Evangelos Thalassinos

Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: A multicenter survey on safety and efficacy

Refractory hepatic encephalopathy (HE) remains a major cause of morbidity in cirrhosis patients. Large spontaneous portosystemic shunts (SPSSs) have been previously suggested to sustain HE in these patients. We aimed to retrospectively assess the efficacy and safety of patients treated with embolization of large SPSSs for the treatment of chronic therapy‐refractory HE in a European multicentric working group and to identify patients who may benefit from this procedure. Between July 1998 and January 2012, 37 patients (Child A6‐C13, MELD [Model of Endstage Liver Disease] 5‐28) with refractory HE were diagnosed with single large SPSSs that were considered eligible for embolization. On a short‐term basis (i.e., within 100 days after embolization), 22 out of 37 patients (59.4%) were free of HE (P < 0.001 versus before embolization) of which 18 (48.6% of patients overall) remained HE‐free over a mean follow‐up period of 697 ± 157 days (P < 0.001 versus before embolization). Overall, we noted improved autonomy, decreased number of hospitalizations, and severity of the worst HE episode after embolization in three‐quarters of the patients. Logistic regression identified the MELD score as strongest positive predictive factor of HE recurrence with a cutoff of 11 for patient selection. As to safety, we noted one major nonlethal procedure‐related complication. There was no significant increase in de novo development or aggravation of preexisting varices, portal hypertensive gastropathy, or ascites. Conclusion: This multicenter European cohort study demonstrated a role for large SPSSs in chronic protracted or recurrent HE and substantiated the effectiveness and safety of embolization of these shunts, provided there is sufficient functional liver reserve. (HEPATOLOGY 2013;57:2448–2457)

Early tacrolimus exposure after liver transplantation: Relationship with moderate/severe acute rejection and long-term outcome

BACKGROUND & AIMS Liver transplant (LT) patients might be overimmunosuppressed as recommendations for tacrolimus trough concentrations (TC) within 4-6 weeks after liver transplantation are set too high (10-15 ng/ml). Early tacrolimus exposure was evaluated in relation to acute rejection and long-term outcomes. METHODS Four hundred and ninety-three consecutive LT patients receiving tacrolimus as primary immunosuppression (1995-2008) were analyzed. Acute rejection was diagnosed using protocol biopsies at day 6.1 ± 2.5. Median follow-up was 7.3 years (IQR 3.9-10.5). Early tacrolimus exposure (<15 days) was evaluated against moderate/severe acute rejection, chronic rejection, graft loss, chronic renal impairment and mortality using multiple logistic and Cox regression. RESULTS Maintenance immunosuppression was tacrolimus monotherapy (48.1%), double therapy combination with antimetabolites or steroids (18%), or triple therapy combination with antimetabolites and steroids (33.9%). Histological grade of acute rejection was moderate in 157 cases (31.8%) and severe in 19 cases (3.9%). Tacrolimus TC>7 ng/ml on the day of protocol biopsy was associated with less moderate/severe rejection (23.8%) compared with<7 ng/ml (41.2%) (p = 0.004). Mean tacrolimus TC 7-10 ng/ml within 15 days after LT were associated with reduced risk of graft loss (RR = 0.46; p = 0.014) compared to TC 10-15 ng/ml. A peak TC>20 ng/ml within this period was independently related to higher mortality (RR = 1.67; p = 0.005), particularly due to cardiovascular events, infections and malignancy (RR = 2.15; p = 0.001). Early tacrolimus exposure did not influence chronic rejection (p = 0.58), or chronic renal impairment (p = 0.25). CONCLUSIONS During the first 2 weeks after LT, tacrolimus TC between 7 and 10 ng/ml are safe in terms of acute rejection and are associated with longer graft survival.

Cost‐effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost‐effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost‐effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta‐analysis to calculate the diagnostic accuracy of various NITs using a bivariate random‐effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality‐adjusted life‐years; QALYs) using data from the meta‐analysis, literature, and national UK data. We compared the cost‐effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost‐effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more‐potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost‐effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost‐effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1‐4, the incremental treatment cost threshold for the “treat all” strategy to remain the most cost‐effective strategy would be £37,500. Above this threshold, the most cost‐effective option would be noninvasive testing with magnetic resonance elastography (ICER = £9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost‐effective strategy with currently available drugs in developed countries. (Hepatology 2014;60:832–843)

Nine scoring models for short‐term mortality in alcoholic hepatitis: cross‐validation in a biopsy‐proven cohort

Several prognostic models have emerged in alcoholic hepatitis (AH), but lack of external validation precludes their universal use.

Biochemical criteria at 1 year are not robust indicators of response to ursodeoxycholic acid in early primary biliary cirrhosis: results from a 29-year cohort study

In primary biliary cirrhosis (PBC), biochemical criteria at 1 year are considered surrogates of response to ursodeoxycholic acid (UDCA). However, due to the slow natural history of PBC, evaluation at 1 year may be suboptimal to assess the therapeutic response, particularly in early disease.

Hepascore and hyaluronic acid as markers of fibrosis in liver disease of mixed aetiology.

Objective To evaluate hyaluronic acid (HA) and Hepascore as diagnostic replacements for liver biopsy in a population with mixed liver disease. Materials and methods The utility of HA concentration and Hepascore for staging fibrosis, detecting any fibrosis and detecting advanced fibrosis, was assessed in 73 consecutive patients, with varied liver pathologies requiring biopsy. Subgroup analyses compared utility of disease-specific and universal cut-offs for HA and Hepascore. Results Forty-one patients (56.2%) had liver fibrosis on biopsy. HA and Hepascore varied significantly with METAVIR stage, although ranges overlapped, precluding their use in staging fibrosis. When detecting any fibrosis (METAVIR F1-F4), HA and Hepascore had areas under the receiver operator characteristic curve of 0.63 and 0.66, respectively, and approximately two-thirds of patients were correctly categorized using optimal cut-offs. For detection of advanced fibrosis (METAVIR F3/4), HA and Hepascore had areas under the receiver operator characteristic curve of 0.81 and 0.80, respectively, and three-quarters of patients were correctly categorized using optimal cut-offs. In subgroup analysis, locally derived, disease-specific cut-offs in hepatitis C virus patients yielded greatest diagnostic efficiency, whereas the tests performed worst in cryptogenic aetiologies. Conclusion HA and Hepascore cannot accurately stage hepatic fibrosis in this population. Locally derived, disease-specific cut-offs for HA gave the higher diagnostic efficiency observed. Although HA and Hepascore may be useful where the disease aetiology is known, particularly in established hepatitis C virus, the high cost of false positives and false negatives are such that neither a reliable enough to replace biopsy without substantial further characterization.

652 DEVELOPMENT OF A FORMULA TO ESTIMATE GLOMERULAR FILTRATION RATE (GFR) IN PATIENTS WITH CIRRHOSIS

651 RELATIONSHIP BETWEEN FEATURES OF CIRRHOTIC CARDIOMYOPATHY AND ADRENAL DYSFUNCTION IN CIRRHOSIS E. Theocharidou, D. Knight, G. Fede, E. Tsochatzis, G. Germani, M.L. Rodriguez, A. Dhar, V. Papastergiou, A.K. Burroughs. The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, Royal Free Hampstead NHS Trust and UCL, Department of Cardiology, Royal Free Hospital, Royal Free Hampstead NHS Trust and UCL, London, UK E-mail: mtsochatzis@med.uoa.gr