New approaches in the therapy of hepatitis C in dialysis patients.

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis. The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma. Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.

Patterns of viraemia in haemodialysis patients with hepatitis C.

Clinical features, aminotransferases levels, and antibody to HCV have only limited correlation with the activity of liver disease and cannot accurately predict persistence versus eradication of the virus in haemodialysis patients. Although permanent loss of serum HCV RNA appears to correlate with resolution of the disease, little is known about the predictive value of a single HCV RNA value. The aim of the study was to evaluate the viraemia in the serum of HCV antibody positive haemodialysis patients during a period of 3 years. The study group consisted of 65 HCV antibody positive patients from our dialysis unit. HCV antibodies were measured every 6 months by ELISA third-generation assay. The presence of serum HCV RNA was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) once a year during the period of 3 years. Serum levels of aminotransferases were measured monthly with standard automated analyzers. There were three different patterns of viraemia after the third assessment of the serum HCV RNA in HCV antibody positive patients: 47% (30/65) were persistently HCV RNA positive, 38% (25/65) were intermittently HCV RNA positive, and 15% (10/65) were persistently HCV RNA negative. The dominant genotype was 1a, detected in 97% of the patients positive for HCV RNA. The HCV RNA persistently positive patients had significantly higher levels of ALT compared to HCV RNA persistently negative patients (50.07 +/- 30.0 vs. 28.5 +/- 10.0 U/L, p < 0.027). There was no significant difference between the three groups of patients according to age, haemodialysis duration, and serum levels of AST. This pattern of intermittent viraemia clearly showed that a single negative result of the presence of serum HCV RNA in an HCV antibody positive patient should not be taken as a proof of a persistent resolution of HCV. Thus, repeated testing for HCV RNA is necessary to assess viraemia accurately in HCV antibody positive patients. HCV antibody positive patients who were persistently serum HCV RNA negative could be potentially infectious because of the possibility of the persistence of occult hepatitis C.

Association between haemoglobin level and all-cause mortality in haemodialysis patients: the link with inflammation and malnutrition.

Although anaemia management has improved in haemodialysis (HD) patients in recent years, many of them still have haemoglobin (Hb) levels below the current recommendations. The consequent anaemia could be one of the links between malnutrition and inflammation, and higher mortality in HD patients. The study objective was to determine the relationship between Hb levels and outcome in patients undergoing HD, accounting for inflammation and malnutrition. We retrospectively analysed a total of 236 patients on HD between January 2003 and December 2005, classified by absence or presence of inflammation and malnutrition (defined as serum albumin levels < 40 g/L and CRP > 8mg/l). Serum levels of Hb, ferritin, creatinine, cholesterol, triglycerides, HDL (high-density lipoprotein cholesterol), LDL (low-density lipoprotein cholesterol), albumin and CRP were measured monthly, fibrinogen was measured every third month. Over the period of three years, 73 out of 236 patients (30%) had died, most from cardiovascular diseases (62%). Presence of inflammation and malnutrition (in 44% of patients) was associated with older age (60.69 -/+ 12.46 vs. 54.52 -/+ 12.37, p = 0.0002), lower levels of Hb (99.53 -/+ 14.97 vs. 111.86 -/+ 10.38 g/l, p = 0.0000), creatinine (835.88 -/+ 179.84 vs. 1069.98 -/+ 821.23-/+mol/l, p = 0.0047), albumin (36.58 -/+ 3.41 vs.40.32 -/+ 2.82 g/l, p = 0.0000), cholesterol (4.32 -/+ 1.04 vs. 4.75 -/+ 1.09 mmol/l, p = 0.0025) and higher levels of fibrinogen (4.94 -/+ 1.18 vs. 4.29-/+0.91g/l, p=0.0000) and CRP (30.42-/+29.47 vs. 5.24-/+4.89 mg/l, p=0.0000). The Kaplan-Meier analysis showed that, irrespective of the absence or presence of inflammation and malnutrition, the all-cause mortality was higher in patients with Hb <110g/l (Log-Rank, p=0.00147; p=0.00222). On the other hand, Kaplan-Meier showed that, irrespective of the absence or presence of anaemia (Hb > 110g/l and Hb < 110g/l), the all-cause mortality was higher in patients with the presence of inflammation and malnutrition (Log-Rank, p=0.00222; p=0.00263). The Cox proportional hazard analysis, adjusting for age, showed that only lower serum levels of Hb and higher CRP were associated with all-cause mortality (chi-square=110,306, p=0.0000). Our findings confirm the association of Hb levels < 110g/L with higher mortality among maintenance HD patients, especially in patients with the presence of inflammation and malnutrition. Further investigation of the relationships among anaemia, inflammation and malnutrition and survival is warranted.

Survival of patients on maintenance haemodialysis over a twenty-year period.

Patient survival is a key index of the overall adequacy of treatment in most chronic diseases. Analyses of survival of patients undergoing haemodialysis is very important, as it may offer clues and ideas for prolonging survival of patients with end-stage renal disease (ESRD). The aims of this study were to describe the characteristics of the patients on maintenance haemodialysis therapy over a period of 20 years, to determine the survival rate of these patients according to ages at the onset of haemodialysis, the primary renal diseases, and the cause of death, and to determine the survival rate at five, ten, fifteen and twenty years of haemodialysis treatment at our centre. The charts of 518 unselected patients, 282 male and 236 female, treated with maintenance haemodialysis therapy in a period of 20 years (1985-2005) were reviewed. At the time of evaluation, 164 patients were currently being treated, and 354 patients overall had been diseased. Statistical analysis was performed to evaluate the relationship between survival and patient characteristics such as age, gender, primary renal disease, and age at dialysis onset. Actual survival rates were determined by the Kaplan-Meier method. The survival rate of our patients treated with maintenance haemodialysis was 60% at 5 years, 37% at 10 years, 25% at 15 years and 9% at 20 years. Female patient survival was superior to male. Patients aged under 40 at the start of dialysis had a better survival probability compared to older patients. Patients with diabetes mellitus and nephroangiosclerosis, had a lower survival rate compared to patients with glomerulonephritis and with adult dominant polycystic kidney disease. Cardiac death was the most common cause of death in patients involved in the study. About 52% of the patients died from cardiovascular disease. Death is the most severe consequence of inadequate dialysis and can be used as an index of the adequacy of the dialysis therapy. Treatment factors that may improve outcomes include an early start of dialysis therapy, a high dose of dialysis (Kt/V over 1.2), correction of anemia, adequate protein and caloric intake, control of calcium and phosphate metabolism, and the use of biocompatible dialyzers.

Inflammation and anaemia as predictors of cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiovascular diseases are the most common causes of death among hemodialysis (HD) patients, yet the risk factors for these events have not been well established. Our study objective was to determine predictors of cardiovascular mortality, considering the non-traditional/disease-related and treatment-related/ cardiovascular risk factor in HD patients. MATERIAL AND METHODS: Disease-related cardiovascular risk factors, such as anaemia, calcium-phosphate disorders, nutrition-inflammation and treatment/dialysis-related cardiovascular risk factors such as HD dose, using the index Kt/V were analyzed in 214 patients on HD. Mortality was monitored prospectively over a two year period. RESULTS: Fifty-three of the 214 HD patients died during the follow-up period and the main cause of death was cardiovascular events (56.6%), followed by infection/sepsis (26.4%). The patients who died were significantly older than those alive, had significantly lower serum levels of hemoglobin (Hb), albumin and Kt/V. Serum levels of calcium, C-reactive protein (CRP) and fibrinogen were significantly higher in patients who died during the follow-up period. Kaplan-Meier analysis showed that the all cause and cardiovascular mortality was considerably higher in patients with Hb<110 g/l, albumin <40 g/l, CRP>8 mg/l and spKt/V<1.2 (log rank, p=0.000/p=0.000, p=0.000/ p=0.001, p=0.000/p=0.000, p=0.000/p=0.000), respectively. No difference in cardiovascular mortality was observed between the fibrinogen <4 g/l> levels. High CRP, low Hb levels and low spKt/V were significant predictors of all-cause mortality, but low albumin and high fibrinogen levels were not in the Cox proportional hazards analysis. When only cardiovascular mortality was entered into the Cox model, high CRP and low Hb levels were the only significant predictors for mortality. CONCLUSIONS: It can be concluded that, inflammation (elevated CRP) and anaemia (decreased Hb), were identified as significant independent non-traditional, disease-related cardiovascular risk factors that predict cardiovascular mortality in HD patients.

Determinants of utilization of antenatal care services in Kumbotso Village, northern Nigeria.

Women of childbearing age in a rural community in Kano state were interviewed to ascertain the determinants of utilization of antenatal care services in the village. Of the 200 women studied, 118 (59%) utilized antenatal care services during pregnancy. A majority (86%) of those who attained secondary school education, all of those with post-secondary education and 83% of those whose husbands had post-secondary education utilized antenatal care services.