[Natural history of HCV infection and risk of death in a cohort of patients on long-term hemodialysis]. / Storia naturale dell'infezione da HCV e rischio di morte in una coorte di pazienti in emodialisi da lungo tempo.

BACKGROUND: HCV infection represents the major cause of chronic liver disease in hemodialysis and renal transplant patients. The clinical course of liver disease in hemodialysis patients is generally asymptomatic. Only few studies describe the natural history of HCV infection in haemodialysis patients, showing an association between HCV infections and poor survival. METHODS: A prospective cohort study of our haemodialysis population was conducted to define the natural history of HCV infection and its relation to mortality. 77 patients on haemodialysis were enrolled, 24 (31%) of whom were anti-HCV and 53 (69%) anti-HCV-negative. RESULTS: The HCV-RNA was positive in 18 of the 24 anti-HCV-positive subjects (75%). None of the anti-HCV-negative subjects was HCV-RNA-positive. Eight of the 18 HCV-RNA-positive patients (40%) developed cirrhosis with portal hypertension and ascites within 7 years after the first increase of GPT. Seven of these died, nobody developed hepatocarcinoma (HCC). During 58+/-37-follow-up months mortality rate was higher among anti-HCV-positive patients than among anti-HCV-negative. Besides, the 6 deaths occurred only among anti-HCV-positive and HCV-RNA-positive patients. CONCLUSION: in our haemodialysis patient population the presence of antibodies anti-HCV and HCV-RNA is associated with an increased risk of developing liver cirrhosis and of death, in comparison to anti-HCV-negative patients. Our data show that anti-HCV-positive patients have an accelerated course towards chronic hepatopathy and cirrhosis.

Clinical pathological correlates of renal biopsy in elderly patients.

BACKGROUND: Reports have shown that well-defined histological patterns do not always correspond to equally clear clinical pictures, particularly so in elderly patients. METHODS: With the aim of assessing clinicopathological correlations in the population aged >65 years with that of lower age, we retrospectively analyzed computerized records of renal needle biopsies consecutively performed in the decade 1991-2000 in our unit. RESULTS: Among the 392 eligible subjects, there were 150 patients 65 years of age and more, 76 of whom were over 70. The average serum creatinine was 2.9 mg/dl, with values > 3.5 mg/dl in 25% of cases. The major indication to biopsy was nephrotic syndrome followed by chronic renal failure both in the young adult and the elderly population. The rapidly progressive form led more often to renal biopsy in the elderly patients, and the different prevalence was statistically significant (p < 0.05), as was the higher prevalence of urinary anomalies in the young-adult population. Regarding renal histology, the crescentic necrotizing forms were significantly more frequent in the elderly patients, while IgAN, minimal change disease and SLE predominate in young adults. The most relevant result is the greater prevalence of crescentic necrotizing glomerulonephritis in elderly patients, not only in the cases presenting clinically as rapidly progressive renal failure and acute renal failure, but also in those with the clinical picture of chronic renal failure. CONCLUSIONS: Re-evaluation of our case files verifies the importance of the bioptic approach in selected cases with stages 3-4 chronic kidney damage. This holds true especially for elderly patients.

Hepatitis C virus infection and acute or chronic glomerulonephritis: an epidemiological and clinical appraisal.

BACKGROUND: The relationship between hepatitis C virus (HCV) infection and acute or chronic glomerulonephritis (GN) is not well understood. METHODS: Two hundred and eighty-four patients with biopsy-proven GN and other renal diseases were studied in a multicentre survey performed during the period 1992-1995. Several clinical parameters were collected for each patient at the time of renal biopsy. We made a multivariate analysis by logistic regression model to evaluate the independent association of clinical and histological patient characteristics with HCV infection, as detected by anti-HCV antibody testing. In addition, three patients with HCV-related liver disease, membranous nephropathy, and proteinuria in the nephrotic range received therapy with interferon-alpha in standard doses. RESULTS: The prevalence of anti-HCV positivity was 13% (38/284). The frequency of anti-HCV positivity ranged between 0 and 100% in the different types of renal diseases, the difference was statistically significant (P = 0.0001). The anti-HCV rate was significantly higher in patients with cryoglobulinaemic membranoproliferative and mesangioproliferative GN than among the other individuals (14/14 (100%) vs 24/270 (9%), P = 0.0002). Our multivariate analysis by logistic regression model showed that age (P = 0.0017) and type of renal diseases (P = 0.0007) were independently and significantly associated with anti-HCV antibody. At the completion of treatment with interferon-alpha, 67% (2/3) of patients with membranous nephropathy had lowering of hepatic enzyme levels into the normal range whereas 100% (3/3) of these did not show significant reduction of proteinuria. CONCLUSIONS: We observed strong association between HCV infection and cryoglobulinaemic GN. Age and type of renal disease were important independent predictors of anti-HCV positivity in our cohort of patients. Three anti-HCV-positive patients with membranous nephropathy did not show significant remission of nephrotic proteinuria after treatment with interferon-alpha. Our data do not appear to support an association between HCV and non-cryoglobulinaemic GN. Further epidemiological surveys, experimental studies and clinical trials are warranted to fully elucidate the role of HCV in non-cryoglobulinaemic GN.

Signal-averaged ECG abnormalities in haemodialysis patients. Role of dialysis.

BACKGROUND: Late potentials (LP) on the signal-averaged electrocardiogram (SAECG) are predictive of malignant ventricular arrhythmias and sudden cardiac death in patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction, both regional and global, as well as supraventricular and ventricular arrhythmias are reported in a high percentage of patients with end-stage renal failure (ESRF). The aim of the study was to assess the prevalence of LP and the effects of haemodialysis on the SAECG of ESRF patients. METHODS: SAECG was recorded immediately before and within 30 min after the end of dialysis in 48 patients in sinus rhythm, free of conduction disturbances on ECG and of signs of congestive heart failure. Serum electrolytes were sampled together with the SAECG recordings. An echo-Doppler exam was performed within 2 weeks of the study. SAECGs were adequate for analysis in 45/48 patients. LP were present when at least two of the following criteria were fulfilled: QRS duration < or = 115 ms, LAS40 < or = 38 ms, RMS40 > or = 38 microV at 40 Hz high pass bidirectional filter, and noise <0.7 microV. RESULTS: LP were detected in 12/45 patients (25%) on the SAECG before dialysis; of these 12 patients, seven had a history of a previous myocardial infarction and two had documented coronary artery disease (CAD). A significant greater wall motion score index--calculated on a 16 segment model--was reported in patients with LP (1.20+/-0.20 vs 1.01+/-0.03, P<0.01), while left ventricular mass was comparable in the two groups of patients. At the end of dialysis, a significant prolongation of fQRS duration was found both at 25 and 40 Hz filters (from 98+/-11 to 106+/-16 ms and from 97+/-12 s to 102+/-13 ms, respectively, P<0.001). A significant inverse relationship was seen between the percentage of dialysis-induced serum potassium reduction and fQRS changes at 40 Hz (r=-0.68, P<0.001). CONCLUSIONS: LP were detected in a significant proportion of dialysis patients, probably related to underlying CAD with left ventricular dysfunction. Prolongation of fQRS after dialysis could be explained by the acute reduction in serum potassium levels.

Convective treatments with on-line production of replacement fluid: a clinical experience lasting 6 years.

BACKGROUND: The introduction of techniques with on-line (OL) production of replacement fluid by filtration of dialysis fluid raises concerns about exposure of dialysis patients to pyrogenic substances. This work was undertaken to evaluate safety and feasibility of OL preparation of replacement fluid for haemodiafiltration (HDF). METHODS: OL HDF was carried out with commercially available monitors without any adjustment in the operational organization of our Centre. Bicarbonate dialysis fluid was filtered twice before being reinjected into the patients. The effects of acute load of OL fluid were assessed by very sensitive in vitro and in vivo tests; the chronic effects were assessed by monitoring the patients for the appearance of any untoward clinical manifestations and by measuring their cytokine response. RESULTS: In a pilot study the membrane filter culture technique of replacement fluid yielded no bacteria or mycetes growth, while LAL test was < 0.01 EU/ml. The normal human monocyte production of TNF alpha, IL-1 beta and IL-1Ra was not significantly different when cells were incubated with OL or commercial replacement fluid. The patients' body temperature profile (continuous recording during treatments and the following 24 h) overlapped with that of the control procedure. Over 6 years we performed 4284 OL treatments (total amount reinjected fluid 102,900 litres) on 13 patients treated for 26 +/- 9 months. In none of these treatments did we observe pyrogenic reactions. In comparison with the previous period on standard bicarbonate haemodialysis, OL HDF afforded significantly better cardiovascular tolerance to fluid removal and higher Kt/V values. The nutritional status did not deteriorate, while the acute-phase reactants and serum beta 2M levels did not increase. Moreover, no translucent cysts or destructive arthropathy were observed on bone X-rays. The patients' plasma cytokine levels and monocytes cytokines production, measured either before or after a single OL HDF, were comparable with the values obtained in controls treated with standard HDF. CONCLUSIONS: We conclude that OL-prepared replacement fluid is as safe as that of the commercial bags with regard to sterility and non-pyrogenicity. OL HDF can be readily implemented in any dialysis centre without bringing any further burden on the staff.

Circulating growth hormone and insulin-like growth factor-I in nonalcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm.

Adult liver is considered the major source of circulating insulin-like growth factor-I (IGF-I). Growth hormone (GH) exerts its effects by stimulating IGF-I release from the liver, which then mediates the somatogenic actions in target tissues. In turn, circulating IGF-I levels operate a negative feedback mechanism on GH release. In cirrhotic patients, single daily determinations, performed after an overnight fast, indicated that serum IGF-I are decreased, whereas GH levels are increased. To verify whether this phenomenon occurs through the 24-h period, we have studied the profiles of GH and IGF-I in cirrhotic patients with or without superimposed hepatocellular carcinoma (HCC) and in a group of control subjects. The results of the present studies suggest that in cirrhotic patients, the above changes are constantly present through the 24-h period, and are associated with a loss of circadian rhythm for both GH and IGF-I. These data are consistent with a failure of the liver to synthesize and release IGF-I in response to GH. In addition, the presence of constantly higher IGF-I levels in cirrhotic patients with superimposed HCC, compared with cirrhotic patients without HCC, raises the hypothesis of a causal relationship between IGF-I and the development of HCC.

[Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study]. / L'emisuccinato dell'acido ursodesossicolico nel trattamento dell'epatite cronica attiva. Studio clinico-terapeutico controllato.

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.