High prevalence, low pathogenicity in hepatitis G virus in kidney transplant recipients

BACKGROUND: Prevalence and pathogenicity of hepatitis G virus infection in long-term renal transplant recipients, are not fully known. AIM: To evaluate long-term impact of HGV infection on liver disease of renal transplanted patients. PATIENTS AND METHODS: A total of 155 hepatitis B surface antigen negative kidney transplant recipients, followed for a mean of 11 years after renal transplantation, were studied. Of these 48 (31%) patients had persistently elevated serum aminotransferase values. Frozen serum samples were tested for HGV-RNA and HCV-RNA by nested reverse transcribed polymerase chain reaction, and for anti-hepatitis G virus and anti-hepatitis C virus by enzyme-linked immunosorbent assay Hepatitis C virus-RNA was typed by a line probe assay and quantified by a branched DNA signal amplification assay RESULTS: Hepatitis G virus-RNA was detected in 37 (24%) patients and anti-hepatitis G virus in another 26 (17%). Seventy (45%) patients had serum anti-hepatitis C virus and 63 of these (90%) had serum hepatitis C virus-RNA. Hepatitis G virus-RNA positive and negative patients were similar in terms of age, sex, duration of dialysis, rate of transfusion, chronic liver disease, rate of hepatitis C virus infection and immunosuppressive therapy. Fifteen (41%) hepatitis G virus-RNA seropositive patients were hepatitis C virus co-infected. Hepatitis C virus-RNA levels were significantly lower in the 15 hepatitis C virus/hepatitis G virus co-infected patients than in the 48 patients with hepatitis C virus infection only (2.2 vs 10.8 MEq/ml, p = 0.02). Only 3 hepatitis G virus carriers had persistently elevated alanine aminotransferase compared to 29 hepatitis C virus carriers (14% vs 60%, p < 0.001), 10 patients co-infected with both hepatitis G virus and hepatitis C virus, and in 6 patients with neither infection (67% vs 8%, p < 0.001). CONCLUSIONS: Hepatitis G virus infection is common among kidney transplant patients, it carries a low risk of chronic liver disease even in long-term follow-up. Low levels of hepatitis C virus-RNA found in hepatitis G virus carriers suggest an interaction between these two viruses in immunosuppressed patients.     

157例丙型肝炎流行病学及临床特点研究

目的 了解丙型肝炎的流行病学及临床特点,为降低丙型肝炎的发病率,及时诊断、治疗和预防提供指导意义。方法 对157例丙型肝炎病人采用回顾性调查的方式,记录其传播途径、临床表现、肝功能、病原学标记检查等,进行统计分析。结果 丙型肝炎经血传播占73.25％(115/157),无明显原因传播者占15.28％(24/157)。所确诊的急性丙型肝炎均急性起病和近期有明确血制品使用史。慢性丙型肝炎症状轻,常有反复轻度ALT异常。HCV可与其它肝炎病毒如HAV或HBV合并感染,使病情加重。结论 丙型肝炎经血传播是首要途径,但无明显原因传播者也不容忽视。急性丙型肝炎一般不易诊断,除非有较明显的症状和病前1～6个月有明确血制品使用史。丙型肝炎易慢性化,且慢性丙型肝炎症状轻,常有反复轻度ALT异常,合并其它肝炎病毒如HAV或HBV可使病情加重、病程缩短、预后不良。     

Coinfection with hepatitis B and C or B, C and δ viruses results in severe chronic liver disease and responds poorly to terferon-a treatment

SUMMARY. Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-α2b (IFN-α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short-and long-term responses to doses of IFN-α that are used to treat HCV are infrequent, but further studies are required to determine whether higher-dose IFN-α may benefit patients with combined hepatitis virus infections.     

Prevalence and histologic features of transfusion transmitted virus and hepatitis C virus coinfection in a group of HIV patients

BACKGROUND: A recently identified DNA transfusion-transmitted virus has been associated with post-transfusion non-A to G hepatitis. AIM: To determine the prevalence of transfusion-transmitted virus in patients with human immunodeficiency virus infection. Its clinical role in the pathogenesis of liver disease was also evaluated in patients with transfusion-transmitted-virus hepatitis C virus coinfection compared with those with hepatitis C Virus infection alone. PATIENTS AND METHODS: We evaluated 312 HIV-hepatitis C virus coinfected patients (225 males, 87 females). All underwent screening for transfusion-transmitted virus DNA using a nested polymerase chain reaction technique. In some transfusion transmitted virus-DNA positive patients, we performed a phylogenetic analysis. In 56 patients (20 transfusion-transmitted-virus-hepatitis C virus and 36 hepatitis C virus alone), liver biopsy was collected. RESULTS: The prevalence of transfusion-transmitted virus was 113/312 (36%). The genotype distribution was similar to that reported in other studies. No difference in liver histology was found between the two groups. CONCLUSION: Transfusion-transmitted virus infection is common in human immunodeficiency virus patients. We found no histologic differences between liver biopsy specimens from patients coinfected with transfusion-transmitted virus plus hepatitis C virus compared with those infected with hepatitis C virus alone. Transfusion-transmitted virus is not clearly associated with a distinct liver injury.     

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.     

Diagnosis and management of hepatitis B virus and HIV coinfection

HIV and hepatitis B virus (HBV) coinfection increases HIV and HBV replication, hepatitis flares, and risk of progression to chronic HBV infection, cirrhosis, and hepatocellular carcinoma. HIV and HBV coinfection decreases frequency of hepatitis Be antibody (anti-HBe) and hepatitis B surface antibody (anti-HBs) seroconversion, increases risk of antiretroviral therapy-related hepatotoxicity, and reduces efficacy of HBV therapy. All newly diagnosed HIV patients should be screened for hepatitis A, B, and C viruses and vaccinated if not immune to hepatitis A or B viruses. HBV serology often is atypical in coinfection. Diagnosis of HBV coinfection in HIV infection is made on the basis of hepatitis B surface antigen (HBsAg)-positive, hepatitis B core antibody (anti-HBc total)-positive, anti-HBs-positive status. Alanine aminotransferase levels in coinfected patients often are not reliable markers of liver inflammation. HBV infection should always be treated if coinfected patients are receiving antiretroviral therapy, since immune reconstitution under antiretroviral therapy poses risk for immune-associated liver damage in these patients. This article summarizes a presentation on HIV and HBV coinfection made by Marion G. Peters, MD, at an International AIDS Society-USA Continuing Medical Education course in San Francisco in May 2007.     

Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.

OBJECTIVES: To assess the incidence and risk factors for hepatotoxicity associated with nevirapine. DESIGN: A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000. METHOD: Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values. RESULTS: Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity. CONCLUSIONS: Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.     

Fulminant non--A-G viral hepatitis leading to liver transplantation

BACKGROUND: All hepatotropic viruses are known to cause fulminant hepatic failure (FHF). However, in 30% to 40% of patients with FHF, the precise cause remains unknown. We aimed to better define this subgroup. METHODS: We evaluated the clinical course and outcome of 7 patients admitted during a 22-month period with fulminant viral hepatitis leading to liver transplantation; none had serologic or molecular evidence of hepatitis A, B, C, D, E, or G viral infection, thus the term non-A-G viral hepatitis. All known etiologies of FHF were excluded. RESULTS: All patients had prodromal symptoms suggestive of viral causes. Mean age was 30 years. The interval between onset of jaundice and appearance of encephalopathy was 23 days (range, 4-50 days). Five patients had grade III/IV encephalopathy. Serum alanine aminotransferase levels showed a single peak of activity. The duration between first symptoms and liver transplantation was 28 days (range, 12-71 days). Results of histological study of the explanted liver showed submassive (4 patients) or massive (3 patients) hepatocyte necrosis. In all patients, results of polymerase chain reaction analysis did not detect hepatitis B virus DNA, hepatitis C virus RNA, or hepatitis G virus RNA in the explanted liver. After transplantation, 2 patients showed (6 months later) increased liver enzyme levels of undetermined cause, and results of a liver biopsy showed mild lobular hepatitis; 1 patient had lymphoproliferative disorder (Epstein-Barr virus-originated); and 1 patient, aplastic anemia, which is known to be associated with seronegative viral hepatitis. The latter patient died, whereas the other 6 patients are alive (survival rate, 86%). CONCLUSIONS: Our patients with non-A-G viral hepatitis had a severe acute onset with progressive FHF requiring liver transplantation. There is some suggestion of recurrent viral disease after transplantation implicating other unknown viruses in the etiology.     

Minimal role of GB virus-C/hepatitis G virus in fulminant and subfulminant hepatitis in Taiwan

BACKGROUND: The role of GB virus-C/hepatitis G virus (GBV-C/HGV) in fulminant hepatitis (FH) and subfulminant hepatitis (SFH) remains unclear. METHODS: Thirty-two FH or SFH patients, with adequate clinical information and serum specimens, were studied. Serum samples were tested for hepatitis markers and genomes of hepatitis A-E viruses, as well as GBV-C/HGV. RESULTS: Of the cases of FH/SFH studied, one (3%) was caused by anti-tuberculosis agents, 26 (81%) had hepatotropic virus infection, and five (16%) had no identifiable cause. Of the 26 patients with hepatotropic virus infection, five had acute hepatitis B infection (one with acute hepatitis D virus (HDV) co-infection), one had acute hepatitis C infection, 16 were hepatitis B surface antigen carriers with reactivation or superimposed by unidentified agent(s) (two had triple virus infections), three were hepatitis B carriers with HDV superinfection, and one had GBV-C/HGV infection in addition to exposure to halothane. GBV-C/HGV-RNA was detected in only three of 32 patients (9%) and all had a history of blood transfusion or co-existing causative factors. Of the 26 patients with hepatotropic virus infection, 18 were tested for antibodies against GBV-C/HGV envelope protein and seven were reactive, suggesting past infection. CONCLUSIONS: The role of GBV-C/HGV in causing FH and SFH is minimal in Taiwan and HBV infection remains the major aetiology. These findings also suggest the existence of as yet unrecognized agents, responsible for such catastrophic illnesses.     

Analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein, and risk factors for blood donors coinfected with HGV and hepatitis C virus

Serologic, biochemical, and molecular analyses were used to study hepatitis G virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors, clinical significance, and the impact of HGV on coexistent hepatitis C virus (HCV). Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive and 44% were anti-E2-positive (total exposure, 56%). HGV RNA and anti-E2 were mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA but anti-E2 persisted. HGV had little impact on alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV infection alone or those coinfected with HCV. A multivariate analysis showed that intravenous drug abuse was the leading risk factor for HGV transmission, followed by blood transfusion, snorting cocaine, imprisonment, and a history of sexually transmitted diseases. In summary, HGV and HCV infections were frequently associated and shared common parenteral risk factors; HGV did not appear to cause hepatitis or to worsen the course of coexistent hepatitis C.     

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.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

Evidence of prior hepatitis B and hepatitis A virus infections in an ambulatory geriatric population

Ninety-five randomly selected patients attending an ambulatory geriatric medical clinic were tested for the presence in their sera of hepatitis B surface antigen and of antibody to hepatitis B and A viruses. Such evidence of past hepatitis infection was correlated with current liver function and history of having received blood transfusions. The results showed that 94% of patients had antibody to hepatitis A virus, and 32% had antibody to hepatitis B virus. Patients with abnormal liver function tests, or those with a history of blood transfusions were no more likely to have hepatitis B antibody than patients with normal liver function tests or those with no history of transfusion.     

血液透析患者乙、丙、庚型肝炎病毒感染状况分析

目的 探讨血液透析病人（HDP）乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、庚型肝炎病毒（HGV）的感染状况、感染方式及预防措施。方法 对160例HDP及30例对照组定期预留血清,检测HBsAg、抗HBs、HBeAg、抗HBe 、抗HBc、HBV DNA、抗HCV、HCV RNA、抗HGV。结果 HDP的HCV、HGV感染率明显高于对照组（P＜0.01及P＜0.05）。HBV感染率高于对照组,但其差异显著性（P＞0.05）。血透加输血组肝炎病毒感染率明显高于单纯血透组（P＜0.01）。肝炎病毒感染率随透析时间的延长,感染率逐渐增高。结论 HDP HCV、HGV感染率高,其中输血是一重要因素,其次与血液透析本身的医源性感染有关。故应加强对献血员的筛选,尽量少输血,加强透析过程中的消毒隔离措施。     

Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis C

OBJECTIVES: Chronic hepatitis C is frequently seen in HIV-positive subjects infected through needle sharing or transfusion of contaminated blood products. Progression to end-stage liver disease seems to occur faster in these patients. As the life expectancy of HIV-infected persons has dramatically improved since the introduction of highly active antiretroviral therapies, cirrhosis and eventually hepatocellular carcinoma (HCC) may be recognized at an increasing rate in patients coinfected with HIV and hepatitis C virus (HCV). METHODS: We identified the main features of HIV-infected individuals with end-stage liver disease due to HCV infection and diagnosed with HCC in three HIV/AIDS referral centers, and compared these features to those of a control group of patients with HCV-related HCC but without HIV infection. RESULTS: Seven HIV-infected patients were identified. Of these, six were <45 yr of age and had been intravenous drug users. The mean time between exposure to HCV and the development of HCC was estimated to be 17.8 yr. Two subjects were coinfected with hepatitis B and delta viruses, respectively. Only one individual had been diagnosed of an AIDS-defining condition before the diagnosis of HCC was made. However, all subjects had < 500 CD4+ T cells at the time of HCC diagnosis. Five died within the first 4 months of follow-up. Patients in the control group (n = 31) were significantly older (68.9 +/- 8.9 vs 42.2 +/- 10.4; p < 0.001) and the duration of HCV infection was significantly longer (28.1 +/- 10.9 vs 17.8 +/- 2.7; p < 0.05) than in those with HIV-HCV coinfection. CONCLUSIONS: HCC seems to occur at a younger age and after a shorter period of HCV infection in subjects coinfected with HIV. Thus, treatment of CHC should be encouraged in HIV-positive patients, and in those with HCV-related cirrhosis the periodic monitoring of alpha-fetoprotein and abdominal ultrasonography should be recommended.     

Viral interaction and clinical implications of coinfection of hepatitis C virus with other hepatitis viruses

Coinfection with other hepatitis viruses modifies the viral profile in serum and leads to more liver damage and more rapid progression during the course of hepatitis C virus infection. The viral interference is not only carried out by virus-virus or by virus-cell interactions but also by an enhanced immune response. A superinfecting viral infection does not crossactivate protective immune responses to the pre-existing virus albeit the latter can become undetectable. The induced cytokine stimulation might enhance the hepatic inflammation. Moreover, hepatitis B virus coinfection increases the risk of development of hepatocellular carcinoma in hepatitis C virus patients through common necro-inflammatory pathways or by direct oncogenic activity of hepatitis B virus. Viral interaction also complicates the management of the coinfection because hepatitis C virus impairs the humoral response to hepatitis A virus and hepatitis B virus vaccines, and because pharmacological suppression of hepatitis C virus endangers dually infected patients with reactivation of coinfected hepatitis B virus. Optimized strategies and follow-up are thus necessary in the treatment of infection with multiple viruses. It seems thus necessary to look for markers of hepatitis B virus and/or hepatitis D virus infection in chronic hepatitis patients positive for hepatitis C virus antibodies but negative for hepatitis C virus RNA, and equally well to search for hepatitis C virus RNA in HBsAg-negative/anti-HBc-positive patients with a low level of serum hepatitis B virus DNA.