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.     

Nosocomial transmission of hepatitis C virus within a British dialysis centre

Patients on renal replacement therapy are recognized as a group at increased risk of infection with hepatitis C virus (HCV). While the risk has been reduced by the use of erythropoietin for treatment of anaemia and the introduction of HCV screening of blood products and potential renal transplant donors, new cases of HCV are still being documented, with patients on hospital haemodialysis appearing to be particularly at risk. The exact mode of transmission of HCV within dialysis units is unclear, although there is evidence to support nosociomial transmission between patients. Third generation HCV antibody testing was performed on all dialysis patients when a new case of HCV was identified within our unit. Stored monthly serum samples were then examined retrospectively to determine when patients became HCV RNA and HCV antibody positive. Viral typing identified two distinct strains of HCV as being responsible for these infections, both of which had previously been identified in dialysis patients within the unit known to have HCV infection. This information, taken in conjunction with knowledge of the location of each patient for dialysis, suggests two separate episodes of nosocomial transmission of HCV between haemodialysis patients. While evidence of nosocomial transmission of HCV is accumulating, with modern dialytic procedures evidence of transmission through the dialysis machine or equipment used for dialysis is lacking. This stresses the importance of strict applications of universal precautions as the key to prevention of further transmission of HCV infection. This information is obviously applicable not only to dialysis units but all units that may potentially come in contact with HCV patients.     

Extrahepatic immunological manifestations of hepatitis C virus in dialysis patients

BACKGROUND: Hepatitis C virus (HCV) infection may be associated with various extrahepatic immunological disorders. Uremic patients on chronic regular dialytic treatment (RDT) frequently develop immunological abnormalities. The aim of this study was to evaluate the probability that HCV infection creates an increased risk for extrahepatic immunological abnormalities in chronic RDT patients. SUBJECTS AND METHODS: In a series of one hundred sixteen chronic RDT patients, HCV status was determined by anti-HCV antibodies, polymerase chain reaction (PCR) RNA and viral genotyping. After excluding four anti-HCV negative/PCRRNA positive patients, a comparison was made between 51 anti-HCV negative/PCR-RNA negative and 61 anti-HCV positive patients, this latter group including seventeen PCR-RNA negative, fifteen genotype 1, thirteen genotype 2, three genotype 3, four genotype 4, four undeterminable genotype and five mixed genotypes. The following investigations were performed: cryoglobulinemia (presence, titer and, when possible, identification), monoclonal gammopathy, antineutrophil cytoplasm antibodies, antidouble stranded DNA antibodies, circulating immunocomplexes and immunoglobulin levels. RESULTS: Cryoglobulinemia was found in 77% of anti-HCV positive versus 29% of anti-HCV negative patients, and cryocrit > 1% in 50% versus 9.8% respectively, p=<0.01. Also cryoglobulin concentration was higher (logarithmic transformation: 4.38 +/- 0.94 vs 3.11 +/- 1.06, p =< 0.001) in anti-HCV positive versus negative patients. Multivariate logistic regression analysis showed a significantly increased odds ratio (12.0, confidence interval 3.0 to 48.3) for having high levels of cryoglobulins (cryocrit >1%) after adjusting for age and dialytic age. The prevalence of this abnormality did not differ significantly among patients infected with different genotypes, but a tendency towards a lower frequency was observed in the anti-HCV positive/PCR negative subgroup. Cryoglobulins were identified as type I (2 anti-HCV positive case), type II (2 anti-HCV positive and 1 anti-HCV negative case) and type 3 (1 anti-HCV negative case). The frequency of monoclonal gammopathy was not significantly different between anti-HCV positive and anti-HCV negative patients (6.5% versus 2%) as well as that of the other parameters evaluated except for IgG concentration which was higher in the anti-HCV positive group (1,685 +/-605 versus 1349 +/- 352 mg/dl, p 0.006). Five events, potentially linked to HCV infection, occurred in our anti-HCV positive patients: 2 cases of porphyria cutanea, 1 case of unexplained peripheral neuropathy, 1 cutaneous leukocytoclastic vasculitis, 1 death for non-Hodgkin's lymphoma. In one anti-HCV positive patient treated with interferon-alpha, the presence of cryoglobulins, monoclonal gammopathy and high IgG levels strictly paralleled that of viremia, disappearing during the recovery phase under treatment and reappearing shortly after stopping treatment. CONCLUSIONS: HCV infection provides a significantly increased risk for developing extrahepatic immunological abnormalities also in chronic RDT patients. It is possible that the clinical relevance of this event might be scant because of the low level of these abnormalities, but an awareness of its possibility should to be taken into account.     

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.     

Seroprevalence of hepatitis C virus and hepatitis B virus among dialysis patients in Bahrain and Saudi Arabia

Dialysis patients are at risk for contracting blood-borne infections, including hepatitis viruses (HBV and HCV). The aim of this study was to assess the prevalence of HBV and HCV infection among hamodialysis patients in Bahrain and Saudi Arabia. Study subjects comprised 81 Bahraini and 34 Saudi dialysis patients, and as control 7714 Bahraini and 2330 Saudi blood donors. Serologic markers of HBV (HBsAg, anti-HBc) and HCV (anti-HCV) were determined by EIA and confirmed by PCR (HBV) and RT-PCR (HCV). Higher prevalence of HCV (9.240% vs 0.300%, P <.001), HBsAg (5.88% vs 0.620%; P <.001), but not anti-HBc (1.7% vs 4.6%; P =.01) were seen in patients compared to controls, respectively. When compared to Bahrainis, higher prevalence of HBsAg (11.8% vs 3.7%) and anti-HCV (14.7% vs 7.4%) were seen among Saudi patients, respectively. Double HCV infection was frequent, and the most prevalent types were HCV1a/1b plus HCV4 in Bahraini, and HCV 2/2a plus HCV 4 among Saudi dialysis patients. Our results are the first report on viral hepatitis among dialysis patients in Bahrain, and the first to compare HBV/HCV rates among dialysis patients in the Eastern Arabian peninsula, and confirms other results that documented increased HBV and HCV infection among dialysis patients. Future studies aimed at assessing the status and to monitor the progress of viral hepatitis infection among dialyzed and transfused patients will have a strong impact on patient diagnosis, follow-up, and treatment.     

Antibody to hepatitis C virus increases with time on hemodialysis.

We studied whether chronic hemodialysis is associated with an increased risk of exposure to hepatitis C virus. Utilizing a first generation Elisa assay (C-100 Elisa, Ortho Diagnostic Systems, Raritan, NJ) and the Chiron RIBA HCV second generation assay (RIBA, Chiron, Emeryville, CA and Ortho Diagnostic Systems, Raritan, NJ), antibody to HCV was found in 31 of 87 hemodialysis patients (36%). Patients on hemodialysis less than 2 years had an antibody incidence of 15% (n = 46), as contrasted with a 59% incidence for patients on dialysis greater than or equal to 2 years (n = 41). We were unable to demonstrate a correlation of HCV-antibody positivity with history of blood transfusion. The overall incidence is higher than previously reported for hemodialysis patients in the United States. The very high incidence found in patients on dialysis greater than or equal to 2 years suggests that factors in the hemodialysis unit might contribute to the spread of virus.     

Improved detection of antibodies to hepatitis C virus in dialysis patients using a second-generation enzyme immunoassay.

We tested serum samples from 99 patients undergoing maintenance hemodialysis for hepatitis C virus (HCV) antibodies using a first-generation, licensed anti-HCV enzyme immunoassay (EIA) and a second-generation anti-HCV EIA that detect three gene products c100-3, NS3, and core. Specimens that were repeatedly reactive by either or both screening assays were further evaluated by testing with supplemental EIAs and a dot blot immunoassay. There was 87.9% agreement between the licensed HCV EIA and the HCV EIA second generation. HCV EIA Second Generation detected 10 more positive specimens than HCV EIA, for an increase in detection from 33.3% (33/99) to 43.4% (43/99). We conclude that HCV EIA Second Generation improves detection of HCV infection in hemodialysis patients.     

Patient to patient transmission of hepatitis C virus in hemodialysis units.

AIMS: In dialysis patients, blood transfusions and long-term dialysis are well known risk factors for transmission of hepatitis C virus. In this study the impact of use of dedicated hemodialysis (HD) units on the anti-HCV conversion rates was studied in patients of two different hemodialysis units in a city, Kayseri, between October 1995, and March 1999. MATERIALS AND METHODS: In the HD Unit of Erciyes University (HUEU), anti-HCV-positive and -negative patients were dialyzed on the dedicated machines in the same big room and seropositive patients for HBsAg in isolated rooms. In the HD Unit of Kayseri State Government Hospital (HUSH) only seronegative for anti-HCV and hepatitis B patients were treated. If a patient became positive, the patient was transferred to HUEU. Seventy-five patients have been receiving hemodialysis therapy in HUEU. Thirteen HBsAg-positive and 62 HBsAg-negative patients were dialyzed in separate rooms. Of 62 HBsAg-negative patients, 22 (35.5%) were already positive for HCV antibody when they started dialysis or before the study period. Forty seronegative patients (64.5%) for anti-HCV (23 males, 17 females) were treated with 22 anti-HCV-positive patients in the same room in HUEU. The mean duration of dialysis treatment was 24.7 +/- 21.0 months (range 4 to 96 months). Of the 40 patients, 28 (70%) became positive during the study period. Of 28 patients who became seropositive, 10 (35.7%) had a history of blood transfusion. Fifty-four patients (21 males, 33 females) were treated in HUSH during the study period. The mean duration of dialysis treatment was 19.3 +/- 9.6 months (range 5 41). Eight patients (14.8%) became anti-HCV-positive. Of these, 7 had received blood transfusion (88%). RESULTS: The seroconversion rate of patients in HUEU was higher than that of HUSH (odds ratio 3) (p < 0.05). Data derived from our patients showed that contamination appeared to be both transfusional and nosocomial and that there is a possibility of transmitting HCV infection in hemodialyzed patients never submitted to blood or blood products transfusion. Nosocomial spread of HCV in HD units which both seropositive and seronegative patients treated together was higher than that of dedicated unit. This is true even though we separated anti-HCV-positive dialysis machine.     

Sexual transmission of hepatitis C virus

Hepatitis C virus (HCV) is usually transmitted parenterally, but sexual transmission is considered likely in the 20% of cases with no other risk factors. Retrospective cohort studies conducted among persons who have never injected drugs show that factors predictive of HCV seropositivity include the number of lifetime sexual partners, high-risk sexual practices, other sexually transmitted infections, and HIV seropositivity. Persons in long-term monogamous heterosexual relationships with a partner seropositive for HCV are at lower risk of HCV acquisition (0 to 0.6% peryear) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4 to 1.8% per year). HCV RNA is detectable in genital fluids, but there is not yet any proof that the HCV RNA in genital secretions represents infectious virus. HCV can be transmitted by sexual intercourse but much less efficiently than other sexually transmitted viruses, such as HBV and HIV. Sexual transmission of HCV may be enhanced by other concomitant sexually transmitted infections with genital erosive lesions or via traumatic sexual intercourse with abrasion of the genital mucosa.     

Transmission of hepatitis C virus in the dialysis setting and strategies for its prevention

Hepatitis C virus (HCV) infection is more common among hemodialysis patients than the general population and transmission of HCV in dialysis clinics has been reported. In the context of the increased morbidity and mortality associated with HCV infection in the end stage renal disease population, it is important that dialysis clinics have processes in place for ensuring recommended infection control practices, including Standard Precautions, through regular audits and training of the staff. This review will summarize the epidemiology of HCV infection and risk factors for HCV transmission among hemodialysis patients. In addition, the proper protocols are required to investigate suspected cases of HCV transmission in dialysis facilities and recommendations for prevention of HCV transmission in will be reviewed.     

Risk of death among chronic dialysis patients infected with hepatitis C virus

Hepatitis C virus (HCV) infection is highly prevalent among chronic dialysis patients (10% to 40%) and is the most common cause of chronic liver disease. However, there are no studies estimating the risk for death among dialysis patients infected with HCV compared with those not infected. We conducted a prospective cohort study to estimate the risk for death among chronic dialysis patients infected with HCV compared with those not infected. In 1992, 200 patients (91%) who had been undergoing dialysis therapy for at least 6 months consented to be screened for HCV infection by enzyme immunoblot assay and polymerase chain reaction (PCR). Information about potential confounders and potential risk factors for death and HCV infection was obtained from the dialysis center database. Patient outcomes collected included death, transplantation, and loss to follow-up. The Cox proportional hazards model was used to estimate the odds of death among dialysis patients who were positive for the HCV antibody and HCV RNA compared with negative patients. Forty-four patients (22%) were HCV antibody positive. Thirty-four patients (17%) were HCV RNA positive. Patients in the HCV RNA-positive group were more likely to be younger (51.8+/-12.6 v 57.2+/-17.3 years of age), men (77% v 54%), and black (65% v 37%). None of the home hemodialysis or peritoneal dialysis patients were HCV RNA positive, whereas one of the home hemodialysis and one of the peritoneal dialysis patients were HCV antibody positive. Two patients became infected with HCV during the follow-up period. Patients who were HCV RNA positive and those who were HCV antibody positive were at increased risk for death compared with patients who were negative (adjusted relative risk [aRR]=1.78; 95% confidence interval [CI], 1.01 to 3.14; P=0.045; and aRR=1.97; 95% CI, 1.16 to 3.33; P=0.012, respectively), after adjusting for time on dialysis, race, transplantation, and age. We conclude that HCV infection increased the risk for death during the study period compared with those not infected. Further studies should assess the measures used to prevent and treat HCV infection.     

Prevalence of antibodies against hepatitis C virus in a dialysis unit.

Anti-HCV was tested in 77 uremic patients, 48 on hemodialysis (HD), 29 on CAPD, by immunoenzymatic 1st and 2nd generation assays (ELISA I, II) and 4-antigen (4-RIBA) immublotting. The investigation was extended to the staff (n = 29) and to HCV-positive patients' families (n = 30). The prevalence using 2nd generation tests was double (21%) that in 1st generation tests (11%). A greater incidence in the HD than in the CAPD group (23 vs. 17%) and a highly significative correlation to dialytic age were observed. No one among the sanitary personnel and only 2 family members were found HCV positive, suggesting a low infectivity via the parenteral inevident route. Extracorporeal circulation and particularly the exposure time to the treatment seem to be the main risk factors.     

Hepatitis C virus antibodies in dialysis pediatric patients.

A new 4-antigen recombinant immunoblot assay (4-RIBA) for confirmation of hepatitis C virus (HCV) C-100 enzyme-linked immunosorbent assay (ELISA) reactivity was tested in serum samples of 11 pediatric patients on dialysis. Of 6 HCV C-100 ELISA-positive samples, all were 4-RIBA positive. The 2nd generation ELISA picked up 1 additional case confirmed by 4-RIBA. The 2nd generation tests increased the prevalence of HCV-positive cases.     

Prevalence of antibodies to hepatitis C virus in hemodialysis patients.

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

Gamma-glutamyltransferase activity in chronic dialysis patients and renal transplant recipients with hepatitis C virus infection

The prevalences of chronic infection by hepatitis C virus (HCV) and its genotypes vary among countries and ethnic groups. Among patients with end-stage renal disease (ESRD) and transplant recipients, the evolution of hepatic disease seems atypical and has not been established. In this study we compared the prevalence and HCV genotypic distribution among Brazilian patients with ESRD on dialysis or with transplantations. Moreover, we sought to compare the behavior of biochemical markers of hepatic activity of HCV infection in both groups. We prospectively evaluated 87 ESRD patients on dialysis and 105 transplant patients. Blood samples were obtained to perform qualitative HCV-RNA, genotyping, and, periodically, serum levels of aminotransferases (ALT, AST), gamma-glutamyltransferase (GGT), alpha-fetoprotein (AFT), and albumin. The prevalence of HCV in ESRD patients was similar to recipients (19.5% vs 25.7%; P = NS) and the most frequent genotype was 1a. There was no difference in the mean values of ALT, GGT, AFT, and serum albumin between both groups with HCV infection. The mean values of aminotransferases were slightly elevated and a high frequency of patients evolved with persistently normal parameters. In contrast, the mean values of the GGT were 3 or 4 times above the reference limit and a greater frequency of patients evolved with values persistently elevated in the 2 groups. In conclusion, in the 2 groups the prevalence of HCV infection was elevated; the most frequent genotype was 1a. Among the biochemical parameters, GGT seemed to be useful as an indirect marker of liver disease.     

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.