Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

Association Between Hepatitis B Virus and Chronic Kidney Disease: a Systematic Review and Meta-analysis

Abstract: Background. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection with hepatitis B virus impacts on the development and progression of chronic kidney disease. Aim. To evaluate the effect of infection with HBV on the risk of chronic kidney disease in the general population. Material and methods. We conducted a systematic review of the published medical literature to determine if hepatitis B infection is associated with increased likelihood of chronic kidney disease. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis B virus across the published studies. Meta-regression and stratified analysis were also conducted. Results. We identified 16 studies (n = 394,664 patients) and separate meta-analyses were performed according to the outcome. The subset of longitudinal studies addressing ESRD (n = 2; n = 91,656) gave a pooled aHR 3.87 (95% CI, 1.48; 6.25, P < 0.0001) among HBV-infected patients and no heterogeneity was recorded. In meta-regression, we noted the impact of male (P = 0.006) and duration of follow-up (P = 0.007) upon the adjusted hazard ratio of incidence of chronic kidney disease (including end-stage renal disease). No relationship occurred between HBV positive status and prevalent chronic disease (n = 7, n = 109,889 unique patients); adjusted odds ratio, were 1.07 (95% CI, 0.89; 1.25) and 0.93 (95% CI, 0.76; 1.10), respectively. Conclusions. HBV infection is possibly associated with a risk of developing reduced glomerular filtration rate in the general population; no link between HBV sero-positive status and frequency of chronic kidney disease or proteinuria was noted in cross-sectional surveys.

Prevalence of hepatitis B and C among patients of chronic renal failure on hemodialysis, and role of appropriate screening test, in Sheikh Zayed Medical College/Hospital, Rahim Yar Khan

To determine prevalence of hepatitis-B and C among patients of CKD on hemodialysis in Sheikh Zayed hospital Rahim Yar khan and assess screening methodology for hepatitis-B and C before hemodialysis in this tertiary care hospital. This descriptive study conducted at the hemodialysis section of Sheikh Zayed Hospital, Rahim Yar Khan from January 2008 to December 2008. All the patients of chronic renal failure who were admitted in medical ward either from OPD, Emergency or from private clinic of consultants they were all screened for hepatitis-B and C by kit method using technique after getting consent for testing during 2008. A total of 190 patients were screened, all patients were re-evaluated for hepatitis-B and C detection on three months basis along with liver enzymes. Among 190 patients 82.6% belongs to RYK while only 17.4% are from other areas. Out of 190 patients 127 were males and 63 were females. And 45% were between the age of 30 to 50 years. 25% were above 50 years of age while 27% were below 30 years. Only one patient was above 80 year. Out of 190 patients 74.7% [142] were BC-ye. 18.9% [36] were c+ve. 5.8% [11] were B+ve. And only 0.5% [01] patient was BC+ve. Hepatitis-B and C detection should be repeated on six month interval along with liver enzyme as CRF patients are more exposed to Hepatitis-B and C. This study gives good idea about proper prevention in these patients where prognosis become more poor when CRF is superadded with B and C infections

Hepatitis B infection in renal disease

Chronic hepatitis B virus [HBV] infection in renal patients could result from nosocomial transmission and outbreaks in dialysis units. Vaccination, universal precautions, regular virologic screening and segregation policy are important and effective control of HBV infection in hemodialysis unit. Chronic HBV infection poses problem to dialysis patients, their diagnosis, treatment of hepatic complications and pre-transplant management. This review summarizes the chronic HBV epidemiology, extrahepatic manifestations, management and prevention

Hepatitis G virus [HGV] infection in Saudi dialysis patients and healthy controls

Viral hepatitis is a global health problem with a high mortality rate. End stage renal disease [ESRD] patients have a high prevalence of Hepatitis B and C virus infection. Present study was done to identify the prevalence and course of a new isolate Hepatitis G virus [HGV] infection in Saudi dialysis patients. The pattern of viral hepatitis infection [HBV, HCV and HGV] was investigated in 109 Saudi patients with ESRD and 100 healthy Saudi blood donors. Donated blood was tested for markers of Hepatitis B, C and G viruses. Liver functions were measured and blood picture and liver biopsies were also performed at regular intervals. Out of the 109 ESRD patients 68 [62.4%] were positive for at least one viral marker: 59 [54.1%] were positive for HCV, six [5.5%] were positive for HGV and three [2.8%] were positive for HbsAg. Four of the six HGV positive patients were also co-infected with HCV. Eight [8%] of the blood donors were positive for at least one viral marker. Elevated ALT levels [>4times normal] were recorded in four out of the six HGV-positive patients including three co-infected with HCV. Our results are in agreement with similar studies from different countries and also raise the question about the causal relationship between HGV and liver disease among dialysis patients

Hepatitis C virus [HCV] antibodies in patients with chronic renal failure and treated with regular hemodialysis and those treated with renal transplantation

This work was carried out to study the prevalence of hepatitis C Virus [HCV] infection, its associated risk factors and possible routes of transmission in chronic renal failure patients treated with either regular hemodialysis or renal transplantation. Seventy patients and 20 normal controls were included in this study. Patients were classified into 2 groups: Group I: 50 hemodialysis patients [HD group] and Group II: 20 renal transplant recipients [RTR group]. Each individual was subjected to full clinical examination, estimation of serum alanine aminotransferase [ALT], testing for antibodies to hepatitis C virus [anti-HCV] by ELISA 2nd generation, screening for hepatitis B surface antigen [HBsAg], antibodies to hepatitis B surface antigen [anti-HBs] and core antigen [anti HBc] by modified ELISA technique. Anti-HCV was found in 72% of hemodialysis patients and 65% of renal transplant patients and in 15% of the control group. There was a significant correlation between the presence of anti-HCV and the duration on dialysis in HD and RTR groups [P < 0.05 in both], while no significant correlation was detected between HCV positive cases and the number of units of transfused blood in HD and RTR groups [P > 0.05 in both]. Serum ALT was elevated in patients with HCV infection, but there was no significant correlation between the presence of anti-HCV and elevated ALT level among the examined groups of patients [P > O.OS in both]. The prevalence of HCV infection was not correlated with the duration of renal transplantation [P>0.05] and the type of immunosuppressive therapy [P > 0.05]. Coinfection with HBV and HCV could occur, as previous infection with HBV was demonstrated. Anti-HBc was found in 33.3% and 30.8% of anti-HCV positive patients in both HD and RTR groups respectively. Anti-HBs was detected in 25% and 15.4% of anti HCV positive in HD and RTR groups. HBsAg was found in 5.6% of anti-HCV positive hemodialysis patients. From this study we concluded that there are high prevalence of antibodies to HCV in serum of these patients with CRF whether treated with regular hemodialysis or with renal transplantation. This may mean high prevalence of HCV infection in these patients. Also it is found that the duration of hemodialysis rather than the number of units of blood transfusion is the main risk factor and that the transmission in hemodialysis units is the most important rather than by blood transfusion although its importance. Also we may recommend [1] All the hygienic measures to prevent spread of hepatitis C virus infection in these patients and treatment of cases. [2] Separate dialysis machines should be used for anti-HCV positive patients as we do for HBsAg positive patients. [3] Routine application of PCR technique in these patients may be useful for accurate diagnosis of the HCV infection. [4] Retrospective study on large number of transplanted patients for all risk factors of HCV infection, in addition to study the causes of this relatively high prevalence of infection inbetween them

Hepatitis B, C and D virus infections in patients and staff in Assiut dialysis unit

Thorough history was taken from 50 HD patients and 30 staff members with special stress on the risk factors that may contribute to hepatitis virus infection in addition to clinical examination, abdominal ultrasound, serological detection of viral markers and liver transaminase estimation. The high percentage of HCV-Ab [74%] and HBs Ag may be due to exposure of uremic patients to various risk factors for virus transmission prior or during HD. The percentage of HCV-Ab [13.3%] in dialysis staff matches that in the community and the absence of HBs Ag could be explained by staff vaccination against HBV

Prevalence of hepatitis cantibodies and hepatitis B markers in Iraq haemodialysis patients

Blood sera from 100 patients on chronic haemodialysis program, cited at Baghdad teaching hospital, Adnan teaching hospital and Al-Yarmouk teaching hospital were collected during the period from November 1994 till July 1995. All sera were tested for anti-HSV [3rd generation ELISA test], HBsAg and IgM anti-HBc. It was found that 62% of the sera were positive for anti-HCV, 30% were positive for both HBsAg and IgM anti-HBc. The seropositivity for both HBsAg and anti-HCV were 15% indicating high prevalence of co-infection of HBV and HCV infection. However 23% of the total sera showed no virological markers

Incidence of hepatitis C virus [HCV] antibodies among haemodialysis patients and staff members

50 patients with chronic renal failure on maintenance hemodialysis, 25 staff members dealing with these patients, and 15 control subjects were examined for anti-HCV using a second generation ELISA test. The incidence was 56% among on hemodialysis program, and 8% for the staff members, while it was nil among healthy subjects 14. 28% of the positive HCV were concurrent carriers of HBs Ag as compared to 4. 58% HBs Ag carriers among HCV negative subjects. We found no significant association between anti-HCV positivity and whether the patients had blood transfusion or not. The incidence of anti-HCV in hemodialysis patients increased with the duration' of dialysis and with the volume of blood transfusion. So, it is recommended to instruct blood banks to add anti-HCV [second generation] testing to their essential tests. Also, every patient undergoing hemodialysis must be examined for anti-HCV and positive cases should be isolated to be dialysed in a separate machine. staff members of dialysis units should be a separate staff, and examined periodically to detect any anti-HCV positive cases

Hepatitis B and hepatitis C viral infections among Egyptian hemodialysis patients: study on some of the contributing factors

In this work we studied the incidence of hepatitis B virus [HBV] and hepatitis C virus [HCV] infections among 150 Egyptian hemodilaysis patients, 70% of them had hepatitis viral infections, 73% were HBV infected, 8% were HCV infected and 25% had combined HBV and HCV infection. When investigating the possible contributing factors, blood transfusion and prolonged hemodialysis were found significantly associated with HCV infection [P<0.05]. Two serum liver function tests were studied as possible non invasive predictors for these viral infections in such patients; the elevated s. bilirubin level was found non significantly associated with HCV infection while elevated sGPT was found significantly associated with HCV infections. These viral infections could be easily predicted by serum biochemical tests, should be screened periodically and precautionary steps have to be set up to reduce the high incidence of infection

impact of CMV seropositivity on T-cell subpopulations in patients with end stage renal failure

Thirty-eight patients with end stage renal failure, half of them were CMV IgM seropositive and the other half with CMV IgM seronegative, all together with 27 normal controls, were studied. T cell subpopulation was assayed by specific monoclonal antibodies for T4 and T8. The result showed decrease in the absolute number of T4 [602 +/- 132 and 680 +/- 210 cells/mm 3] for the dialysis population compared to the normal controls. The absolute number of the T8 cells was also decreased [347 +/- 95 and 452 +/- 68 cells/mm 3] for the dialysis and controls, respectively. The T4/T8 ratio was found preserved 1.6: 1 and 1.5: 1 in the dialysis population and controls. A marked decrease was found in the absolute number of helper T4 for CMV seropositive patients [382 +/- 112] compared to the CMV seronegative ones [563 +/- 95] with slight difference in the absolute number of T4/T8 ratio in the seronegative patients [1.5: 1]. CMV infection seems to increase the immunosuppressive effect produced by uremic toxins making such patients more vulnerable for other opportunistic infections