Interferon treatment on glomerulonephritis associated with hepatitis C virus

We report on a 10-year-old girl with glomerulonephritis associated with hepatitis C virus infection, who was treated with interferon-α. On the first renal biopsy at 8 years of age, mild mesangial hypercellularity in a segmental to semiglobal pattern was present in all glomeruli. After 6 months interferon-α therapy, proteinuria diminished completely. However, mesangial proliferation was advanced on the second biopsy at 10 years of age. We concluded that the interferon-α was effective in the treatment of proteinuria despite the lack of pathological improvement. Received: 15 March 2000 / Revised: 11 July 2000 / Accepted: 14 July 2000     

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.     

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.     

Incidence and risk factors of hepatitis C virus infection in a haemodialysis unit

BACKGROUND: Hepatitis viruses have become one of the main infectious problems in patients on maintenance haemodialysis. The aim of this study was to prospectively investigate the incidence of de novo hepatitis C virus (HCV) infection in a haemodialysis unit and to identify factors currently involved in HCV transmission to haemodialysis patients. METHODS: One hundred and fourteen anti-HCV negative and HCV-RNA negative patients who started long-term haemodialysis were followed for a mean period of 36 months (range 18- 56). Liver tests and anti-HCV were performed at 6-month intervals. Factors that might be implicated in HCV transmission, such as blood transfusions, sexual habits, surgery and other invasive procedures, were recorded. HCV markers were re-examined in transfused blood and the HCV genotype was investigated in seroconverters to anti-HCV and in patients with previous HCV infection who were treated in the vicinity of those who seroconverted. RESULTS: Eight patients (7%) seroconverted to anti-HCV and seven of them became HCV-RNA positive. HCV markers, including HCV-RNA, were negative in the blood transfused to seroconverters. No differences between seroconverters and non- seroconverters. No differences found in other risk factors not directly related to haemodialysis. The investigation of HCV genotype suggested that HCV transmission was not restricted to patients treated in the vicinity of previously HCV infected patients. Occasional failure to observe strict measures of asepsis was detected in the haemodialysis unit and this was the only factor that might be incriminating. CONCLUSIONS: HCV acquisition in patients on haemodialysis is currently not related to blood transfusion, and nosocomial transmission within the haemodialysis unit seems to be the main mechanism of HCV infection. Extremely careful observation of preventive measures seems essential to eradicate HCV transmission in haemodialysis units.      

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.     

Individualized treatment of hepatitis C virus infection

The current treatment of chronic hepatitis C since several years, the association of pegylated interferon and ribavirine, allows to obtain a virological eradication in around 55% of patients, including 45% of those infected with the genotype 1. The cure, defined by an undetectable viremia 24 weeks after the discontinuation of treatment, is associated to an improvement of the prognosis of the patients with a decrease of mortality and morbidity. If the virologic recovery allows fibrosis regression, including cirrhosis reversal, why not to treat every HCV-infected patient? Because first therapy is not mandatory in all the patients (minim liver disease, co-morbidities which may be contraindications to therapy), second adverse events are frequent and may be severe, third costs are high (the antiviral treatment but also hematological growth factors…) and finally the treated patients do not recover constantly. This has resulted in personalized therapies based on the severity of the disease, the early viral kinetics, pharmacologic monitoring, genetic and immunological factors. In addition to these factors of personalization, the development of new anti-viral C molecules, the protease inhibitors (boceprevir or telaprevir which are about to be approved in combination with pegylated interferon and ribavirine) will allow to achieve a sustained virologic response in around 75% of cases.     

Interferon combined with cyclosporine treatment as an effective countermeasure against hepatitis C virus recurrence in liver transplant patients with end-stage hepatitis C virus related disease

Hepatitis C virus (HCV) is the most common cause of end-stage liver disease in transplant recipients. Progression of recurrent HCV infection is accelerated. Cyclosporine is not only an immunosuppressive drug, but also an anti-HCV drug. We reported here the beneficial effect of combined interferon and cyclosporine treatment for chronic hepatitis C. We recommend this protocol for established HCV-related graft disease.     

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.     

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.     

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.     

Occult hepatitis C virus infection among hemodialysis patients

Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.     

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.     

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.     

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.