Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany

Objectives: This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods: Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results: 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions: Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT

The Role of miRNA-34a as a Prognostic Biomarker for Cirrhotic Patients with Portal Hypertension Receiving TIPS

Background-Circulating miRNA-34a is increased in blood of patients with different liver diseases when compared to healthy controls. However, the origin of miRNA-34a and its possible relationship with hemodynamics and outcome in cirrhotic patients with portal hypertension is unknown. We analyzed the levels of miRNA-34a in cirrhotic patients with severe portal hypertension. Methods: We included 60 cirrhotic patients receiving TIPS for prevention of rebleeding and/or therapy-refractory ascites. miRNA-34a levels were measured using qPCR and normalized by SV-40 in the portal and hepatic venous blood of these patients taken at TIPS procedure. Hemodynamic and clinical parameters were assessed before TIPS and during follow-up. Results: Levels of miRNA-34a were higher in the hepatic vein than in the portal vein. Circulating miRNA-34a in the hepatic vein correlated with ALT, CHE and sodium excretion after TIPS. miRNA-34a showed no correlation with portal pressure, but its levels in the portal vein correlated inversely with the congestion index. Interestingly, the levels of miRNA-34a in the portal and hepatic vein showed inverse correlation with arterial pressure. Furthermore, levels of miRNA-34a in the hepatic vein had a predictive value for survival, but MELD, creatinine at short-time follow-up 14 days after TIPS-insertion and portal pressure after TIPS performed better. Conclusion: This study demonstrates for the first time, that miRNA-34a may originate to a large extent from the liver. Even though higher levels of miRNA-34a are possibly associated with better survival at long-term follow-up in cirrhotic patients with severe portal hypertension receiving TIPS, classical prognostic parameters predict the survival better

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients - Fig 1

<p>Correlation between TE and APRI score (A) and FIB4 score (B). Panel C depicts the prevalence of fibrosis and cirrhosis stratified by the different cART regimes. The TE levels in patients with and without history of ddI (D) and AZT (E).</p

Main liver specific characteristics of the study population (n = 333) stratified by grade of fibrosis assessed by transient elastography.

<p>Main liver specific characteristics of the study population (n = 333) stratified by grade of fibrosis assessed by transient elastography.</p

Multivariate analysis of the factors associated with significant fibrosis (TE ≥ 7.1 kPa) according to logistic regression forward step-wise likelihood quotient in the whole cohort (n = 333).

<p>Multivariate analysis of the factors associated with significant fibrosis (TE ≥ 7.1 kPa) according to logistic regression forward step-wise likelihood quotient in the whole cohort (n = 333).</p

Clinical parameters of the patients (n = 60) at TIPS placement.

<p>There was no significant difference in any variable between the groups.</p><p>MELD, model for end-stage liver disease.</p

Survival 5 years after TIPS stratified using the median of circulating miRNA-34a (A) in the hepatic vein as well as MELD (B), creatinine in short-term follow-up (C) and portal pressure after TIPS (D).

<p>Patients were stratified for circulating miRNA-34a (A) measured in the hepatic vein, MELD-Score before TIPS (B), creatinine in short-term follow-up (C) and portal pressure after TIPS insertion (D) to higher and lower levels of the median of these parameters. Survival rates are shown using Kaplan-Meier plots and analyzed by log-rank test.</p

Serum levels of miRNA-34a in portal and hepatic vein before TIPS placement and its correlation with ALT-levels.

<p>(A) The levels of miRNA-34a measured in portal vein and hepatic vein before TIPS showed significant increase of miRNA-34a levels across the liver (p = 0.019). Data were shown paired and analyzed by Wilcoxon test. Of note, data of six patients lay outside of the shown range, and were not shown to increase readibility. (B) Levels of circulating miRNA-34a in the hepatic vein correlated significantly with ALT before TIPS (r_s = 0.409; p = 0.001). Data are presented using Spearman coefficient r_s and p-values. The levels of miRNA-34a were normalized to SV40 and are displayed as the x-fold of SV40.</p

Univariate time-to-event analysis of patient characteristics (including variables of table 1, 2 and 3). In the table are shown only significant variables.

<p>MELD, model for end-stage liver disease.</p

Biochemical and hemodynamic parameters before TIPS insertion and at a short-term follow-up after a median of fourteen days (n = 60) compared using with Wilcoxon test.

<p>BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γGT, gamma-glutamyl transpeptidase; INR, International Normalized Ratio; PHPG, portal hepatic pressure gradient.</p