Peir-Haur Hung

Pegylated interferon α-2a versus standard interferon α-2a for treatment-naïve dialysis patients with chronic hepatitis C: a randomised study

Background: Chronic hepatitis C virus (HCV) infection is prevalent in dialysis patients, and standard interferon monotherapy is the current standard of care for such patients. Aim: To investigate whether pegylated interferon has a better therapeutic efficacy and safety profile than standard interferon in dialysis patients with chronic hepatitis C. Methods: 50 such patients were randomly assigned to receive either pegylated interferon α-2a 135 μg subcutaneously once per week or standard interferon α-2a 3 million units subcutaneously thrice per week for 24 weeks. The primary efficacy and safety end points were sustained virological response (SVR) by intention-to-treat analysis and treatment-related withdrawal rate during the study. Results: In univariate analysis, patients receiving pegylated interferon α-2a tended to have a higher sustained virological response (SVR) than those receiving standard interferon α-2a (48% vs 20%, p = 0.07). By using multivariate analysis, treatment with pegylated interferon α-2a (p = 0.02) and pretreatment HCV RNA level <800 000 IU/ml (p = 0.007) were independently predictive of an SVR. All patients failing to achieve a rapid virological response (RVR) could not achieve an SVR. In addition, patients receiving pegylated interferon α-2a had a significantly lower treatment-related withdrawal rate than those receiving standard interferon α-2a (0% vs 20%, p = 0.04). Conclusions: Pegylated interferon α-2a once weekly provides more effective and safer therapy than standard interferon α-2a thrice weekly for treatment-naïve dialysis patients with chronic hepatitis C.

Pegylated Interferon-α2a With or Without Low-Dose Ribavirin for Treatment-Naive Patients With Hepatitis C Virus Genotype 1 Receiving Hemodialysis: A Randomized Trial

BACKGROUND Data are limited on the efficacy and safety of pegylated interferon plus ribavirin for patients with hepatitis C virus genotype 1 (HCV-1) receiving hemodialysis. OBJECTIVE To compare the efficacy and safety of combination therapy with pegylated interferon plus low-dose ribavirin and pegylated interferon monotherapy for treatment-naive patients with HCV-1 receiving hemodialysis. DESIGN Open-label, randomized, controlled trial. (ClinicalTrials.gov: NCT00491244). SETTING 8 centers in Taiwan. PATIENTS 205 treatment-naive patients with HCV-1 receiving hemodialysis. INTERVENTION 48 weeks of pegylated interferon-α2a, 135 µg weekly, plus ribavirin, 200 mg daily (n = 103), or pegylated interferon-α2a, 135 µg weekly (n = 102). MEASUREMENTS Sustained virologic response rate and adverse event-related withdrawal rate. RESULTS Compared with monotherapy, combination therapy had a greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95% CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs. 6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving combination therapy required a higher dosage (mean, 13 946 IU per week [SD, 6449] vs. 5833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-β than patients receiving monotherapy. The adverse event-related withdrawal rates were 7% in the combination therapy group and 4% in the monotherapy group (risk difference, 3% [CI, -3% to 9%]). LIMITATION Open-label trial; results may not be generalizable to patients on peritoneal dialysis. CONCLUSION In treatment-naive patients with HCV-1 receiving hemodialysis, combination therapy with pegylated interferon plus low-dose ribavirin achieved a greater sustained virologic response rate than pegylated interferon monotherapy. PRIMARY FUNDING SOURCE National Center of Excellence for Clinical Trial and Research.

Transient Elastography to Assess Hepatic Fibrosis in Hemodialysis Chronic Hepatitis C Patients

BACKGROUND AND OBJECTIVES Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan(®)) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard. RESULTS The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P<0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P=0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P=0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93-100%) and specificity (88-99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively. CONCLUSIONS TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.

Pegylated Interferon Alfa-2a Monotherapy for Hemodialysis Patients with Acute Hepatitis C

BACKGROUND Hemodialysis patients are at risk of hepatitis C virus (HCV) infection. However, little is known about the efficacy and safety of pegylated interferon (IFN) therapy for hemodialysis patients with acute hepatitis C. METHODS From 2005 through 2008, 35 hemodialysis patients with acute hepatitis C who did not have spontaneous clearance of HCV by 16 weeks were treated with pegylated IFN alfa-2a at a dosage of 135 microg weekly for 24 weeks. In contrast, 7 patients with clearance of HCV by 16 weeks were under observation only. Thirty-six hemodialysis patients from 2002-2005 who had acute hepatitis C but did not receive treatment served as historical controls. The primary efficacy and safety end points were sustained virologic response (undetectable HCV RNA levels at 24 weeks after therapy) by intention-to-treat analysis and treatment-related withdrawal. RESULTS The rate of sustained virologic response in the treatment group was significantly higher than the rate of spontaneous HCV clearance in the control group (88.6% vs 16.7%; P < .001). Two patients (5.7%) prematurely terminated treatment at 8 and 10 weeks because of constitutional symptoms, and both did not have sustained virologic response. All but one patient had rapid virologic response (undetectable HCV RNA levels at 4 weeks of therapy), and all patients who received >12 weeks of therapy had early and end-of-treatment virologic responses. All patients who had clearance of HCV by 16 weeks had undetectable HCV RNA levels until the end of follow-up. CONCLUSIONS Pegylated IFN alfa-2a monotherapy is safe and efficacious for hemodialysis patients with acute hepatitis C. It is suggested that patients without spontaneous clearance of HCV by week 16 should receive therapy.

Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial

Objective Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited. Design In this randomised trial, 172 patients received 24 weeks of peginterferon alfa-2a 135 μg/week plus ribavirin 200 mg/day (n=86) or peginterferon alfa-2a 135 μg/week (n=86). The efficacy and safety endpoints were sustained virological response (SVR) rate and adverse event (AE)-related withdrawal rate. Results Compared with monotherapy, combination therapy had a greater SVR rate (74% vs 44%, relative risk (RR): 1.68 [95% CI 1.29 to 2.20]; p<0.001). The beneficial effect of combination therapy was more pronounced in patients with baseline viral load ≥800 000 IU/mL than those with baseline viral load <800 000 IU/mL (RR: 3.08 [95% CI 1.80 to 5.29] vs RR: 1.11 [95% CI 0.83 to 1.45]; interaction p=0.001). Patients receiving combination therapy were more likely to have a haemoglobin level of <8.5 g/dL (70% vs 8%, risk difference (RD): 62% [95% CI 50% to 73%]; p<0.001) and required a higher dosage [mean: 13 417vs 6667 IU/week, p=0.027] of epoetin β to manage anaemia than those receiving monotherapy. The AE-related withdrawal rates were 6% and 3% in combination therapy and monotherapy groups, respectively (RD: 2% [95% CI −4% to 9%]). Conclusions In treatment-naive haemodialysis patients with HCV-2 infection, combination therapy with peginterferon plus low-dose ribavirin achieved a greater SVR rate than peginterferon monotherapy. Most haemodialysis patients can tolerate combination therapy. Trial registration number ClinicalTrial.gov number, NCT00491244.

Pegylated interferon α-2a plus low-dose ribavirin for the retreatment of dialysis chronic hepatitis C patients who relapsed from prior interferon monotherapy

Chronic hepatitis C (CHC) remains frequent in dialysis patients.1 Currently, interferon (IFN) monotherapy is the standard of care for dialysis CHC patients.2 In a previous paper published in the journal, we demonstrated that treatment with weekly pegylated IFNα-2a had a significantly higher sustained virological response (SVR) rate than that with thrice weekly standard IFNα-2a in such patients (48% vs 20%, p = 0.02).3 Although dialysis CHC patients responded better to IFN monotherapy than those with normal renal function, the overall SVR rates are far from satisfactory.4 5 Retreatment with pegylated IFN plus ribavirin in ordinary CHC patients who relapsed from prior standard IFN had an SVR rate of 52%.6 Among these patients, the SVR rates for genotype 1 and 2/3 patients were 47% and 63%, respectively. Although ribavirin is contraindicated in dialysis CHC patients for the risk of …

The ratio of aminotransferase to platelets is a useful index for predicting hepatic fibrosis in hemodialysis patients with chronic hepatitis C

Percutaneous liver biopsy is the gold standard for staging hepatic fibrosis of hemodialysis patients with chronic hepatitis C before renal transplantation or antiviral therapy. Concerns exist, however, about serious post-biopsy complications. To evaluate a more simple approach using standard laboratory tests to predict hepatic fibrosis and its evolution, we studied 279 consecutive hemodialysis patients with chronic hepatitis C and a baseline biopsy. Among them, 175 receiving antiviral therapy underwent follow-up biopsy to evaluate the histological evolution of fibrosis. Multivariate analysis of routine laboratory tests at baseline showed the aspartate aminotransferase-to-platelet ratio index was an independent predictor of significant hepatic fibrosis. The areas under curves of this ratio to predict fibrosis stages F2-4 were 0.83 and 0.71 in the baseline and follow-up sets; and 0.75 and 0.80 respectively, for patients with sustained or non-sustained virological response groups in the follow-up sets. By a judicious setting of cut-off levels for the baseline and non-sustained groups, and the sustained virological response group, almost half and 60 percent of the baseline and follow-up sets could be correctly diagnosed without biopsy. Our study found the aminotransferase-to-platelet ratio index is accurate and reproducible for assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C. Applying this simple index could decrease the need of percutaneous liver biopsy in this clinical setting.

Poor renal outcome of antineutrophil cytoplasmic antibody negative Pauci-immune glomerulonephritis in Taiwanese.

BACKGROUND/PURPOSE Pauci-immune glomerulonephritis (GN) is an important cause of crescentic GN, acute renal failure and mortality. However, data are limited on the clinical presentation and outcome in antineutrophil cytoplasmic antibody (ANCA) negative patients, especially in Asians. METHODS This retrospective study analyzed medical records and pathology slides of patients who received renal biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay was used routinely for ANCA testing in all patients. RESULTS Among 637 patients with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42 patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p = 0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that ANCA negativity was associated with less crescent formation (p < 0.001) but more chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p = 0.055). CONCLUSION This study illustrates the necessity for pathologic diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis associated with ANCA negativity in this study may be partly due to delayed diagnosis since these patients frequently lacked systemic involvement.

The aggressiveness of urinary tract urothelial carcinoma increases with the severity of chronic kidney disease

To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT‐UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end‐stage renal disease (ESRD) have a higher incidence of UT‐UC, but the relationship between early stages of CKD and characteristics of UT‐UC are less well known.

Association of hepatitis C virus infection and malnutrition–inflammation complex syndrome in maintenance hemodialysis patients

BACKGROUND Patients undergoing maintenance hemodialysis (MHD) have a significantly higher prevalence of hepatitis C virus (HCV) infection and malnutrition-inflammation complex syndrome (MICS). In the present study of Taiwanese MHD patients, we determined the clinical characteristics and influence of HCV infection on MICS by calculation of the malnutrition-inflammation score (MIS). METHODS This was a prospective longitudinal study performed at a single hemodialysis (HD) center in Taiwan from September 2007 through March 2008. The study enrolled 58 patients (38%) in the active HCV group and 95 patients (62%) in the non-HCV group. The two or three weekly HD sessions of all patients were followed for 7 months. The MIS was assessed using 10 components, 7 from the conventional subjective global assessment of nutrition and 3 additional elements, body mass index, serum albumin and total iron-binding capacity. RESULTS HD vintage and total MIS score were greater in patients with active HCV. The active HCV group had significantly longer dialysis vintage and lower total cholesterol but higher total MIS score than the non-HCV group. The MIS 5 score, a measure of major comorbid conditions (including number of years on dialysis), was also significantly higher in the active HCV group. CONCLUSION MHD patients with active HCV infections have more severe MICS-associated metabolic and physiological disease than MHD patients without active HCV infection.