Incidence of HCV infection in French hemodialysis units: a prospective study

A large prospective study was carried out from 1997 to 2000 in 25 French hemodialysis units including 1,323 patients to determine the incidence of hepatitis C virus (HCV) infection. Monthly testing of alanine aminotransferase (ALT) activity, and assessment of HCV RNA and anti-HCV antibodies if the ALT activity was elevated, identified 14 new infections in 7 different units, giving an incidence of 0.4% new HCV infections per year. Molecular analyses and epidemiological data indicated that five patients became infected with HCV outside the unit where they were dialyzed, while the nine remaining patients acquired HCV from infected patients on dialysis during the same shift at the same unit. HCV was cleared in six of the seven (85.7%) patients with acute hepatitis C who were given standard doses of alpha-interferon (alpha-IFN). The persistence of nosocomial transmission of HCV in hemodialysis units emphasizes the need to implement infection control practices. Identifying new infections is crucial because alpha-IFN treatment results in long term clearance of HCV RNA in a large proportion of patients.     

Hepatitis C virus infection in 2,744 hemodialysis patients followed regularly at nine centers in Hiroshima during November 1999 through February 2003

Patients on maintenance hemodialysis (HD) are at increased risk of infection with hepatitis C virus (HCV). A prospective follow-up study on HCV infection from November 1999 to February 2003 was conducted in nine hemodialysis (HD) units in Hiroshima. A total of 2,744 HD patients were surveyed regularly for HCV RNA in serum. The prevalence of HCV RNA decreased from 15.7% (262/1,664) on the first survey to 12.9% (242/1,882) in the last one (P<0.05). This decrease may be attributed to the inclusion of patients with a lower prevalence of HCV RNA compared to patients leaving dialysis centers (111/1,080 [10.3%] vs. 132/862 [15.3%], P<0.01). During the 40 months of this study, 16 de novo HCV infections were documented in the nine HD units corresponding to an incidence of 0.33% per year. These cases included eight new HCV infections, three re-infections, and five infections that presumably occured in the window period when tested during the first survey. Our study shows that the annual incidence of de novo HCV infection during HD was 0.33%, and emphasizes the need for frequent serum HCV RNA testing and for stringent disinfection procedures in order to prevent the transmission of HCV in these settings.     

Prevalence and risk factors of hepatitis C and B virus infections in hemodialysis patients and their spouses: A multicenter study in Beijing,China

Hemodialysis patients are at risk for hepatitis C and B virus infections. This study investigated the prevalences and risk factors of HCV and HBV infection and the distribution of HCV genotypes among hemodialysis patients and their spouses. From August to November 2011, a cross‐sectional study was conducted on 20 hemodialysis units in Beijing to investigate prevalences and risk factors for markers of HCV and HBV among 2,120 patients and 409 spouses. In hemodialysis patients, prevalences of anti‐HCV, HCV RNA, and hepatitis B surface antigen (HBsAg) were 6.1%, 4.6%, and 7.0%, respectively. The prevalence of HCV antibodies among spouses was 0.5%, of HCV RNA was 0.2%, and of HBsAg was 4.2%. Risk factors for HCV infection were dialysis duration, blood transfusion, and attending more than one dialysis unit. HBV infection was independently associated with age, family member with hepatitis infection, gender, and surgery. The predominant HCV genotypes were 1b (89.0%) and 2a (7.7%), and genotypes 3a, 3b, and 6a were each 1.1%. A significant decrease in HCV and HBV prevalences in Chinese dialysis units showed that infection control measures were effective. However, because nosocomial transmissions persist, strict adherence to infection control measures should be emphasized to reduce the risk of transmission. J. Med. Virol. 85:425–432, 2013. © 2013 Wiley Periodicals, Inc.     

Hepatitis C virus infection in hemodialysis patients in southern Sweden: Epidemiological,clinical, and diagnostic aspects

A prevalence of hepatitis C virus (HCV) antibodies of 12% was found in 276 patients from 11 dialysis units. Between zero and 22% of the patients in the different units were anti-HCV positive. The epidemiology of HCV was studied in two units during a 2 year period by antibody assays and the polymerase chain reaction and correlated with clinical manifestations. Two types of epidemiologic patterns were found that may explain the wide difference of HCV prevalence described in different dialysis units. In one unit there was no evidence of spread within the unit, and the prevalence of HCV was dependent on the status of the patients entering for treatment. In the other unit, a clustering of infected patients could be seen in which 13 of 36 were infected during a 3 year period. Some patients who had not received blood transfusions were among the infected. Hepatitis C infection was the most common explanation for repeated abnormal transferase levels. Most of the HCV-infected patients reacted both for anti-HCV and HCV RNA. HCV RNA was in general detected earlier than anti-HCV seroconversion. Among 20 HCV RNApositive serum samples that were anti-HCV ELISA-positive 18 had indeterminate and two negative reactions by immunoblot (RIBA 2). Thus the RIBA 2 test should be used with caution as a confirmatory antibody test in this group of patients. © 1993 Wiley-Liss, Inc.     

Prevalence of TT virus infection in Italian dialysis patients

OBJECTIVE: A novel DNA virus, transfusion-transmitted virus (TTV) is identified from the serum of a patient from acute hepatitis non-A-E. Few reports have been published on patients with renal disease. Patients on dialysis were at high risk of blood-borne viral infections and little is known about the prevalence of this virus in dialysis patients. In order to verify the prevalence of infection from TTV in these patients, we have examined the incidence of TTV in Italian patients with dialysis. METHODS: Serum samples of 85 patients and 65 healthy individuals were examined. In order to evidence the presence of the TTV virus, a method of the seminested polymerase chain reaction (PCR) with TTV-specific primers derives from the N22 region deIl'ORF-1 of the virus has been used and products were analyzed by agarose-gel electrophoresis. All serum samples were also analyzed to markers HBV and HCV. RESULTS: The prevalence of TTV DNA in dialysis patients [35/85 (41.7%)] was significantly higher than in healthy population [7/65 (10.7%)]. Among TTV positive dialysis patients, HCV coinfection was present in six cases. The positivity rate for TTV-DNA tends to increase with age. CONCLUSION: Transfusion-transmitted virus had a high prevalence in Italian-dialysis patients. In our study the virus did not have an important clinical effect on patients; but remains the possibility that it may aggravate liver disease caused by HCV. However, the question of whether TTV infection might have a possible effect on dialysis patients requires further investigation in larger groups.     

Prevalence of hepatitis C virus infections in dialysis patients and their contacts using a second generation enzymed-linked immunosorbent assay

The prevalence of antibodies to the hepatitis C virus (HCV) was determined in 498 hemodialysis patients from three german dialysis units, 121 staff members and 42 family members using an enzyme-linked immunosorbent assay (ELISA) of the second generation which detects antibodies to a structural (C22) and to non-structural (C33c, C100, 5-1-1) recombinant antigens to HCV. Using the second generation ELISA 115 patients (23.1 %) were anti-HCV positive versus 77 (15.5%) when sera were tested by an ELISA of the first generation containing only a non-structural antigen (C100). In 34 of these 40 discordant sera antibodies against at least one viral protein was found by a recombinant immunoblot assay. Of 5 sera containing antibodies to only one viral protein (C22) 3 were HCV RNA positive by polymerase chain reaction. Epidemiological evaluation of the patients revealed that the prevalence of anti-HCV was correlated to the duration of dialysis but not to the number of blood transfusions. Of 121 staff members 2 (1.6%) and 2 of 42 family members (4.7%) were positive indicating a low risk of the patients' contacts of acquiring HCV infection.Supported by the Kuratorium für Dialyse und Nierentransplantation e.V., Emil-von-Behring Passage, W-6078 Neu Isenburg, FRG     

Prevalence of anti-HCV and HCV viremia in hemodialysis patients in Taiwan.

Hepatitis C viral infection in 125 hemodialysis patients from Taiwan was studied using a second-generation anti-HCV immunoassay (EIA II) (Abbott HCV 2.0 EIA) and the polymerase chain reaction (PCR) to detect the HCV RNA in the serum. A total of 59 patients (47.2%) were positive by EIA II. In comparison, the conventional C100-3 anti-HCV assay was positive in 40 (32.0%). HCV RNA was found in 47 patients (37.6%). Patients with elevated serum transaminase level had a higher positive rate of anti-HCV and HCV RNA. The dialysis time was longer for those patients positive for anti-HCV than for those who were negative. A total of 57 of the 59 EIA II-positive cases had a history of blood transfusion. The HBsAg status did not influence the anti-HCV positivity. Among the 59 EIA II-positive patients, 66.1% were also positive for HCV RNA, and of the 47 HCV RNA-positive cases 83.0% were positive for EIA II. It is concluded that the high prevalence of specific HCV infection and HCV viremia was present in these patients. Prevention of cross-contamination during dialysis and blood screening before transfusion are important for the control of HCV infection in these patients.     

Prevention and treatment of hepatitis C in patients on dialysis

Nosocomial transmission of blood-borne pathogens, including hepatitis C virus infection, is the most common one in a dialysis center setting. The prevalence of HCV antibodies is by far higher in patients undergoing maintenance hemodialysis therapy than in those on peritoneal dialysis. Standard infection prevention measures in hospital settings and measures of infection prevention in dialysis units should be performed. They include serologic testing for HCV of every new patient in a dialysis unit as well as routine testing of all patients every six months. Hepatitis C therapy is recommended in patients on dialysis who have detectable HCV RNA, positive liver biopsy (portal or bridging fibrosis or moderate stage of necroinflammation), younger patients (less than 65 years), and transplantation candidates. When evaluating ALT, it should be kept in mind that ESRD patients have ALT levels lower than general population, making ALT level not relevant parameter of liver disease activity in these patients. Results of hepatitis C therapy with interferon alpha and peginterferon alpha are similar to those in the general population but with more common side effects, which may require therapy discontinuation. Due to the possibility of anemia, ribavirin is contraindicated in patients with ESRD. Around 30% of patients treated with peginterferon have sustained viral response, 25%-45% of them have end of treatment viral response, and 50%-80% have end of treatment biochemical response (ALT normalization). Numerous clinical trials have established that the decrease in HCV load and prolonged suppression of viral replication during interferon therapy significantly reduce hepatic inflammation and consequently postpone progression of fibrosis to cirrhosis.     

High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence.

The prevalence of hepatitis C virus (HCV) infection was evaluated in 227 hemodialysis patients from four units in Caracas, Venezuela, by using different second- and third-generation enzyme immunoassays (EIAs) and immunoblot assays. HCV antibodies were detected in 162 patients (71%) by the recombinant-based second-generation assays (Abbott and Ortho) and in 161 patients by the synthetic peptide-based EIA (UBI). Of the 162 HCV antibody-positive serum samples, 161 were confirmed to be positive by RIBA 3. HCV RNA was detected in 49 of 68 (72%) of the seropositive patients and in 5 of 21 (24%) of the seronegative ones. HCV RNA was not always correlated with an increase in alanine aminotransferase (ALT) levels. Among 20 patients positive for HCV RNA and for HCV antibodies (without any hepatitis B virus [HBV] marker), only 10 had elevated ALT levels. The possible interference of HBV for HCV replication was evaluated. No significant difference was found between the presence of HCV RNA and the presence of any HBV serological markers. The possible routes of transmission of HCV in hemodialysis patients are multiple, and some of them are still controversial. Of the HCV-positive patients, 30% received a blood transfusion, significantly more than the 15% found for the HCV-negative group. However, blood transfusions alone could not account for the high incidence observed in this group of patients (38% from 1994 to 1995). In conclusion, about one-quarter of the apparently non-HCV-infected patients were probably seroconverting, ALT may not be a useful indicator of HCV infection in hemodialysis patients, and nosocomial transmission of HCV may play a role in the spread of HCV in this group.     

Low prevalence of anti-hepatitis C virus antibodies in female hemodialysis patients without blood transfusion: A multicenter analysis

To investigate whether nosocomial infection with hepatitis C virus (HCV) in chronic hemodialysis patients is related primarily to hemodialysis procedures, a multicenter analysis was carried out on 2,132 chronic hemodialysis patients (male: 1,274, female: 858) from 23 dialysis units using a second-generation anti-HCV antibody assay. The prevalence of anti-HCV antibodies in patients with blood transfusion (29.9%) was significantly higher (P < .0001) than in those without blood transfusion (7.6%). Although the prevalence of anti-HCV antibodies increased with the length of hemodialysis in males without blood transfusion, it did not increase even after long-term hemodialysis (more than 5 years) in females without blood transfusion, who exhibited a rate (1.9%) similar to that of healthy blood donors in Japan. There was a significant correlation between the presence of anti-HCV antibodies and anti-HBs antibody in males without blood transfusion. In anti-HBs antibody-negative male patients without blood transfusion, the prevalence of anti-HCV antibodies was significantly lower compared with anti-HBs antibody-positive male patients without blood transfusion. There was marked difference in the prevalence rate in patients without blood transfusion among dialysis units, and there was no correlation between the prevalence and the mean period of dialysis of each dialysis unit. Although nosocomial infection with HCV appears to be related to the hemodialysis environment, the low prevalence of anti-HCV antibodies in females suggests that dialysis procedures per se may not present the risk of hepatitis C virus infection. © 1996 Wiley-Liss, Inc.     

Hepatitis C virus infection in the family setting of patients with occult hepatitis C

Family members of patients with chronic hepatitis C virus (HCV) infection are at increased risk of HCV infection but the prevalence of HCV among family members of patients with occult HCV infection is not known. Anti‐HCV, serum HCV RNA and levels of liver enzymes were determined in 102 family members of 50 index patients with occult HCV infection and in 118 family members of 59 chronic hepatitis C index patients. HCV RNA and/or anti‐HCV were detected in 10/102 (9.8%) relatives of patients with occult HCV infection and in 4/118 (3.4%) of patients with chronic hepatitis C. Fourteen additional family members (seven were relatives of index patients with occult HCV infection) had abnormal values of liver enzymes without serological markers of HCV infection. Two of these patients (who were relatives of two index patients with occult HCV infection) underwent a liver biopsy and were diagnosed with an occult HCV infection because HCV RNA was detected in the liver cells in the absence of serological HCV markers. In conclusion, the prevalence of HCV infection among family members of patients with occult HCV infection was similar to that found among family members of patients with chronic hepatitis C. This stresses the need to adopt strategies to prevent the transmission of HCV in the family setting of patients with occult HCV infection. J. Med. Virol. 81:1198–1203, 2009. © 2009 Wiley‐Liss, Inc.     

Profiles of GBV-C/hepatitis G virus markers in patients coinfected with hepatitis C virus.

GBV-C/Hepatitis G virus (GBV-C/HGV) is a newly discovered viral agent, found widely among healthy blood donors and among individuals at risk of parenterally transmitted infections. GBV-C/HGV is found frequently in coinfection with HCV. A population of 109 HCV positive patients was examined for the presence of GBV-C/HGV RNA and antibodies to E2. Of the 109 patients, 23 (21%) had serum GBV-C/HGV RNA in serum, 39 (36%) had only antibodies to E2 and 8 (7%) were positive for both markers, with an overall prevalence of 64%. Different serologic and virological patterns were observed in GBV-C/HGV exposed patients according to their infection status. Active infection was characterized by positive RT/PCR signal with primers for both the 5'UTR and NS5 genomic regions, viremia levels above 10(4) copies/mL by real time quantitative RT/PCR and absence of detectable anti-E2. In the transition phase between active infection and recovery, GBV-C/HGV RNA was only detectable by RT/PCR using primers from the 5' untranslated region and viremia levels were below 10(4) copies/ml by quantitative PCR, with or without simultaneous presence of anti-E2 antibodies. Resolved infection was characterized by absence of detectable viremia and, in most patients, by the presence of anti-E2.     

Hepatitis C virus-Epstein-Barr virus interaction in patients with AIDS

Immortalization of B cells by Epstein-Barr virus (EBV) and their subsequent proliferation leads to B-cell non-Hodgkin's lymphoma in immunocompromised patients. The role of hepatitis C virus (HCV) in B-cell non-Hodgkin's lymphoma has recently been raised, and an interaction between HCV and EBV is supported by recent in vitro experiments. The aim of this study was to investigate in vivo interactions between HCV and EBV in patients with AIDS, i.e., patients exposed to the risk of EBV-related B-cell non-Hodgkin's lymphoma. A total of 135 patients were prospectively studied. Serological and molecular markers of HCV, EBV, and human immunodeficiency virus (HIV) infection were sought. All the patients harbored latent EBV infection, and 20% had detectable HCV RNA in serum. No significant relationship was found between HIV, HCV, and EBV viral load in peripheral blood mononuclear cells or plasma. There was no difference between anti-HCV-positive and -negative patients or between HCV RNA-positive and -negative patients with regard to the prevalence of EBV markers, especially EBV replication markers. The presence of EBV replication markers was not related to HCV RNA seropositivity or to HCV viral load. Five patients subsequently developed B-cell non-Hodgkin's lymphoma, none of whom had markers of EBV or HCV replication. These results argue against an in vivo interaction between HCV and EBV in patients with AIDS, and against a role of HCV infection in the occurrence of B-cell non-Hodgkin's lymphoma in these patients.     

Sécurité transfusionnelle et drépanocytose à Bamako,Mali. Séroprévalence des infections à VIH,VHB, VHC et allo-immunisation anti-Rh et Kell chez les drépanocytaires

Red cell transfusion is one of the main treatments in sickle cell disease. However there are potential risks of blood transfusions. In order to propose strategies to improve blood safety in sickle cell disease in Mali, we conducted a prospective study of 133 patients with sickle cell anemia recruited at the sickle cell disease research and control center of Bamako, November 2010 to October 2011. The study aimed to determine the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections by serum screening and the frequency of red cell alloimmunization before and after blood transfusion. The diagnosis of sickle cell syndrome was made by HPLC, the detection of markers of viral infection was performed by ELISA, and the diagnosis of alloimmunization was conducted by the Indirect Coombs test. Prevalence of viral infections observed at the time of enrolment of patients in the study was 1%, 3% and 1% respectively for HIV, HBV and HCV. Three cases of seroconversion after blood transfusion were detected, including one for HIV, one for HBV and one another for HCV in sickle cell anemia patients. All these patients had received blood from occasional donors. The red cell alloimmunization was observed in 4.4% of patients. All antibodies belonged to Rh system only. Blood transfusion safety in sickle cell anemia patients in Mali should be improved by the introduction of at least the technique for detecting the viral genome in the panel of screening tests and a policy of transfusions of blood units only from regular blood donors.     

Blood‐borne virus infections in dialysis units—A review

Hepatitis outbreaks in haemodialysis unit patients and staff were reported in the late 1960s. In 1972, the Rosenheim report in the UK established guidelines which included routine tests for hepatitis B surface antigen and isolation facilities for dialysing patients with hepatitis B virus which resulted in a dramatic fall in cases of hepatitis. However, since these guidelines were introduced, other blood‐borne viruses, notably HCV and HIV have been discovered, and failures of infection control practices still lead to outbreaks of HBV in haemodialysis units. The prevalence of HCV in dialysis patients varies considerably throughout the world, with reported prevalence ranging from 3·9% to 71%. The number of blood transfusions and the length of time on dialysis have consistently been associated with HCV prevalence. Several reports provide evidence of patient‐to‐patient HCV transmission with environmental blood contamination the most significant factor in intra‐unit transmission. There is no evidence that HCV has been transmitted by re‐use of dialysis machines but being dialysed next to an HCV positive patient is associated with a significant risk of HCV acquisition. Several studies have shown that dialysing HCV positive patients in a separate unit or in a defined sector of a dialysis unit significantly reduces nosocomial HCV infection. HGV is prevalent in dialysis units where there is evidence of transmission to patients but no evidence of associated symptoms. HIV is infrequently transmitted in dialysis units and several units treating many HIV‐positive patients have shown no evidence of transmission. Careful attention needs to be paid to infection control procedures and regular virological testing. Copyright © 1999 John Wiley & Sons, Ltd.     

Failure to diagnose recent hepatitis C virus infections in London injecting drug users

Hepatitis C virus (HCV) infection results in chronic liver disease in a substantial proportion of those infected. Most new cases of HCV infection in the UK are associated with intravenous drug use. It is important to identify these infections because of the implications for the future health of the individuals concerned and for the control of further spread of infection. However, as hepatitis C infection is characterised by a relatively long asymptomatic period of seronegative viraemia, a laboratory diagnostic protocol that does not test HCV seronegative samples for the presence of HCV RNA may wrongly designate HCV viraemic seronegative individuals as uninfected. Amongst 424 injecting drug users whose serum was sent to our diagnostic laboratory for "HCV screening" over a 14-month period, the prevalence of HCV seropositivity was 48.4%. We retrospectively identified seven individuals for whom there was evidence of recent acquisition of HCV infection. Three of these infections were identified using our routine diagnostic protocol: testing for the presence of HCV-specific antibody and performing HCV RNA testing only on seropositive and seroindeterminate specimens. However, four cases were only identified by HCV RNA testing of HCV seronegative serum. On the basis of these observations, we estimate the incidence of HCV infection amongst London injecting drug users as being 14.3 per 100 person-years. We advocate that all HCV seronegative blood samples obtained from injecting drug users should be tested for the presence of HCV RNA, and suggest that this could be done efficiently by nucleic acid testing the specimens in small pools. .