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.     

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.     

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 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 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.     

Genotype distribution and transmission of hepatitis C virus (HCV) in French haemodialysed patients

BACKGROUND: HCV genotyping was performed to identify the source of HCV infectionin haemodialysed patients. METHODS: Specimens from 48 HCV-infected patients treated in the samedialysis unit were genotyped by line probe assay (LiPA). RESULTS: Thirty-seven patients (77 %) were infected by genotype lb. Onlyfour of the 48 patients were never transfused and three of themhad genotype lb. In two of the three genotype lb-infected patients,seroconver-sion was observed during the follow-up, suggestinga nosocomial HCV infection. Ten of the 44 transfused patientswere infected with genotypes other than lb. Blood products werevery probably the source of infection in these patients. The34 other patients (77.3%) were infected with genotype lb andretrospective analysis failed to identify nosocomial and transfusionalorigin. Eight of the 11 patients with genotypes different from lb werefound in the 16 patients who were more than 55 years old. Onlythree of the eight originated from France. CONCLUSIONS: Blood transfusions and nosocomial infections were the main causesof HCV transmission in haemodialysed patients. Both screeningof blood donors and aseptic measures in haemodialysis unitsmay prevent HCV transmission.     

Efficacy and tolerance of interferon-alpha(2b) in the treatment of chronic hepatitis C virus infection in haemodialysis patients. Pre- and post-renal transplantation assessment.

BACKGROUND: Hepatitis C virus (HCV) infection represents an important problem for the dialysis population due to its high prevalence and the long-term development of chronic liver disease, particularly following renal transplantation. METHODS: In order to assess the efficacy and tolerance of interferon (IFN) in the treatment of chronic hepatitis C in haemodialysis (HD) patients and their clinical course following renal transplantation, a multicentre, randomized, open-label study was conducted to compare IFN therapy vs a control group. RESULTS: Nineteen HCV RNA-positive patients received 3 x 10(6) U of IFN s.c., three times a week (post-HD), and 17 HCV RNA-positive patients were assigned to the control group. Tolerance to IFN therapy was good in nine patients, while treatment was discontinued in the other 10 due to the occurrence of side effects. HCV RNA was negative at the end of treatment in 14 out of 19 patients (74%) receiving IFN and in one patient (5%) in the control group. Six out of the 14 patients who initially responded to IFN therapy had a virological relapse (43%). Eight patients (42%) remained HCV RNA-negative, three of them until the day that renal transplantation (RT) was performed (7, 12 and 27 months, respectively), as did five patients on HD during the follow-up (27+/-5 months). Eight out of the nine patients (89%) who completed therapy were HCV RNA-negative at the end of treatment, and seven of them (78%) remained HCV RNA-negative during the follow-up on dialysis (21+/-8 months). Mean transaminase (ALT) values were significantly decreased following IFN therapy, while no changes were observed during the follow-up period in the control group. Fifteen patients (10 in the treatment group and five in the control group) underwent RT. Three patients in the treatment group were HCV RNA-negative at RT, and one of them had a virological relapse 20 months after RT, while the other two remained HCV RNA-negative at 3 months and 24 months after RT, respectively. In contrast to the control group, transaminase (ALT) remained within normal limits in all patients in the treatment group. Finally, during the post-RT follow-up, the transaminase mean values were significantly lower in treated patients vs patients in the control group (P<0.05). CONCLUSIONS: It is concluded that the biochemical and virological response to IFN therapy is good in HD patients. In addition, IFN therapy appears to exert a beneficial effect on the course of liver disease following RT, regardless of the virological response. Despite the fact that IFN therapy was discontinued in 10 out of the 19 patients due to the occurrence of side effects, these disappeared following discontinuation of therapy. Therefore, IFN therapy is advisable for HCV-infected dialysis patients who are candidates for RT.     

Effectiveness of a fixed combination formula of ombitasvir/paritaprevir/ritonavir for hepatitis C virus infection in patients on maintenance haemodialysis

A fixed‐dose formula that combines Ombitasvir (OBV), Paritaprevir (PTV) and Ritonavir (RTV) has been launched into the field of anti‐HCV therapy in Japan for patients infected with HCV genotypes 1 and 2 in 2015. However, little is yet known as to the efficacy and safety of this novel therapy in patients on maintenance haemodialysis (HD). The present report describes a preliminary experience in 10 patients (five males and five females) who underwent maintenance HD. All of them had HCV genotype 1b, without having the resistance‐associated variants at Y93 or L31 in the nonstructural proteins 5A (NS5A) region. After the treatment, eight patients successfully achieved virus eradication and sustained a virological response at 12 weeks (SVR12). In addition, mac‐2 binding protein glycosylation isomer (M2BPGi), a biomarker for liver fibrosis, was reduced after the therapy. Two patients withdrew from the therapy due to the development of erythema multiforme and a strong drowsiness, respectively. These results suggest that triple therapy combining OBV, PTV and RTV is effective in achieving SVR12 in most of the HCV‐infected patients on HD. In addition, this combination therapy contributed to retard the progression of liver fibrosis. However, we suggest that further trial will be required to establish its clinical efficacy and safety.     

Hepatitis infection in haemodialysis patients

SUMMARY: Known hepatitis infections among haemodialysis patients include hepatitis B, hepatitis C, hepatitis G and TT virus. Haemodialysis patients with hepatitis B and/or hepatitis C infection may progress to develop significant morbidity, such as cirrhosis, hepatitic failure or hepatocellular carcinoma. Hepatitis B infection may be treated with α-interferon or lamivudine. Hepatitis C infection may be treated with α-interferon, but frequent severe adverse effects were observed, while ribavirin is contraindicated for patients with renal failure. Treatment for hepatitis B and/or hepatitis C are costly, and the risk of post-transplant reactivation of hepatitis has been reported. Prevention of nosocomial transmission of hepatitis infection with strict infection control and universal precautions is more important. Accumulating evidence suggests that both hepatitis G virus and TT virus (TTV) are not significant causes of liver disease. Routine screening for hepatitis G or TTV viraemia in haemodialysis patients is not indicated at present.     

Prevalence of antibodies to hepatitis C in dialysis patients and transplant recipients with possible routes of transmission.

The prevalence of hepatitis C infection and possible predisposing factors was assessed in a renal unit. Of 343 patients at our renal dialysis centre, 37 (10.8%) were anti-HCV positive by a 1st-generation assay (ELISA, Ortho/Chiron) and confirmed positive in 35 (10.2%) with a 2nd-generation test (UBI, New York). Anti-HCV positivity was significantly associated with: duration of renal replacement therapy (P < 0.0001); quantity of blood transfused (P < 0.002); duration of hospital haemodialysis (P = 0.0001); duration with a functional renal transplant (P = 0.039); and aspartate aminotransferase (P < 0.0001). Logistic regression determined the following variables to be independent risk factors: duration of renal replacement therapy with a relative risk of 34.3 for 5-9 years and 87.4 when the duration was in excess of 10 years; renal transplant for less than 1 year (relative risk of 5.0); transfusion in excess of 50 units of blood (relative risk of 11.6). Clinical assessment of anti-HCV-positive patients revealed peripheral signs of chronic liver disease in 40%, hepatomegaly in 34%, and splenomegaly in 9%. This prevalence of hepatitis C infection is similar to other European and North American centres, but contrasts with low prevalence rates reported from dialysis populations in the UK. It adds further support for routine screening of blood and possibly organ donors and implementation of further infection control measures in dialysis centres.     

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.     

Clinical significance of SEN virus infection in patients on maintenance haemodialysis.

BACKGROUND: The SEN virus (SENV) has been identified as a putative new hepatitis virus. This study was conducted to clarify the clinical significance of SENV infection in patients on haemodialysis. METHODS: A total of 189 patients on maintenance haemodialysis and 60 healthy controls were enrolled. Of the 189 patients, 154 were followed up for 2 years. SENV DNA (genotypes D and H) was measured by means of polymerase chain reaction. RESULTS: SENV infection was significantly (P=0.012) more prevalent in patients on haemodialysis (38%) than in controls (22%). SENV infection was not associated with the amount of transfusion or duration of haemodialysis, while hepatitis C virus (HCV) infection was significantly associated with both of these factors. Elevation of alanine aminotransferase was significantly associated with HCV, but not with SENV viraemia. Of the 154 patients who were followed up, 63 (41%) remained negative, 34 (22%) gained positivity, 28 (18%) lost it and 29 (19%) remained positive for SENV infection. Episodes of alanine aminotransferase elevation were recorded for 3% of the patients who incurred SENV infection and this rate was similar to that observed in patients who were continuously negative for SENV infection (5%). CONCLUSIONS: SENV infection was common in patients on haemodialysis. No evidence was obtained that suggested involvement of the hepatitis virus in the pathogenicity of SENV.     

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.     

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.     

Hepatitis E virus (HEV) infection in haemodialysis patients

BACKGROUND.: The aim of this study was to determine the prevalence of hepatitisE virus (HEV) infection among patients undergoing haemodialysis(HD) and to evaluate whether chronic haemodialysis is associatedwith an increased risk of HEV infection. METHODS.: Serum samples from 420 HD patients and 316 healthy volunteerswere tested for IgG and IgM antibodies to HEV (anti-HEV). Anti-HEVtesting was done by an enzyme immunoassay (EIA) based on recombinantproteins of HEV (Abbott Labs). All anti-HEV IgG positive serawere confirmed using synthetic peptides. RESULTS.: Anti-HEV IgG was confirmed in 27/420 (6.4%) of the HD patientsand in 7/316(2.2%) of the reference group (P=0.007). However,multiple logistic regression analysis showed that the prevalenceof anti-HEV IgG was not significantly higher in HD patientscompared with the reference group, after controlling for ageand sex. No patient was found positive for anti-HEV IgM. Thepresence of anti-HEV was associated with sex in HD patients(P=0.04). No significant association was found between anti-HEVand underlying renal disease, anti-HCV, anti-HBc, blood transfusions,history of elevated transaminases, history of clinical hepatitisand renal transplantation. A marginal association, which wasobserved with the duration of haemodialysis in univariate analysis(P=0.07), was not confirmed in multivariate analysis. CONCLUSIONS.: Chronic haemodialysis is not associated with an increased riskof exposure to HEV, and the high prevalence of anti-HEV IgGin HD patients reported in uncontrolled studies is possiblydue to the confounding effect of age and sex.     

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.     

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.