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Background. It is known that alterations of the sleep-wake cycle are present from the early stages of hepatic encephalopathy (starting with grade I on the West Haven criteria). However, minimal hepatic encephalopathy (which is not included in the West Haven criteria) defi nes the earliest form of HE, with no obvious clinical manifestations, but with subtle alterations in cognitive domains such as attention, visuo-spatial perception, psychomotor speed and response inhibition. Aim. To determine if liver cirrhosis in otherwise asymptomatic individuals (without clinically manifest hepatic encephalopathy) is associated with an increased risk of altered sleep rhythm or excessive daytime sleepiness. Additionally, to determine if this risk is correlated with liver disease severity or other clinical and biological parameters. Material and methods. Cross-sectional study involving 25 adult patients with liver cirrhosis. Patients were evaluated through a standard neurological examination and with the Epworth Sleepiness Scale. Liver disease severity was measured using the MELD and Child-Pugh scores. Blood ammonia levels were also measured. Results. Mean age of the patients was 50±12 years-old. There was a predominance of males (68%, n=17). Mean MELD score was 17±7 points. Mean Child-Pugh score was 8±2 points. Mean blood ammonia level was 34±17 μg/dL. Subjective daytime somnolence was reported by 24% of patients (n=6). Mean ESS score was 6±5 points. No correlation was noted between the ESS scores and liver disease severity as measured by the Child-Pugh and MELD scores. Only three patients (12%) scored over 10 points on the ESS (none of them obese) and were consequently diagnosed with excessive daytime sleepiness (EDS). This proportion falls into the accepted prevalence of EDS in the general population. Conclusions. In our study, liver cirrhosis was not associated with a higher prevalence of excessive daytime sleepiness than in the general population. [ABSTRACT FROM AUTHOR]

Patient and liver graft survival rates have improved significantly in the last decades, leading to complications mainly related to long-term immunosuppression. Prevention of, screening for metabolic syndrome, cardiovascular disease, de novo diabetes mellitus, renal dysfunction, and malignancies and their management are mandatory due to important causes of morbidity and mortality in this patient population. Quality of life (QoL) and functional benefits are clearly better compared to preoperative status; however, post-liver transplantation (LT) complications may impair and alter QoL scores. Individualized immunosuppression managed by transplant physicians and collaboration with other non-transplant specialists for recognition and treatment of medical complications and comorbidities after LT is the key to enhanced QoL and life expectancy of this patient population. [ABSTRACT FROM AUTHOR]

Background & Aims: Elimination of hepatitis C worldwide is more feasible if micro-elimination screening strategies are adopted. We aimed to screen hepatitis C virus (HCV) in specific high-risk populations in certain sub-regions of Romania and link them to antiviral treatment. Methods: A multicenter prospective study was conducted among the hospitalized or ambulatory adult patients from March 2019 to March 2020 in more than 20 medical institutions from 4 Romanian cities (Bucharest, Iasi, Timisoara, Cluj-Napoca). A rapid diagnostic test for HCV diagnosis was performed to all admitted patients and the positive ones were sent to gastroenterology departments for confirming the active infection, staging and treatment prescription. Results: In total, 25,141 subjects signed the informed consent and were consequently enrolled into the study. The prevalence of anti-HCV antibodies was 1.39% (95%CI: 1.25-1.54) and increased with the number of risk factors presented by one subject. There was a positive association between the presence of anti-HCV antibodies and female gender (p<0.001), rural area of residence (p<0.001), advanced age (p<0.001), as well as a negative association with the education level (p<0.001). Conclusions: In a hospital-based screening micro-elimination program in Romania, HCV prevalence was lower than previously reported. This is a first step towards a cost-effective screening in a well-defined group of persons at risk and provides sufficient capacity to deliver access to HCV treatment and linkage to care in Romania. [ABSTRACT FROM AUTHOR]

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 posttreatment 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background & 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/mm? (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. [ABSTRACT FROM AUTHOR]

Introduction: Nonalcoholic fatty liver disease (NAFLD) has an increasing incidence worldwide, reflecting the epidemics of obesity and metabolic syndrome. Data on knowledge, attitude and management by the Romanian gastroenterologists with regard to NAFLD are lacking. Methods: We assessed current diagnostic and treatment patterns of the management of NAFLD among 102 Romanian board certified gastroenterologists using a survey developed to collect information regarding participants' clinical practice, diagnostic tools and usage of medication in patients with NAFLD. Results: 71.6% of the surveyed gastroenterologists (SG) had more than 5 years of gastroenterology practice, were university affiliated and 37.3% had predominant activity in hepatology (>60%). In Romania, 60.8% of the SG would diagnose NAFLD only if all other causes of liver disease were absent. All practitioners use a noninvasive tool for staging NAFLD, 45.1% use both serum markers and transient elastography. Liver biopsy is performed by 61.8% of the SG in the presence of a discordant result in two noninvasive methods of fibrosis evaluation. The most frequently prescribed drugs are: silymarin (88.2%), vitamin E (78.4%) and ursodeoxycholic acid (77.4%). Conclusion: The results of this survey suggest that clinical practice patterns among Romanian gastroenterologists for the diagnosis (mainly liver biopsy) and management of NAFLD frequently diverge from published practice guidelines. Nonalcoholic steatohepatitis is probably underdiagnosed, especially in patients with normal transaminase levels and is also overtreated with drugs that are not recommended in the guidelines. [ABSTRACT FROM AUTHOR]

Background: A number of high quality randomized clinical trials examining the efficacy and safety of triple therapy in genotype-1 HCV-infected patients have been published. However, these trials included a small number of patients with advanced fibrosis, and selected a population different from that in real-world settings. Aim: To determine the efficacy of boceprevir, pegInterferon and ribavirin regimen in genotype-1 treatment-experienced HCV-infected patients with cirrhosis and bridging fibrosis in real-life setting. Method: 167 treatment-experienced patients (85.6% relapsers) out of which 33.5% had cirrhosis, with a mean age of 52.6 years, registered in the Romanian Name Patient Program Database were included into the study. Results: 16.7% of patients had a viral load >100 IU/mL. Undetectable HCV RNA was encountered in 77.3% of patients at week 12. Multiple logistic regression analysis revealed the following independent predictors, measured at week 8, for an HCV RNA =100 IU/mL at week 12 of triple therapy: alanine aminotransferase values (p=0.01), hemoglobin level (p=0.04) and <2log drop of viral load (p<0.0001). A stopping score at 8 weeks was created as the sum of these 3 parameters, with a total of 4 possible points. AUROC of this score was 0.84, with a sensitivity of 75% and a specificity of 86.2%. Conclusion: Triple therapy in this cohort of real-life genotype-1 HCV-infected patients with advanced fibrosis showed robust early virological response (EVR) rates. A week 8 model predicting lack of EVR was created, with good clinical utility that can be validated in prospective larger cohorts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. To identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. 174 LT recipients were enrolled. Liver biopsy, liver functional tests, cytokine quantitation in serum, as well as soluble MHC class I polypeptide-related sequence A and B (sMICA/sMICB) and soluble UL16 binding protein 2 (sULBP2) were performed. Patients with late graft dysfunction had a significantly higher donor age, lower albumin level, higher alanine (ALT) and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin and alkaline phosphatase (ALP), higher sMICA, sULBP2, higher interleukin (IL) 6, interferon γ and lower IL10 in serum as compared to recipients without allograft dysfunction. In order to provide a better statistical accuracy for discriminating 5-year allograft dysfunction from other less progressive subtype of allograft injury, we established a predictive model, based on 7 parameters (serum ALP, ALT, AST, GGT, sMICA, IL6 and albumin) which provided an Area Under the Receiver Operating Characteristics (AUROC) curve of 0.905. Blood-based biomarkers can significantly improve prediction of late liver allograft outcome in LT patients. The new developed score comprising serum parameters, with an excellent AUROC, can be reliably used for diagnosing late allograft dysfunction in transplanted patients. [ABSTRACT FROM AUTHOR]

Background Biliary strictures after liver transplantation ( LT) are a major cause of morbidity and reduced graft survival. Aims The purpose of this study was to investigate genetic, immunological and clinical risk factors for the occurrence of post- LT ischaemic type biliary lesions ( ITBLs) and biliary anastomotic strictures ( AS). Methods Clinical and laboratory data, chemokine receptor ( CCR) genotypes, chemotactic cytokines and anti-major-histocompatibility complex antibodies in serum were investigated in 162 LT patients. Results In the univariate analysis, older donor and recipient age, partial LT, high peak aspartate aminotransaminase ( AST) levels and CC chemokine receptor 5 delta32 loss-of-function mutation ( CCR5Δ32) were associated with ITBL, whereas LT for acute liver failure ( ALF), ABO-compatible non-identical LT, presence of donor-specific anti-human leucocyte antigen ( HLA) class II antibodies and fractalkine receptor ( CX3 CR1)-249 II allele were associated with AS. In the multivariate analysis, CCR5Δ32 was an independent risk factor for ITBL, whereas LT for ALF, ABO-compatible non-identical LT, and CX3 CR1-249 II allele remained predictive for AS. Serum levels of interferon-gamma and interleukin ( IL)-6 as well as IL-10 were significantly increased in patients with biliary strictures. Conclusion Specific chemokine receptor polymorphisms of the recipient are associated with development of post- LT biliary strictures. Altered cytokine profile may contribute to enhanced fibrotic tissue remodelling and biliary stricture formation. Screening of anti- HLA antibodies might be useful for early identification of at-risk patients who could benefit from closer surveillance and tailored immunosuppressive regimen. Our findings may have relevance for prediction and management of post- LT biliary strictures. [ABSTRACT FROM AUTHOR]

Background & Aim. Wilson's disease (WD) is a rare autosomal recessive disease. More than 500 mutations have been described so far, out of which 29 in exon 14. H1069Q mutation in the exon 14 of ATP7B gene is the most frequently encountered in Europe. The aim of the present study was to evaluate the incidence of mutations occurring in exon 14 of ATP7B gene in Romanian patients referred to a tertiary gastroenterology center, with known or suspected WD and in asymptomatic first degree relatives of index cases. methods: 93 patients were included in the study. Exon 14 of ATP7B gene has been amplified by PCR from genomic DNA and mutations identified by sequencing. Results: Only H1069Q missense mutation was detected in our study group. In patients with an established diagnosis of WD (38 cases), 34.2% were heterozygous for H1069Q and 21.1% were homozygous, with an allelic frequency of 38.1%. In paediatric WD patients (12 cases) 25% were heterozygous and 16.7% were homozygous (not significant versus adult population). Among asymptomatic first degree relatives of patients with WD (12 siblings, 25 parents) there were 40.5% cases heterozygous for H1069Q. In patients with suspected WD (17 cases), only 5.9% were heterozygous and no homozygous patient was identified. In our study group, H1069Q screening alone could not raise the Leipzig score to confirm diagnosis in patients with suspected WD or in asymptomatic first degree relatives. Conclusion: H1069Q mutation is highly prevalent in Romanian WD patients and first degree relatives, similar to other central and continental western European populations. [ABSTRACT FROM AUTHOR]

Background: Antiviral therapy for chronic hepatitis D (delta) is not yet satisfactory, although it appears to be the only means to alter the progressive natural course of chronic hepatitis D virus (HDV) infection. Aim: To assess safety and efficacy, evaluated by virological, biochemical and histological end-of-treatment (EOT) and end-of-follow-up (EOF) response to Peg-Interferon α-2b 1.5μg/kg body weight weekly in a Romanian cohort of naïve patients with chronic hepatitis delta. Results: 49 Caucasian patients (55.1% men, 44.9% females) with a mean age of 37.95 years received study medication; per-protocol population consisted of 36 subjects. Virological EOT response was present in 33.3% and EOF response was maintained in 25% of patients. 50% of study population showed normalization of ALT level at EOT and 25% at EOF. A combined biochemical and virological response was observed in 19.4% of patients at EOT and in 16.7% at EOF. At baseline, the necroinflammation quantified by histological activity index (HAI) score was 9.72 and the mean fibrosis score was 2.03; there was a significant decrease of HAI score to 7.44 (p=0.01) at EOT, but not for fibrosis score (1.33, p=0.37). However, only 8.3% of patients at EOT and 19.4% at EOF had progressive histological disease. Conclusions: Treatment with Peg-Interferon α-2b succeeded in obtaining a negative HVD RNA in 25% of patients after 104 weeks of follow-up, although combined biochemical and virological response was present in only 16.7%. Necroinflammation decreased significantly in treated patients. Longer treatment periods with pegylated interferon or combination regimen peginterferon-nucleotide analogues should be tested in order to increase efficacy. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the efficacy, safety, and immunosuppressant adherence in 125 stable liver transplant (LT) patients converted from twice-daily tacrolimus (TAC BID) to once-daily TAC (TAC OD). Tacrolimus trough levels, laboratory parameters, metabolic disorders, selected patient reported outcomes, and adverse events were assessed. Mean TAC trough level concentration was 6.1 ± 2.3 ng/ml at study entry, decreased to 5.5 ± 2.1 ng/ml ( P = 0.016) and 5.5 ± 2.2 ng/ml ( P = 0.019) after 1 and 2 weeks, respectively, and tended to equal the baseline value during further follow-up. At week 1, TAC concentrations were lower in 62.4% of patients and higher in 36.0% when compared with baseline. Renal and cardiovascular risk factors remained stable and no rejection episodes occurred over 12 months. Adverse events were consistent with the safety profile known from previous studies with TAC BID. Nonadherence measured by the 'Basel Assessment of Adherence Scale to Immunosuppressives' was evident in 66.4% at study entry and decreased to 30.9% postconversion ( P < 0.0001). Prevalence of nonadherence at baseline was significantly higher in patients converted >2 years after LT and in those ≤60 years of age. Conversion to TAC OD is safe, enhances immunosuppressant adherence and should be accompanied by a close TAC level monitoring during the initial period. [ABSTRACT FROM AUTHOR]

Background: Small nodules (<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±10.7 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 of <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>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>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. [ABSTRACT FROM AUTHOR]

Background & 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. [ABSTRACT FROM AUTHOR]

Background and Aim. The number of patients with hepatocellular carcinoma (HCC) listed for liver transplant (LTx) has increased significantly and many of them are now receiving transarterial chemoembolization (TACE) to prevent disease progression. The aim of the study is to analyze the course of disease in patients with HCC who received TACE before LTx. Methods. Patients and tumor characteristics were compared between recipients who received TACE and those who did not. Kaplan-Meier method was used to compare patient survival. Results. Thirty-one patients treated with sequential TACE of a total of 63 patients with proven HCC that underwent LTx between 2013 and 2018 were included in the study. Altogether, 51 TACE procedures were accomplished (range 1-6). Twenty two patients (70.9%) received TACE with Lipiodol while the rest were treated with Debdox. Forty patients were within the Milano criteria and twelve patients (19.04%) had a complete response after TACE. Follow up duration was 72.3 months (62-114) and thirteen patients (20.6%) developed HCC recurrence after LTx. The recurrence free survival was 85.7 %, 69.6% and 58.9% at 1, 3 and 5 years, respectively. There was no significant difference in survival in patients that received TACE compared to those that did not (p=0.455). In the univariate analysis an AFP value greater than 100ng/mL, absence of tumor tissue at the time of LTx and a tumor within Milan criteria were found to be predictive factors for survival but only Milan criteria was significantly associated with survival in multivariate analysis (p=0.007; CI 95%: 0.1262 to 0.7266). Conclusion. TACE is an effective method for the therapy of the HCC before LTx in selected patients Milano criteria is the best predictive factor for survival in HCC patients undergoing liver transplant. [ABSTRACT FROM AUTHOR]

Background & Aims: To evaluate the predictive factors for recurrence of the disease and overall survival (OS) after achieving complete response (CR) in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Methods: From January 2013 to December 2017, 168 treatment-naïve patients diagnosed with HCC underwent TACE as a first-line therapy and the gathered data was retrospectively reviewed. We determined the predictive factors for complete response (CR), for recurrence after CR and for survival using the Cox proportional hazard model. Results: Median follow-up was 27.4 months (range 4-65 months). The mean patient age was 62.2±7.9 years. Eighty-three patients had an α-fetoprotein (AFP) level > 20ng/mL. The median maximal diameter of the tumors was 3.5 cm. Sixty-three patients (37.5%) achieved CR after TACE, and recurrence after CR was detected in 37 patients (58.7%). In multivariate analysis, tumor size (≤4.5 cm) and a single tumor were found to be predictive factors for CR, with hazard ratios (HRs) of 2.352 (p=0.022) and 3.964 (p<0.0001), respectively. After achieving CR the median time to recurrence was 12 months (range 6-24 months). Elevated serum AFP > 25 ng/mL and multiple tumors were demonstrated to have a significant relationship with recurrence after CR, with HRs of 1.650 (p=0.05) and 3.932 (p=0.038), respectively. Increased initial serum AFP > 22 ng/mL, tumor size > 4.5 cm, outside Milan criteria, not receiving a liver transplant and presence of portal vein thrombosis (PVT) were correlated with poor survival. Conclusions: In patients treated with TACE as an initial therapy, tumor size (≤4.5 cm) and single tumor were predictive factors for CR. Multiple nodules and an elevated serum AFP > 25 ng/mL were predictive factors for recurrence after CR. Outside Milan criteria tumors, elevated AFP levels and the presence of PVT were significantly correlated with decreased survival. [ABSTRACT FROM AUTHOR]

Introduction. Patients with end-stage liver diseases, included on the waiting list (WL) for liver transplant (LT) can develop complications that increase the morbidity and mortality, due to different risk factors. The aim was to evaluate different prognostic factors for mortality in patients included on the WL for LT. Materials and Methods. We performed a singlecenter retrospective cohort study from 1 January, 2018 to 31 December, 2022, in 120 patients included on the WL for LT. We analyzed the following prognostic factors: MELD, MELD Na, MELD 3.0, ALBI, occurrence of acute-on-chronic liver failure (ACLF) from grade 1 to 3, occurrence of liver cirrhosis complications, infections, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, plateletto-lymphocyte ratio, using univariable and multivariable Cox proportional hazards models. Results. From 120 patients included, 63.3% were males, with a median age of 55 ± 11.55 years. The most frequent etiology of the liver disease was B + delta hepatitis viral infection in 35.8%, followed by alcoholic etiology in 35% of cases. 30.8% of patients had hepatocellular carcinoma. The median MELD Na score at the inclusion on the waiting list was 17 ±7.3. During the follow-up on the waiting list, 39.2% of patients had infectious complications, such as spontaneous bacterial peritonitis (SBP), pneumonia, urinary tract infections and cellulitis. The median waiting time for all patients was 300 ± 686 days. Liver transplant was performed in 66.7% of cases, and 22.5% patients died during follow-up. Univariate analysis demonstrated that the following factors were associated with higher death rates: presence of ACLF (p<0.0001), refractory ascites (p=0.012), acute kidney injury (p=0.0007), hepatic encephalopathy (p=0.0064), infectious complications (p=0.0077), higher MELD score (p=0.043), MELD Na score (p=0.0048) and MELD 3.0 (p=0.0053), higher NLR (p=0.0011). Multivariate analysis was performed and the presence of ACLF (p=0.0051) and a higher NLR (p=0.042) were found to be independent predictors for mortality. Conclusions. In patients included on the waiting list for liver transplant, occurrence of acute-on-chronic liver failure and neutrophil-to-lymphocyte ratio can be used as predictive factors for mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: The available chemotherapeutic regimens for metastatic pancreatic ductal adenocarcinoma (mPDAC) in Romania include FOLFIRINOX (FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem). The purpose of our study was to compare the efficacy of FFX, GB, and Gem in patients with mPDAC in real-world scenarios. Our research revealed that the overall survival (OS) of patients receiving FFX or GB was comparable, twice as long as that of patients receiving Gem, and the progression-free survival (PFS) was highest for patients receiving FFX as first-line chemotherapy (L1). Male gender, Eastern Cooperative Oncology Group Performance (ECOG-PS) 0/1, the FFX regimen, and neutrophil-to-lymphocyte ratio (NLR) > 4.15 were all independently linked to a longer OS. L1 with FFX improved both OS and PFS for second-line chemotherapy (L2). Purpose: To assess the efficacy of FOLFIRINOX(FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: This is a retrospective study that included 83 patients with mPDAC treated with first-line chemotherapy (L1) with either FFX, GB or Gem between 2015 and 2017. Progression-free survival (PFS) for L1 and second-line chemotherapy (L2) (PFS-L1 and PFS-L2) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: Median PFS-L1 for FFX, GB and Gem groups was 9 months (95% (Confidence Interval) CI 2.76–15.24), 5 months (95%CI 3.44–6.56), and 5 months (95%CI 3.76–6.24), respectively (p = 0.04). OS was 14 months (95%CI 11.16–16.85), 12 months (95%CI: 9.44–11.56), and 7 months (95%CI: 5.7–8.3) for patients treated with FFX, GB, and Gem, respectively (p = 0.0001). ECOG-PS (0/1) (Hazard Ratio (HR) 6.74, p = 0.002), age > 70 years (HR 0.25, p = 0.04), body tumors (HR 2.8, p = 0.048), CA19–9 > 39 U/mL (HR 0.26, p = 0.02), and neutrophil-to-lymphocyte ratio (NLR) > 4.15 (HR 6.76, p = 0.001) were independent prognostic factors for PFS-L1. Male gender (HR 3.02, p = 0.026), ECOG-PS (0/1) (HR 4.21, p = 0.003), L1 with FFX (HR 0.255, p = 0.007), and NLR > 4.15 (HR 2.65, p = 0.04) were independent prognostic factors of OS. PFS-L2 (HR 6.91, p = 0.013) and OS-L2 (HR 6.95, p = 0.037) were significantly higher in patients first treated with FFX. Conclusions: The OS of patients who receive FFX or GB is comparable. The best PFS-L1 belongs to the FFX group. Male gender, ECOG-PS 0/1, the FFX regimen, and NLR > 4.15 were independent predictors of OS. PFS-L2 and OS-L2 were favorably impacted by L1 with FFX. [ABSTRACT FROM AUTHOR]

Hepatitis C viral (HCV) treatment has rapidly advanced with the use of direct-acting antivirals (DAA), and many patients achieve sustained virological response (SVR). Although the risk of liver tumors is greatly reduced, there are still patients who achieve SVR but will progress to hepatocellular carcinoma (HCC). HCV infection is also a known risk for cholangiocellular carcinoma (CLC), although it is considered a relative infrequent liver malignancy. We report a series of five cases of CLC in patients that achieved SVR after HCV treatment with DAA. There were three women and two males with a median age of 62 years (range 49 to 77 years). Four patients had liver cirrhosis at the time of their HCV treatment. The interval from achieving SVR until CLC diagnosis varied, ranging from 4 to 36 months (median=12). Three patients presented with advanced disease and had extrahepatic spread at the time of their diagnosis. One patient had a resectable tumor, with no recurrence 4 years later. In one case, the tumor was initially considered an atypical HCC and was treated by radiofrequency ablation. Three years later, she was diagnosed with a large tumor recurrence that was demonstrated to be a CLC on liver biopsy. The last two patients were older males with HCV compensated cirrhosis diagnosed with CLC more than two years after achieving SVR. Palliative chemotherapy was started in both. Only a handful of CLC cases have been reported in HCV patients after SVR. Clinicians should take into account the possible development of an aggressive CLC. [ABSTRACT FROM AUTHOR]

Background: Hepatitis delta virus (HDV) infection is associated with accelerated progression of fibrosis, early occurrence of hepatic decompensation and an increased risk for hepatocellular carcinoma. Epidemiological data on hepatitis delta virus (HDV) in Romania are still lacking. Aim: To assess the prevalence, virological, clinical and epidemiological features of HDV infection in Romanian patients. Methods: We conducted a multicenter study in 10 centers. Data on sociodemographic characteristics and potential risk factors were collected through a questionnaire. Virological markers of HBV and HDV infection, biochemical and clinical features of liver disease were evaluated. Results: The study population comprised 2,761 HBsAg(+) patients with a mean age of43.8±13.8years, out of whom 5.2% were HBeAg(+) and 55.7% were males. Liver cirrhosis was detected in 17.9% of patients, while 80.4% had chronic hepatitis. The prevalence of IgG anti-HDV(+) patients was 23.1%, out of whom 16.4% were HDV RNA positive. The highest prevalence of HDV infection was encountered in patients aged 50-59 years (28.9%) and patients aged >60 (24.8%) (p=0.0001). Seroprevalence of HDV was significantly higher in AgHBs(+) cirrhotics vs. noncirrhotics (43.4% vs 19.0%, p=0.0001). Risk factors for HDV infection were: occupational hazard, no HCV chronic infection, lack of anti-HBV vaccination, presence of blood transfusions, any previous surgery, frequent hospitalization or endoscopies, tattoos, body piercing, use of glass syringes, number of female sexual partners. Conclusions: HBsAg(+) population in Romania is characterized by a high prevalence of HBeAg(-) HBV infection as well as HDV co-infection. A cohort phenomenon for HDV prevalence is also observed similar to that of HCV/HBV monoinfections. [ABSTRACT FROM AUTHOR]

Background & Aims: Oncogene polycomb group protein enhancer of zeste homolog 2 (EZH2) has been proposed to be a target gene of putative tumor suppressor microRNA-101 (miR-101). The aim of our study was to investigate the functional role of both miR-101 and EZH2 in human hepatocellular carcinoma (HCC). Methods: MiR-101 and EZH2 expressions were evaluated in tumor tissues of 99 HCC patients and 7 liver cancer cell lines by real-time PCR. Luciferase reporter assay was employed to validate whether EZH2 represents a target gene of miR-101. The effect of miR-101 on HCC growth as well as programmed cell death was studied in vitro and in vivo. Results: MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH2. Luciferase assay results confirmed EZH2 as a direct target gene of miR-101, which negatively regulates EZH2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo. Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. Conclusion: Tumor suppressor miR-101 represses HCC progression through directly targeting EZH2 oncogene and sensitizes liver cancer cells to chemotherapeutic treatment. Our findings provide significant insights into molecular mechanisms of hepatocarcinogenesis and may have clinical relevance for the development of novel targeted therapies for HCC. [Copyright &y& Elsevier]

• The SarQoL questionnaire is the only validated instrument to measure quality of life in sarcopenia. • In this meta-analysis, data on individual patients from 32 studies were combined. • Sarcopenia is associated with lower quality of life measured with SarQoL. • Activities of daily life and locomotion are the two most impacted domains. Age-related sarcopenia, resulting from a gradual loss in skeletal muscle mass and strength, is pivotal to the increased prevalence of functional limitation among the older adult community. The purpose of this meta-analysis of individual patient data is to investigate the difference in health-related quality of life between sarcopenic individuals and those without the condition using the Sarcopenia Quality of Life (SarQoL) questionnaire. A protocol was published on PROSPERO. Multiple databases and the grey literature were searched until March 2023 for studies reporting quality of life assessed with the SarQoL for patients with and without sarcopenia. Two researchers conducted the systematic review independently. A two-stage meta-analysis was performed. First, crude (mean difference) and adjusted (beta coefficient) effect sizes were calculated within each database; then, a random effect meta-analysis was applied to pool them. Heterogeneity was measured using the Q-test and I2 value. Subgroup analyses were performed to investigate the source of potential heterogeneity. The strength of evidence of this association was assessed using GRADE. From the 413 studies identified, 32 were eventually included, of which 10 were unpublished data studies. Sarcopenic participants displayed significantly reduced health-related quality of life compared with non-sarcopenic individuals (mean difference = −12.32; 95 % CI = [−15.27; −9.37]). The model revealed significant heterogeneity. Subgroup analyses revealed a substantial impact of regions, clinical settings, and diagnostic criteria on the difference in health-related quality of life between sarcopenic and non-sarcopenic individuals. The level of evidence was moderate. This meta-analysis of individual patient data suggested that sarcopenia is associated with lower health-related quality of life measured with SarQoL. [ABSTRACT FROM AUTHOR]

Background & Aims: Bowel ultrasound (BU) is a non-invasive, inexpensive, widely available tool, valuable for inflammatory bowel disease (IBD) assessment. The aim of the present study was to investigate the clinical utility of BU to predict the need to intensify therapy in IBD patients. Methods: One hundred seventeen IBD patients (89 Crohn's disease, and 28 ulcerative colitis) diagnosis established at least 6 months before enrolment, undergoing maintenance therapy were prospectively included in the study. Bowel ultrasound investigated the following parameters: the bowel wall thickness (BWT), loss of wall stratification, the presence of the bowel wall Doppler signal, the visible lymph nodes, the mucosal hyperechoic spots, and the irregular external bowel wall. The patients were followed-up for 6 months, registering the need to escalate the treatment regimen. Subgroup analyses were conducted for patients requiring immediate treatment intensification (37 subjects), due to active disease at baseline and patients with subsequent treatment intensification, in the 6 months follow-up period (21 cases) in comparison to patients that required no therapeutic optimization (59 cases). Results: During the follow-up, 49.6% of patients needed treatment escalation. All the investigated BU variables were significantly associated with the main outcome. In the multivariate analysis, the mean BWT (p<0.0001), and the presence of the bowel wall Doppler signal (p=0.007) were independent predictors of the main outcome. For the subgroup analyses: mean BWT (p=0.0001) and the presence of the bowel wall Doppler signal (p=0.01) were independent predictors for immediate treatment intensification (active disease at baseline) and mean BWT (p=0.0003) and the lack of bowel wall stratification (p=0.05) were independent predictors for the need of subsequent therapeutic optimization. Logistic regression prediction models and prediction scores (BU score) had the best AUROC values (>0.91) when compared to traditional biomarkers of active inflammation, such as C reactive protein or fecal calprotectin. Conclusion: Bowel ultrasound could be used as a non-invasive, easy to use diagnostic tool to predict the need to intensify therapy in patients with IBD. [ABSTRACT FROM AUTHOR]

Aims: This study was aimed at determining the seroprevalence of hepatitis C virus (HCV) infection in Romania and the possible risk factors and modality of HCV transmission. Methods: A nationwide cross-sectional survey among the adult population was conducted between 2006-2008 in Romania through a population multicenter stratified random cluster sampling. Serum samples from 13,460 subjects were tested with a 3rd generation ELISA and a standardized questionnaire concerning the socio-demographic characteristics and potential risk factors was used. Results: The prevalence rate of HCV infection in Romanian adult population was 3.23% with significant differences between the main geographical regions (Moldavia 4.25%, Wallachia & Dobrogea 3.35% and Transylvania & Banat 2.63%), as well as between different counties (maximum 7.19%, minimum 0.56%). Overall participation rate to the survey of the selected subjects was 74.69%. Risk factors for HCV infection were: blood/blood products transfusions (p=0.0001), previous surgery (elective and emergency, p=0.0001 and p=0.043, respectively), frequent hospitalizations (p=0.0001), injections at home (p=0.0001), accidents/trauma (p=0.0001), occupational hazard related to blood exposure (p=0.025), intravenous drug administration (p=0.002), a partner chronically infected with HCV/hepatitis B virus (HBV) (p=0.046), first sexual intercourse <18 years (p=0.019), familial exposure to HCV/HBV infection (p=0.001) or to chronic HBV/HCV liver disease (p=0.001), personal history of chronic HBV infection (p=0.001). HCV RNA positivity was detected in 91% of the anti HCV positive subjects. Conclusions: Overall HCV prevalence in Romania is 3.23%. Both nosocomial and non-nosocomial routes are implicated as risk factors for HCV infection. [ABSTRACT FROM AUTHOR]

A case study is presented on the prevalence of hepatitis B and C virus infections in the Roma population in Romania, highlighting higher infection rates in this group compared to the general population and the importance of screening. However, itraises concerns about the limited sample size and lack of a clear methodology in the study, questioning its representativeness for the broader Roma population.

Background & Aims: Inflammatory bowel diseases (IBD) patients management has been challenging during the ongoing coronavirus disease 2019 (COVID-19) pandemic, due to lockdowns, limitation of access to medical facilities and new recommendations regarding patient management. The implications of the COVID-19 pandemic on IBD patients' management were assessed in our Tertiary Gastroenterology Center in Bucharest, Romania. Methods: Medical records of IBD patients admitted between 15th of March and 15th of August 2020 were retrospectively reviewed and compared to a control cohort of consecutive IBD patients admitted to our unit during the corresponding period of 2019. Results: There was a highly significant shift towards one-day hospitalization during the referral period in 2020 for IBD cases (91% in 2020 vs 82.2% in 2019, p=0.0001). There was no statistically significant difference between the distribution of patient's gender, IBD phenotype or newly diagnosed IBD cases. A significantly lower proportion of admitted patients received 5-aminosalicylic acid (29% vs 41.2%, p=0.0001), whereas a substantially higher number of patients were prescribed biological therapy in 2020 in comparison to the corresponding 2019-time frame (79.5% vs 57.9%, p<0.0001). The distribution of the biological agent used was significantly different in 2019 in comparison to the 2020 period mainly due to the increase in vedolizumab prescription in 2020 (p<0.0001). During the study period in 2020, seven IBD patients (1.7%) were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection, all of them with mild symptoms without impact on the IBD course. Conclusions: The COVID-19 pandemic led to reorganizing medical care, limiting the hospital admissions in favor of severe IBD cases, favoring telemedicine for mild disease and optimization of treatment for moderate to severe IBD with an increased use of biologicals aimed to maximize the risk/benefit ratio. Incidence of SARS-Cov2 infection during the first wave of COVID-19 infection in our study group was 1.7% and did not adversely impact the IBD disease course. [ABSTRACT FROM AUTHOR]

Background & Aims: Ledipasvir/Sofosbuvir (LDV/SOF) with or without Ribavirin (RBV) has shown good results in terms of efficacy and safety in clinical trials in advanced liver cirrhosis, but real-life data are still needed in order to confirm this profile. We investigated the efficacy and safety of LDV/SOF in a large Romanian population with liver cirrhosis and genotype 1b hepatitis C virus (HCV). Methods: We analyzed a multicentric retrospective cohort enrolling 349 patients with decompensated liver cirrhosis due to HCV who received LDV/SOF±RBV 12/24 weeks (301/48). Patients were included between 2017-2018, all with genotype 1b. Main inclusion criteria were liver cirrhosis and detectable HCV RNA. The cases were followed-up monthly during therapy and 12 weeks after the end of therapy. Results: The cohort included 60% females with a median age of 61, 16% interferon (IFN) pre-treated, 53% with comorbidities, 40/53/7% with Child Pugh A/B/C, 4% with virus B co-infection and 8% with previously treated hepatocellular carcinoma. Mean initial MELD score was 11.92 (6.82÷ 24.5). Six patients were lost during follow-up. Sustained virologic response (SVR) in intention-to-treat was reported in 85.1%. Predictive factors of SVR in decompensated cirrhosis were female gender (p=0.01), advanced age (p<0.001), lower bilirubin levels (p=0.002) and lower CTP score (p=0.02). In patients with CTP score B or C low bilirubin levels (p=0.003), low INR (p<0.001), increased platelet count (p=0.04), low CTP score (p<0.001), lack of encephalopathy (p=0.02), serum albumin >3.5g/dl (p=0.002) predicted improvement of liver function. Serious adverse events were reported in 16/349 (4.6%), most of them due to severe liver decompensation (9/16). Conclusions: LDV/SOF±RBV proved to be highly efficient in our difficult to treat population with 85.1% SVR. [ABSTRACT FROM AUTHOR]

Background: In Romania, 23 patients have been diagnosed with hereditary transthyretin amyloidosis (ATTRh), 18 of whom have the Glu54Gln mutation. This retrospective cohort included all patients with Glu54Gln-mutated ATTRh who were diagnosed in Romania from 2005 to 2018.Results: Of 18 patients, 10 were symptomatic, five were asymptomatic carriers and three died during the study. All originated from North-East Romania. Median age at symptom onset was 45 years; median age at death was 51 years. All patients had cardiac involvement, including changes in biomarkers (mean N-terminal-pro B-type natriuretic peptide: 2815.6 pg/ml), electrocardiography (15% atrial fibrillation, 38% atrioventricular block, 31% right bundle block), and echocardiography (mean interventricular septum: 16 mm, mean left ventricular ejection fraction: 49%). Scintigraphy showed myocardial radiotracer uptake in all patients. In addition, 92% of patients had polyneuropathy at diagnosis and 53% had carpal tunnel syndrome; 69% exhibited orthostatic hypotension and 31% suffered from diarrhea. No renal or liver involvement was observed.Conclusions: This is the largest Glu54Gln-mutated ATTRh cohort diagnosed to date, and to our knowledge the first describing this variant worldwide. Clinical features of this variant are early onset, neurological and cardiac involvement, aggressive disease progression and short survival. Early diagnosis and therapeutic intervention have potential to improve prognosis in ATTRh. [ABSTRACT FROM AUTHOR]

Background: The biliary complications (BC) have been always considered the „Achilles' heel" of liver transplantation (LT), being one of the leading causes of postoperative morbidity. Aim: To analyse predictors of BC, by monitoring in the peripheral blood the biomarkers involved in the inflammation and hepatic fibrosis, such as the matrix metalloproteinases (MMP 2, 9) and their tissue inhibitors (TIMP1), the interleukins (IL 2, 8), alfa-TNF, the endothelins and their receptors. Methods: Thirty LT patients were followed-up prospectively for 5 years. The mRNA for the following biomarkers was quantified in the peripheral blood by qRTPCR and protein expression investigated by ELISA: MMP 2, 9, TIMP1, IL 2, IL 8, TNF-alfa, and endothelins and their receptors. Results: Five patients developed anastomotic stenosis (AS). There was no difference regarding mRNA levels for all studied genes between AS and non-AS patients. Two cytokines were significantly different: pre-LT TNF alpha was higher in the non-AS group and post-LT endothelin-1 at day 7 and month 3 were higher in the AS group. There was a trend for lower levels of serum cytokines for patients without AS compared to patients with AS. Conclusion: BC play an important role in the patients' postoperative morbidity and molecular biomarkers prediction should improve their early recognition and treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about the reactions of somatic mutation (V617F) in the Janus tyrosine kinase-2 (JAK2) gene of Budd-Chiari syndrome which appeared in the September 2009 issue.

Background & Aims. Serological markers have been widely used for diagnostic purposes and disease stratification in inflammatory bowel diseases (IBD). The aim of this study was to investigate the seroprevalence and the correlations of anti-Saccharomyces cerevisiae antibodies (ASCA) titers with different clinical phenotypes in Romanian patients with Crohn's disease (CD). Methods. The study included 107 CD and 86 ulcerative colitis (UC) patients from the Gastroenterology Departments of three University Hospitals, and 60 healthy subjects. ASCA IgA and IgG titers were determined using ELISA test. For CD patients the phenotype was established according to the Montreal classification. The differences in ASCA titers for different CD phenotypes were assessed using the Mann-Whitney U test. Results. ASCA prevalence was 33.6% in CD group, 12.8% in UC group and 6.6% in the control group. Significantly higher IgA (p=0.05) and IgG (p=0.03) titers were found in patients from the Montreal A1+A2 groups (age at onset below 40) compared with the older patients (A3). Higher titers were found in patients with extensive ileo-colonic lesions (L3) and upper gastrointestinal tract involvement (L4) than in patients having only colonic disease (L2). Significantly higher IgA (p=0.03) and IgG (p=0.03) titers were observed in patients with stenosing (B2) and penetrating (B3) disease compared with the nonstricturing, nonpenetrating (B1) phenotype. No correlation between ASCA titers and disease duration was found. Conclusion. ASCA seropositivity in Romanian CD patients is lower than in Western Europe. Higher ASCA IgA and IgG titers are associated with a younger age at diagnosis and more aggressive phenotypes. [ABSTRACT FROM AUTHOR]

Background: An overall prevalence rate of HCV infection in Romanian adult population was recently estimated to be 3.23%. The proportion of treated patients with chronic hepatitis C in our country has never been assessed. Aims: 1) to analyze the quality and quantity of antiviral therapy delivery; 2) to determine the proportion of patients being annually and ever treated with antiviral therapy in Romania and 3) to identify barriers against treatment of HCV infected-population in Romania. Results: The number of annually treated patients remained relatively stable between 2002 and 2007 (1,813 patients treated with pegylated interferon and ribavirin in 2002 and 2,446 in 2007). There was a doubled increase in reimbursed treatment in 2008 and 2009 (4,503 and respectively 4,701 treated patients) due to a special campaign organized to increase awareness and prevention of HCV transmission. The median time to therapy approval varies from county to county; overall it is 10.23 months. A total number of 25,318 patients with chronic C hepatitis were treated between 2002-2009, corresponding to a cumulative proportion of 4.1% of the prevalent cases of HCV infection treated in Romania until 1st January 2010. The main limiting factor of access to antiviral therapy for hepatitis C in Romania remains the lack of funds. Conclusions: This is the first analysis of the nationwide practice for treatment of hepatitis C in Romania. Increased public health efforts are required to improve access to antiviral therapy for hepatitis C in Romania. [ABSTRACT FROM AUTHOR]

Background: Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion. Methods: Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRTPCR and western blotting analysis. Results: A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells. Conclusions: Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC. [ABSTRACT FROM AUTHOR]

A 46-yr-old female with hepatocellular carcinoma and severe hepatitis B-related liver cirrhosis received a domino liver graft from a 25-yr-old female with homozygous familial hypercholesterolemia (HFHC) in September 2001. Hypercholesterolemia occurred in the graft recipient within one yr after transplantation and was partially controlled by atorvastatin. Three yr after transplantation, an autologous CD34+ cell transplantation was performed in order to better control the hypercholesterolemia. Only preliminary results of this domino liver transplantation (DLT) were published in 2003, without a long-term analysis of the hypercholesterolemic effects in recipient. Subsequent to DLT, the average plasma cholesterol level in the domino donor rapidly normalized and seven yr after had a value of 182 mg/dL. After seven-yr follow-up, the domino recipient has no hepatocarcinoma recurrence. Moreover, no signs of cardiovascular or atherosclerotic lesions were noted despite an elevated plasma cholesterol level (339 mg/dL after seven yr of follow-up) resistant to drug therapy and stem cell autotransplantation. In conclusion, DLT using a liver graft from a patient with HFHC provides a viable option for marginal recipients. [ABSTRACT FROM AUTHOR]

Highlights from the article: All patients had positive family history, the average age at diagnosis was 46.5 years (excluding the 16-year-old carrier - the son of one of the patients), of which 5 male and 4 female patients. Onset symptoms were carpal tunnel syndrome (4 patients), peripheral neuropathy (all patients), diarrhoea (1 patient), constipation (2 patients), cardiac failure (4 patients) and weight loss (4 patients). The age at diagnosis in patients with transthyretin Glu54Gln hereditary amyloidosis is around 46, they have positive family history as well as a long personal history of axonal sensory-motor neuropathy with autonomic symptoms and restrictive cardiomyopathy.

Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression and therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCC patients who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes—freedom of liver recurrence (FLR), disease-free survival (DFS) and overall survival (OS)—was tested using univariate and multivariate Cox regression analyses. Results: Survival outcomes associated with sVEGFR1, VEGF and VEGF-C in LT patients and with IL-10 in LR patients. Moreover, in LT patients within Milan criteria, higher plasma VEGF and sVEGFR1 were associated with worse outcomes, while in those outside Milan criteria lower plasma VEGF-C associated with better outcomes. Multivariate analysis indicated that adding plasma VEGF or VEGF-C to a predictive model including Milan criteria and AFP improved prediction of DFS and OS (all p < 0.05). Conclusion: Survival outcomes after LR or LT differentially associated with angiogenic and inflammatory biomarkers. High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification. [ABSTRACT FROM AUTHOR]