The Role of Beta-7 Integrin and Carbonic Anhydrase IX in Predicting the Occurrence of de Novo Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients.

Background: Liver transplant (LT) recipients are at increased risk for developing metabolic syndrome. Early detection of NAFLD and other components of the metabolic syndrome is an important step in reducing morbidity and mortality. Methods: We assessed 60 liver transplant recipients for clinical and biological features, performed abdominal ultrasound and transient elastography (TE) Fibroscan© with controlled attenuation parameter (CAP), calculated non-invasive scoring systems APRI, FIB-4, NAFLD score, cardiovascular risk (Framingham risk score) and for the presence of metabolic syndrome and performed two biomarkers: beta 7 integrin and carbonic anhydrase IX. Results: Sixty liver transplant recipients underwent clinical and biochemical evaluation, abdominal ultrasound and TE with CAP. The median age was 56.5 years and the median time from transplantation 35 months. The Spearman correlation coefficient of beta 7 integrin and the liver stiffness measurement values obtained via Fibroscan© we obtained a moderate correlation r=0.31, but a significant association (p=0.01). The univariate analysis showed significant association between both biomarkers and liver fibrosis assessed with a cut-off value of advanced fibrosis of 8.7 kPa. The carbonic anhydrase IX showed a better correlation when compared to the liver stiffness with a correlation coefficient of 0.43 and p-value=0.0007 and a moderate correlation when compared to both FIB-4 (r=0.27) and APRI (r=0.27) score for liver fibrosis but with a significant p value=0.04, respectively 0.03. CONCLUSION: We consider very important for our patients the development of new non-invasive biomarkers for early diagnosis of NAFLD and NASH, as the "gold-standard" of liver biopsy is not easily accepted in clinical practice. Also NAFLD and NASH are dynamic processes that need prospective and repeated assessments, a need that cannot be met by the classical liver biopsy.

The Romanian National Program for Liver Transplantation - 852 Procedures in 815 Patients over 17 Years (2000-2017): A Continuous Evolution to Success.

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.

Anticoagulation Therapy for Portal Vein Thrombosis in Patients with Cirrhosis in a Tertiary Center Experience.

BACKGROUND AND AIMS: The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates. METHODS: This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events. RESULTS: The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008). CONCLUSIONS: In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.

Pre and post-liver transplant outcome of cirrhotic patients with acute on chronic liver failure.

Acute on chronic liver failure (ACLF) is a dynamic syndrome, but frequently associated with a high 1 month mortality rate. This is the first study applying the new European Association for the Study of the Liver- chronic liver failure consortium criteria to explore mortality on the waiting list (WL) and early after liver transplantation (LT) in a cohort of Romanian cirrhotic patients that improved or recovered after an episode of ACLF.To assess frequency and waitlist mortality for different grades of ACLF.An observational study was conducted; 257 patients with liver cirrhosis included on the WL between 2015 and 2017 were analyzed. The cumulative incidence of waitlist mortality or removal was calculated for combination of competing events using multivariable competing risks regression.ACLF-1 occurred in 12.07%, ACLF-2 in 7.39% and ACLF-3 in 8.56% of patients. Median Model for End Stage Liver Diseases (MELD) score at the moment of ACLF was 29. The main event while on the WL was death, followed by ACLF; patients with ACLF-3 had a significantly greater subhazard ratio for mortality of 2.25 (1.55-3.26) compared to patients with ACLF-1 or 2. LT proved to be associated with a significantly lower risk of death on the WL at 6 months after inclusion. One and 12 months post-transplant survival of patients with or without ACLF was similar (P = .77).Occurrence of an ACLF episode while on the WL is associated with a significantly high mortality rate, as well as MELD score at inclusion on the WL, renal and liver failure, presence of hepatic encephalopathy. Overall patient short and long term survival after LT is similar to non-ACLF patients in good selected cases.

100% sustained virological response and fibrosis improvement in real-life use of direct acting antivirals in genotype-1b recurrent hepatitis C following liver transplantation.

BACKGROUND: Nowadays, interferon-free therapy using new direct-acting antivirals (DAA) has dramatically increased the cure rate across different HCV-infected patient populations, including groups traditionally viewed as difficult-to-treat (patients with co-infections, cirrhosis and liver transplant - LT recipients) with marked improvement in safety and tolerability. AIM: To present our experience with DAA therapy in LT recipients, as well as to compare pre- and post-treatment liver stiffness (LS) and noninvasive fibrosis scores. METHODS: Our cohort consisted of 89 patients with genotype 1 (GT1) recurrent hepatitis C after LT. Seventy six patients received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin and 13 sofosbuvir/ledipasvir+/-ribavirin. Fibroscan®, FIB4 and APRI scores were performed in all patients before and 12 weeks after DAA therapy. RESULTS: We analyzed 45 (50.5%) males and 44 (49.5%) females with a mean age of 55+/-7.7 years. Median time since LT was 20.9 months. At baseline, 53 (59.6%) of patients had severe necroinflammation at Fibromax®; advanced fibrosis (F3, F4) was encountered in 35 (39.4%) and grade 3 steatosis in 33 (37.1%) of LT recipients. End of therapy (EOT) virological response (VR) was 100%. Sustained virological response 12 weeks after therapy (SVR12) was 97.7% in the intention-to-treat analysis and 100% in per protocol analysis. There was a significant improvement in LS between antiviral therapy initiation and SVR12: 11.9+/-1.05kPa vs 8.8+/-0.6kPa (p<0.0001), as well as in APRI (2.7+/-0.3 vs 0.4+/-0.05, p<0.0001) and FIB4 (4.6+/-0.5 vs 2.5+/-0.2, p<0.0001) scores. CONCLUSIONS: In HCV positive recipients, DAA regimens are highly effective and safe. A significant decrease of LS by transient elastography and fibrosis non-invasive scores can be observed after successful therapy.

Dynamics of the Romanian waiting list for liver transplantation after changing organ allocation policy.

AIM: The aim of the present study was to characterize the dynamics of the Romanian waiting list (WL) for liver transplantation (LT) over two periods: 2004-2007 vs. 2008-2011. METHODS: 1,085 patients listed for LT during the time period 2004-2011 were included in our analysis. RESULTS: Death on the WL was significantly higher before 2008 (37% vs. 26.4%, p=0.0001) and risk of dying while on WL was 60% higher. Waiting time on the WL was 75% longer and time until LT was 102% longer before 2008 compared to the second time period (p=0.0001). After 2008, 62.3% of patients were listed for LT with Child Pugh class C compared to 22.1% before 2008 (p<0.0001). CONCLUSION: A significant reduction of mortality has been registered on the Romanian WL for LT after 2008, despite the increased severity of liver disease in patients listed for LT.