorders who receive blood transfusion and/or blood products during treatment. Blood samples were taken from 75 patients. TTV infection was identified when TTV DNA was detected in serum by a polymerase chain reaction (PCR) assay. Hepatitis C virus (HCV) and hepatitis G virus (HGV) RNA were also assayed by PCR. TTV DNA was detected in 38 of 75 patients (51%). In 4 of 38 patients, the amount of blood transfused was less than 3 units. By time since last transfusion, TTV DNA was detected in 12 of 35 patients after more than 4 years, 12 of 21 between 1 and 4 years, and 14 of 19 within 1 year. Six patients had mixed infection of TTV and HCV, and 12 patients had mixed infection of TTV and HGV. Three different kinds of virus were found simultaneously in serum from 3 patients. Eight out of 75 patients showed abnormal levels of alanine aminotransferase (ALT) (>40 IU/liter), and 3 of them had TTV DNA. All patients who had TTV DNA and elevated ALT levels also were positive for HCV RNA and HGV RNA. The prevalence of TTV infection is high in patients with pediatric malignancies and hematological disorders after episodes of blood transfusion. Transfusion is one of the most important risk factors for TTV infection regardless of the amount of blood transfused.     

Clinical implications of TT virus superinfection in patients with chronic hepatitis C

OBJECTIVE: TT virus (TTV) has been identified as a candidate agent of non-A-E hepatitis virus. We investigated superinfection of TTV in patients with chronic hepatitis C and studied the susceptibility to interferon (IFN) treatment and its association with liver disease caused by hepatitis C virus (HCV). METHODS: TTV DNA was examined using the seminested polymerase chain reaction (PCR), and its virus level was measured by the real-time fluorometric PCR. RESULTS: TTV DNA was detected in 20 of 102 (19.6%) patients examined. There was no significant difference in the alanine aminotransferase (ALT) level between patients with or without TTV DNA. Quantitative analysis of HCV RNA and TTV DNA revealed no correlation between virus levels in HCV/TTV-coinfected patients. Both TTV and HCV were sensitive to IFN therapy. Complete response to IFN with a sustained loss of viremia for 24 wk after completion of IFN treatment was found in 11 of 20 (55%) patients with respect to TTV DNA and in five of 20 (25%) patients with respect to HCV RNA. The mean pretreatment HCV RNA level was significantly lower in the complete-response cases than in the no-response cases, but there was no significant difference in the pretreatment TTV DNA levels between them. ALT normalization resulting from IFN therapy was not attributable to the eradication of TTV DNA but was attributable to that of HCV RNA. Superinfection by TTV did not influence the effect of IFN against HCV. No specific TTV genotype correlating with IFN sensitivity was found. CONCLUSIONS: These results suggest that TTV infection stands independent of HCV infection, with no influence on liver injury as a result of HCV infection.     

Effect of TT virus co‐infection on interferon response in chronic hepatitis C patients

Abstract: Aim: TT virus (TTV) is a single stranded DNA virus found in serum of patients with post‐transfusion non‐A to ‐G hepatitis. TTV‐DNA has been investigated in sera of patients with various liver diseases. This study aimed at finding whether co‐infection with TTV in HCV patients, may influence the effect of interferon (IFN) in complete elimination of HCV, and analysed the correlation between HCV and TTV by semi‐quantification of both HCV RNAs and TTV DNA. Methods: In 28 chronic hepatitis C (CH‐C) patients with TTV co‐infection, the presence of TTV DNA was checked in sera six months before and after the end of IFN therapy. Result: Five out of 28 patients became negative for both HCV‐RNA and TTV‐DNA following IFN therapy. But 10 out of 28 patients persistently remained positive for both. Among the remaining 13 patients, 5 tested negative for HCV‐RNA but positive for TTV‐DNA. Post IFN therapy changes in serum alanine aminotransferase (ALT) levels did not appear to be influenced by the presence of TTV co‐infection. HCV‐RNA was found to be the most important predictor of IFN response in CH‐C patients with TTV co‐infection. TTV DNA level in sera had no correlation with IFN response. In addition, there was no relationship between HCV RNA and TTV DNA. Conclusion: Based on these results, it can be concluded that the effectiveness of IFN in eliminating HCV does not seem to be influenced by co‐infection.     

Influence of TT virus co-infection on IFN-beta therapy in patients with chronic hepatitis C

Although results of IFN alpha therapy in chronic hepatitis C (C-CH) patients co-infected with TT virus (TTV) have been reported, no results of IFN beta therapy or IFN beta and alpha combination therapy have been reported. In this study, we retrospectively investigated whether co-infection with TTV affects the results of IFN therapy by using stored sera from 60 C-CH patients co-infected with TTV who underwent IFN beta therapy or IFN beta and alpha combination therapy. The stored sera were from 29 complete responders, 10 incomplete responders, and 21 non-responders, and they were used for qualitative and quantitative analysis of HCV RNA, HCV genotype analysis, and qualitative and quantitative analyses of TTV DNA. TTV DNA was detected in 23 (38.3%) of the 60 C-CH sera. The TTV DNA-positive rate was 17.2% among the complete responders to IFN therapy, versus 58.1% in the incomplete responders and non-responders, and the difference was significant (p < 0.01). While the complete response prediction rate based on two factors, HCV RNA level and HCV genotype, was 80.8% (21/26) in the C-CH patients, the prediction rate based on three factors, these two factors plus TTV DNA, was higher, 90.0% (18/20). It was concluded that determination of HCV RNA concentration, HCV genotype, and TTV DNA, before IFN beta therapy or IFN beta and alpha combination therapy is useful for predicting the results of treatment of C-CH patients.     

Effects of HAART on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with haemophilia

In multiply coinfected human immunodeficiency virus (HIV)-positive patients, we investigated the effects of high-activity antiretroviral therapy (HAART) using HIV protease inhibitors on three other viruses: hepatitis C virus (HCV), hepatitis G virus (HGV), and TT virus (TTV). Viral concentrations were measured serially by polymerase chain reaction methods in five patients with quadruple infection (HIV, HCV, HGV, and TTV) and in two patients with triple infection (HIV, HCV, and HGV) before and during HAART. In addition, CD4+ cell counts and serum alanine aminotransferase (ALT) levels were measured serially. Generally we observed no difference in serum HCV RNA, HGV RNA, or TTV DNA concentrations between samples obtained before and after initiation of HAART, whereas HIV RNA concentration decreased and CD4 counts increased in most patients. However, two patients had markedly decreased concentrations of HCV RNA and HGV RNA, respectively, more than 12 months after beginning HAART. Normalization of serum ALT levels was observed in a patient with decline of HCV RNA concentrations. No interactions were observed among these four viruses. HAART had no apparent direct effects on HCV, HGV, or TTV. Further studies will be required to elucidate whether the restoration of immune status through suppression of HIV replication by HAART may affect HCV or HGV RNA concentrations.     

A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia

A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread.     

A survey of current liver biopsy practice patterns

GOALS: To study transfusion-transmitted virus (TTV) infection in 75 patients on hemodialysis and examine its relationship with age, sex, duration of dialysis, history of transfusion, and chronic elevation of alanine aminotransferase (ALT) levels. STUDY: Serum TTV was analyzed by polymerase chain reaction (PCR), TTV genotypes by restriction fragment length polymorphism, and hepatitis C virus (HCV) RNA by PCR. RESULTS: Transfusion-transmitted virus was detected in 32 patients (42.7%). Transfusion-transmitted virus genotypes were as follows: G1 in 16 patients; G2, 3; G3, 1; G4, 2; G2-G5, 6; and unclassified, 4. Mean duration of dialysis was 37 +/- 32 months for TTV-positive patients and 43 +/- 37 months for TTV-negative patients (not significant). Twenty-seven (84%) TTV-positive patients and 27 (63%) TTV-negative patients had a history of transfusions ( p = 0.04). Chronic ALT elevation was observed in 9 patients; 5 of them were TTV-positive (16%) and 4 were TTV-negative (9%) (not significant). Four (40%) HCV RNA-positive patients and 5 (8%) HCV RNA-negative patients had chronic ALT elevation ( p = 0.003). Three TTV-positive patients with chronic ALT elevation were also infected with HCV. The two patients with isolated TTV infection did not have another clinical feature to explain their ALT elevation. CONCLUSIONS: Transfusion-transmitted virus had a high prevalence in the patients on hemodialysis; genotype G1 accounts for half of the cases. Transfusion-transmitted virus infection depends on the transfusional antecedent but not on the duration of dialysis. Chronic ALT elevation is significantly associated with HCV infection but not TTV infection. However, TTV could be a causative agent of chronic ALT elevation in some patients.     

TTV与其它肝炎病混合感染及其基因型的研究

研究TTV与其它肝炎病混合感染对肝脏病变的影响及本地区TTVDNA的基因型。选TTV ORF1的保守序列作内外引物,采用微板核酸杂交－ELISA方法检测患者血清TTVDNA并对检测结果和临床资料进行统计学分析。选取异源性大于50％的序列作显色探针Ⅰ和显色探针Ⅱ,进行分型研究。学生、非甲－非戊型肝炎、慢性乙型肝炎和肝硬化患者血清TTV阳性率分别为3．3％、14．3％、12％、16％。TTV阳性和TTV阴性的慢性乙型肝炎及肝硬化患者,在年龄、性别、ALT和TBil之间无显著差异（P＞0．05）。本地区流行的TTV可分为两个主要的基因型,即I型（66．75）、Ⅱ型（25％）,部分存在混合感染（8．3％）。TTV可能与HBV、HCV有类似的传播途径,故常重叠感染。TTV与乙型肝炎及肝硬化混合感染后不影响两者的肝脏病变。TTV不是本地区非甲－非戊型肝炎的主要病因。     

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)     

TT virus infection in hemodialysis patients

OBJECTIVE: Recently, TT virus (TTV), associated with posttransfusion hepatitis, was discovered. Prevalence of TTV infection in maintenance hemodialysis (HD) units and its pathogenicity to liver was investigated. METHODS: A total of 115 patients on HD were assessed for presence of serum TTV. DNA was purified from sera, and nested polymerase chain reaction was done for the detection of TTV DNA. RESULTS: TTV was detected in 59 patients on HD (51.3%), as compared with healthy blood donors (15 of 91 [16.5%], p < 0.0001). Serum HCV RNA and HBs antigen were positive in 16 and three patients, respectively. The prevalence rate of TTV was already 58.3% in the patients on HD for only 1 yr, and did not change according to the duration of HD until 15 yr on HD. TTV was positive in 51.2% (43 of 84) of the patients with history of blood transfusion, and in 51.6% (16 of 31) of those without it. In HCV-negative patients, alanine aminotransferase (ALT) levels of TTV-positive patients were similar to those of TTV-negative patients. Contrarily, in HCV-positive patients, ALT levels were more frequently > or =15 IU/L in TTV-positive patients (14 of 18) than in TTV-negative patients (five of 15) (p < 0.05). CONCLUSIONS: TTV infection is remarkably prevalent in patients on HD and in healthy blood donors. It is suggested that TTV generally does not cause liver disease by itself, but there remains the possibility that TTV may aggravate liver disease caused by HCV.     

Infection of TT virus in patients with idiopathic pulmonary fibrosis

The precipitating factors of idiopathic pulmonary fibrosis (IPF) have not been elucidated. Recently, a novel DNA virus named TTvirus (TTV) was discovered in a patient with post-transfusion hepatitis of unknown aetiology TTV is a circular, single-stranded DNA virus of 3.8 kB. To evaluate the relationship between TTV and IPF, the sera of 33 patients with IPF were tested for the presence of TTV DNA by semi-nested polymerase chain reaction. TTV DNA was detected in 12 (36.4%) IPF patients. The serum lactate dehydrogenase (LDH) level was significantly higher in the IPF patients withTTV than in those without TTV (802 +/- 121 vs. 530 +/- 49 IU l(-1), p < 0.05). Six (50%) of 12 patients in theTTV DNA-positive group died during the observation period, while only six (28.6%) of 21 patients in theTTV DNA-negative group died. The 3-year-survival rate was significantly lower in the TTV DNA-positive group than in theTTV DNA-negative group (58-3% vs. 95.2%, P <0-02). Replicative intermediate forms of TTV DNA were detected in the lung specimen from a TTV-infected IPF patient. TTV infection influences the disease activityand prognosis of IPF in some cases. Further studies are required to elucidate the clinical significance of TTV in IPF.     

Prevalence and Genotypic Variability of TTV in HIV-Infected Patients

TT virus is a small, circular DNA virus, that has been associated with transfusion hepatitis. We sought to determine the prevalence of TT virus (TTV) in patients with human immunodeficiency virus (HIV) infection and to characterize the virus in terms of genotypic variability and in the relationship to CD4⁺, HIV viral loads, HCV/HIV coinfection, and ALT abnormalities. A cross-sectional analysis of HIV-infected patients in the United States, including 86 HIV-positive subjects and 118 HIV-negative controls was performed. TTV was detected using a seminested PCR technique. Samples underwent cloning and sequence analysis and/or RFLP to determine genotype. Thirty-eight percent of HIV-positive patients had TTV infection versus 14.4% of patients within the matching cohort (P = 0.0009). The highest rate of TTV infection was in patients with concurrent HCV/HIV infection (54% vs 30%, P = 0.038). HIV-infected subjects with TTV had lower ALT levels than those without TTV (P = 0.036). Intravenous drug use was the leading factor associated with TTV positivity among HIV-positive subjects. Mixed genotypes were more common in those with HIV. Therefore, TTV prevalence, ALT levels, and genomic heterogeneity of TTV all seem to be altered in patients with HIV.     

长春地区TT病毒的基因分型及其临床意义

为调查各种急、慢性肝炎中TT病毒的感染状况及临床意义,并检测TTV基因的分型。利用半套式PCR（semi-nested PCR）方法检测了TTV-DNA。利用邻近丁（neighbor-joining）法画出系统树。TTV-DNA的阳性率在非甲非乙非丙型急性肝炎中为42.3%,在非乙非丙型慢性肝炎中为45.5%。基因型可分为1a、1b、2a、2b等型。TTV-DNA在非甲非乙非丙型急性非乙非丙型慢性肝炎中的感染率最高;在TT病毒与乙型、丙型肝炎病毒混合感染的慢性肝炎中,TT病毒干涉乙型及丙型肝炎病毒造成的肝细胞损伤的可能性很小。     

TT virus infection in patients with chronic hepatitis C virus infection--effect of primers, prevalence, and clinical significance. Hepatitis Interventional Therapy Group

BACKGROUND/AIM: A novel DNA virus, TT virus (TTV), was recently identified in patients with post-transfusion non-A-G hepatitis. The aim of this study was to determine the prevalence and clinical significance of TTV infection in patients with chronic hepatitis C virus (HCV) infection. METHODS: We analyzed pretreatment serum samples from 171 United States and European patients who relapsed after interferon-alpha treatment and were recruited into an interferon-alpha-2b/ribavirin combination treatment trial. TTV DNA was detected by PCR using two different set of primers (TTV-A and TTV-B) derived from open reading frames 1 and 2, respectively. RESULTS: TTV was detected in 29.2% of the patients with the TTV-A primer set, 70.8% with the TTV-B primer-set, and 72.5% if positive by either/both sets of the primers. The amplicons generated by primer set A were sequenced and a phylogenetic tree was constructed. The 50 isolates belonged to group la (n=8), 1b (n=17), 2a (n=21), 2b (n=3), and 4 (n=1). There was no difference in demographic (age, sex distribution, estimated duration of HCV infection), biochemical (serum ALT levels), virologic (serum HCV RNA levels, HCV genotype distribution), or histologic scores, and their subsequent response to either interferon-alpha-2b or interferon-alpha-2b/ribavirin combination treatment. CONCLUSIONS: The prevalence of TTV infection reported previously may have been significantly underestimated, based on the primers originally described and used by most studies. Although TTV infection is very common in patients with chronic HCV infection, it has no identifiable clinical significance.     

Effect of TT virus co-infection on interferon response in chronic hepatitis C patients

AIM: TT virus (TTV) is a single stranded DNA virus found in serum of patients with post-transfusion non-A to -G hepatitis. TTV-DNA has been investigated in sera of patients with various liver diseases. This study aimed at finding whether co-infection with TTV in HCV patients, may influence the effect of interferon (IFN) in complete elimination of HCV, and analysed the correlation between HCV and TTV by semi-quantification of both HCV RNAs and TTV DNA. METHODS: In 28 chronic hepatitis C (CH-C) patients with TTV co-infection, the presence of TTV DNA was checked in sera six months before and after the end of IFN therapy. RESULT: Five out of 28 patients became negative for both HCV-RNA and TTV-DNA following IFN therapy. But 10 out of 28 patients persistently remained positive for both. Among the remaining 13 patients, 5 tested negative for HCV-RNA but positive for TTV-DNA. Post IFN therapy changes in serum alanine aminotransferase (ALT) levels did not appear to be influenced by the presence of TTV co-infection. HCV-RNA was found to be the most important predictor of IFN response in CH-C patients with TTV co-infection. TTV DNA level in sera had no correlation with IFN response. In addition, there was no relationship between HCV RNA and TTV DNA. CONCLUSION: Based on these results, it can be concluded that the effectiveness of IFN in eliminating HCV does not seem to be influenced by co-infection.     

Hepatitis G virus infection in Japanese haemophiliacs

The recently identified hepatitis G virus (HGV) (also known as GB virus-C) has been considered as a blood-transmissible agent. As many haemophiliacs have risk factors for infectious agents, to clarify the frequency of HGV infection is important. HGV-RNA was investigated in 77 Japanese haemophiliacs who had been treated with nonvirus-inactivated concentrates derived from pooled plasma. Detection of HGV-RNA was performed with a nested RT-PCR that recognizes the 5'-NCR of the HGV genome. HGV-RNA was detected in 19 (24.7%), including four (21.0%) infected with HGV alone, 12 (63.2%) co-infected with HCV and three (15.8%) who were HBV carriers. The patients infected with HGV alone showed a normal ALT level of 18.7 ± 4.1 IU L⁻¹. Most (36/37, 97.3%) of the patients with abnormal ALT levels had HCV-RNA. Patients infected with HCV alone or co-infected with HCV and HGV showed higher ALT levels of 108.8 ± 90.2 IU L⁻¹ ( n = 39) and 67.6 ± 62.6 IU L⁻¹ ( n = 11), respectively. However, there was no significant difference ( P = 0.16) in ALT levels between HCV infection alone and HCV/HGV co-infection. On the other hand, four of the patients who could be followed over 10 years showed HGV-RNA persistently. In two who underwent liver biopsy, the histological evidence showed no definitive fibrotic and necro-inflammatory changes. These results indicate that HGV infection has frequently occurred in haemophiliacs. It is possible that HGV infection does not cause aggressive hepatitis with elevated ALT levels, and that co-infection with HGV may not aggravate hepatitis caused by HCV.