Sameer Huraib

Interferon-α in chronic hepatitis C infection in dialysis patients

Abstract This study assesses the efficacy and adverse effects of interferon-α (IFN-α) administered at a dosage of 3 million units three times weekly for 1 year in 17 hemodialysis patients with hepatitic C virus (HCV)-associated chronic hepatitis (biopsy proven). The patients were prospectively followed up for a period of 18 months. Liver biopsy was repeated after 6 months of treatment in 13 patients. Patients were classified according to the histological activity index. Biochemical and virological responses were evaluated at the end (end-of-treatment response) and 6 months after completion of therapy (sustained response). HCV RNA became negative in 76% of the patients after 12 weeks of treatment, in 88% after 12 months of treatment, and in 71% of the patients 6 months after completion of therapy. HCV genotype 4 was found in 60% of our population. Alanine aminotransferase (ALT) levels were initially increased in only 6 patients and normalized in 4 of these patients after 12 weeks of therapy, with end-of-treatment and sustained biochemical responses of 83% and 67%, respectively. Of 13 patients who underwent liver biopsies after 6 months of therapy, 11 patients (85%) showed histological improvement. One patient could not tolerate therapy because of marked lethargy and myalgia; the other patients had minor side effects that did not require discontinuation of treatment. Two patients received a cadaveric renal transplant after 1 year of IFN treatment, and they continued to maintain biochemical and virological responses after a follow-up of 17 and 28 months, respectively.

Interferon-alpha facilitates renal transplantation in hemodialysis patients with chronic viral hepatitis

Interferon-alpha has not been used previously in hemodialysis patients with chronic hepatitis B and C. This uncontrolled report evaluates the biochemical and/or histologic profile resulting from the administration of interferon-alpha in seven hemodialysis patients, two with chronic hepatitis B and five with hepatitis C. Biochemical improvement was noted in all patients. Histologic progression did not occur in the two cases in which such assessment was made, and five of them were subsequently transplanted without recurrence of disease.

Sustained Virological and Histological Response with Pretransplant Interferon Therapy in Renal Transplant Patients with Chronic Viral Hepatitis C

Patients who are anti-HCV positive before renal transplantation (Tx) have a significantly increased risk of posttransplant liver disease. We conducted a prospective, controlled study to evaluate the posttransplant outcome of renal graft candidates with HCV-associated chronic hepatitis (n = 30). Patients were randomly assigned to either of two groups. All patients on enrollment underwent liver biopsy, which showed mild-to-moderate hepatitis activity (mean 4.1, range 2–6). Half the patients received interferon-alpha (IFN-a) administered at a dosage of 3 million units three times weekly for 1 year. Liver biopsy was repeated for treated patients at the end of IFN-a treatment. Of these, 11 patients received renal transplant (group A). The other half did not receive IFN-a and to date 10 patients have been transplanted (group B). Renal transplant recipients were prospectively followed for a period of 12 months and a follow-up liver biopsy was also done at the end of this period (end of study). Biochemical and virological responses were evaluated and the histologic activity index (HAI) scoring according to Knodell was assessed. The mean pretreatment serum HCV RNA level was 1.14 ± 0.84 and 1.0 ± 0.89 mEq/ml for groups A and B, respectively (bDNA assay sensitivity threshold is <0.2 mEq/ml). HCV RNA became undetectable in 4 patients of group A. At the end of study period the mean quantitative HCV RNA titers were 1.43 ± 4.07 and 15.18 ± 11.08 mEq/ml in groups A and B, respectively (p < 0.0001). In group A, the mean HAI score decreased from 4.27 ± 1.19 to 1.64 ± 0.67 after IFN-a treatment (p < 0.0001). This score was maintained till the end of the study period with a mean of 1.82 ± 0.6. Mean HAI score of group B on enrollment was 3.9 ± 1.2 and at the end of study increased to 5.5 ± 1.35 (p = 0.01). There was statistically significant difference (p value less than 0.0001) between the HAI scores at the end of the study period between the two groups. These results demonstrate that interferon therapy while on dialysis is associated with less viremia and decreased progression of chronic liver disease in renal transplant patients with hepatitis C.

Percutaneous Needle Biopsy of the Transplanted Kidney: Technique and Complications

Over 11 1/2 years, 420 percutaneous needle biopsies were obtained from the transplanted kidneys of 205 patients at one institution. The procedure was performed by one nephrologist and 55 nephrology trainees. No limit was placed on the number of biopsies performed on one kidney, and the highest number was seven. The complications were macroscopic hematuria in 28 biopsies, prolonged hematuria (greater than 24 hours) in eight, transient anuria in five, and prolonged anuria requiring surgical intervention in one. Perinephric hematoma occurred in three patients; retroperitoneal hematoma led to compression of the iliac vein in one. None of these complications led to loss of the transplant. It is suggested that the freedom from serious complication is related to the safety of the technique and the precautions applied to preparation of the patient. These are described in detail.

Effect of Vitamin-E-Modified Dialysers on Dialyser Clotting, Erythropoietin and Heparin Dosage: A Comparative Crossover Study

We performed a crossover study to compare the effects of different dialysis membranes on 20 patients with frequent dialyser clotting and requiring >5,000 units of heparin per dialysis session. Low-flux dialysers are C15NL (cellulose - Terumo) and E15NL (vitamin-E-coated - Terumo) while high-flux dialysers were F60 (polysulphone) and EE15NL (vitamin-E-coated - Terumo). Ten patients underwent dialysis for 2 months with C15NL then switched to E15NL for 2 months. Similarly, the other 10 patients were started on the high-flux dialyser F60 and then switched over to EE15NL for 2 months. The following parameters were measured at the beginning of the study, 2 weeks, 1 month and then at 2 months: hemoglobin, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, protein C, protein S, antithrombin III (ATIII) and factor 12 activity. Dialyser clotting, heparin and erythropoietin requirements were assessed during each dialysis session. There was a significant reduction in clotting with E15NL in comparison to C15NL (22.8 +/- 17 and 44.1 +/- 22.8 (p = 0.0233), respectively). Similarly, heparin requirements were less in the vitamin-E-coated (E15NL) dialysers, 4,754 +/- 1,427 vs. 6,011 +/- 856 units (p = 0.0281) and erythropoietin usage was also significantly reduced, 4,630 +/- 2,620 vs. 7,850 +/- 4,069 units (p = 0.049). There was a significant increase in hemoglobin with E15NL compared to C15NL, 115 +/- 10.4 vs. 108 +/- 13.1 (p = 0.0343). When the high-flux dialysers were compared there was a tendency towards less dialyser clotting with the EE15NL compared to F60, though this did not achieve statistical significance (p = 0.0561). We could not demonstrate any significant changes between the different dialysers with regards to PT, PTT, fibrinogen factor 12 activity, protein C, protein S and ATIII. In conclusion, we have shown that the use of vitamin-E-modified dialysers is associated with less clotting in patients with persistent clotting problems. In addition, this was associated with less heparin and erythropoietin requirements.

Reversible uremic deafness : Is it correlated with the degree of anemia?

Hearing loss is a common finding in patients with end-stage renal failure. Uremic toxins, ototoxins, and axonal uremic neuropathy appear to be likely pathogenic factors. We analyzed whether an improvement in hearing capacity can be achieved with an improvement of anemia by erythropoietin (EPO) administration. Fifty patients on long-term hemodialysis in a single center were examined audiologically by otoscopy, tympanometry, pure tone audiometry, and the short increment sensitivity index. Twenty-five patients were treated with EPO in a dose of 120 U/kg per week over a period of 5 to 8 months, and the remaining 25 patients were not treated with EPO (controls). Both groups were reexamined audiologically after the study period, and the results were compared. In the group treated with EPO, the hemoglobin level increased from 7 ± 0.9 to 11 ± 0.8 g/dL, as against the control group, whose hemoglobin increased from 7.1 ± 0.9 to 8 ± 0.8 g/dL. The audiologic tests were repeated at the end of the study period, and a significant improvement of hearing was found in the patients treated with EPO as compared with the control group (p < .001). Our study suggests that improvement of anemia in patients on long-term hemodialysis by administration of EPO is associated with an improvement in hearing capacity in a significant number of patients. Thus, anemia seems to be an important factor responsible for hearing disorders in patients with end-stage renal failure. Studies with larger numbers of patients are required to confirm this observation.

ANTI-HCV POSITIVE HEMODIALYSIS PATIENTS: CLINICAL, BIOCHEMICAL, HISTOLOGIC AND VIROLOGIC STUDY AND A PROPOSED MANAGEMENT SCHEME

The significance of suchfindings is not totally understood; this may reflect eitherpast, resolved infection, or active infection with viralreplication and chronic hepatitis. There is incomplete dataon the clinical, biochemical, histological and virologicfeatures of these patients. In addition, there are no reportsthat address all these issues simultaneously in the samegroup of patients. The significance of anti-HCV positivityin hemodialysis units is important for the followingreasons: 1) these patients are potentially kidney transplantcandidates; 2) many of these patients exhibit no clinical orbiochemical abnormalities of the liver;

Efficacy of fosinopril in the control of 24-hour blood pressure in hemodialysis patients using ambulatory blood pressure monitoring

Abstract Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was used to assess the efficacy and tolerability of fosinopril, an angiotensin-converting enzyme inhibitor, in 20 hemodialysis patients (12 men, 8 women; aged 28 to 64 years [mean, 54 ± 9 years]) with mild-to-moderate hypertension. After a 4-week washout period, during which the lowest possible dry weight was achieved, patients were given fosinopril 10 mg/d orally if their preanalysis blood pressure (BP) was ≥140/90 mm Hg. If BP was not controlled, the dosage was increased every 2 weeks as needed to a maximum of 40 mg/d. Fosinopril was administered for a total duration of 12 weeks. ABPM was done at the beginning of the study and repeated after 6 and 12 weeks of treatment. Significant changes in mean 24-hour systolic and diastolic BP were seen from baseline to week 12 (from 150.3 ± 4.8 to 138.2 ± 3.1 mm Hg and from 95.0 ± 2.8 to 84.3 ± 3.1 mm Hg, respectively) ( P P