Liver disease in dialysis patients with antibodies to hepatitis C virus

Eighty-three patients with chronic end-stage renal failure,including 65 on haemodialysis and 18 on intermittent peritonealdialysis, were evaluated for hepatitis B virus profile and antibodiesto hepatitis C virus (HCV). All those positive for HBsAg wereexcluded from the study. Nineteen patients were found to bepositive for antibodies to HCV by the ELISA II test. Eight caseswere already positive for HCV antibody when they started dialysisin our unit, the other 11 became positive during dialysis inour unit. Only one of the patients on peritoneal dialysis waspositive for HCV. A liver biopsy was obtained from 17 patients,who consented to the procedure. All the cases were evaluatedfor the number of blood transfusions received, HIV infectionand the approximate time of contracting the HCV infection. Liverenzymes were determined every month. Only three patients hadabnormally raised serum aminotransferase at the time of biopsy.The various histopathological lesions detected were chronicactive hepatitis (n=3, including one with changes consistentwith cirrhosis), chronic persistent hepatitis (n = 4), non-specifichepatitis (n = 3) and haemosiderosis (n=3); four biopsy sampleswere normal. There was no correlation between the biochemicaland histopathological changes. Moreover, patients with normalserum aminotransferase levels had abnormal histopathologicalchanges. All were negative for HIV and none of the patientshad received a renal graft. Twelve patients had received bloodtransfusions varying from 2 to 12 units, four had not receivedany blood, and in one the history of blood transfusion couldnot be confirmed. The four patients with anti-HCV antibodieswho had not received blood transfusion had relatively mild disease-non-specifichepatitis (n=2) or normal biopsy (n=2). One patient with cirrhosis died 30 months after liver biopsyfrom hepatic insufficiency and three received renal transplants.Others are continuing on dialysis and their biochemical testsare within normal limits 12–45 (30± 14) monthsafter biopsy. In conclusion, biochemical tests are poor indicators of liverdisease, and liver biopsy is a definitive way of evaluatingthe patients of dialysis with positive HCV antibodies for prognosis.     

Hepatitis C virus infection in chronic haemodialysis patients, a clinicopathologic study.

Fifty-two patients on regular haemodialysis at our institution were evaluated for the presence of HCV infection. Evaluation included detailed history, clinical examination, and monthly screening for anti-HCV antibody, liver enzymes (ALT, AST), serum iron and ferritin. Also, three-monthly screening for other viral markers, HBV (HBsAg, HBsAb, HBcAb), CMV (IgG and IgM), EBV, and HIV. Anti-HCV antibody was found in 21 patients (40.4%). There was a significant (P less than 0.05) relationship between presence of anti-HCV antibody and proportion of patients who received blood transfusion. During a 12-month follow-up, four (11.4%) patients seroconverted to be Anti-HCV positive while one case (4.8%) seroconverted to be anti-HCV negative. The frequency of elevation of liver enzymes was significantly higher in Anti-HCV positive cases (14/18) than in negative cases (11/28, P = 0.01). Evaluation of liver biopsies of 13 patients showed chronic persistent hepatitis in six and chronic active hepatitis in seven cases. We concluded that hepatitis C is a common problem among chronic haemodialysis patients at our institution; HCV infection is documented in 70% of all clinically diagnosed NANB hepatitis. Presence of anti-HCV antibodies cannot differentiate between active and past infection and cases with early HCV infection can be missed when relying on the mere detection of anti-HCV antibodies.     

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.     

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.     

The prevalence of serological markers for hepatitis B virus infection amongst anaesthetists in the Oxford region

A total of 125 anaesthetists from nine hospitals within the Oxford region were surveyed to study the prevalence of serological markers for hepatitis B virus (HBV) infection. No anaesthetists were positive for Hepatitis B Surface Antigen (HBsAg) and only four (3.2%) were positive for HBsAg antibody (anti-HBsAg). This result is in marked contrast to other studies and suggests that anaesthetists in the United Kingdom do not constitute a high risk population. The reasons for this are discussed.     

Antibodies to hepatitis C virus (HCV) in chronic renal failure (CRF) patients on conservative therapy: prevalence, risk factors and relationship to liver disease

There are no data regarding HCV prevalence in CRF patients notrequiring dialysis. In order to assess prevalence and risk factorsfor HCV infection in CRF patients on conservative therapy wetested, by second-generation assays such as Ortho 2 and 4-RIBA,221 predialysis CRF patients attending our Department. Forty-four(20%) patients were anti-HCV positive. Anti-HCV positivity wasrelated to blood transfusion requirement, past or current elevationsof transaminase levels and, to a lesser degree, CRF duration.The prevalence of anti-HCV positivity among CRF patients whowere never transfused was about 10 times higher than that ofblood donors. Our data show that predialysis CRF patients shouldbe considered a specific risk group for HCV infection; bloodtransfusion history and duration of CRF are risk factors foracquisition of HCV infection; HCV infec tion may play a rolein the development of liver disease in this clinical setting.     

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.     

Relationships between plasma ferritin and aminotransferase profile in haemodialysis patients with hepatitis C virus

BACKGROUND.: HCV infection is a major complication among patients undergoingdialysis therapy throughout the world. In the years prior tothe use of human recombinant erythropoietin (rHuEpo), patientsundergoing haemodialysis were subjected to an excessive ironload as a consequence of frequent blood transfusions. Recentdata in the non-dialysis population have shown a positive correlationbetween iron deposits and the severity of HCV hepatitis andbetween iron deposition and an impaired response to interferontherapy. METHODS.: One hundred and five haemodialysis patients were studied. Everypatient was screened for HCV infection by ELISA II and HCV RNA.Serum biochemistries were analysed by SMAC20. Ferritin was measuredby radioimmunoassay. RESULTS.: The aminotransferase levels for the HCV positive (n=39) andnegative patients (n=66) were below the normal levels for thegeneral population. The mean values of aminotransferases andplasma ferritin were, however, higher in the HCV-positive patientsthan in the HCV-negative patients. A positive correlation betweenaminotransferases and plasma ferritin was evident in HCV-positivepatients, which was absent in the HCV-negative individuals.The histological severity of liver disease (n=7) was, however,not statistically related with the levels of either ferritinor aminotransferases. CONCLUSIONS.: HCV infection is a relevant variable when estimating iron depositsby measuring plasma ferritin. Accordingly, a misinterpretationof the actual amount of iron deposits may occur in HCV-positivepatients, which should be taken into account at the time ofplanning their iron reposition therapy. On the other hand, thelevel of iron deposits might have a significant role in theevolution of HCV-related liver disease.     

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.     

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.     

Antibodies to hepatitis C virus (HCV) and transaminase concentration in chronic haemodialysis patients: a study with second-generation assays

We used first- and second-generation assays such as Ortho I,Ortho 2 and 4-RIBA to define prevalence and nsk factors foranti-HCV antibodies in haemodialysed patients. Forty-nine (24%)subjects were found to be anti-HCV positive. Anti-HCV positivity was related to duration of dialysis and past or currentelevations of GOT and GPT; the frequency of transfused patientswas greater in HCV-positive than in HCV-negative subjects; therewere 31 patients (pre valence of 20%) with anti-HCV antibodiesamong non-transfused patients. These findings show that, testedby second-generation assays, HCV infection is detected morethan twice as commonly in haemodia lysis patients and may beresponsible for a significant proportion of liver disease inthis clinical setting Acquisition of hepatitis C virus by dialysispatients is not only through blood transfusions but also secondaryto hepatitis C virus presence within the unit itself.     

Prevention of hepatitis C infection in haemodialysis units. A prospective study

A prospective study was begun in our haemodialysis unit afterfour previously negative patients were found to be anti-HCVpositive. A dedicated area and dedicated dialysis equipment(but not a separate room) were assigned to anti-HCV-positivepatients and testing for HCV antibodies was performed every3 months. A total of 131 patients were treated during the studyperiod of 18 months. Of these, 50 patients were dialysed duringthe entire 18 months, and 21 were available to be tested sixor more months after having left the centre. During the first6 weeks after implementing the precautions two more anti-HCV-positivepatients were detected. However, during the rest of the studyperiod no further newly infected patients were found. It isconcluded that the spread of HCV infection in a haemodialysisenvironment can be prevented by limited isolation procedures.     

Occult hepatitis B virus infection in liver transplant recipients with recurrent hepatitis C: relationship with donor age and fibrosis progression

Abstract:  Liver transplantation (OLT) recipients who receive a graft from donors positive for hepatitis B virus (HBV) anti-core antibodies may develop overt " de novo " HBV infection. The study was undertaken to explore how often HBV infection may remain occult after OLT for hepatitis C, and whether it may represent a factor of graft fibrosis progression. We studied 30 consecutive patients transplanted for hepatitis C liver disease. Specimens from the native liver and from the graft were searched for occult HBV infection (O-HBV). In the native liver, 8/30 patients had detectable O-HBV; during the follow-up, O-HBV infection was demonstrated in 14 graft specimens. Graft O-HBV was associated with older donor age (≥50 yr; 8/9 vs. 6/21, p < 0.005). Recipients with graft O-HBV and no O-HBV in the native liver who received their grafts from donors aged >40 yr had faster fibrosis progression than recipients with no post-transplant O-HBV, whose grafts came from donors aged >40 yr and recipients whose grafts came from donors aged ≤40 yr (4/7 vs. 1/7 vs. 2/16, p < 0.05). In OLT recipients, O-HBV is more likely to occur when grafts are obtained from aged donors and may affect the rate of fibrosis progression because of recurrent hepatitis C.     

Incidence of seroconversion for hepatitis C virus in chronic haemodialysis patients: a prospective study

We conducted a prospective study in HD patients of our unitto evaluate the incidence of seroconversion for HCV in thishigh-risk group. Two hundred and thirty-five patients were observedduring the average follow-up of 29.4 months: 183 were seronegativeand 52 seropositive for anti-HCV antibodies at the start ofthe study. During the observation period two of 183 patientsdeveloped anti-HCV antibodies late in the study, while the other181 patients remained seronegative throughout the observationperiod; anti-HCV antibodies persisted through the follow-upin the 52 HCV-positive patients at the beginning of the study.Our results showed a very low incidence of HCV seropositivity(0.44% per year) after implementation of our operative protocolincluding ‘universal precautions’ and other infectioncontrol procedures. Once infected, there is no disappearancerate of anti-HCV. The 4-RIBA results did not change during thefollow-up period. Prevalence of HCV RNA by PCR technique was41% (22 of 54) among anti-HCV-positive patients. Future investigationsare warranted to clarify the exact route of transmission ofHCV among HD patients and to reduce the rate of HCV transmissionin this clinical setting.     

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。     

Prevalence and risk factors for hepatitis C virus infection in continuous ambulatory peritoneal dialysis patients

BACKGROUND.: Studies on hepatitis C virus antibodies (Anti-HCV) in CAPD patientsare scarce and include a small number of patients. Nevertheless,risk factors related to Anti-HCV in these patients are stillsubject to controversy. PURPOSE OF THE STUDY.: To analyse the incidence and risk factors associated with thepresence of Anti-HCV in CAPD patients. METHODS.: We studied 255 patients from five different treatment centresof our region. The analysis was repeated after excluding 161patients who had previously received haemodialysis treatmentat least once. Anti-HCV testing was made by the 2nd-generationELISA. As a supplementary test we used RIBA-4 in three centersand INNOLIA in the other two. Risk factors were analysed usinglogistic regression model for multivariate analysis. RESULTS.: In the whole group, 29 patients (11.4%) were anti-HCV positive.Logistic regression analysis determined the following variablesas independent risk factors: hepatitis previous to CAPD (P<0.0001,odds ratio (OR): 44.9), Anti HBc positivity (P=;0.019, OR: 9.24),blood transfusions previous to CAPD (P=;0.015, OR: 1.05) andCAPD duration (P=0.025, OR: 1.02). When patients who had previouslyundergone haemodialysis were excluded, the prevalence of HCVantibodies was 8.5% (8/94). In this group multivariate analysisshowed that Anti-HCV positivity correlated with hepatitis previousto CAPD (P<0.0003, OR: 126) and Anti HBc positivity (P=0.002,OR: 41.9). CONCLUSIONS.: Our prevalence of hepatitis C virus (HCV) infection in CAPDpatients was lower than other renal replacement therapy modalities,and correlated to events occurring mainly before starting CAPDtreatment. This technique could be considered as low risk forHCV infection.     

The changing epidemiology of hepatitis C virus (HCV) infection in haemodialysis: European multicentre study.

BACKGROUND: The high prevalence of anti-hepatitis C virus (HCV) antibodies in HD patients has been known since the early 1990s but its evolution over the last decade is poorly documented. METHODS: All chronic HD patients from 15 Belgian units were tested at (re)start of HD and every 18 months for anti-HCV antibodies (ELISA 2 in May 1991 and November 1992, then ELISA 3 until May 2000). All chronic HD patients from HD units from eight other European countries, whose prevalence of anti-HCV (+) patients had been studied in 1991-1994 (and published except in one country), were tested for anti-HCV antibodies in 1999. RESULTS: Anti-HCV (+) prevalence decreased (P<0.001) from 13.5 (1991) to 6.8% (2000) in the Belgian cohort (n = 1710). Prevalence also decreased (P<0.05) in the participating units from France (42-30%), Sweden (16-9%) and Italy (28-16%), tended to decrease in the participating units from UK (7-3%, P = 0.058) and Hungary (26-15%, P = 0.057) but did not change (NS) in the participating units from Germany (7 to 6%), Spain (5 to 12%) and Poland (42 to 44%). In the Belgian cohort, the prevalence of anti-HCV(+) at (re)start of HD did not change significantly over 1991-2000. CONCLUSION: The prevalence of anti-HCV(+) in HD has decreased markedly over the last decade in the participating units from most European countries. This decrease should reduce further the risk of nosocomial and occupational HCV infection in HD and ultimately contribute to improved long-term prognosis of HD patients and kidney graft recipients.