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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.

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., (Celsius.)

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.

Background and Aims: Ombitasvir/Paritaprevir/ritonavir/Dasabuvir (OBV/PTV/r+DSV) is one of the elective direct-acting antivirals (DAAs) recommended by international guidelines and the only one covered by the National Insurance System in Romania until November 2016. Our aim was to present the first prospective Romanian cohort evaluating the effectiveness and safety in clinical practice of this 3DAA combination in patients with HCV genotype-1b Child A liver cirrhosis., Methods: 681 patients received OBV/PTV/r+DSV+RBV for 12 weeks and were assessed clinically and biologically at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained viral response, SVR)., Results: Per protocol, EOT virological response was 99.8% and SVR12 rate was 99.4%. Adverse events were present in 36.4% of patients. Permanent discontinuation of 3DAA regimen due to side effects was reported in 11 patients (1.6%). In 47.6% (185/389) of patients, Transient Elastography values were >20kPa (defined as clinically significant portal hypertension, CSPH) at baseline. Independent variables associated with CSPH were: baseline cholesterol level (p=0.003), platelet count <120,000/mm³ (p=0.02), MELD score (p=0.01). Liver stiffness measurement has significantly improved between baseline (26.6+/-12.7kPa) and SVR12 (21.6+/-11.8kPa) (p<0.0001). The same was true for APRI score (2.66+/-0.15 at baseline vs 0.85+/-0.02 at SVR12, p<0.0001) and FIB4 score (5.53+/-0.28 vs 3.24+/-0.08, p<0.0001), but not for Lok score (0.57+/-0.01 vs 0.63+/-0.01, p<0.0001)., Conclusions: We report a high efficacy of the 3DAA regimen in a homogeneous compensated HCV genotype-1b liver cirrhosis population, in a real-life setting. Noninvasive fibrosis scores significantly improved at SVR12.

Background: Small nodules (under 3 cm) detected on ultrasound (US) in cirrhotics represent the most challenging category for noninvasive diagnosis of hepatocellular carcinoma (HCC)., Aim: To evaluate real-time sonoelastography as a noninvasive tool for the diagnosis of small HCC nodules in cirrhotic patients., Methods: 42 cirrhotic patients with 58 nodules (1-3 cm) were evaluated with real-time elastography (Hitachi EUB-6500); the mean intensity of colors red, blue, green were measured using a semi-quantitative method. Analysis of histograms for each color of the sonoelastography images was performed for quantifying the elasticity of nodule tissue in comparison with the cirrhotic liver tissue. AUROC curves were constructed to define the best cut-off points to distinguish malignant features of the nodules. Univariate and multivariate logistic regression analysis was performed., Results: 595 sonoelastography images from 42 patients (25 men; 17 women) were analyzed. The mean age was 56.4 +/- 0.7 years and 69% patients were in Child-Pugh class A, 19% class B, 11% class C. For the mean intensity of green color AUROC=0.81, a cut-off value under 108.7 being diagnostic for HCC with a Sp=91.1%, Se=50%, PPV=92.1%, NPV=47.1%. Mean intensity of blue color proved to be an excellent diagnostic tool for HCC (AUROC=0.94); for a cut-off value greater than 128.9, Sp=92.2%, Se=78.9%, PPV=95.4%, NPV=68%. Independent predictive factors of HCC for a small nodule in cirrhotic patients were: blue color over 128.9 at sonoelastography and hypervascular appearance at Doppler US., Conclusions: US elastography is a promising method for the non-invasive diagnosis of early HCC. Blue color at elastography and hypervascular aspects are independent predictors of HCC.

Background: Patients with mild hepatitis C have a significant risk of disease progression at medium- and long-term follow-up and should be considered for antiviral therapy., Aim: To evaluate the rate of sustained viral response (SVR) and predictive factors of SVR in HCV genotype 1 patients with mild hepatitis C (fibrosis stage F0/F1) treated with combination antiviral therapy., Methods: 260 naïve patients were followed-up during 72 weeks in three referral hepatology centers between 2004 and 2006. Univariate and multivariate logistic regression analysis was conducted., Results: Early virological response was 88.1% and SVR was 74.2%. In the univariate analysis, SVR was associated with young age (p=0.001), very low (< or = 400,000 IU/mL) baseline viremia (p=0.03) and high aminotransferase levels (p=0.04) and was not associated with gender, body mass index, inflammatory activity, steatosis, ribavirin and peginterferon dose changes, premature cessation of therapy. Multivariate analysis identified the following independent predictors of SVR: age <50 years (p=0.0009), viral load < or = 400,000 IU/mL (p=0.03) and aminotransferase level >2 times normal value (p=0.02)., Conclusions: Genotype 1 HCV patients with mild hepatitis have a high rate of SVR, similar to genotype non-1. Young age, very low viremia and significant hepatocytolisis are independent predictors of SVR in patients with mild hepatitis.

Background/aims: To evaluate the efficacy and safety of prophylactic band ligation and propranolol versus propranolol alone for the primary prophylaxis of variceal bleeding in patients with high-risk esophageal varices listed for liver transplantation., Methodology: Out of 152 cirrhotic patients included on the waiting list between January 2001 and January 2003, high-risk esophageal varices were detected in 72. These patients were randomized to undergo combined therapy or propranolol monotherapy. The actuarial probabilities of bleeding from esophageal varices and bleeding-related death were calculated by Kaplan-Meier method and compared using the log-rank test., Results: Variceal eradication was achieved in 33 patients (91.6%) in 2.5 +/- 1.4 ligation sessions. The mean daily dose of propranolol was 72 +/- 25mg in the propranolol group and 68 +/- 21 mg in the ligation group. Six percent of patients in the ligation group and 31% in the propranolol group had one episode of bleeding during the 18 months of follow-up (p = 0.03). The actuarial probabilities of bleeding-free survival after 18 months of follow-up, in the ligation and monotherapy groups were 96% and, respectively, 69% (p = 0.04)., Conclusions: Endoscopic band ligation associated with propranolol significantly reduces the occurrence of the first episode of variceal bleeding and improves bleeding-related survival in cirrhotics included on the waiting list.

Aim: The aim of this study was to define the natural long-term course of HDV compensated cirrhosis., Methods: 166 consecutive patients with compensated HDV-related cirrhosis diagnosed since 1994 were followed up until the first decompensation and then until death, liver transplantation or 31st of December 2004. The survival during follow-up and the survival according to the type of first decompensation were calculated using the Kaplan Meier method. Survival curves were compared using the log-rank test., Results: 56 females (33.7%) and 110 males (66.3%) with a mean age of 40.7+/-7.9 years were included in the study. The mean Child Pugh and MELD score at the first episode of hepatic decompensation was 8.6+/-2.08 and 15.19+/-5.42, respectively. The median survival was 58.3 months since the diagnosis of compensated cirrhosis and the mean time to first decompensation was 21+/-19 months. The probability of survival after the diagnosis of compensated cirrhosis was 94.3%, 82.5%, and 51.5% at 1, 2, and 5 years, respectively. Ascites was the most frequent first decompensation (80.7%), followed by jaundice (30.1%), portal hypertensive gastrointestinal bleeding (PHGIB) (28.9%), hepatic encephalopathy (HE) (12%), hepatocellular carcinoma (HCC) (12%), portal vein thrombosis (8.4%), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome. 86 patients (51.8%) presented more than one complication at initial decompensation. Survival was worse in patients with jaundice and SBP (p=0.001), followed by patients with HE (p=0.05) and patients who presented more than one initial complication (p=0.03). In the multivariate survival analysis only PHGIB as first decompensation and MELD score>15 were independent predictors of death., Conclusion: HDV-related cirrhosis in Romania is an aggressive disease with a median time to decompensation less than 2 years and a median survival less than 5 years. Jaundice, the main clinical consequences of portal hypertension and HCC are the most frequent causes of decompensation and more than half the patients present two or more concomitant initial complications.

Background and Aims: Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus., Methods: We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis., Results: From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis., Conclusions: Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

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