Prevalence and incidence of hepatitis C virus (HCV) in hemodialysis patients: study of risk factors.

The prevalence of antibodies against hepatitis C virus (HCV) was assessed in 246 hemodialysis patients who attended a dialysis unit in Bari, using a recombinant enzyme immunoassay test (Abbot Lab.). Fifty-six (22.8%) sera were reactive to anti-HCV. The reactivity was confirmed in 46 specimens (18.7%) using the Abbott EIA HCV neutralization test. The anti-HCV prevalence was higher in males than in females and increased with age, duration of dialysis and number of transfusions. Moreover, a correlation between the presence of anti-HCV and the persistent increase of ALT was noted. The HCV-infection attack rate was calculated using the frozen sera collected from 1984 to 1990: the incidence of infection in the first year was 6.1%, and in following years 4.6%, 4.9%, 3.1%, 2.1% and 2.2%, respectively.     

Prevalence of antibodies to hepatitis C virus in the hemodialysis unit.

An enzyme immunoassay was used to detect antibodies to hepatitis C virus (anti-HCV) in 261 patients and 69 staff members of a hemodialysis unit. The prevalence of anti-HCV was 46.7% in patients and 2.9% in staff members (p less than 0.001). The prevalence of anti-HCV increased significantly with increasing duration of hemodialysis (p less than 0.001), but was not related to age, sex, history of blood transfusion, status of hepatitis B or hepatitis A virus infection, or serum ALT. Patients with hepatitis episode increased with increasing duration of hemodialysis and showed a significantly higher prevalence of anti-HCV than those without (63.1 vs. 34.7%, p less than 0.001). The prevalence of anti-HCV in patients with hepatitis also increased with increasing duration of hemodialysis (p = 0.05). Thus, HCV appears to be the major cause of hepatitis in hemodialysis patients. Besides strict infection control measures, further studies are needed to determine the mode of HCV infection and its prevention in the hemodialysis unit.     

血液透析患者丙型肝炎病毒标志检测

研究血透患者的丙型肝炎病毒感染。方法 在60倒尿毒症血透患者中,采用第二代酶联免疫法测定抗丙型肝炎病毒(HCV)抗体,同时采用套式多聚酶联反应(PCR)法测定HCV-RNA。结果 27例抗HCV-HgG阳性,24例抗HCV-IgM阳性,37例HCV-RNA阳性,总阳性率为63.3％;输血组的HCV感染率为69.6％,而非输血组HCV感染率仍高达42.9％;透析时间大于3年者,HCV的感染率达100％。结论 血透患者HCV感染是相当严重的,其中输血为HCV传染的主要途径,但可能还存在经透析装置等其它传播途径。     

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。     

False-positive results of screening for antibodies to human immunodeficiency virus in chronic hemodialysis patients

Eighty-three chronic hemodialysis patients were tested for human immunodeficiency virus (HIV) infection. Testing included screening enzyme immunoassay (EIA) for HIV antibodies, competitive EIA for envelope and core antibodies, EIA for HIV antigen, and lymphocyte culture. Five (6%) of the patients had positive screening EIA at low reactivity. Four of these five had antibodies to H-9 cellular antigens. Comparison of the five seropositive patients to matched controls showed no significant differences in number of lymphocytes or helper/suppressor ratio. Six months later, the five patients had negative screening EIA results using a kit with a manufacturing change approved by the Food and Drug Administration that provided improved specificity. In addition, their Western blot analysis was negative. We conclude that (1) false-positive screening EIA results are more common in chronic hemodialysis patients than other populations; (2) evaluation of chronic hemodialysis patients for HIV infection requires confirmatory tests; and (3) newer EIA screening kits appear to have improved specificity.     

Decline of high hepatitis C virus prevalence in a hemodialysis unit with no isolation measures during a 6-year follow-up

AIMS: It has been recently suggested that isolation measures may be necessary to avoid hepatitis C virus (HCV) spread in hemodialysis units with a high HCV prevalence. To assess the variation in prevalence and long-term incidence of HCV infection, we studied our hemodialysis patients during a 6-year follow-up period. MATERIAL AND METHODS: We compared anti-HCV prevalence in 1994, 1996, 1998 and 2000 according to the anti-HCV status, and we analyzed the seroconversion of anti-HCV. Strict adherence to universal precautions has been fulfilled since 1993 and systematic anti-HCV testing in blood donors has been performed since 1994. No isolation measures were adopted. RESULTS: In 1994,22 of 53 (41.5%) patients tested positive for anti-HCV; in 1996, 18 of 67 (26.9%); in 1998,9 of 75 (12.0%); and in 2000, 7 of 82 (8.5%) (p < 0.001). In 2000, 7 of 14 (50.0%) patients who had been attending the unit since 1994 and 0 of 68 (0%) who had entered after 1994 were anti-HCV-positive (p = 0.000). Eight of 1 71 (4.7%) patients who entered the unit and 24 of 142 (16.9%) who left it were anti-HCV-positive (p < 0.001). Two patients became anti-HCV-negative. Seroconversion of anti-HCV was observed in 3 patients. The yearly seroconversion rate was 0.5% during the period 1994-1996 (1 of 98 patients at risk), 0.5% during the period 1996-1998 (1 of 91 patients at risk), and 0.4% during the period 1998-2000 (1 of 120 patients at risk). CONCLUSIONS: It was possible to reduce a high HCV prevalence in a hemodialysis unit when a low incidence was achieved without taking isolation measures. All anti-HCV-positive patients in 2000 had been undergoing hemodialysis since 1994.     

Outbreak of hemodialysis-associated non-A, non-B hepatitis and correlation with antibody to hepatitis C virus.

Between January 1987 and October 1988, 35 (45%) of 77 patients undergoing chronic hemodialysis at one unit developed serum alanine aminotransferase (ALT) elevations suggestive of non-A, non-B hepatitis (NANBH). Patients were grouped by level of ALT elevation and presence of other etiologies for liver injury. All dialysis patients and staff were tested for antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay on three occasions, 9 months apart; anti-HCV repeatedly reactive specimens were tested by the HCV neutralization assay. Household and sexual contacts of patients were tested once for anti-HCV. Case-patients were classified on the basis of clinical case definitions as probable, possible, questionable, and noncases, and by anti-HCV testing. Case-patients who had no history of transfusions or parenteral drug use were compared with noncases for common exposures. A total of 35% (27/77) of patients and none (0/24) of staff were anti-HCV-positive. Anti-HCV was found in 82% of probable cases, compared with 44% of possible cases, 44% of questionable cases, and 12% of noncases (P less than 0.01). Neither a common source nor direct person-to-person transmission could be documented; however, inadequate infection control measures demonstrated by lack of glove use and poor handwashing occurred during the exposure period. The incidence of HCV infection in patients over an 18-month period was 5%. Transmission of HCV to household or sexual contacts of patients did not appear to occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibodies against hepatitis C virus in hemodialysis patients in the central Italian region of Umbria: evaluation of some risk factors.

The epidemiology of non-A, non-B hepatitis (NANBH) is still incomplete. To define the prevalence of antibodies against the main causative agent of NANBH, the hepatitis C virus (HCV) and the role of some risk factors, we tested sera from 269 patients on chronic dialysis at the hemodialysis units in our region in central Italy. We utilized the recently developed serological assay. Twenty-nine hemodialysis patients (13.3%) and 3 peritoneal dialysis patients (4.8%) were anti-HCV positive. Of these, 13 (40.6%) had antibodies to hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection. The anti-HCV seropositive patients had been on dialysis longer than the seronegative ones; they had received more transfusions than the others but without a significant difference. The prevalence rate of anti-HCV was statistically significantly higher among hemodialysis patients utilizing the same dialysis equipment for the previous 12 months.     

Patterns in the prevalence of hepatitis C virus infection at the start of hemodialysis in Japan

Background Although hepatitis C virus (HCV) infection is a persistent public health concern in hemodialysis patients, there seem to have been only a few reports on the prevalence of HCV at the start of hemodialysis. In this study we investigated whether patients starting on hemodialysis therapy are positive for anti-HCV antibody or not. Methods The 400 patients who began regular hemodialysis between February 2003 and June 2007 were enrolled in this study. Clinical data such as age, anti-HCV antibody and primary cause of end-stage kidney disease (ESKD) were examined. As healthy controls we used 70,717 healthy blood donors in 2005 whose data were obtained from Tokyo Metropolitan Red Cross Blood Center. Anti-HCV antibody was used as an indicator of HCV infection. Since the prevalence of HCV infection is affected by age in Japan, we classified the patients by age group. Results The anti-HCV antibody prevalence rate among the patients who were new to hemodialysis was 7.3%, as opposed to 0.15% in the healthy volunteers. The prevalence of HCV in the 31–45-, 46–60-, and 61-year-old groups was significantly higher among the hemodialysis patients than among the healthy volunteers (P = 0.0209, <0.0001, and <0.0001, respectively). The prevalence rate of anti-HCV antibody was higher among men (10.0%) than among women (1.5%, P < 0.0001) in the hemodialysis patients. The anti-HCV-antibody-positive patients were significantly older than the anti-HCV-antibody-negative patients (66.4 ± 14.3 years versus 58.6±16.6 years; P = 0.0152). Diabetic nephropathy was a more frequent cause of ESKD among the anti-HCV-antibody-positive patients (30.4%) than among the anti-HCV-antibody-negative patients (19.9%, P = 0.0122). Among the anti-HCV-antibody-positive patients, 55.2% had received a blood transfusion. The rate was significantly higher than that among the anti-HCV-antibody-negative patients (19.4%, P < 0.0001). Conclusion The results showed a much higher rate of anti-HCV antibody positivity in patients new to hemodialysis than in healthy volunteers. Older age, blood transfusion, male gender, and diabetic nephropathy seemed to be risk factors for anti-HCV antibody positivity in Japan.     

Environmental Transmission of Hepatitis B and Hepatitis C Viruses Within the Hemodialysis Unit

Abstract: The hepatitis B virus (HBV) can be transmitted in the dialysis setting through blood transfusions and environmental surfaces. Transfusion related hepatitis C virus (HCV) infection is very well known, but only recently the environmental transmission of this virus was postulated. In order to study the prevalence, mechanisms of transmission, and the ALT patterns of HBV and HCV infections in hemodialysis and CAPD patients before the implementation of HBV vaccination and HCV screening in the blood bank, we conducted a study from January 1987 to January 1990. Sera from 185 hemodialysis and 124 CAPD patients were stored in this period and later analyzed for HBsAg, anti-HBc, anti-HBs, and anti-HCV (second generation ELISA). The prevalence of any HBV marker was 55.7% (103/185) for hemodialysis patients and 31.5% (39/124) for CAPD patients (hemodialysis vs. CAPD, p < 0.001). The prevalence of positive anti-HCV was 35.1% (65/185) for hemodialysis and 33.9% (42/124) for CAPD patients (not significant). There was a significant association between HBV markers positivity and anti-HCV positivity. The multivariate analysis of risk factors revealed an association of the positivity of each virus with the duration of renal replacement therapy (RRT), number of previous blood transfusions, and past history of hemodialysis treatment. Thus, besides the transfusion-related transmission, hemodialysis environmental transmission may also occur for both viruses. The findings of a high prevalence of both viruses and evidence for environmental transmission in the dialysis setting are of major importance for the planning of future preventive measures.     

Infection of hepatitis C virus in patients with chronic renal failure undergoing hemodialysis therapy and staff members]

The prevalence of antibody to hepatitis C virus (anti-HCV) was determined in 564 patients and 145 staff members of nine hemodialysis (HD) units in Nagano Prefecture using an enzyme-linked immunosorbent assay based on the C 100 HCV antigen (the first generation anti-HCV assay). And also serum HBV markers were tested in these subjects. One hundred patients (18%) were anti-C100 HCV positive, indicating that this figure represents a much higher prevalence than that (0.9%) among general population in the same geographical area. Out of 141 patients without history of blood transfusion, 17 (12%) were positive for anti-C 100 HCV, suggesting that blood-transfusions-unrelated acquisition of HCV infection can occur. Anti-HCV prevalence correlated with both the blood units transfused and the duration of HD treatment. There was a significant difference in the prevalence of anti-C 100 HCV in individual dialysis units ranging from 0% to 53%. In the dialysis unit with prevalence of 53%, approximately half of the anti-HCV positive patients were found to have chronic liver disease. The prevalence of hepatitis B virus (HBV) markers among HD patients, on the other hand, was 36% (202/564). Fifty one (51%) of 100 anti-C 100 HCV positive patients and 151 (33%) of 464 anti-C 100 HCV negative patients were positive for HBV markers, with significant difference in HBV infection rate between the 2 groups. The prevalence of chronic liver disease, defined as abnormal serum transaminase levels for more than 6 months was significantly higher in anti-HCV positive patients than in anti-HCV negative ones (39% vs 10%, p less than 0.05), suggesting that HCV infection may contribute to chronic liver disease in HD patients. Among 145 staff members, only 3 (2%) were positive for anti-HCV, whereas 25 (17%) were positive for hepatitis B core antibody (anti-HBc), indicating prior HBV infection. With applying the second generation anti-HCV assay, which can detect antibodies to both capsid and nonstructural products of HCV gene, anti-HCV prevalence increased by two times in HD patients, but didn't change in HD staff members.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical characteristics and mortality in hepatitis C-positive haemodialysis patients: a population based study.

BACKGROUND: The association between hepatitis C virus (HCV) infection and clinical and laboratory measures in maintenance haemodialysis (MHD) patients are poorly understood. METHODS: We analyzed data from over 37,000 MHD patients who underwent MHD for at least 3 months in DaVita dialysis clinics across USA in July 2001. RESULTS: The presence of HCV infection was determined using enzyme immunoassay (EIA), which was performed in 2778 MHD patients and was positive in 363 (13%) individuals. In a multivariate logistic regression model that adjusts for case-mix and available surrogates of malnutrition-inflammation complex syndrome (MICS), the following were independent predictors of HCV infection: younger age, male gender, Black race, Hispanic ethnicity, higher haemoglobin, lower serum albumin, higher total iron binding capacity, higher creatinine, and higher serum glutamic oxaloacetic transaminase (SGOT). Among receiver operating characteristics of commonly measured laboratory values in this population, the SGOT had the highest area. An SGOT > or =25 u/l had an adjusted odds ratio of 4.96 (95% confidence interval: 3.75-6.57) for HCV antibody positivity (sensitivity 50%, specificity 87%). HCV EIA positivity among MHD patients younger than 65 years was associated with 40-80% higher hazard ratio of all-cause and cardiovascular death during the 2 year follow-up (July 2001 to June 2003) after adjustment for case-mix and measures of MICS. CONCLUSION: HCV infection, as diagnosed by EIA, has distinct racial, age and laboratory predilections in MHD patients. HCV positivity among MHD patients younger than 65 years is associated with significantly higher cardiovascular mortality. More diligent HCV detection and treatment may improve cardiovascular survival in MHD patients.     

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.     

Hepatitis C virus infection among kidney transplant recipients.

The extent of hepatitis C virus (HCV) infection among kidney recipients was investigated in 67 patients by testing for anti-HCV paired serum samples, collected at time of transplantation and during follow-up (average 32 +/- 20 months). Prevalence of anti-HCV at transplant time was 48%, and was related to the time on dialysis and to the amount of blood transfusions. Following transplantation, nine (28%) seropositive patients lost anti-HCV and five (14%), previously seronegative, seroconverted. Anti-HCV was found to be positive in 92% of the patients with chronic liver disease who were on hemodialysis, but in 56% in kidney recipients with chronic hepatitis. Anti-HCV was positive in 50% of patients with resolving hepatitis before transplantation, but only in 21% of those with acute hepatitis following transplantation. This study confirms the high risk of HCV infection among hemodialysis and kidney recipient populations, and also that HCV is closely related with the length of time the patient is on hemodialysis as well as the number of blood units transfused. HCV is the main cause of acute and chronic liver disease in hemodialysis patients and of chronic liver disease in kidney recipients, but does not clearly influence the survival of the allograft nor that of patients.     

维持性血液透析患者HCV检测方法的比较

目的 探讨维持性血液透析(HD)患者丙型肝炎病毒(HCV)的检测方法 .方法 对108例HD患者,采用荧光定量PCR法测定血清HCV RNA,用酶联免疫吸附实验(ELISA)检测血清HCV抗体(抗-HCV)和HCV核心抗原(HCV-cAg),并同时检测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST),计算其变动率. 结果 HD患者荧光定量PCR HCV RNA检出率为33.3%(36/108),抗-HCV阳性率为32.4%(35/108),HCV-cAg阳性率为26.9%(29/108),HCV标志阳性患者中仅4例ALT和AST均升高.在抗-HCV阳性患者中,HCV RNA检出率为82.9%(29/35);在抗-HCV阴性患者中,HCV RNA检出率为9.6%(7/73);在HCV RNA阴性患者中,抗-HCV阳性率为8.3%(6/72),两者符合率为88%[(29+66)/108];在HCV RNA阳性患者中HCV-cAg检出率为80.6%(29/36).结论 ALT不能作为血液透析患者HCV诊断和反映病情的一项敏感指标,荧光定量PCR技术可弥补ELISA检测的不足,在抗-HCV阴性的血液透析患者中检测HCV RNA具有重要意义,对监测无症状的HCV携带者或新发现的感染者,应用ELISA法检测HCV-cAg将是有意义的发展方向.     

Prevalence of hepatitis C infection in a hemodialysis unit.

To define the prevalence of NANB hepatitis, anti-HCV antibodies were determined in 51 patients on renal replacement therapy, in 7 transplanted patients and 17 staff members of the hemodialysis unit. Anti-HCV antibodies were evaluated using immunoenzymatic methods (Ortho HCV ELISA Test System, 1st and 2nd generation). Among hemodialysis patients, seroconversion was respectively documented in 17.6% (9/51) and 52.9% (27/51); none of the transplanted patients were positive with the 1st generation test, while 3/7 were positive with the 2nd. No statistically significant difference was found in the prevalence antibodies between transfused and nontransfused patients. ALT levels were statistically greater in patients with anti-HCV antibodies (X2 2nd generation = 8.83; p less than 0.01). Our results suggest: (1) that hemodialysis represents a risk factor; (2) the validity of substitute markers and (3) more sensitivity of the 2nd than 1st generation test.     

Acquisition of hepatitis C virus in hemodialysis patients: a prospective study by branched DNA signal amplification assay

Serological data indicate that hepatitis C virus (HCV) infection is very common among chronic hemodialysis (HD) patients. Circumstantial evidence suggests that hemodialysis per se is an important risk factor for this infection. We used a novel methodology, the branched DNA (bDNA) signal amplification assay, which is capable of detecting HCV RNA and of quantifying HCV viral load in serum, to prospectively determine the rate of acquisition of HCV infection in 274 anti-HCV-negative patients undergoing HD treatment in four hemodialysis units. Moreover, we used bDNA testing to analyze the dynamics of HCV acquisition among HD patients, a high-risk group for HCV infection with immune compromise conferred from uremia. Two patients were identified with de novo acquisition during 1 year of prospective bDNA testing. Thus, the HCV incidence was 0.73% per year. De novo acquisition of HCV infection was observed in the absence of identifiable parenteral risk factors. Both patients showed the same pattern of HCV acquisition: they underwent an initial viremic phase that was associated with an increase in alanine transaminase (ALT) activity and that preceded the anti-HCV seroconversion. This was followed by HCV RNA clearance and normalization of ALT activity. Anti-HCV positivity occurred 1 and 2 months after the ALT increase in the first and second patients, respectively. Although HCV incidence was low (0.73%), further research is warranted to set the optimal policy for eliminating the risk of nosocomial transmission of HCV in the HD setting. Our findings show the pattern of HCV acquisition in chronic HD patients and emphasize the need to screen the HD population for ALT measurement combined with anti-HCV testing for detecting hepatitis C. HCV RNA testing can identify HCV before seroconversion in individuals with deranged liver function tests. The acquisition of HCV in HD patients without identifiable risk is confirmed.