慢性丙型肝炎病毒感染者外周血淋巴细胞增殖反应

目的　观察慢性丙型肝炎患者外周血淋巴细胞对丙型肝炎病毒（ＨＣＶ） 抗原刺激的增殖反应．方法　外周血单个核细胞（ＰＢＭＣ） 与ＨＣＶ 抗原ｃ２２ 、ｃ３３ 、ｃ１００ － ３ 、ＮＳ５ 和植物血凝素（ＰＨＡ） 分别共同孵育,加入胸腺嘧啶核苷（３ ＨＴｄＲ） ,然后收集细胞于液闪仪测定每分钟脉冲数（ｃｐｍ） ．结果　根据对不同ＨＣＶ 抗原的淋巴细胞增殖反应发现,以ｃ２２免疫原性最强,ｃ１００ － ３ 次之：淋巴细胞激活与ＨＣＶ 基因型关系不大;健康对照和慢性乙型肝炎患者对各ＨＣＶ 抗原未能显示有效的淋巴细胞增殖反应;与健康对照比较,慢性丙型肝炎和乙型肝炎患者对ＰＨＡ 刺激的淋巴细胞增殖反应降低．结论　ＨＣＶ 抗原ｃ２２ 免疫原性最强,丙型肝炎患者对ＨＣＶ 抗原的淋巴细胞增殖反应系特异性;慢性丙型肝炎和乙型肝炎患者存在抑制的细胞免疫应答．     

Low levels of hepatitis C virus (HCV) neutralizing antibodies in patients coinfected with HCV and human immunodeficiency virus

The hepatitis C virus (HCV) neutralizing antibody (nAb) response in 37 subjects with HCV monoinfection and 37 HCV-infected subjects with well-controlled human immunodeficiency virus (HIV) infection was evaluated using a focus reduction neutralization assay. HCV nAb levels were retrospectively studied in both groups of patients, who were matched on the basis of sex, age, and HCV genotype. The mean HCV nAb level (+/- standard deviation) among coinfected patients (1.613+/-0.416) was significantly less than that among monoinfected patients (1.912+/-0.578) (P= .013). Lower HCV nAb titers in coinfected patients could help worsen the outcome of HCV infection. These results favor starting HCV therapy as soon as possible in coinfected patients.     

Optimizing hepatitis C therapy in HIV/hepatitis C virus (HCV) coinfected patients: Analysis of HCV viral kinetics on treatment

INTRODUCTION:

Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported.

METHODS:

Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks.

RESULTS:

There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders.

DISCUSSION:

High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy.     

Compartmentalization of hepatitis C virus (HCV) during HCV/HIV coinfection

Extrahepatic replication has important implications for the transmission and treatment of hepatitis C virus (HCV). We analyzed longitudinal HCV diversity in peripheral-blood mononuclear cells (PBMCs) and serum during HCV monoinfection and HCV/HIV coinfection to determine whether distinct amino acid signatures characterized HCV replicating within PBMCs. Analysis of E1-HVR1 sequences demonstrated higher serum genetic distances among HCV/human immunodeficiency virus (HIV)-coinfected persons. Moreover, consensus PBMC sequences were rarely identical to those in the corresponding serum, suggesting divergence in these 2 compartments. Three of 5 HCV/HIV-coinfected participants showed evidence of HCV compartmentalization in PBMCs. Additionally, signature sequence analysis identified PBMC-specific amino acids in all HCV/HIV-coinfected persons. To our knowledge, this is the first study to identify specific amino acids that may distinguish HCV variants replicating in PBMCs. It is provocative to speculate that extrahepatic HCV diversity may be an important determinant of treatment response and thus warrants additional study, particularly during HCV/HIV coinfection.     

Liver histology in co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV)

As little is known about liver histology in the co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6) and HCV isolated infection (n = 16). Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.     

Prevalence of hepatitis G virus in hepatitis C virus (HCV)-infected patients and in HCV-contaminated intravenous immunoglobulin products

Hepatitis GB virus C/hepatitis G virus (HGV) is an RNA virus, which appears to be transmitted by parenteral exposure to contaminated blood and blood products, and may be associated with clinical hepatitis in humans. The prevalence of HGV was investigated in hepatitis C virus (HCV)-infected patients, and (HCV)-contaminated immune globulin intravenous products (IGIV), manufactured prior to the introduction of viral inactivation processing, and in recipients of these lots. Nested primers, specific for the 5' non-coding region of HGV, were designed and used to test 100 chronic HCV patients, 10 HCV RNA-positive IGIV lots and 36 of the recipients of these products. Hepatitis G virus specificity of the polymerase chain reaction (PCR) products was confirmed by sequencing a number of the amplified products and comparing the results with the published prototype sequence for HGV RNA. HGV RNA was detected in 23 of the 100 (23%) HCV-infected patients. The level of alanine aminotransferase (ALT) was lower in HCV–HGV coinfected patients than those with HCV infection alone. Hence, the severity of HCV infections is not influenced by HGV. Two of the 10 (20%) IGIV lots tested positive for HGV RNA; however, none of the serum samples from recipients of IGIV contained detectable HGV RNA although many were infected with HCV. This suggests that the transmission of HGV RNA from IGIV to the recipients is less efficient than that seen for HCV.     

长春地区丙型肝炎病毒基因分析

目的了解长春地区HCV基因分型情况，为HCV感染者的诊断和治疗提供重要的科学依据。方法荧光定量RT-PCR检测97例抗-HCV阳性血清标本，并对89例HCV-RNA阳性的血清标本应用基因芯片法进行HCV基因分型。结果89例阳性标本中HCV1b型49例，HCV2a型37例，HCV1b／2a混合型3例。结论长春地区HCV基因型主要为1b型，2a型次之，同时存在HCV1b／2a混合型。     

The extrahepatic manifestations in hepatitis C virus (HCV) infection

The hepatitis C virus (HCV) infection could affect not only the liver, but also other tissues, organs and systems. The number of the reported in the literature extrahepatic lesions by HCV incessantly increases. A reliable association between the infections by HCV and the mixed cryoglobulinaemias, membrano-proliferative glomerulonephritis and porphyria cutanea tarda is confirmed. The participation of HCV in the pathogenesis of some diseases of the thyroid gland, the lymphocytic sialadenitis, lichen planus, diabetes mellitus, thrombocytopenia, antiphospholipid syndrome, etc., is assumed. The extrahepatic lesions by HCV are probably connected with the participation of the immune system, but they may be as well due to the replicating virus in the affected tissues, organs and systems. The pathogenetic mechanisms of the extrahepatic and autoimmune manifestations of the infection with HCV are not elucidated, which poses difficult therapeutic problems regarding the choice of interferon and/or corticosteroid hormones.     

Treatment of chronic hepatitis C virus infection in human immunodeficiency virus (HIV) infected patients

Treatment of chronic hepatitis C Virus (HCV) infection in human immunodeficiency virus (HIV) infected patients has become a topic of great importance, since the complications of chronic hepatitis are the first one cause of mortality among HIV patients. The aim of this study is to review the biological and epidemiological data in HIV-HCV coinfection, to establish treatment guidelines taking in consideration drugs' adverse effects and interactions, and to report the results of the main studies carried out. The treatment currently accepted includes pegylate interferon andribavirin, which have improved prior treatments, but the response rate depends on HCV genotype.     

Prevalence of antibodies to hepatitis C virus (HCV) in haemophiliacs

Summary The prevalence of 1) hepatitis C virus (HCV), an agent likely to be responsible for parenter transmitted hepatitis non-A, non-B, 2) hepatitis B virus (HBV) and 3) human immunodeficiency virus (HIV) infection was studied in 211 patients with clotting disorders(78% of the patients had residual factor activities of 2%). Of these patients 71% were positive for HBV markers and 44% for HIV markers. Using a new ELISA technique, 80% were anti-HCV-positive. The prevalence of anti-HCV was greater in patients with more severe clotting disorders and was related to the total amount of replacement therapy received; the prevalence was less in older patients. Seroconversion after a single exposure to dry heat-treated factor concentrates was documented in 3 patients 3–4 months after exposure.     

Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia

BACKGROUND/AIMS: Most patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated. METHODS: In vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity. RESULTS: A TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-gamma production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA. CONCLUSIONS: Patients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.     

Bone alterations in hepatitis C virus infected patients

Background and aimsMost studies have shown that patients with chronic hepatitis C virus (HCV) infection are affected by osteoporosis. However, liver function impairment and deranged nutrition may both play a role in the bone alterations observed. In some works no osteoporosis was found, and some cases of osteosclerosis have been reported. The aim of the study is to assess bone alterations in treatment-naïve, well-nourished HCV patients, in order to discern whether or not HCV infection causes osteoporosis.MethodsWhole-body bone densitometry and assessment of T-score at lumbar spine and hip were performed to 40 patients and 40 age‐ and sex-matched controls, with a Lunar Prodigy Advance (General Electric, Piscataway, NJ, USA). All the patients underwent liver biopsy. Nutritional evaluation was performed by subjective nutritional assessment, body mass index (BMI), and densitometric assessment of total lean mass and total fat mass. Serum osteocalcin, osteoprotegerin, RANKL, PTH, crosslaps, vitamin D3, testosterone, IGF-1, and estradiol were determined.ResultsPatients did not show differences in total bone mineral density (BMD) or T-score with controls. On the contrary, about a third of them showed positive T scores. Patients showed lower IGF-1, vitamin D3 and testosterone, but higher telopeptide levels, and a trend to higher osteoprotegerin levels. Multivariate analyses disclosed that age, sex, and total lean mass were the only parameters independently related with BMD.ConclusionsTherefore, chronic HCV infection in well nourished patients with preserved liver function does not cause osteoporosis.     

Reproducibility of liver stiffness measurements in hepatitis C virus (HCV)-infected patients in Egypt

Summary. Elastometry has demonstrated good accuracy, but little is known about its reproducibility. The aim of this study was to assess the intra‐ and inter‐operator reproducibility of liver stiffness measurement among hepatitis C virus (HCV)‐infected patients in Egypt. The study was conducted among HCV‐infected patients referred for treatment evaluation in two hepatitis treatment centres of Cairo. Two operators took liver stiffness measurement two times per patient the same day. Intra‐ and inter‐reproducibility were estimated by different methods: Bland and Altman graphics, variation coefficient, intraclass correlation coefficient and Kappa coefficient; 7.1 kPa was used as the threshold of significant (≥F2) fibrosis whenever needed. Fifty‐eight patients were included in the study, and 216 measurements were taken. Failure rate was 7% and associated with overweight. For a value of 7.1 kPa, the inter‐operator 95% limits of agreement were estimated at ±2.88 kPa. Intra‐ and inter‐operator coefficients of variation ranged between 11% and 15%, intraclass correlation coefficients [95% confidence interval] between 0.94 [0.86–0.97] and 0.97 [0.95–0.99], and Kappa coefficients between 0.65 [0.44–0.88] and 0.92 [0.81–1.00]. The reliability of liver stiffness measurement is questionable when considering the decision to initiate antiviral therapy because of the percentage of discordance between measurements is notable, especially in the intermediate fibrosis stages.     

Knowledge and attitudes about hepatitis C virus (HCV) infection and its treatment in HCV mono‐infected and HCV/HIV co‐infected adults

Hepatitis C virus (HCV) treatment is rapidly changing but little is known about patients' attitudes and knowledge about HCV. This study used a cross‐sectional survey to examine the relationship between HCV knowledge and attitudes towards HCV in patients with HCV mono‐infection and HIV/HCV co‐infection. Subsequently, an education intervention was developed with an abridged version of the cross‐sectional survey administered before and after the education session to assess changes in knowledge and attitudes. 292 people participated in the cross‐sectional survey, and 87 people participated in the education intervention. In the cross‐sectional survey, the mean knowledge score regarding HCV was low (<50% of the total possible score). Mono‐infected and co‐infected individuals shared similar knowledge deficits and attitudes towards HCV despite having distinct demographic differences. Attitudes endorsed by patients included the following: 57% feared the consequences of HCV on their life, 37% felt HCV was not fatal, 27% did not believe they needed HCV medication, 21% felt ashamed of having HCV and 16% felt HCV treatment was not important. Attitudes that reflected indifference and shame towards HCV were associated with lower knowledge scores (HCV knowledge score of 15.1 vs. 17.5, P < 0.01 for indifference and 15.3 vs. 17.2 for shame, P = 0.02). The education intervention improved knowledge scores but did not modify the assessed attitudes. Intervention studies are needed to effectively change attitudes towards HCV infection and treatment.     

Maintenance hemodialysis decreases serum hepatitis C virus (HCV) RNA levels in hemodialysis patients with chronic HCV infection

OBJECTIVE: Hepatitis C virus (HCV) infection is a major complication among hemodialysis patients the world over. To determine the natural course of HCV viremic levels in patients on maintenance hemodialysis, we prospectively quantified the HCV RNA levels in serial blood samples from hemodialysis patients and compared them with those in nonuremic subjects. METHODS: The population studied included 98 hemodialysis patients and 228 nonuremic subjects with chronic HCV infection. HCV RNA was detected by polymerase chain reaction (PCR) and the levels were determined by branched DNA probe assay. HCV RNA genotypes were determined by PCR using type-specific primers. RESULTS: HCV RNA levels were significantly lower in hemodialysis patients (median, 0.4x10(6) genome equivalent [Meq]/ml) than in nonuremic subjects (median, 3.0 Meq/ml) (p<0.05). HCV of genotype 1b was prevalent in the hemodialysis patients (81.6%) and nonuremic subjects (88.6%). HCV RNA levels in 20 hemodialysis patients with genotype 1b were significantly reduced after each hemodialysis procedure (p<0.05). The 3-yr prospective observation from 1995 to 1998 showed a significant decrease of HCV RNA levels in 47 hemodialysis patients with genotype 1b (median, 1.9-0.9 Meq/ml, p<0.05), whereas levels in 155 nonuremic subjects with genotype 1b did not decrease (median, 2.6-3.0 Meq/ml). There were no patients or nonuremic subjects with undetectable HCV RNA by a PCR assay during the observation period. CONCLUSIONS: These observations suggest that maintenance hemodialysis decreases the HCV RNA levels in hemodialysis patients with chronic HCV infection, but does not produce clearance of the viremia.