Occult hepatitis C virus infection among hemodialysis patients

Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.     

维持性血液透析患者感染乙型和丙型肝炎的分析

目的为了评价血液透析（血透）患者乙型和丙型肝炎（HBV、HCV）感染状态及对临床情况和肝功能的影响。方法对62例血透患者应用ELISA法和RT-PCR法检测抗-HCV和HCVRNA，采用斑点杂交法和固相放免法检测HBV标志，并检测肝功能和血浆蛋白电泳。结果62例患者中，抗-HCVIgM阳性27例（43．6％），抗-HCVIgG阳性29例（46．8％），HCVRNA阳性34例（54．8％），三项任一项阳性37例（59．7％），5例（8．1％）HBsAg阳性，其中HBeAg和HBVDNA阳性3例。结论向透患者中HCV感染严重，临床情况及预后差，检测血浆蛋白和电泳较肝功能酶学能更好地作为肝炎诊断和反映病情的指标。     

Hepatitis G virus infection in hemodialysis patients and its relationship with hepatitis C virus infection

Our aim was to study the characteristics of hepatitis G virus (HGV) infection in hemodialysis (HD) patients. We evaluated 108 patients from two different units (A: 67 patients; B: 41 patients). HGV RNA and HCV RNA were detected by PCR. Nineteen patients (17.6%) were HGV RNA positive (20.9% in unit A and 12.2% in unit B (NS)). HCV RNA was positive in 19 patients (17.6%) (28.4% in unit A and 0 in unit B (p < 0.01)). Eight patients were HGV RNA and HCV RNA positive (group I), 11 HGV RNA positive (group II), 11 HCV RNA positive (group III), and 78 negative for both viruses (group IV). Time on HD was 51.3 +/- 37.0 months for group I, 36.0 +/- 27.9 months for group II, 63.5 +/- 40.2 months for group III, and 26.4 +/- 27.1 months for group IV (p < 0.01 for I and III). Seven patients (87.5%) from group I, 9 (81.8%) from group II, 10 (90.9%) from group III, and 44 (56.4%) from group IV had a history of transfusion (p < 0.03 for I, II and III). Two patients (25%) from group I, none from group II, 5 (45.4%) from group III, and 6 (7.7%) from group IV had chronic ALAT elevation (p < 0.01 for I and III). We conclude that HGV infection was frequent in our HD patients, related to transfusions and independent of HCV prevalence, and that HGV infection itself was not a cause of ALAT elevation suggesting chronic hepatitis.     

Leukopenia and thrombocytopenia in hemodialysis patients with hepatitis B or C virus infection and non-hemodialysis patients with hepatitis cirrhosis

AIMS: To investigate the relation of leukopenia and thrombocytopenia in hemodialysis (HD) patients with hepatitis C virus (HCV) infection. MATERIALS AND METHODS: The study included 86 HD patients with hepatitis B surface antigen-negative and hepatitis C antibody-negative, 28 HD patients with hepatitis C antibody-positive, 22 HD patients with hepatitis B surface antigen-positive, 78 non-HD patients with hepatitis B-induced liver cirrhosis and 38 non-hemodialysis patients with hepatitis C-induced liver cirrhosis. The following parameters were checked: anti-HCV, hepatitis B surface antigen, hemoglobin, hematocrit, white blood cells, platelets, calcium, phosphate, iron, ferritin, albumin, globulin, aspartate transaminase (AST), alanine transaminase (ALT) and C-reactive protein. The history of blood transfusions, medications, erythropoietin doses and adequate dialysis (KTNV) for 6 consecutive months was also recorded from charts. RESULTS: The HD patients with positive serum anti-HCV and non-HD patients with hepatitis B- or C-induced liver cirrhosis had higher prevalences of leukopenia (39.3%, 43.6% and 50% vs. 15.1%; p < 0.001) and thrombocytopenia (67.9%, 89.7% and 81.6% vs. 34.9%: p < 0.001) than HD patients with serum anti-HCV(-)HbsAg(-). The WBC (4,432 +/- 1,394, 4,792 +/- 2,263 and 4,624 2,446 vs. 5,590 +/- 1,500/mm3; p < 0.001) and platelet counts (140 +/- 45, 80 +/- 50 and 89 +/- 65 vs. 186 +/- 62 x 10(3)/mm3; p < 0.001) of HD patients with positive serum anti-HCV and non-HD patients with hepatitis B- or C-induced cirrhosis were also lower than HD patients without anti-HCV antibody. The liver cirrhosis patients had more thrombocytopenia than the HD patients with anti-HCV(+). The WBC and platelet counts did not vary between HD patients with HbsAg(+) and HD patients with anti-HCV(-)HBsAg(-). The durations of HD, hepatitis and liver cirrhosis were not related to the leukopenia or thrombocytopenia (p > 0.05). CONCLUSIONS: HCV infection associated with leukopenia and/or thrombocytopenia in HD patients is as common as in non-HD patients with liver cirrhosis. This may be due to the direct effect of hemopoiesis rather than the hyperspleenism of liver cirrhosis patients. There is a need for further prospective investigation to ascertain the clinical significance of leukopenia and thrombocytopenia in HD patients with anti-HCV(+). The prevalence of leukopenia and thrombocytopenia was higher in HD patients with hepatitis C than in HD patients with hepatitis B and HD patient without hepatitis.     

维持性血液透析患者丙型肝炎病毒感染情况的调查与护理预防

目的 调查本透析中心6年间维持性血液透析患者丙型肝炎病毒的感染率变化情况,分析丙型肝炎病毒感染的易感因素,探讨预防丙型肝炎病毒传播的措施.方法 检测所有长期维持性血液透析患者丙型肝炎抗体,丙型肝炎RNA,并收集相关临床资料.结果 2004年155例透析患者中丙型肝炎感染率为10.3%.2009年228例患者中丙型肝炎抗体阳性率为8.8%.2010年300例丙型肝炎的感染率为7.3%.其中111例患者在我中心透析6年以上,累计透析85100余次,没有新发丙型肝炎感染.显示输血次数和肾移植病史是并发丙型肝炎的危险因素.结论 近6年来我中心的血液透析患者丙型肝炎感染率呈下降趋势.通过减少输血,严格执行血液透析时防止血源性传播疾病操作规程,能够减少丙型肝炎在透析患者之间的传播.

Abstract：

Objective To investigate the hepatitis C virus (HCV) infection in patients with maintained hemodialysis for 6 years in the hemodialysis center of Beijing Friendship Hospital, and to analyse the risk factor of HCV infection. Methods HCV RNA , the serum virus antibody were detected in hemodialysis patients . The relationship between the infection of hepatitis virus and the dialysis time, blood infusion and hepatic function was analysed. Results The percentage of HCV infection patients was 10.3% ,8.8%, and 7.3% in 2004,2009,2010 respectively. 111 patients were treated in our center for more than 6 years. There was no new HCV infection in these group patients during 6 years. Blood infusion and the history of kidney implantation were the risk factors. Conclusion The percentage of HCV infection in hemodialysis patients was reduced in our dialysis center. Avoidance blood transfusion and infection control of blood purification standard operating procedure are the major ways to prevent transmit HCV in patient with MHD.     

Occult hepatitis B virus infection in hemodialysis patients with chronic HCV infection

BACKGROUND: The aim of this study was to determine the prevalence of occult hepatitis B infection in hemodialysis patients with chronic HCV infection and to compare it with that of HCV-infected patients with normal renal function. METHODS: Forty-nine patients on maintenance hemodialysis and 48 HCV-infected but otherwise normal patients, both groups HCV RNA-positive and HBsAg-negative and matched for age and sex, were evaluated for the presence of HBV DNA in serum by polymerase chain reaction (PCR). A proportion of patients (11/49 and 39/48, respectively) were also examined for HBV antigens in hepatocytes by immunohistochemistry. RESULTS: HBV DNA was detected by PCR in 10/49 (20.4%) hemodialysis patients and in 3/48 (6.3%) patients with normal renal function (p=0.041). HBV DNA concentrations were low (<10 3 copies/mL) in both groups. HBV DNA-positive hemodialysis patients had a significantly lower prevalence of past HBV vaccination and lower anti-HBs titers in serum than HBV DNA-negative patients of the same group. No positive staining for HBsAg or HbcAg was observed in the liver biopsies of either group. CONCLUSIONS: Occult HBV infection is more frequent in HCV-infected hemodialysis patients than otherwise normal patients with chronic HCV infection, probably because of impaired immune function in uremic patients and high risk of parenteral exposure to HBV. The clinical significance of this finding is unknown, but HBV vaccination of hemodialysis patients and staff could be an effective way of limiting the risk of transmission of HBV infection within dialysis units.     

Lower erythropoietin and iron supplementation are required in hemodialysis patients with hepatitis C virus infection

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common infectious agent in chronic hemodialysis (HD) patients. In this prospective case-control study, we aimed to investigate the influence of chronic HCV infection on erythropoietin (EPO) and iron requirement in HD patients. PATIENTS AND METHODS: 49 HD patients (24 male, 25 female, mean age 47 +/- 15 years) were included. The mean time spent on dialysis was 39 +/- 38 months, and follow-up time was 1 year for this study. Biochemical analyses and complete blood counts together with iron status of the patients (transferrin saturation and serum ferritin levels) were measured monthly. Highly sensitive C-reactive protein (hs-CRP) levels were measured within 3-month intervals. Endogenous EPO levels were measured by enzyme-linked immunoassay 2 weeks after cessation of EPO treatment. RESULTS: Eleven of the HD patients (22%) were anti-HCV(+). There was no difference in age, sex, time on dialysis, distribution of primary renal diseases, predialytic BUN, Kt/V, albumin and i-PTH levels between HCV(+) and (-) patients. Anti-HCV-positive patients required significantly lower weekly doses of EPO (87 +/- 25 IU/kg vs 129 +/- 11 IU/kg, p = 0.042) and iron (16.8 +/- 12.2 mg vs 32.6 +/- 16.1 mg, p = 0.02) replacement than anti-HCV(-) group; hs-CRP levels were similar between study groups. Serum endogenous EPO levels were significantly higher in HCV(+) patients than HCV(-) HD patients (9.43 +/- 6.47 mU/ml vs 3.59 +/- 2.08 mU/ml, p = 0.008). CONCLUSION: Anti-HCV(+) HD patients had higher serum EPO levels and required less EPO and iron replacement as compared to anti-HCV(-) patients. Because of the changes in iron metabolism, iron treatment should be carefully administered in HD patients with HCV.     

Hand contamination with hepatitis C virus in staff looking after hepatitis C-positive hemodialysis patients

BACKGROUND: Hepatitis C virus (HCV) is a major cause of hepatitis in hemodialysis (HD) patients. Routes other than blood transfusion play a role in the spread of HCV in HD patients. Molecular studies of HCV implicate nosocomial transmission of the virus in HD units. We conducted a clinicovirological study in our HD unit to investigate if the hands of dialysis personnel could represent a mode of transmission of HCV among HD patients. METHODS: One liter of sterile water was used for each handwashing of dialysis personnel. The washing was collected in a sterile container and tested for HCV-RNA by polymerase chain reaction (PCR) within 3 h of collection. Eighty handwashings from nurses dialyzing HCV-positive patients (groupe A) and 100 handwashing from nurses dialyzing HCV-negative patients (group B) were tested for HCV-RNA. As a control, 60 handwashings were collected from the dialysis personnel before entering the dialysis unit (group C) and tested for HCV-RNA. RESULTS: HCV-RNA was positive in 19 (23.75%) of samples of group A, in 8 (8%) of samples of group B (p < 0.003) and in 2 (3.3%) of samples of group C (p < 0. 35). These two positive samples of group C were from nurses who had dialyzed HCV-negative patients. CONCLUSION: These results indicate the presence of HCV-RNA on the hands of some dialysis personnel in our HD unit, in spite fo adherence to the standard precautions. The hands of dialysis personnel are therefore a potential mode for facilitating transmission of HCV between HD patients.     

维持性血液透析患者丙肝病毒感染预后分析

目的 探讨丙肝病毒感染对维持性血液透析患者预后的影响.方法 对106例死亡的维持性血液透析患者按丙肝阳性和丙肝阴性分组进行回顾性分析.结果 两组年龄、性别、原发病、肾功能、血糖、血脂、Hb、 Kt/V无统计学差异.阳性组出现肝酶升高、血白蛋白降低,较阴性组有显著性差异.阳性组透析龄59个月较阴性组85个月明显缩短,心血管事件为两组最常见死亡原因.结论 丙肝病毒感染维持性血液透析患者肝功能异常,生存时间缩短.     

Prevalence,incidence, and risk factors for hepatitis C virus infection in hemodialysis patients

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Bone mineral density in patients on maintenance hemodialysis and effect of chronic hepatitis C virus infection

OBJECTIVE: To determine the prevalence of osteopenia and osteoporosis in HD patients at our center; to investigate whether HCV infection affects BMD in hemodialysis patients; to test for correlations between bone mineral density (BMD) and clinical and laboratory parameters in this population. SUBJECTS AND METHODS: The study involved 76 end-stage renal disease patients. Forty-three (56.6%) patients were tested negative for anti-HCV antibodies and HCV-RNA. Thirty-three (43.4%) of them had positivity of anti-HCV antibodies and permanent or intermittent HCV-RNA positivity at least for two years. Mean HD duration was 86.4 months. Patients completed a standard questionnaire that listed age, sex, occupation, education level; cause of renal failure, smoking history, dialysis duration, and sports activities engaged in during life, and pathologic bone fractures. The women answered additional items about age at menarche, number of pregnancies and menopausal status. Each subject underwent a baseline physical examination, including measurement of body weight and height for calculation of body mass index. The results of laboratory tests that had been done at monthly visits in the previous year were retrospectively evaluated, and mean levels for the year were used for correlation testing. Bone mineral density was measured in the spine, femoral neck and forearm. Relationships between BMD values and chronic HCV infection, laboratory results and clinical parameters were analyzed. RESULTS: In the 43 patients who were negative for anti-HCV antibodies and HCV-RNA, spine BMD testing showed osteopenia in 16 (37.2%) cases and osteoporosis in 7 (16.3%) cases. The corresponding values for the neck of the femur were 14 (32.6%) and 6 (14.0%), and for the forearm were 19 (44.2%) and 15 (34.9%). In the 33 anti-HCV antibodies and HCV-RNA positive patients; spine BMD testing showed osteopenia in 10 (30.3%) cases and osteoporosis in 7 (21.2%) cases. The corresponding values for the neck of the femur were 17 (51.5%) and 4 (12.1%), and for the forearm were 4 (12.1%) and 25 (75.8%). Bone mineral density decreased as dialysis duration increased (p<0.05). There was no statistical difference between BMD measurements of chronic HCV infection positive and negative group. CONCLUSION: However the mean BMD values for all three sites in the 76 HD patients were low HCV infection may not be a risk factor for low BMD in this population.     

Hepatitis B and hepatitis C virus infection and outcome of hemodialysis and kidney transplant patients

AIM: A comparison of the outcome of hepatitis virus-positive and -negative kidney transplant and hemodialysis patients was the aim of this investigation. MATERIALS AND METHODS: The study involved 384 kidney transplant patients (67 HBsAg positive, 39 anti-HCV positive, 278 hepatitis negative), transplanted between 1987 and 2001, and 403 hemodialysis patients (128 HBsAg positive, 83 anti-HCV positive, 192 hepatitis negative) who had started hemodialysis and were referred to the kidney transplant waiting list during the same period. RESULTS: Hemodialysis patients were older than transplant patients. Comparison of the groups' survival rates, adjusted for patient age, showed that all kidney transplant patients survived longer than hemodialysis patients (p < 0.001). HBV infection had a negative impact on patient survival, especially in hemodialysis patients. HCV infection did not have a significant influence on patient survival. Cardiovascular disease was the main cause of death of all hemodialysis- and hepatitis-negative transplant patients. Liver failure was one of the leading causes of death in HBV-positive transplant patients. Mortality risk was higher for older patients, HBV-positive and -negative hemodialysis patients. CONCLUSIONS: Kidney transplantation offers longer survival for hepatitis-positive and -negative hemodialysis patients. HBV but not HCV infection had a negative impact on ESRD patient survival.     

Treatment of hepatitis C virus with interferon in hemodialysis patients awaiting kidney transplant

INTRODUCTION: Hepatitis C virus (HCV) infection is associated with worsening disease progression after renal transplant, and to date there is no available treatment for use at this stage. It has therefore been recommended to treat HCV infection with interferon (IFN) during the dialysis period while the patient is on the waiting list for transplantation. METHODS: We analyzed data from 27 patients on hemodialysis awaiting transplant, who were under IFN treatment for chronic HCV infection (dominant genotype, 1b). The starting regime was IFN alpha-2b, 3 MU x 3/week (n = 20) or pegylated IFN alpha-2a, 135 mg/week (n = 7). If there was clearance of HCV RNA in the first 3 to 6 months, we attempted to prolong IFN treatment for 1 year, although in many patients the dose had to be reduced. A sustained response was defined as viral clearance for at least 12 months after the end of treatment. RESULTS: Viremia was negative in 13 patients (48.1%) at the end of treatment, but two of these patients relapsed, to give an overall long-term response rate of 11 patients (40.7%) and incomplete follow-up in three patients. Viral clearance was not achieved in 11 patients. In three patients (12%), IFN had to be suspended before finishing the third month of therapy due to side effects (mainly pancytopenia and intolerance of a previous kidney graft). Seven patients showing a sustained response underwent transplant, maintaining a negative viremia result. CONCLUSIONS: IFN treatment was effective in a high proportion of dialysis patients with HCV infection, with response rates possibly even higher than for the general population. However, its use is restricted by a high incidence of side effects.     

Prevalence of antibodies to hepatitis C virus in hemodialysis patients.

Due to frequent parenteral contact with blood transfusions hemodialysis patients are prone to acquire hepatitis C virus (HCV) infection. To determine the role of HCV infection we investigated the prevalence of antibodies to HCV in 188 hemodialysis patients. The prevalence of antibodies to HCV was 7.4%. As compared to anti-HCV-negative patients, anti-HCV-positive patients had slightly elevated transaminases which were independent of the presence of markers for hepatitis B virus infection. We conclude that HCV infection is common among dialysis patients.