Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C.

BACKGROUND: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival. AIM: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. METHODS: 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. RESULTS: The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11±3.5 years (range, 5-24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p=0.007), treatment duration >80% of the scheduled period (p=0.027), and early virological response (p=0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p=0.008). CONCLUSIONS: Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival.

Degree of bile-duct dilatation in liver-transplanted patients with biliary stricture: a magnetic resonance cholangiography-based study.

PURPOSE: This study assessed whether the degree of bile-duct dilatation in liver-transplanted patients is correlated with the time from intervention and the type of underlying biliary stricture. METHODS AND MATERIALS: Fifty-seven 3D magnetic resonance cholangiograms (MRCs) performed on 42 liver-transplanted patients were retrospectively evaluated. Diameter was measured at the level of the extrahepatic bile duct (EBD), right hepatic duct (RHD), left hepatic duct (LHD), anterior and posterior right hepatic ducts (aRHD, pRHD) and left lateral and medial ducts (LLD, LMD). Data were stratified according to the type of biliary stricture (all types, anastomotic, ischaemic-like, mixed) and compared, on a per-examination basis: (a) between two groups based on time from transplantation using a 1-year threshold (nonlongitudinal analysis); (b) among 26 repeated examinations on 11 patients (longitudinal analysis); (c) among different stricture groups. RESULTS: The biliary tree was slightly dilated within 1 year from transplantation (2.9±1.3 to 6.1±3.2 mm). In general, nonlongitudinal analysis showed minimally larger duct size after 1 year (mean +1.4±0.5 mm) despite significant differences at most sites of measurement considering all types of strictures (p<0.01; Mann-Whitney U test). Longitudinal analysis showed diameter increase over time, although without statistically significant differences (p>0.01; Kruskal-Wallis test). No significant difference in bile-duct size was observed when comparing types of stricture (p>0.01; Kruskal-Wallis test). CONCLUSIONS: Biliary dilatation after liver transplantation is mild and develops slowly regardless of the underlying type of stricture, possibly in relation to graft properties. MRC has a potential role as first-line imaging modality for a reliable assessment of biliary dilatation and the presence of a stricture.

Carriage of the EGF rs4444903 A>G functional polymorphism associates with disease progression in chronic HBV infection.

Because epidermal growth factor (EGF) up-regulation is characteristic of the cirrhotic liver, we hypothesised that the EGF rs4444903 A > G functional polymorphism might be associated with a worse disease course in patients with chronic HBV infection. To verify this hypothesis, 170 HBV-positive patients (125 males) with a median age of 52 years were studied. Sixty-two of these patients were followed longitudinally for a median time of 21 years. Genotyping for the EGF rs4444903 A > G polymorphism was performed by the polymerase chain reaction-based restriction fragment length polymorphism assay. In the cross-sectional study, the EGF rs4444903 A > G polymorphism genotypic frequencies significantly differed between transplant patients (A/A = 20·4%, A/G = 52·3%, G/G = 27·3%) and HBsAg+ carriers (active and inactive: A/A = 35·7%, A/G = 47·6%, G/G = 16·7%, P = 0·036 for the linear trend). In the longitudinal study, the EGF rs4444903 A > G polymorphism was found to be an independent predictor of cirrhosis development (O.R. 7·73, 95% C.I. 1·21-49·5, P = 0·007). Three groups of patients were identified: A/A female homozygotes (n = 9), A/A male homozygotes (n = 13) and carriers of the G allele of either gender (n = 40). Cirrhosis did not occur among A/A females (n = 0/9), seldom occurred among A/A males (n = 2/13) and reached the highest frequency among G/* patients (n = 13/40, P = 0·026). In conclusion, the EGF rs4444903 A > G polymorphism appears to be associated with an unfavourable disease course of chronic HBV infection and cirrhosis development. This effect might be modulated, at least in part, by the gender of the patient.

Impact of magnetic resonance cholangiography in managing liver-transplanted patients: preliminary results of a clinical decision-making study.

PURPOSE: This study was performed to assess the role of magnetic resonance cholangiography (MRC) in the clinical decision-making process of referring physicians when managing liver-transplanted patients. MATERIALS AND METHODS: Over a 6-month period, 21 liver-transplanted patients with a suspected biliary complication were referred for MRC. Referring physicians were asked to prospectively state, before and after MRC, the leading diagnosis; the level of confidence (on a 0-100% scale); the most appropriate diagnostic/therapeutic plan. Data analysis assessed was the diagnostic yield of MRC; the proportion of change in the leading diagnosis; the therapeutic efficacy (i.e. proportion of change in the initial diagnostic/therapeutic plan); the diagnostic thinking efficacy (i.e., gain in diagnostic confidence). Statistical significance was assessed with the Mann-Whitney U test. MRC accuracy was also calculated. RESULTS: Data analysis showed a diagnostic yield of 85.7%; a proportion of change in leading diagnosis of 19.0%; a therapeutic efficacy of 42.8%; a diagnostic thinking efficacy for concordant and discordant leading diagnoses of 18.8% and 78.7%, respectively (p<0.01). MRC accuracy was 92.3%. CONCLUSIONS: MRC significantly increased the diagnostic confidence, irrespective of the concordance between pre- and posttest diagnoses. Moreover, MRC determined a change in patient management in a significant proportion of cases, leading to clinical benefits.

Cardiovascular risk factors and immunosuppressive regimen after liver transplantation.

Cardiovascular and metabolic diseases represent important long-term complications after liver transplantation (LT), impairing long-term and disease-free survivals. A few mechanisms underlie the development of those complications, but the role of immunosuppressive drugs is major. Although several patients develop temporary metabolic diseases, which normalize after a short postoperative period and do not need long-term drug therapy, the incidences of de novo long-lasting arterial hypertension, hyperlipidemia, and diabetes mellitus are high during the first year after LT. The aim of this retrospective study was to evaluate new-onset arterial hypertension, hyperlipidemia, or diabetes among 100 LT patients at a single institution. We used chi-square statistical analysis to compare incidences during tacrolimus versus cyclosporine therapy. Hypertension did not seem to be more strongly related to tacrolimus than to cyclosporine, nor did diabetes, whereas there was a difference for the development of hyperlipidemia.

Diffusion-weighted MRI in evaluating liver fibrosis: a feasibility study in cirrhotic patients.

PURPOSE: This study was designed to establish whether the measurement of apparent diffusion coefficients (ADCs) is clinically accurate in diagnosing liver fibrosis in a selected series of cirrhotic patients. MATERIALS AND METHODS: Twenty-eight cirrhotic patients (mean age 58.1 years) with histologically proven liver fibrosis and 29 healthy controls (mean age 43.8 years) underwent liver diffusion-weighted magnetic resonance (MR) using a 1.5-Tesla (T) magnet equipped with a phased-array coil. Diffusion studies with parallel imaging [generalized autocalibrating partially parallel acquisitions (GRAPPA)] were performed within a single breath-hold using a single-shot spin-echo echo-planar sequence (TE 74 ms) using four b values: b=0, 150, 250 and 400 s/mm(2). A unidirectional diffusion gradient was applied. ADCs were measured on ADC maps. RESULTS: Mean ADC was significantly lower in cirrhotic livers than in controls (1.11+/-0.16 vs. 1.54+/-0.12.10(-3)mm(2)/s) (p<0.0001). Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.96 [confidence interval (CI) 95%:(0.87; 0.94)], demonstrating higher sensitivity and specificity (92.9% and 100%, respectively) for an ADC cutoff of 1.31.10(-3)mm(2)/s. Positive predictive value (PPV), negative predictive value (NPV) and overall accuracy were 100%, 99.9% and 96.4%, respectively. CONCLUSIONS: Diffusion-weighted MRI is an accurate tool in evaluating advanced liver fibrosis if an optimised single-shot spin-echo echo-planar sequence with maximum intermediate b value is used. The ADC threshold for liver fibrosis was 1.31.10(-3)mm(2)/s.

On the Intensifying Property of a Pile-of-Gratings.

The intensification property of a multilayer structure of aligned plane transmission diffraction gratings (pile-of-gratings) is described. A first-order analysis is given, based on addition of intensities, and the conditions under which intensification is possible are derived. Supporting experimental results are described.