Fibrosing cholestatic hepatitis (FCH) has been described as a specific manifestation of hepatitis B virus (HBV) infection in liver allograft recipients characterized by a rapid progression to liver failure. Only sporadic cases have been reported in other immunocompromised groups infected with HBV and in a few transplant recipients with hepatitis C virus (HCV) infection. We present the occurrence of FCH in 4 HCV-infected renal transplant recipients within a series of 73 renal transplant recipients with HCV infection followed up closely serologically and with consecutive liver biopsies. All 4 patients received the triple-immunosuppressive regimen (azathioprine, cyclosporine A, methylprednisolone). The interval from transplantation to the appearance of liver dysfunction was 1 to 4 months and to histological diagnosis, 3 to 11 months. The biochemical profile was analogous to a progressive cholestatic syndrome in 3 patients, whereas the fourth patient had only slightly increased alanine aminotransferase and ␥-glutamyl transferase (␥GT) levels. Liver histological examination showed the characteristic pattern of FCH in 2 patients, whereas the other 2 patients had changes compatible with an early stage. All patients were anti-HCV negative at the time of transplantation, whereas 2 patients, 1 with incomplete and 1with complete histological FCH features, seroconverted after 3 and 31 months, respectively. The patients were HCV RNA positive at the time of the first liver biopsy and showed high serum HCV RNA levels (14 to 58 ؋ 10 6 Eq/mL, branched DNA). HCV genotype was 1b in 3 patients and 3a in 1 patient. After histological diagnosis, immunosuppression was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months posttransplantation, whereas the seroconverted patients showed marked improvement of their liver disease, which was histologically verified in 1 patient. In conclusion, FCH can occur in HCV-infected renal transplant recipients. It seems to develop as a complication of a recent HCV infection during the period of maximal immunosuppression and is associated with high HCV viremia levels. There are indications that drastic reduction of immunosuppression may have a beneficial effect on the outcome of the disease.

Atrial fibrillation (AF), the most common sustained arrhythmia in clinical practice, is associated with increased mortality and cardiovascular morbidity both in nonuremic and (recently) in dialysis patients. The aims of this study are: (i) to assess the prevalence of AF, the risk factors, and predictors of its presence in a cohort of incident hemodialysis (HD) patients in Greece and (ii) to report on current practices in the management of these patients. This is a prospective, cross-sectional, multicenter study of 574 patients on a regular HD program for >6 months. Demographic characteristics, cause of renal disease, cardiovascular risk factors, medication use, dialysis data (Kt/V, dialysis method, type of dialysate), 12-lead electrocardiogram (ECG) (interdialytic day), and cardiac echo data were collected. Pertinent demographic, ECG, and echocardiographic data were entered into univariate and multivariate analyses to evaluate associations with AF. The CHADS2 score (congestive heart failure [HF], hypertension, age ≥ 75, diabetes, previous stroke/transient ischemic attack [TIA]) was estimated and clinical practices in high-risk (CHADS2 score ≥ 2) patients were evaluated. The cohort included 368 men (64.1%) and 206 (35.8%) women (mean age 65.1 ± 14.4 years) with a mean duration on dialysis of 72.1 ± 60.4 months. Hypertension (75.6%) and coronary artery disease (47.2%) were the commonest cardiovascular risk factors for AF. The prevalence of AF was 23.2% and showed an age-dependent increase; in patients <50 years, AF was present in 9.3%, while in patients ≥ 80 years, its prevalence increased to 36.4%. Furthermore, 8.3% of patients had permanent, 1.8% persistent, 12.7% paroxysmal AF, while the prevalence of paroxysmal atrial flutter and sick sinus syndrome were 1.2 and 2%, respectively. Logistic regression analysis showed that age, smoking, left atrial and aortic root diameter, β-blocker and α-calcidol use, HF, and the presence of valvular calcifications (VC) on cardiac echo were independently associated to the presence of AF. VC on cardiac echo had an almost sevenfold increased association with AF (odds ratio 6.72, 95% confidence interval 3.23-13.98, P < 0.0001). Only 25.5% of high-risk (CHADS2 score ≥ 2) patients were receiving anticoagulants. AF is a frequent arrhythmia in HD patients. Apart from well-known risk factors, VC merits special attention in this patient population. Less than one-third of high-risk AF patients receive anticoagulants, possibly reflecting the absence of definite guidelines for the management of AF in HD patients.

A progressive cholestatic syndrome due to bile duct damage and loss may develop in renal transplant patients with HCV infection. The occurrence of the lesions after the appearance of anti-HCV antibodies and the high HCV RNA levels are indicative of viral involvement in the pathogenesis. Withdrawal of immunosuppressive therapy may have a beneficial effect on the outcome of the disease.

We present two distinct types of cholestatic syndrome identified in eight renal transplant (RTx) patients with HCV infection. Four patients developed fibrosing cholestatic hepatitis (FCH) and four, vanishing bile duct syndrome (VBDS). All patients with FCH were anti-HCV (-) at the time of Tx and developed a cholestatic profile 1-4 months post-Tx, with high HCV-RNA levels. Immunosuppressive therapy was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months post-Tx, and the other two showed marked improvement and seroconverted to anti-HCV. Regarding the patients with VBDS, three were anti-HCV (-) and one was anti-HCV (+)/HBsAg (+) at the time of RTx. Two patients became anti-HCV (+) 1 year, and one patient, 3 years post-Tx. Two patients developed progressive VBDS and died of liver failure 2 and 3 years after onset, and two showed marked improvement after withdrawal of immunosuppression. In two of the patients, the progression of the disease coincided with elevation in serum HCV RNA levels. We concluded that a progressive cholestatic syndrome acquiring features of FCH or VBDS may develop in HCV-infected RTx patients. The association with high viral load implicated the virus in the pathogenesis. Drastic reduction of immunosuppression may favourably affect the outcome.

We present two distinct types of cholestatic syndrome identified in eight renal transplant (RTx) patients with HCV infection. Four patients developed fibrosing cholestatic hepatitis (FCH) and four, vanishing bile duct syndrome (VBDS). All patients with FCH were anti-HCV (-) at the time of Tx and developed a cholestatic profile 1-4 months post-Tx, with high HCV-RNA levels. Immunosuppressive therapy was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months post-Tx, and the other two showed marked improvement and seroconverted to anti-HCV. Regarding the patients with VBDS, three were anti-HCV (-) and one was anti-HCV (+)/HBsAg (+) at the time of RTx. Two patients became anti-HCV (+) 1 year, and one patient, 3 years post-Tx. Two patients developed progressive VBDS and died of liver failure 2 and 3 years after onset, and two showed marked improvement after withdrawal of immunosuppression. In two of the patients, the progression of the disease coincided with elevation in serum HCV RNA levels. We concluded that a progressive cholestatic syndrome acquiring features of FCH or VBDS may develop in HCV-infected RTx patients. The association with high viral load implicated the virus in the pathogenesis. Drastic reduction of immunosuppression may favourably affect the outcome.