Digital image analysis of liver collagen predicts clinical outcome of recurrent hepatitis C virus 1 year after liver transplantation.

Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation. Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow-up of 76 months were evaluated. At 1 year, median CPA was 4.6% (0.2%-36%) and Ishak stage was 0-2 in 101 patients, 3-4 in 23 patients, and 5-6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15-138). Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037-1.317). Area under the ROC curve was 0.97 (95%CI, 0.94-0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained. When both cutoffs of CPA > 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1-year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG.

Fibrosis staging in chronic hepatitis C: analysis of discordance between transient elastography and liver biopsy.

In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir > or = F2) is variable. Constitutional and liver disease-related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)-RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy-six of 286 (26.6%) had stage > or =F2 and TE < 7.1 kPa (false negative); 21 of 286 (7.3%) had stage or = 7.1 kPa (false positive). No patient with discordant results had cirrhosis. By Dale model, aspartate aminotransferase (AST) was found to be the unique variable significantly related (P = 0.046) with discordance between biopsy and TE. Discordance rate was 43.4% (82 patients) with AST < 1.5 x UNL vs 25.8% (25 patients) with AST > or = 1.5 x UNL (P = 0.004). False negative rate was 43.4 (82 patients) with AST < 1.5 x UNL vs 17.1% (13 patients) with AST > or = 1.5 x UNL (P < 0.001). Areas under the receiver operating characteristic (AUROC) for F > or = 2, according to AST < 1.5 x UNL vs > or = 1.5 x UNL were 0.738 (95% CI: 0.683-0.812) and 0.854(95% CI: 0.754-0.907). Transient elastography is not adequate on its own to rule out or to rule in significant fibrosis, as it is influenced by major variations in biochemical activity of liver disease. Liver stiffness, at low levels of AST, can underestimate fibrosis.

Impact of tips preliver transplantation for the outcome posttransplantation.

The effects of transjugular intrahepatic portocaval shunt (TIPS) on the survival of grafts and patients after liver transplantation (LTx) have only been documented in small series and with only a comparative description with non-TIPS recipients. We evaluated 61 TIPS patients who had a subsequent LTx and compared these with 591 patients transplanted with cirrhosis without TIPS. Pretransplant characteristics were similar between groups. Graft survival at 1, 3 and 5 years post-LTx was 85.2%, 77% and 72.1% (TIPS) and 75.3%, 69.8% and 66.1% (controls). Patient survival at the same points was 91.7%, 85% and 81.7%, respectively (TIPS) and 85.4%, 80.3% and 76.2% (controls). Cox regression showed the absence of TIPS pre-LTx, transfusion of >5 units of blood during LTx, intensive care unit (ICU) stay post-LTx >3 days and earlier period of transplant to be significantly associated with a worse patient and graft survival at 1 year. Migration of the TIPS stent occurred in 28% of cases, increasing the time on bypass during LTx, but was not related to graft or patient survival. TIPS may improve portal supply to the graft and reduce collateral flow, improving function. This may account for the improved adjusted graft and patient survival by Cox regression at 12 months. Long-term survival was not affected.

Pegylated-interferon and ribavirin in liver transplant candidates and recipients with HCV cirrhosis: systematic review and meta-analysis of prospective controlled studies.

SUMMARY: Pegylated interferon with ribavirin (Peg/R) is the most effective therapy for chronic hepatitis C virus (HCV) but its utility and effectiveness after liver transplantation has been difficult to assess. We evaluated efficacy, tolerability, and safety of Peg/R in liver transplant candidates and recipients with HCV cirrhosis. We searched medical databases and conference proceedings between January 1999 and January 2008 selecting randomized and nonrandomized studies. Primary end points meta-analytically were: (1) sustained viral response (SVR) and (2) histological response. Secondary end points were: (1) treatment discontinuation, (2) mortality, and (3) rejection episodes. Pegylated interferons using either 1-1.5 mcg/kg of pegylated interferon alpha-2b or 180 microg (pegylated interferon alpha-2a combined with ribavirin 800-1200 mg/day were the most effective compared to any other regimen or no therapy. In three pretransplant studies the median SVR was 19.6% (19.6-50%). In six postransplant studies where a meta-analysis was done the cumulative risk difference in SVR was 0.31% (95% CI, 0.18-0.44, p < 0.001). However histological response was not significantly better compared to no therapy or other antiviral regimens. There were no significant differences in discontinuation of therapy, acute or chronic rejection or mortality between optimal Peg/R vs no treatment or other regimens. Hence pegylated interferon plus ribavirin in full doses is effective pre and post transplant but has a low SVR rate. To date no significant histological improvement has been reported.

Models for non-alcoholic fatty liver disease: a link with vascular risk.

Non alcoholic fatty liver disease (NAFLD) is often part of the metabolic syndrome which includes central obesity, dyslipidaemia, insulin resistance/type 2 diabetes mellitus and hypertension. In turn, NAFLD may be associated with an increased vascular risk. Several experimental models which express histological steatosis or steatohepatitis with fibrosis have been described. This review identifies those models of NAFLD with features of vascular risk.

Correlation between esophageal contraction amplitude and lower esophageal sphincter pressure in patients with nutcracker esophagus.

Nutcracker esophagus (NE) is a primary esophageal motility disorder characterized by high-wave amplitude at the distal esophagus. The aim of this study was to analyze patients with NE and determine the relationship between distal esophageal contraction amplitude and lower esophageal sphincter (LES) pressure. Esophageal manometry tracings of patients with NE, defined as the presence of distal contraction amplitude of more than 182 mmHg after wet swallow, were analyzed. LES pressure was measured as the mean end-expiratory value. Spearman's correlation coefficient analysis was used to compare esophageal contraction amplitude with LES pressure. This comparison was also performed in patients with isolated hypertensive LES (HLES) and in subjects with normal manometry. Forty patients (25 female, 15 male; mean age 54 years) with NE were included in the study. Mean (SD) distal esophageal contraction amplitude was 230 (35.7) mmHg and mean LES pressure was 27.3 (5.7) mmHg. Esophageal contraction amplitude showed a positive correlation with LES pressure (r = 0.49, P < 0.01). In contrast, no correlation was found in patients with HLES (r = 0.21, P > 0.05) and in those with a normal manometric study (r = 0.18, P > 0.05). It is concluded that in patients with nutcracker esophagus a positive correlation exists between distal esophageal contraction amplitude and LES pressure, suggesting a diffuse hypertensive pattern involving smooth muscle at the distal esophagus and adjacent LES.