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。     

TT virus infection in haemodialysis patients.

BACKGROUND: The recent discovery of a new parenterally transmitted DNA virus called TT virus (TTV) led us to investigate its prevalence in haemodialysis patients, a high-risk group for blood-borne infection, and to evaluate its role in liver disease. Moreover, we compared the TTV prevalence with the prevalence of other hepatitis virus coinfections. METHODS: Serum samples of 78 patients on maintenance haemodialysis were tested for TTV-DNA, hepatitis G virus (HGV)-RNA, anti-E2, anti-hepatitis C virus (HCV) and HCV-RNA. TTV-DNA was detected by semi-nested PCR using the primers from open reading frame 1 (ORF). HGV-RNA was detected by PCR using specific primers for the NS3 and the 5'-UTR genome regions while anti-E2 were checked by an enzyme immunological test. Anti-HCV was tested by the second generation Chiron RIBA HCV test system. HCV-RNA was evaluated by nested PCR with primers directed to the highly conserved 5' non-coding region of the HCV genome. RESULTS: TTV prevalence in our patients was 19% (15/78) while the prevalence of HCV and HGV infection proved to be 20 and 15.4%, respectively. Among TTV positive patients HGV co-infection was present in five cases (33%), HCV in six cases (39.9%), while HBV co-infection was not present in any of the patients. Only three patients proved positive for all three viruses. ALT levels were normal in most cases (13/15; 86%). In particular, patients with TTV infection alone showed normal ALT levels and HCV coinfection was found in the two patients with moderate ALT increases. CONCLUSIONS: TTV prevalence in haemodialysed patients is significant though the real clinical impact is still unclear. However, we must keep in mind that the epidemiological relevance of TTV infection is probably underestimated due to the impossibility in detecting the corresponding antibody.     

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.     

Interferon treatment for hepatitis C virus infection in patients on haemodialysis

BACKGROUND: This study examined the efficacy and tolerability of interferon alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in patients on maintenance haemodialysis. METHODS: A 24- month prospective cohort study was performed in 11 HCV RNA-positive haemodialysis patients, who were treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and virological monitors included serum alanine aminotransferase levels, and HCV RNA by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were determined by PCR and nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients respectively. Six (55%) patients had biochemical and/or histological features of chronic active hepatitis before treatment. All 11 patients became HCV RNA-negative by PCR, with normalization of deranged aminotransferase levels, within 2-8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks after the cessation of IFN, while biochemical relapse occurred in six (55%) patients. Sustained eradication of HCV was achieved in three (27%) patients. Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before and after IFN treatment in non-responders and relapsers. Persistent malaise and poor appetite were noted in eight (73%) patients during IFN therapy. Other side-effects of IFN included the exacerbation of anaemia, induction of resistance to erythropoietin, weight loss, and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be achieved in 27% of haemodialysis patients. Predictors of sustained response include low baseline HCV RNA level and mild liver pathology. Virological relapse can occur despite normal liver biochemistry. Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute the side-effects of IFN that deserve special attention in uraemic subjects.      

Travel-associated acquisition of hepatitis C virus infection in patients receiving haemodialysis.

BACKGROUND: It has been proposed that hepatitis C virus (HCV)-infected patients with end-stage renal disease undergoing maintenance haemodialysis may lack HCV antibody (anti-HCV) despite chronic HCV viraemia. This carries important implications for the design of surveillance policies. METHODS: To characterize the prevalence of antibody-negative/RNA-positive HCV infection, patients attending seven haemodialysis units underwent anti-HCV testing using a third-generation assay and HCV RNA testing using real-time PCR. RESULTS: At screening, anti-HCV prevalence was 12/360 (3.3%; 95% CI 1.7-5.8%); 7/12 (58.3%) anti-HCV positive samples were HCV RNA positive. Among anti-HCV-negative samples, 2/348 (0.6%; 95% CI 0.2-2.1%) tested HCV RNA positive (genotype 1a). Retrospective testing of stored sera dated the infections to a period of holiday in the Indian subcontinent. The two infections were unrelated by HCV-NS5B sequencing. Only one of the two newly infected persons showed raised transaminases. Both developed anti-HCV within 8-13 weeks of follow-up. Prospective surveillance of travellers to resource-limited countries returning to the units showed a HCV incidence of 4/153 travel episodes (2.6%; 95% CI 0.7-6.6%) among 131 persons (3.1%; 95% CI 0.8-7.6%). CONCLUSIONS: Among haemodialysis patients in the United Kingdom, antibody-negative/RNA-positive HCV status is associated with newly acquired infection, rather than lack of antibody responses in chronic HCV infection. There is a significant risk of HCV infection associated with travel to resource-limited countries. Given that transaminase levels may be normal, HCV RNA testing is recommended in patients re-entering a dialysis unit following haemodialysis in settings where suboptimal infection control policies pose a risk of exposure to blood-borne viruses.     

Comparison of parenteral iron sucrose and ferric chloride during erythropoietin therapy of haemodialysis patients

Aim:   To compare the effects of i.v. iron sucrose and Fe chloride on the iron indices of haemodialysis patients with anaemia.
Methods:   One hundred and eight haemodialysis patients receiving recombinant human erythropoiesis-stimulating agent (ESA) (mean age 59.37 years) were enrolled and randomly assigned to an iron sucrose or an Fe chloride group. Iron supplements were administered at 100 mg/week during the first 4 weeks (loading dose). Ferritin and transferrin saturation (TSAT) were then measured and dose adjusted. Ninety-eight subjects completed treatment; 51 in the iron sucrose group and 47 in the Fe chloride group. Ferritin, TSAT, haematocrit (Hct), reticulocyte count, serum albumin, fractional clearance of urea (Kt/V) and intact parathyroid hormone (iPTH) were measured.
Results:   There was no significant difference in baseline characteristics between the groups. Significant differences between the groups were observed in both iron indices and ESA dosage. Hct at week 24 (31.1% vs 29.7%, P  = 0.006) and ferritin at week 20 (731.3 vs 631.7 ng/mL, P  = 0.006) in the iron sucrose group were significantly higher than in the Fe chloride group. ESA dosage used in the iron sucrose group at week 8 was significantly lower than in the Fe chloride group (244.9 vs 322.6 U/kg per month, P  = 0.003), and iron sucrose group received significantly lower iron dose than the Fe chloride group at week 8 ( P  = 0.005).
Conclusion:   Although the differences in ESA dosage, ferritin and iron dosage between two groups were found during the study period while similar results were shown at the end of 24 week study. Thus, iron sucrose and Fe chloride are safe and work equally well for haemodialysis patients.     

Anti-hepatitis C virus antibodies and hepatitis C virus viraemia in haemodialysis patients

Sera from 82 haemodialysis patients were tested for anti-HCV,HCV-RNA, and HBsAg. Alanine aminotransferase (ALT) activitywas monitored weekly for 2 months. Anti-HCV was positive in31 patients (37.8%), showing different single-peptide patterns.HCV-RNA was detected in 26 anti-HCV-positive patients (84%)and also in two of 21 anti-HCV-negative patients. Twenty-seven(87%) of the 31 anti-HCV-positive patients had persistentlynormal ALT values; 22 of these patients were HCV-RNA positive.The four patients with elevated ALT values had HCV viraemia.HBsAg was positive in nine anti-HCV-negative patients. The closecorrelation between HCV viraemia and HCV status, independentlyof ALT values, requires that anti-HCV dialysis patients mustbe considered potentially infective and dialysed with reservedmachines and/or in separate shifts.     

Prevalence of hepatitis C virus infection and related risk factors among Iranian haemodialysis patients

Hepatitis C virus (HCV) infection is common among patients undergoing haemodialysis, and liver disease is an important cause of morbidity and mortality in this population. Management of HCV-related liver disease is a major health concern in patients with end-stage renal disease (ESRD) undergoing haemodialysis. To investigate the prevalence of HCV infection in patients on haemodialysis and its associated risk factors, we conducted a prospective case series study of 838 patients on haemodialysis in Tehran, Iran. Patients were selected randomly (cluster sampling) and all were screened for anti-HCV antibodies, using ELISA 3rd generation and confirmed by using RIBA 2nd generation. We found that 111 patients (13.2%) were infected. By applying univariate analysis, longer duration on haemodialysis (P = 0.000), more weekly dialysis sessions (P = 0.03), history of blood transfusion (P = 0.03) and history of previous renal transplantation (P = 0.01) were found to be associated with a higher rate of HCV infection. Multivariate analysis revealed that only length of time on dialysis (P = 0.000) and history of blood transfusion (P = 0.02) were significantly associated with HCV infection. The more the units transfused, the higher the rate of HCV infection. Our results suggest that early transplantation and avoidance of blood transfusion, as much as possible, are the two most important practical interventions to reduce the HCV exposure rate in our patients on haemodialysis.     

Beneficial effect of atorvastatin on erythropoietin responsiveness in maintenance haemodialysis patients

Aim: To evaluate the effect of atorvastatin on erythropoietin responsiveness and whether this effect is mediated by C‐reactive protein (CRP) reduction in prevalent dyslipidemic, haemodialysis patients. Methods: We studied prospectively 33 stable, iron‐repleted haemodialysis patients with low‐density lipoprotein cholesterol (LDL) ≥2.58 mmol/L, who received 20 mg atorvastatin aiming to achieve the target of LDL <2.58 mmol/L, over a period of 9 months. Twenty‐five patients completed the study, 15 men, with mean age 66.1 ± 8.2 years. The duration of haemodialysis was 56.6 ± 63.1 months and 5/25 patients were diabetics. Total serum cholesterol, triglycerides, high‐density lipoprotein cholesterol, LDL, haemoglobin, albumin, intact parathyroid hormone, serum iron, ferritin, total iron binding capacity, CRP and weekly dose of erythropoietin/body weight/haemoglobin were analysed. Results: Twenty of the 25 patients (80%) achieved the goal of LDL <2.58 mmol/L. There was a significant decrease in total cholesterol (5.77 ± 0.88 to 4.16 ± 0.96 mmol/L, P < 0.001) and LDL (3.59 ± 0.77 to 1.94 ± 0.77 mmol/L, P < 0.001). Haemoglobin increased from 121 ± 11 to 126 ± 7 g/L (P < 0.05), while weekly dose of erythropoietin/body weight/haemoglobin decreased significantly from 8.34 ± 3.70 to 7.87 ± 3.11 IU/kg per haemoglobin (P < 0.05). CRP decreased not significantly from 7.0 ± 6.1 to 4.5 ± 2.2 mg/L. Conclusion: Dyslipidemia of haemodialysis patients was treated safely and effectively with atorvastatin, but a fifth of the patients failed to achieve the therapeutic target. Statin therapy resulted in a significant increase of haemoglobin levels and improvement of erythropoietin responsiveness without a significant reduction in CRP levels, suggesting that the beneficial effect of statins on erythropoietin responsiveness may be driven by a mechanism other than CRP reduction.     

Incidence and risk factors of hepatitis C virus infection in a haemodialysis unit

BACKGROUND: Hepatitis viruses have become one of the main infectious problems in patients on maintenance haemodialysis. The aim of this study was to prospectively investigate the incidence of de novo hepatitis C virus (HCV) infection in a haemodialysis unit and to identify factors currently involved in HCV transmission to haemodialysis patients. METHODS: One hundred and fourteen anti-HCV negative and HCV-RNA negative patients who started long-term haemodialysis were followed for a mean period of 36 months (range 18- 56). Liver tests and anti-HCV were performed at 6-month intervals. Factors that might be implicated in HCV transmission, such as blood transfusions, sexual habits, surgery and other invasive procedures, were recorded. HCV markers were re-examined in transfused blood and the HCV genotype was investigated in seroconverters to anti-HCV and in patients with previous HCV infection who were treated in the vicinity of those who seroconverted. RESULTS: Eight patients (7%) seroconverted to anti-HCV and seven of them became HCV-RNA positive. HCV markers, including HCV-RNA, were negative in the blood transfused to seroconverters. No differences between seroconverters and non- seroconverters. No differences found in other risk factors not directly related to haemodialysis. The investigation of HCV genotype suggested that HCV transmission was not restricted to patients treated in the vicinity of previously HCV infected patients. Occasional failure to observe strict measures of asepsis was detected in the haemodialysis unit and this was the only factor that might be incriminating. CONCLUSIONS: HCV acquisition in patients on haemodialysis is currently not related to blood transfusion, and nosocomial transmission within the haemodialysis unit seems to be the main mechanism of HCV infection. Extremely careful observation of preventive measures seems essential to eradicate HCV transmission in haemodialysis units.      

Prevalence of hepatitis B and hepatitis C in haemodialysis patients

The prevalence of hepatitis B surface antigen (HBsAg), hepatitis B exposure and antibodies against the hepatitis C virus (anti-HCV) was assessed in 86 haemodialysis patients at the National Kidney and Transplant Institute (NKTI) using the commercial radioimmunoassay and ortho HCV ELISA assay. Of the 86 patients included in the study, 42 were male with a mean age of 44.9 years and a mean duration of dialysis of 2.4 years. Forty-four were female with a mean age of 48.4 years and a mean duration of dialysis of 2.3 years. Hepatitis B exposure was 57% and 12.8% of haemodialysis patients were positive for HBsAg, whereas 39.8% of patients were positive for anti-HCV. There was a significant correlation ( P =0.00007) between anti-HCV positivity and the length of time on haemodialysis. However, there was no significant correlation found between the number of blood transfusions received and anti-HCV positivity. There was also no significant correlation found between HBsAg and antibodies to hepatitis B core antigen (anti-HBc) positivity and the number of blood transfusions or the length of time on haemodialysis, nor between hepatitis B and C exposure and elevated aminotransferase levels.     

Prevalence of hepatitis B and hepatitis C in haemodialysis patients

SUMMARY: The prevalence of hepatitis B surface antigen (HBsAg), hepatitis B exposure and antibodies against the hepatitis C virus (anti-HCV) was assessed in 86 haemodialysis patients at the National Kidney and Transplant Institute (NKTI) using the commercial radioimmunoassay and ortho HCV ELISA assay. of the 86 patients included in the study, 42 were male with a mean age of 44.9 years and a mean duration of dialysis of 2.4 years. Forty-four were female with a mean age of 48.4 years and a mean duration of dialysis of 2.3 years. Hepatitis B exposure was 57% and 12.8% of haemodialysis patients were positive for HBsAg, whereas 39.8% of patients were positive for anti-HCV. There was a significant correlation ( P = 0.00007) between anti-HCV positivity and the length of time on haemodialysis. However, there was no significant correlation found between the number of blood transfusions received and anti-HCV positivity. There was also no significant correlation found between HBsAg and antibodies to hepatitis B core antigen (anti-HBc) positivity and the number of blood transfusions or the length of time on haemodialysis, nor between hepatitis B and C exposure and elevated aminotransferase levels.     

Experience of iron saccharate supplementation in haemodialysis patients treated with erythropoietin

SUMMARY: We assessed the efficacy of intravenous (i.v.) iron saccharate (VENOFER) vs oral iron supplementation in haemodialysis patients treated with low-dose erythropoietin (EPO). Twenty haemodialysis patients with serum ferritin >200 ng/mL and transferrin saturation >30% were assigned to one of the two groups. In Group 1, 10 were given i.v. iron saccharate (100 mg i.v. twice weekly) post dialysis. In Group 2, oral ferrous sulphate 200 mg was given thrice daily. In both groups, subcutaneous EPO 25 units/kg body weight (BW) was started simultaneously, twice weekly. After 3 months (study completion) the mean haemoglobin and haematocrit was significantly increased in Group 1 than in Group 2 (Hb 11.60 ± 0.64 G/ dL vs 10.5 G/dL ± 1.14 P <0.01). the final mean EPO dose was 25% lower in Group 1 than in Group 2 (3400 ± 1356 U/week vs 4600 ± 1356 U/week P =0.10) and the mean serum ferritin was higher in the i.v. iron group than the oral group (671 ng/mL ± 388 vs 367 ng/mL ± 238 P =NS). the same was also observed with transferrin saturation (44.6%± 19.8 in Group 1 vs. 29%± 11.0 in Group 2 P =NS). No adverse effects were seen during the study. In conclusion, we observed that regular use of i.v. iron had a significantly enhanced haemoglobin response, better maintained serum ferritin and lower EPO dosage requirement than the oral iron group.     

Experience of iron saccharate supplementation in haemodialysis patients treated with erythropoietin

We assessed the efficacy of intravenous (i.v.) iron saccharate (VENOFER) vs oral iron supplementation in haemodialysis patients treated with low-dose erythropoietin (EPO). Twenty haemodialysis patients with serum ferritin >200 ng/mL and transferrin saturation >30% were assigned to one of the two groups. In Group 1, 10 were given i.v. iron saccharate (100 mg i.v. twice weekly) post dialysis. In Group 2, oral ferrous sulphate 200 mg was given thrice daily. In both groups, subcutaneous EPO 25 units/kg body weight (BW) was started simultaneously, twice weekly. After 3 months (study completion) the mean haemoglobin and haematocrit was significantly increased in Group 1 than in Group 2 (Hb 11.60±0.64 G/dL vs 10.5 G/dL±1.14 P <0.01). The final mean EPO dose was 25% lower in Group 1 than in Group 2 (3400±1356 U/week vs 4600±1356 U/week P =0.10) and the mean serum ferritin was higher in the i.v. iron group than the oral group (671 ng/mL±388 vs 367 ng/mL±238 P =NS). The same was also observed with transferrin saturation (44.6%±19.8 in Group 1 vs. 29%±11.0 in Group 2 P =NS). No adverse effects were seen during the study. In conclusion, we observed that regular use of i.v. iron had a significantly enhanced haemoglobin response, better maintained serum ferritin and lower EPO dosage requirement than the oral iron group.     

Relationship between iron replacement and hepatic functions in hepatitis C virus-positive chronic haemodialysis patients

AIM: To investigate the effects of intravenous (i.v.) iron replacement on hepatic functions of hepatitis C virus (HCV)-positive haemodialysis patients. METHODS: The present retrospective study included 89 HCV-positive and 57 HCV-negative haemodialysis patients. Alanine aminotransferase (ALT) levels were accepted as sustained high if the last three values were >/=20 U/L. All patients and the HCV-positive group were dichotomised into subgroups by the median for dialysis duration, the amounts of i.v. iron administered per year and totally. RESULTS: Sustained high levels of ALT were significantly more frequent in the HCV-positive group (P < 0.001). In HCV-positive patients, the subgroup with ALT levels >/=20 U/L had significantly higher serum iron levels and mean amounts of i.v. iron administered per year and totally (P < 0.001) and the subgroup with the high mean total amount of i.v. iron had significantly higher serum ALT and iron levels (P < 0.001). Significant positive correlations were found in HCV-positive patients between ALT and serum iron levels (P < 0.001), as well as between ALT both with the mean amounts of i.v. iron administered per year (P = 0006) and totally (P = 0.015). Regression analysis showed that the main parameters effecting ALT were the serum iron level (P < 0.0001) and the mean amount of parenteral iron administered per year (P = 0.032). CONCLUSION: We conclude that parenteral iron replacement might contribute to hepatocellular injury in HCV-positive haemodialysis patients.     

Incidence of and risk factors for hepatitis B virus and hepatitis C virus infection among haemodialysis and CAPD patients: evidence for environmental transmission

Hepatitis B virus (HBV) serum markers (HBsAg, anti-HBs, anti-HBc)and antihepatitis C antibody (anti-HCV) were prospectively followedin haemodialysis and CAPD patients. From January 1987 to January1990, 185 patients on haemodialysis and 124 on CAPD were analysed.Among patients susceptible to HBV (69 on haemodialysis and 70on CAPD), there were 17 HBsAg seroconversions on haemodialysis(0.19/patient-year) and 1 on CAPD (0.01/patient-year). A Coxproportional hazards model showed that haemodialysis treatmentwas the only risk factor significantly associated with HBV infection,thus suggesting transmission through the environment. Regarding hepatitis C, 83 anti-HCV-negative patients on haemodialysisand 46 on CAPD were followed. There were 18 seroconversionson haemodialysis (0.15/patient-year) and two seroconversionson CAPD (0.03/patient-year). Haemodialysis treatment was alsothe only risk factor significantly associated with a higherrisk of HCV infection. The hazard ratio for HCV infection inhaemodialysis patients was 5.7 compared to CAPD patients. Nevertheless,for one patient on CAPD treatment transfusions were the onlypossible source of HCV infection. In conclusion, both viruses were transmitted mainly throughthe haemodialysis environment, but the role of transfusionscould not be excluded.