Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus

Summary. In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57=75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.     

Characteristics of hepatitis C virus infection in HIV-infected people.

Knowledge pertaining to hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection is currently incomplete or conflicting. Several points are well studied, however. Plasma HCV RNA levels are higher in matched HIV-infected people than in HIV-seronegative control subjects and are inversely correlated with CD4(+) T lymphocyte counts. HCV genotype does not appear to influence this value. Co-infected individuals develop histological and clinical features of HCV liver disease more rapidly than HIV-seronegative patients. Co-infected individuals appear to respond to interferon-alpha therapy equally as well as HIV-seronegative HCV-infected adults, but minimal information exists regarding the efficacy and toxicity of combination HCV therapy (interferon-alpha plus ribavirin) in this population. Adverse consequences of highly active antiretroviral therapy in co-infected patients include hepatic toxicity and, in a minority of patients, an 'immune restoration syndrome'. It is unclear whether long term, highly active antiretroviral therapy positively or negatively influences the natural history of HCV infection.     

人类免疫缺陷病毒感染者混合感染丙型和乙型肝炎病毒后对高效抗逆转录病毒治疗疗效的影响

目的 观察HIV感染者合并HCV和HBV感染后对高效抗逆转录病毒治疗(HAART)疗效的影响.方法 对某地区HIV、HCV共感染患者166例(HIV+HCV组),HIV、HCV和HBV混合感染患者23例(H1V+HCV+HBV组)及单纯HIV感染者178例,给予1年的HAART治疗,观察3组患者病毒学反应、免疫学反应和肝功能动态变化.以流式细胞仪检测外周血CD4+T淋巴细胞;实时PCR定量检测HCV、HIV和HBV病毒载量.结果 单纯HIV感染组、HIV+HCV+HBV组和HIV+HCV组经HAART 1年后,HIV病毒载量分别由治疗前(6.78±1.08)、(6.23±1.34)、(6.54±1.23)lg拷贝/ml下降至(0.53±0.15)、(0.67±0.16)、(0.43±0.11)lg拷贝/ml(P值均＜0.001).CD4+T淋巴细胞计数分别由治疗前的(197±127)、(184±113)、(213±143)个/μl上升至(382±74)、(383±70)、(378±76)个/μl(P值均＜0.001).3组之间各时间点CD4+T淋巴细胞、HIV病毒载量差异无统计学意义.3组患者ALT、AST、总胆红素治疗前后无显著变化,相同时间点组间比较差异无统计学意义.HAART前后,HCV病毒载量差异无统计学意义.结论 HIV感染者混合感染HBV和(或)HCV,不影响HAART的疗效;HAART对HCV复制无抑制作用.     

人类免疫缺陷病毒和丙型肝炎病毒重叠感染者的临床及免疫特征

目的 观察人类免疫缺陷病毒(HIV)和HCV重叠感染者与慢性丙型肝炎患者临床特征及HCV特异性细胞毒性T淋巴细胞(CTL)的数量及功能,探讨两组患者免疫功能的差异及其可能的影响因素.方法 以HIV和HCV重叠感染患者59例、慢性丙型肝炎患者36例为研究对象,取治疗前外周血检测肝脏生物化学指标、血常规、外周血T淋巴细胞亚群(CD4+T、CD8+T淋巴细胞计数)及HIV、HCV病毒载量,以酶联免疫斑点法检测HCV特异性CTL的数量和功能,统计学分析两组问免疫功能的差异及与上述检测指标的相关性. 结果 中国河南省有偿献血、单采血浆人群HIV感染者中HIV和HCV重叠感染率达60.8%.ALT、AST值在重叠感染组与HCV组间差异无统计学意义;球蛋白在重叠感染组为(40.3±5.8)g/L,HCV组为(32.8±6.3)g/L,差异有统计学意义(P＜0.01).重叠感染组外周血CD4+T淋巴细胞数明显低于HCV组(P＜0.01),而CD8+T淋巴细胞数高于HCV组(P＜0.01).重叠感染组HCV RNA定量高于HCV组(P＜0.01).重叠感染组对HCV-NS3区肽段的反应强度(每106个外周血单个核淋巴细胞中斑点形成细胞的个数)较HCV组弱,649.34±685.90对比1233.70±1085.16,差异有统计学意义(P＜0.05).重叠感染组白蛋白与HCV病毒载量呈现负相关(r=0.540);重叠感染组对HCV-NS3区肽段反应强度与HIV病毒载量负相关(r=0.356);重叠感染患者CD4+T淋巴细胞数与血小板正相关(P＜0.05).但未见重叠感染组HCV RNA与CD4+T淋巴细胞数量及HIVRNA水平有相关关系.结论 重叠HIV感染有利于HCV的复制,而HIV载量可影响针对HCV的特异性免疫反应,HIV载量高则不利于HCV的清除.慢性丙型肝炎患者重叠HIV感染时,病情易慢性化,预后更差.     

人类免疫缺陷病毒与重叠丙型肝炎病毒感染者免疫指标比较

目的 分析HIV/HCV重叠感染人群与HIV单独感染人群治疗前临床特征及免疫功能的差异,探讨其可能的影响因素.方法 以HIV/HCV重叠感染患者59例、HIV单独感染患者38例为研究对象,取患者治疗前外周血,检测其肝功能、血常规、外周血T细胞亚群(CD4+、CD8+)及HIV、HCV病毒载量,酶联免疫斑点法(ELISPOT)检测HIV特异性细胞毒性T淋巴细胞(CTL)的数量和功能.结果 HIV/HCV重叠感染率达60.8%.重叠感染组ALT、AST均明显高于HIV组(49.8 U/L比23.6 U/L,49.1 U/L比32.3 U/L,P值分别为0.000、0.013);重叠感染组PLT明显低于HIV组[(167.3±59.2)×109/L比(198.0±63.9)×109/L,P=0.040].外周血T细胞亚群检测结果两组间差异无统计学意义.重叠感染组HIV RNA定量为(4.046±0.541)lOglo拷贝/mL,低于HIV组的(4.394±0.507)log10拷贝/mL(P=0.018).重叠感染组对HIV-Gag全序列肽段的阳性孔斑点数(平均秩次30.85)较HIV组(平均秩次44.34)低,阳性孔数(4.60±5.52)低于HIV组(6.24±6.93),但两组比较差异无统计学意义.重叠感染组Alb与HCV病毒载量呈负相关(r=-0.540),CD4+与PLT呈正相关(P=0.000).结论 单采血浆感染HIV患者中,有较高的HIV/HCV重叠感染率和较低的细胞免疫功能.     

Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis C in the United States

Hepatitis C virus (HCV) RNA status and HCV genotype have become important tools in the diagnosis and monitoring of therapy in chronic HCV infection. To establish a database with respect to HCV genotype and serum HCV RNA concentrations in chronic hepatitis C patients in the United States, we analysed 6807 chronic hepatitis C patients who had HCV RNA and HCV genotype tests conducted at a central laboratory. The HCV RNA concentration cut-off for the lower 25th percentile of this population (low titre) was 0.9 × 10⁶ copies ml^–1. The median HCV RNA concentration was 3.5 × 10⁶ copies ml^–1 and the cut-off for the upper 25th percentile (high titre) was 5 × 10⁶ copies ml^–1. Male patients had a median HCV RNA concentration of 3.9 × 10⁶ copies ml^–1, which was significantly higher than the median HCV RNA level for females (2.75 × 10⁶ copies ml^–1; P  < 0.001). HCV genotype 1 was detected in 73% of patients; genotype 2 in 14%; genotype 3 in 8%; mixed genotype in 4%; and genotypes 4, 5 and 6 with a frequency of < 1%. Patients from the Northeast, Southeast and Midwest had significantly ( P  < 0.001) more infections with genotype 1 than patients from the Western and Southern regions. African–American patients were more likely to be infected with genotype 1 when compared with Caucasian, Hispanic or Asian Pacific Islanders ( P  < 0.001). Patients infected with HCV genotype 1 and mixed HCV genotypes had significantly higher serum HCV RNA concentrations when compared with HCV genotypes 2 and 3 ( P  < 0.001 for all comparisons).     

Significance of immune status, genotype and viral load in the severity of chronic hepatitis C in HIV infected haemophilia patients

Chronic hepatitis C is associated with more severe liver disease in patients coinfected with HIV, but the pathogenic mechanism of this more aggressive course is still unclear. The aim of this study was to assess the relationship of HCV genotype, viral load and epidemiological factors with the histological severity of chronic hepatitis in haemophilia patients with HCV/HIV coinfection, taking into consideration the immune status of the patients. Twenty-one HIV/HCV coinfected haemophilia patients, with mean age +/- SD 35.7 +/- 8.7 years, underwent transcutaneous liver biopsy 6-15 years (median 12 years) after HIV and 6-32 (median 21.5 years) years after HCV infection. Twelve patients were stage A (CDC), six stage B and three stage C. CD4 cells were < 50 microL(-1) in three patients (14.3%), 50-200 in 11(52.4%) and > 200 in 7(33.3%). Mean +/- SD log(10) HCV-RNA was 6.87 +/- 0.7 copies mL(-1) (range 5.4-7.9), and mean +/- SD log(10) HIV-RNA was 3.75 +/- 0.98 copies mL(-1) (range 2.7-6), at the time of liver biopsy. Minimal hepatitis was diagnosed in five patients (24%), mild in 10 (48%) and moderate in six (28%). Hepatitis stage 0-2 was found in seven cases (33%) and cirrhosis in six (29%). Statistical analysis showed a significant association of CD4 count < 50 with minimal hepatitis and of CD > 200 with mild and moderate hepatitis (P = 0.033). In addition, minimal hepatitis was found only in patients with stage C, while the majority of subjects with HIV stage A showed mild and moderate hepatitis (P = 0.003). Moreover genotype 1 was independently associated with advanced hepatitis stage (P = 0.04). No relationship was found between hepatitis severity, HIV or HCV RNA levels, patient's age and duration of HIV or HCV infection. Our results suggest that HCV/HIV coinfection may aggravate the course of hepatitis in the phase of immunocompetence, most probably through an immune mediated process. Genotype 1 seems to be associated with advanced liver disease.     

Effect of human immunodeficiency virus infection on hepatitis C virus infection in hemophiliacs

Chronic liver disease due to hepatitis C virus (HCV) infection is a major problem in hemophiliacs. Recent reports suggested that hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus (HIV) have an increased incidence of liver failure but the mechanism of accelerated liver injury is not clear. We tested plasma from 100 hemophiliacs for anti-HCV by second generation ELISA, anti-HIV by EIA, and HCV RNA and HIV RNA by branched DNA and polymerase chain reaction assays to determine if hemophiliacs coinfected with HCV and HIV have higher HCV RNA levels and more active liver disease. Seventy-nine (79%) patients were anti-HCV positive, of whom 85% were HCV RNA positive. None of the anti-HCV-negative patients had detectable HCV RNA in plasma. Forty-two (42%) patients were anti-HIV positive, of whom 47% had detectable HIV RNA. All the anti-HIV-positive patients were also anti-HCV positive. The prevalence of both anti-HCV and anti-HIV increased significantly with age. There was no difference in HCV RNA levels between anti-HIV-positive and anti-HIV-negative patients (mean: 21±4 vs 18±5 Meq/ml), although HCV RNA levels were significantly higher in anti-HIV-positive patients with CD4 counts<200/mm³ (P=0.008). There was an inverse correlation between HCV RNA levels and CD4 counts but no correlation was found between HCV RNA and serum aminotransferase levels. We found a high prevalence of HCV and HIV coinfection in our hemophiliacs. Hepatitis C virus replication appears to be increased in patients with severe immunodeficiency secondary to progressive HIV infection. However, there was no correlation between HCV RNA and serum ALT level, suggesting that HCV is not directly cytopathic.     

Virological characteristics of HCV infection in Japanese haemophiliacs

It has been found that almost all haemophiliacs treated with pooled concentrates of clotting factor VIII or IX before 1985/6 have been infected with hepatitis C virus (HCV). In order to clarify the characteristics of HCV infection in Japanese haemophiliacs, we investigated the HCV genotype and HCV-RNA level in 80 patients with haemophilia who had been confirmed to be positive by a second-generation HCV antibody test. HCV-RNA was detected in 60 (75.0%) individuals and various HCV genotypes were found. Although 80% (48/60) of the patients had genotype 1b, the frequency of each genotype was quite different from that in HCV-infected non haemophiliac Japanese. Particularly, multiple HCV genotypes were observed in 27 (46.7%) patients. The mean (± SD) level of HCV-RNA was 5.3 × 10⁵ ±  1.1 × 10⁶ copies mL⁻¹. The viral load in patients with genotype 2a was significantly less common than those with genotype 1a ( P = 0.0007), genotype 1b ( P = 0.0009) and combined genotype 1a/1b ( P = 0.0019). In patients co-infected with human immunodeficiency virus (HIV), the HCV-RNA level was significantly higher ( P = 0.05) than in those without co-infection. However, there was no significant difference ( P = 0.25) in the HCV-RNA level with HCV/HIV co-infection among the 40 patients with group 1 genotypes. We conclude that this biased distribution of HCV genotypes in Japanese haemophiliacs reflects their specific mode of HCV infection. Moreover, these results suggest that super-infection with HIV does not greatly influence the HCV load in patients with no marked immunological deterioration.     

Plasma Hepatitis C Virus Viral Load Among Hepatitis C Virus Mono-Infected and HCV/HIV Co-Infected Individuals in Yunnan Province,China

Background

Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection has become a serious public health problem especially in high risk groups such as injection drug users in China. However, the impact of HIV infection and antiretroviral therapy (ART) on HCV viral load which is usually regarded as a predictor of liver disease progress had not been well studied in this country.

Objectives

To explore correlations of HIV co-infection and ART with plasma HCV load among HCV-infected patients in an ethnic minority area in Yunnan Province, China.

Patients and Methods

HCV/HIV co-infected patients and HCV mono-infected controls were examined and compared for plasma HCV RNA and related risk factors.

Results

A total of 145 HCV/HIV co-infected patients and 25 HCV mono-infected controls were studied. The majority of the participants were male, belonged to an ethnic minority and were younger than 45 years old. HCV viral suppression rate with undetectable plasma HCV viral load was 28.3% in the HCV/HIV co-infected patients, 36% among HCV mono-infected controls and 29.4% overall. ART-prescribed HCV/HIV co-infected patients had significantly higher HCV viral loads (IQR: (3.80-6.44)*log₁₀ copies ml-1) than those naïve to ART (IQR: (undetectable-6.41)*log₁₀ copies ml-1) and HCV mono-infected patients (IQR: (undetectable-5.44)*log₁₀ copies ml-1). Men, from the Dai minority and those with more than six years education, were also shown to have a higher plasma HCV viral load,according to multiple logistic regression analysis.

Conclusions

ART potentially increases the plasma HCV viral load among HCV/HIV coinfected patients in an ethnic minority area in China. Future large scale prospective cohort studies are needed to address the controversy associated between HIV co-infection and the natural history of HCV.     

Hepatitis C virus infection in patients with clinically diagnosed alcoholic liver diseases

Summary To determine the incidence of hepatitis C virus (HCV) infection in patients with alcoholic liver disease (AID), serum samples from 252 patients with AID were tested for anti-HCV and HCV RNA. Serial sera of these patients were collected and stored under optimal conditions to allow exact quantification of HCV RNA. Fifteen patients who visited our hospital during the same period of time with chronic HCV infections served as controls. In those with AID, anti-HCV and HCV RNA were positive in 55.5% and 41.2%, respectively. Patients with histologically diagnosed chronic hepatitis and hepatocellular carcinoma had much higher prevalence rates of HCV RNA (84% and 100%, respectively) compared to those with fatty liver (4.3%), hepatic fibrosis (10.1%) and alcoholic hepatitis (22.2%) ( P < 0.01). Although no difference in serum HCV RNA levels was observed between the patients with both AID and chronic HCV infection and those with chronic HCV infection alone, HCV RNA levels significantly (10-fold) dropped after abstinence in nearly half of the patients ( P < 0.01). These data indicate that HCV infection in patients with AID promotes progression of liver disease, and abstinence from alcohol is associated with a reduction in serum HCV RNA levels.     

Analytical and clinical sensitivity of the Procleix Ultrio HIV-1/HCV/HBV assay in samples with a low viral load

BACKGROUND AND OBJECTIVES: The Procleix Ultrio human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus (HCV)/hepatitis B virus (HBV) (Ultrio) assay simultaneously detects HIV-1 RNA, HCV RNA and HBV DNA in individual blood donations. The main objective of the study was to assess the analytical and clinical sensitivity of the multiplex and discriminatory probe assays in samples with a low viral load. MATERIAL AND METHODS: The VQC HIV RNA genotype B, HCV RNA genotype 1 and HBV DNA genotype A standard dilutions were tested in 26 repeats. The probability of detection by Ultrio was compared with previously obtained data of the Procleix Duplex HIV-1/HCV assay on the same reference panels. A selection of 121 anti-HIV-1, 138 anti-HCV and 190 HBsAg positive samples from patients receiving antiviral therapy were tested. The majority of patient samples had a viral load below the detection limit of the diagnostic nucleic acid test assays, which made them suitable to evaluate the performance of the multiplex and discriminatory assays on yield cases with a similar low viral load. RESULTS: The 95% and 50% detection end-points of the Ultrio assay along with the corresponding 95% confidence intervals are 53.7 (32.9-117.2) and 8.6 (6.2-12.1) geq/ml for HIV-1 RNA, 30.3 (19.0-62.4) and 5.2 (3.7-7.2) geq/ml for HCV RNA and 393.7 (147.9-6978) and 54.5 (22.4-143.8) geq/ml for HBV DNA. The analytical sensitivity of Ultrio expressed as a potency factor relative to previously obtained Duplex results on the same HIV-1 RNA and HCV-RNA standard dilutions was 1.09 (0.20-6.10) and 1.11 (0.21-5.89), respectively. The assay detected all 22 HIV-1 infected patients with viral load > 50 copies/ml, and 41 of 99 patients (41%) with viral load < 50 copies/ml, of which 23 (56%) were detected by the discriminatory assay. All 47 patients with HCV RNA load > 521 IU/ml and 10/91 polymerase chain reaction-negative patients with viral load < 50 IU/ml tested positive in Ultrio assay of which five were missed in the discriminatory test. The assay detected 53/55 HBV infected patients (96%) with viral load > 250 copies/ml and 108/135 patients (80%) with viral load < 250 copies/ml of which 17 (16%) were missed by the discriminatory test. CONCLUSIONS: The new Procleix Ultrio assay is as sensitive as the Procleix Duplex assay for HIV-1 and HCV detection meeting the requirements of universal guidelines. The ability of the assay to detect HBV DNA in low viral load samples could be useful for screening blood. Inevitable negative results of discriminatory probe assays caused by stochastic sample variation will reduce the chance of recognizing low viraemic blood donors detected by individual donation nucleic acid test.     

Intrahepatic hepatitis C virus replication is increased in patients with regular alcohol consumption

AIMS: To assess clinical significance of liver hepatitis C virus RNA levels and their relationship with epidemiological, biochemical and histological factors. METHODS: A total of 50 patients (mean age 35.5+/-7 years) with biopsy-proven chronic hepatitis C infection were recruited. Risk factors were drug abuse (n=21), transfusion (n=16), other parental routes (n=8; surgery=3, tattooing=5), and idiopathic (n=5). Duration of infection was 16+/-9 years. All patients showed abnormal alanine aminotransferase levels and positive serum hepatitis C virus RNA. Hepatitis C virus genotype was assessed by Inno-Lipa. Liver biopsy was performed for histology and for hepatitis C virus RNA quantification by Amplicor-HCV-Monitor Daily alcohol consumption was recorded on two occasions by anamnesis. Inflammation grade was mild (n=31) or severe (n=19). Fibrosis was early stage (n=42) or advanced (n=8). RESULTS: Mean hepatitis C virus RNA levels were 9.4x10(5)+/-1.5x10(6) copies/microg of total RNA in liver tissue, and 9.1x10(5)+/-1.3x10(6) copies/ml in serum. Viral load in liver was positively correlated with that in serum (r=0.51, p<0.001) and there was a significant relationship between daily alcohol consumption and intrahepatic hepatitis C virus burden (r=0.53; p<0.001). Patients infected with genotype 3a showed lower intrahepatic hepatitis C virus load than patients infected with genotype 1b; albeit without reaching statistical significance (0.49x10(6)+/-0.89x10(6) vs 1.44x10(6)+/-1.9x10(6) copies/microg of total RNA; p=NS). No relationships were observed between liver viral burden and age, risk factor status, duration of infection, ferritin and alanine aminotransferase levels or with grading and staging. CONCLUSIONS: Hepatitis C virus load in serum is a mirror of intrahepatic hepatitis C virus levels. Chronic alcohol consumption enhances intrahepatic hepatitis C virus concentration.     

Impact of hepatitis G virus co-infection on the course of hepatitis C virus infection before and after liver transplantation

Background/Aims: Hepatitis G virus (HGV), a new RNA virus that is parenterally transmitted, has frequently been found in patients with chronic hepatitis C (HCV) infection but its role in chronic liver disease is unknown. The purpose of this study was to determine the prevalence of HGV infection in transplantation patients infected with hepatitis C and to assess the impact of HGV co-infection on the course of HCV infection after liver transplantation.Methods: Eighty-nine liver transplantation recipients with persistent hepatitis C viremia detected by polymerase chain reaction (PCR) were evaluated. Serum samples were tested before and after liver transplantation for HGV RNA by two different PCR methods: LC^TM assay (Abbott Laboratories) and an RT-PCR procedure which we developed using the silica gel technique for extraction of the HGV RNA. E2 antibodies were detected before orthotopic liver transplantation by an EIA-test. HCV RNA was quantified by branched DNA assay, and HCV genotype was determined. A mean of nine liver biopsy specimens were examined for each patient and the severity of the lesions was compared in HCV-positive patients with or without HGV co-infection.Results: The concordance between the two HGV RNA detection methods was excellent and the reproducibility of our RT-PCR procedure was confirmed. The prevalence of pretransplantation and posttransplantation HGV infection was 11% and 19%, respectively. Pretransplantation HGV infection was positively correlated with posttransplantation HGV infection (p<0.001). Before transplantation the E2 antibodies seroprevalence was 34%. Seven patients became HGV RNA positive after transplantation, but all of them were negative for E2 antibodies. Among the patients who remained RNA negative after liver transplantation, 40% were positive for E2 antibodies (p = 0.04). Pretransplantation clinical features (except AST mean value) were not different in patients with HCV and HGV co-infection and those with HCV only. After a mean follow-up of 34 months (range: 6 to 70), (75%) patients developed histological features of recurrent hepatitis but the frequency of the occurrence of graft hepatitis was not different between HGV/HCV co-infected patients and those with HCV alone (p=0.89). The mean interval from orthotopic liver transplantation to recurrence was 12.2 months (range: 3–63), which was not different for HVG/HVC-co-infected patients and HCV-infected patients. The histological severity of posttransplantation liver disease, and the graft and patient survival were not different for patients with and without HGV co-infection.Conclusions: Our results suggest the general persistence of HGV infection after liver transplantation, but HGV co-infection did not appear to influence the posttransplantation course of HCV infection. Before transplantation the prevalence of E2 antibodies was 34%, and our data clearly indicate that E2 antibodies were protective against HGV infection.     

Hepatitis C virus genotypes and hepatic fibrosis regulate 24-h decline of serum hepatitis C virus RNA during interferon therapy in patients with chronic hepatitis C

BACKGROUND AND AIMS: Recently, hepatitis C virus (HCV) dynamics during interferon (IFN) therapy have been studied in detail. We examined factors that regulate the viral kinetics and the relationship between the viral kinetics and clinical effect of IFN therapy. METHODS: Eighty-eight patients with chronic hepatitis C entered this study. All patients had been treated with 3 MU of IFN-beta twice a day for the first 2-4 weeks, then IFN-alpha for the next 20-22 weeks (three injections per week). The levels of serum HCV RNA were determined by Amplicor HCV Monitor version 1.0, before and 24 h after the first injection of IFN; then the decline of HCV was calculated. Liver inflammation and fibrosis were scored as 0 (none), 1 (mild), 2 (moderate) or 3 (severe) using biopsy specimens. RESULTS: The decline of serum HCV RNA was 1.42 +/- 0.65 log copies/mL in genotype 1b and 1.83 +/- 0.72 in genotype 2a or 2b (P < 0.01). By a logistic regression model, genotype (1b, 2a or 2b) and hepatic fibrosis (0 or 1, 2 or 3) associated with 24-h decline of serum HCV RNA, independently. As the predictor of IFN therapy, the decline of serum HCV RNA and serum HCV RNA levels before IFN therapy were the independent significant factors (P < 0.001). CONCLUSIONS: The decline of serum HCV RNA during the first 24 h of IFN therapy was regulated by genotypes and hepatic fibrosis. The decline of serum HCV RNA and initial HCV load were independent factors that can be the predictor of the subsequent sustained viral response to IFN therapy.     

Biochemical and virologic parameters in patients co-infected with hepatitis C and HIV versus patients with hepatitis C mono-infection

BACKGROUND: Previous studies of patients with hepatitis C virus (HCV) infection looking at the effect of human immunodeficiency virus (HIV) co-infection on biochemical parameters and HCV RNA level have shown conflicting results. Accurate characterization of the effect of HIV is important for evaluation and treatment of HCV in co-infected persons. METHODS: We studied 315 HCV mono-infected and 75 HCV-HIV co-infected subjects to determine the effect of HIV on biochemical parameters and HCV RNA and to determine the predictors of elevated serum alanine aminotransferase (ALT) levels and HCV RNA levels. RESULTS: The co-infected subjects were more likely to be African-American (55% vs 26%, P < 0.0005), have used injection drugs (68% vs 60%, P = 0.02), have detectable HCV RNA (84% vs 70.5%, P = 0.018), have HCV RNA levels >6 log10 IU/mL (60% vs 38%, P = 0.001), and have lower mean serum ALT levels (50.4 IU/mL vs 73.7 IU/mL, P = 0.006). In multivariable analyses, the following factors predicted an ALT level >50 IU/mL: log10 HCV RNA (OR, 1.15; 95% CI, 1.00 to 1.32); HIV co-infection (OR, 0.48; 95% CI, 0.25 to 0.89); and having ever been treated for HCV (OR, 1.92; 95% CI, 1.16 to 3.18). The only significant predictor of HCV RNA level >6 log10 IU/mL was HIV co-infection (OR, 2.75; 95% CI, 1.46 to 5.15). Significant predictors of having a detectable HCV RNA level were female sex (OR, 3.81; 95% CI, 1.18 to 12.25); HIV co-infection (2.45; 95% CI, 1.14 to 5.26); and ever being treated for HCV (OR, 1.96; 95% CI, 1.10 to 3.48). CONCLUSIONS: HCV-HIV co-infected persons have higher HCV RNA levels but lower serum ALT levels than HCV mono-infected patients. Criteria for performing liver biopsy and treating HCV infection in co-infected patients may need to be revisited.     

Liver damage and kinetics of hepatitis C virus and human immunodeficiency virus replication during the early phases of combination antiretroviral treatment

In order to assess the relationship between human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, CD4, CD8, and liver enzymes during combination antiretroviral therapy, these parameters were measured in 12 HIV-HCV-coinfected patients (who were naive for antiretrovirals) on the day before and 3, 7, 14, 28, 56, and 84 days after initiating the following treatments: stavudine and lamivudine in all patients, indinavir in 6 patients, and nevirapine in 6 patients. HIV RNA declined rapidly, CD4 cells increased slowly, and CD8 cells and liver enzymes were stable. HCV RNA showed a transient significant increase at days 14 and 21 (7.33+/-0.16 [mean +/- SE] and 7.29+/-0.2 log copies/mL vs. 7+/-0.2 log copies/mL at baseline; P<.05). These changes were similar in both treatment groups. A 2-fold alanine aminotransferase increase was observed in 4 of 12 patients; 4 of 4 patients showed increased HCV RNA. The relationship between HCV RNA increase and HIV RNA decrease indicates virus-virus interference. An HCV RNA increase may cause significant liver damage only in a minority of patients.