Interferon treatment for hepatitis C virus infection in patients on haemodialysis

BACKGROUND: This study examined the efficacy and tolerability of interferon alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in patients on maintenance haemodialysis. METHODS: A 24- month prospective cohort study was performed in 11 HCV RNA-positive haemodialysis patients, who were treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and virological monitors included serum alanine aminotransferase levels, and HCV RNA by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were determined by PCR and nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients respectively. Six (55%) patients had biochemical and/or histological features of chronic active hepatitis before treatment. All 11 patients became HCV RNA-negative by PCR, with normalization of deranged aminotransferase levels, within 2-8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks after the cessation of IFN, while biochemical relapse occurred in six (55%) patients. Sustained eradication of HCV was achieved in three (27%) patients. Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before and after IFN treatment in non-responders and relapsers. Persistent malaise and poor appetite were noted in eight (73%) patients during IFN therapy. Other side-effects of IFN included the exacerbation of anaemia, induction of resistance to erythropoietin, weight loss, and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be achieved in 27% of haemodialysis patients. Predictors of sustained response include low baseline HCV RNA level and mild liver pathology. Virological relapse can occur despite normal liver biochemistry. Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute the side-effects of IFN that deserve special attention in uraemic subjects.      

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.     

Cost-effectiveness of hepatitis B vaccination in haemodialysis patients.

BACKGROUND: Vaccination against hepatitis B virus is an important means of controlling the infection, but its role in haemodialysis patients has been questioned due to the latter's impaired immune response. METHODS: Forty-eight of 79 haemodialysis patients who were negative for antibodies to both hepatitis B surface and core antigens were entered into a vaccination programme. Standard doses of a plasma-derived vaccine were administered into the deltoid muscle at 0, 1, 2 and 4 months, and the antibody response was measured at 1 and 2 months after the third and fourth doses. RESULTS: The peak mean antibody titre of 372 IU/l was recorded at 1 month after the fourth dose, and the maximum response rate was achieved at 2 months after the final dose. Seroconversion occurred in 26 of 36 patients (72%) who completed the programme, and protective levels of antibody above 10 IU/l were found in 25 of 36 patients (69%). Cost analysis of the project revealed a net saving of +/- R90/patient entered at the end of the first year, due to the reduced number of patients requiring monthly surveillance tests for hepatitis B surface antigen. After that, an annual saving of +/- R380/patient is projected. CONCLUSION: In view of the high prevalence of chronic hepatitis B carriers in the South African population, the reduction in the number of patients at risk of infection, combined with a net cost saving, makes it reasonable to recommend vaccination in all non-immune haemodialysis patients despite a reduced response rate.     

Antibodies to hepatitis C virus in kidney transplantation.

Ninety patients on dialysis, 241 cadaveric kidney donors and 27 cadaveric kidney recipients with a follow-up of 2 years, have been investigated as for anti-HCV positivity by means of 3 tests. As for patients on dialysis and cadaveric donors, the prevalence was 32 and 4%, respectively. As for transplanted patients, it must be noted that 4 negative recipients from positive donors seroconverted, but without any change in hepatic enzymes, while in 2 or 9 anti-HCV-positive recipients, hepatic enzymes increased after transplantation. Seroconversion in patients transplanted from a negative donor was not significantly different. We conclude that, according to their experience, anti-HCV positivity in the donors is not associated with a significant risk of infection in recipients of cadaveric grafts.     

Abnormal alanine aminotransferase activity reflects exposure to hepatitis C virus in haemodialysis patients.

Prospective studies have shown that the annual incidence of non-A, non-B (NANB) hepatitis may be high in haemodialysis patients. To assess whether hepatitis C virus (HCV), the major causative agent of post-transfusion and community-acquired NANB hepatitis, has a role in the pathogenesis of liver disease in dialysed patients, we have studied the prevalence and significance of antibodies to HCV in a cohort of patients with end-stage renal disease on chronic haemodialysis treatment. Seventy-four (30%) had circulating antibodies to HCV. Statistically significant associations with the anti-HCV carrier status were duration of haemodialysis treatment, blood transfusions, and the finding of abnormally elevated ALT on retrospective analysis. In contrast, only one of 103 dialysis staff members showed transient positivity for anti-HCV, suggesting a low risk of professional exposure to HCV. These findings suggests that HCV infection is relatively frequent in haemodialysis patients and may be responsible for a significant proportion of liver disease in this clinical setting.     

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.     

Hepatitis type B virus DNA in patients receiving hemodialysis: correlation with other HBV serological markers

Possible presence of hepatitis type B virus (HBV) was assessed in 239 end-stage renal failure patients who were receiving long-term maintenance hemodialysis (average 30.8 months; duration: 1-94 months), and who had not shown any other symptom of HBV infection. Their HBV serological markers, including HBV DNA, were evaluated together with those of normal control individuals. HBV surface antigen (HBsAg) was detected in 42 of the 239 dialysis patients, 15 of whom also positive for HBV DNA (mean +/- SD = 56.2 +/- 23.7 pg/100 microliters of serum). HBV DNA was also found in 22 of the 197 (11.2%) dialysis patients who were negative for HBsAg, with an average of 36.2 +/- 19.0 pg/100 microliters of serum. This rate of detecting HBV DNA in HBV seronegative dialysis individuals was significantly higher than the rate of 1.83% found among healthy HBsAg(-) individuals. Among these 22 dialysis patients who were HBsAg(-) but HBV DNA(+), 15 were found to possess antibodies against HBsAg (anti-HBs) and/or antibody against HBV e antigen (anti-HBe). These data suggested that the absence of serum HBV antigen or the presence of antibodies against HBV markers might not be sufficient to identify possible HBV infection in immunocompromised hosts such as hemodialysis patients.     

Changing of hepatitis B virus markers in patients with bone marrow transplantation

The hepatitis B virus (HBV) infection and its resulting hepatic abnormalities are very high in prevalence among the Taiwan population. They also seem to compose a major problem to patients subjected to bone marrow transplantation (BMT) due to intensive chemoradiotherapy. In this study, the sera of 42 patients were investigated before and after BMT to detect the presence of HBV markers and to test their liver function (LF). Being followed-up for 3-12 months after BMT, 12 out of 27 were found to have altered HBV markers according to the classification of the following: seroconversion of HBsAg, clearance of HBsAb, appearance of HBeAg, clearance of HBeAb, and acute hepatitis. Thirty-seven out of 42 patients (88.1%) were found in routine LF test to develop one or more abnormality; however, 90% of them turned normal within one year after BMT. Only one patient died of complications associated with fulminant hepatitis. In conclusion, the previous hepatic damage from HBV infection appears unlikely to increase the risk of posttransplant morbidity and mortality.     

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.     

Antibodies against hepatitis C virus among renal transplant patients in Greece

To evaluate the prevalence of hepatitis C virus (HCV) infection in Greek renal transplant (RT) patients and its association with abnormal liver function tests (LFTs), serum anti-HCV was determined (Ortho-ELISA test system) in 206 RT and 245 haemodialysis patients (HD) as controls. The prevalence (10.2%) of anti-HCV in RT patients was significantly higher (P < 0.0001) than in the Greek general population (0.7%) and lower (P < 0.0001) than in the HD patients (23.8%), and was not related to the patients' age, post-transplant time or pre-transplant HD time. None of the anti-HCV RT patients was HBsAg +, whereas 13 (62%) and 12 (57%) of them were anti-HBsAg + and anti-HBc +, respectively. The incidence of abnormal LFTs in anti-HCV + HBsAg ? and anti-HCV ? HBsAg + RT patients was similar. Our findings indicate that: (a) the prevalence of serum anti-HCV in the Greek RT population is high, although considerably lower than in HD pts; (b) anti-HCV + RT patients have a high incidence of abnormal LFTs, comparable to that seen in HBsAg + RT patients; and (c) in a substantial proportion of anti-HCV + RT patients there is evidence of previous HBV infection.     

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.     

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.     

Changes in serological markers of hepatitis B virus after renal transplantation

An estimated 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Immunosuppression after renal transplantation seems to enhance viral replication and increase the risk of developing cirrhosis and hepatocellular carcinoma. This retrospective study was performed to assess the prevalence among and serological status of HBV infection after renal transplantation at a single university Brazilian center. Thirty six (4.2%) patients among 850 kidney recipients showed positive HBsAg for more than 6 months; 31 were hepatitis B surface antigen (HBsAg) positive at transplantation. Of the 15 hepatitis B e antigen (HbeAg) positive patients, six had spontaneous HBeAg seroconversion and three also had HBsAg clearance. An additional two showed HBeAg clearance with Lamivudine without seroconversion. Among 15 HBeAg-negative patients, three developed HBeAg reversion with no elevation of alanine transferase (ALT) levels and one had HBsAg clearance. Only one patient had acute exacerbation of hepatitis B (ALT > 20 times normal range) but remained HbeAg negative. During follow-up, five patients became HBsAg positive; two reactivations of resolved hepatitis B, two with previous anti-HBS induced by vaccination, and one with no serological marker for HBV. Lamivudine was prescribed for 16 patients, two of whom had HbeAg clearance without seroconversion and five who developed viral resistance to Lamivudine after a mean of 29.2 months. No hepatocellular carcinoma or deaths related to hepatitis B were seen in this group. In summary, prevalence of HBV in kidney transplant patients was 4.2%. Immunosuppression after renal transplantation in HBV infection led to an increased risk of liver complications and changes in HBV serological status.     

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.