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To identify baseline OCT predictors of the 3-year visual outcome for type 3 (T3) macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) treated by anti-vascular endothelial growth factor (VEGF) therapy.Retrospective longitudinal study.Forty eyes of 30 patients affected by exudative treatment-naive T3 MNV were enrolled.Baseline best-corrected visual acuity (BCVA) and several baseline OCT features were assessed and included in the analysis. Univariate and multivariate analyses served to identify risk factors associated with the 3-year BCVA.Baseline OCT features that are associated with bad or good visual outcomes of T3 MNV treated by anti-VEGF injections.Mean baseline BCVA was 0.34 ± 0.28 logarithm of the minimum angle of resolution (LogMAR), which significantly decreased to 0.52 ± 0.37 LogMAR at the end of the 3-year follow-up (P = 0.002). In the univariate analysis, the following baseline features were associated with the 3-year BCVA outcome: baseline BCVA (P = 0.004), foveal involvement of exudation (P = 0.004), and presence of subretinal fluid (SRF; P = 0.004). In the multivariate model, baseline BCVA (P = 0.032), central macular thickness (P = 0.036), number of active T3 lesions (P = 0.034), and presence of SRF (P = 0.008) were associated with the 3-year BCVA outcome. Interestingly, 3-year BCVA was significantly lower in 19 eyes with SRF at the baseline (0.69 ± 0.42 LogMAR) than 21 eyes without SRF (0.37 ± 0.24 LogMAR; P = 0.004).We identified structural OCT features associated with BCVA outcome after 3-year treatment with anti-VEGF injections. In contrast to previous studies on neovascular AMD, in our series, the presence of SRF at baseline was the most significant independent negative predictor of functional outcomes. Current findings may be employed to identify less favorable T3 patterns potentially deserving a more intensive treatment.

Wilson's disease (WD) is a rare inherited disorder of human copper metabolism, with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations. In healthy individuals, the bile is the main route of elimination of copper. In WD patients, copper accumulates in the liver, it is released into the bloodstream, and is excreted in urine. Copper can also be accumulated in the brain, kidneys, heart, and osseous matter and causes damage due to direct toxicity or oxidative stress. Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood. Adherent, non-cirrhotic WD patients seem to have a normal life expectancy. Nevertheless, chronic management of patients with Wilson's disease is challenging, as available biochemical tests have many limitations and do not allow a clear identification of non-compliance, overtreatment, or treatment goals. To provide optimal care, clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment. The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD. In particular, it summarises current knowledge on Wilson's disease clinical and biochemical monitoring and treatment. It also analyses available evidence on pregnancy and the role of low-copper diet in WD. Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.

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Table S1. Characteristics of the healthy subjects (HS) and patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC)

Introduction Published data on possible ocular adverse events potentially associated with vaccination with the SARS-Cov-2 mRNA-1237 vaccine are scarce. In this report, we describe the case of a patient who had a hemispheric retinal vein occlusion potentially associated with being vaccinated with the second dose of the SARS-Cov-2 mRNA-1237 vaccine. Methods Case report including a discussion on multimodal imaging. Results A 74-year-old woman presented with painless vision loss in the right eye experienced 48 hours after receiving a second dose of the mRNA-1237 vaccine. The patient was receiving oral anticoagulant therapy for atrial fibrillation. Her best-corrected visual acuity (VA) was 20/32, and fundus examination showed venous congestion and widespread blot haemorrhages in the inferior quadrants. Based on multimodal imaging evaluation, the diagnosis of hemispheric retinal vein occlusion was made. Due to the development of cystoid macular oedema with intraretinal fluid and the decline in VA, the patient was treated with two injections of intravitreal ranibizumab, leading to functional improvement and regression of oedema. Conclusions We report a case with retinal vein occlusion 48 hours after vaccination with the SARS-Cov-2 mRNA-1237 vaccine; however, the relationship between these two events remains unclear. Further research is warranted to better understand the potential link between retinal thrombotic events and vaccination.

To investigate fellow eyes of newly diagnosed unilateral exudative Type 3 (T3) macular neovascularization (MNV) patients by assessing the presence and progression of a preclinical neovascular component during a 3-year follow-up.This is a longitudinal study involving three retinal referral centers. Patients affected by unilateral exudative treatment-naive T3 MNV were enrolled.Twenty-four eyes of 24 patients (79 ± 6 years old) were enrolled. Nine eyes (37%) displayed a nonexudative T3 MNV at baseline that developed exudation after a mean of 9 ± 9 months. Fifteen eyes that did not display a nonexudative Type 3 MNV at baseline. Five eyes (21%) did not display neovessels at baseline, but showed a nonexudative T3 after 13 ± 9 months, and exudation after 8 ± 3 months. Five eyes (21%) developed active exudative T3 MNV after 23 ± 9 months, with no detectable nonexudative stage at baseline. Five eyes (21%) did not show MNV, but progressed to geographic atrophy by 36 months of follow-up. Overall, T3 MNV in the fellow eye accounted for 79%, all developing exudation over 3 years of follow-up.The occurrence of a nonexudative T3 MNV is a frequent event in the fellow eye of patients newly diagnosed with unilateral exudative T3 MNV and it precedes the development of exudation over 3 years (prevalence of 37% and cumulative incidence of 79%). Optical coherence tomography angiography approach may be used to perform an early diagnosis and treatment of patients with T3 MNV.

Introduction To report two cases of Acute Macular Neuroretinopathy (AMN) presented as the first stage of SARS-CoV-2 infection in two European countries during the third wave of pandemic viral infection in the early months of 2021. Observations A unilateral case of type 1 AMN in a man and a bilateral case of type 2 AMN in an otherwise heathy patients were reported. Sudden onset of paracentral scotoma characterized the cases with no systemic symptoms. Structural optical coherence tomography (OCT) shows multifocal middle and inner retinal hyperreflective infarctions. OCT-Angiography showed the presence of hypoperfusion of the deep capillary plexus (DCP) corresponding to the hyperreflective lesions visible on structural OCT, confirming the diagnosis. Conclusions and importance Type 1 and type 2 AMN may be the first stage of SARS-CoV-2 infection. We suggest testing all patients with AMN for SARS-CoV-2. In our cases, the natural history of AMN associated with SARS-CoV-2 infection was similar to already described cases of AMN.

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis (PBC), affecting over 50% of PBC patients. One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life. Fatigue is made up of a central and a peripheral component, whose pathophysiology is still greatly unresolved. Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities (lack of intention). Peripheral fatigue includes neuromuscular dysfunction and muscle weakness (lack of ability). Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time. As opposed to itching, and with the exception of end-stage liver disease, fatigue is not related to disease progression. The objective of this review is to outline current understanding regarding the pathophysiology of fatigue, the role of comorbidities and contributing factors, the main tools for fatigue assessment, the failed therapeutic options, and future treatment perspectives for this disabling symptom. Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients, further research is warranted to understand its causative mechanisms and to find an effective treatment.

Introduction Lyme borreliosis may present with different systemic manifestations and also the ocular involvement may be difficult to diagnose because of its multifaceted presentation. Considering the growing incidence of Lyme disease in European countries, ophthalmologist should be trained to distinguish ocular borreliosis. Case Report Several clinical presentations have been previously described, including uveitis, unilateral or bilateral chorioretinitis, keratitis, episcleritis, papillitis and ischemic optic neuropathy, retinal vasculitis and acute posterior multifocal placoid pigment epitheliopathy (APMPPE); however our case report showed a rare presentation with the presence of unilateral uveitis with vitreitis and multiple, patchy, yellowish lesions, in association with retinal vasculitis. This clinical picture was to be considered in differential diagnosis with ocular Toxoplasmosis. Conclusions The appropriate management of this patient was made possible by the combination of multimodal imaging and appropriate laboratory tests, representing the optimal process in the diagnostic and therapeutic pathway in high-risk patients for ocular Lyme disease.

Heavy-duty mobile machines (HDMMs), are a wide range of off-road machinery used in diverse and critical application areas which are currently facing several issues like skilled labor shortage, safety requirements, and harsh work environments in general. Consequently, efforts are underway to increase automation in HDMMs for increased productivity and safety, eventually transitioning to operator-less autonomous HDMMs to address skilled labor shortages. However, HDMM are complex machines requiring continuous physical and cognitive inputs from human operators. Thus, developing autonomous HDMM is a huge challenge, with current research and developments being performed in several independent research domains. Through this study, we use the bounded rationality concept to propose multidisciplinary collaborations for new autonomous HDMMs and apply the transaction cost economics framework to suggest future implications in the HDMM industry. Furthermore, we introduce and provide a conceptual understanding of the autonomous HDMM industry collaborations as a unified approach, while highlighting the practical implications and challenges of the complex nature of such multidisciplinary collaborations. The collaborative challenges and potentials are mapped out between the following topics: mechanical systems, AI methods, software systems, sensors, data and connectivity, simulations and process optimization, business cases, organization theories, and finally, regulatory frameworks., MORE Project

Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies. Significance: This study uncovers a link between a central effector of DNA damage response, CHK2, and cellular metabolism, revealing potential therapeutic strategies for targeting hepatocellular carcinoma.

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries' economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy.We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress.Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44 ± 15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin's lymphoma in 10.5%).Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)-infected patients in the Tuscan public health care system. METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

Aims Fibroscan® is a non-invasive method to evaluate liver stiffness (LS), however, its accuracy in alcohol-related liver diseases (ALD) especially with respect to active or stopped alcohol drinking is largely unknown. We prospectively evaluated the LS changes in patients with ALD following alcohol withdrawal. Methods Sixty-four patients were evaluated by FibroScan® and lab tests at baseline and after 4 weeks of abstinence. Results At baseline, 21 patients (33%) had an abnormal LS (> 7 kPa) and 32 patients (50%) had abnormal liver function tests. More specifically, 3 and 11 subjects had a LS higher than 9.6 kPa and 12.5 kPa, respectively. The LS significantly declined in abstinent from 9.2 ± 10.1 (M±SD) at the baseline to 6.9 ± 6.1 kPa at 4 weeks ( P = 0.03), respectively, while did not change significantly in drinkers. In addition, 80% of abstainers had a significant LS reduction (−2.6 ± 5.5 kPa), compared to drinkers (2.2 ± 3.6 kPa) ( P = 0.004). After 6 months, 27 patients accepted a further evaluation: 22 abstinent and 5 relapsed to drink. At the final evaluation, only 4 out of 22 abstainers had still a LS higher than 7 kPa. Conclusions During active drinking LS is probably overestimated by Fibroscan® in ALD, since 1 month after abstinence it is dramatically reduced, especially in subjects with baseline values higher than 7 kPa. Short summary We prospectively evaluated liver stiffness by Fibroscan® in patients with alcohol-related liver disease at baseline and following abstinence. After 1 month of abstinence, the LS is dramatically reduced, especially when values are greater than 7 kPa and transaminase elevated at baseline.

Background & Aims Different prevalence of favourable IL28BCC genotype have been reported in studies performed in different countries around the world. Data on distribution of IL28B genotypes in healthy Italian subjects are lacking. Methods Studies on prospectively collected untreated chronic HCV-infected Italian patients led to conflicting results. To investigate the prevalence of IL28B genotypes in untreated HCV-infected patients and in subjects able to clear HCV, and to compare them to the prevalence registered in healthy Italian controls. To evaluate IL28B prevalence across different HCV genotypes. Results IL28BCC was observed in 30.9% of chronic HCV patients, in 71.0% of subjects able to clear HCV infection and in 41.6% of the Italian controls. The frequency of IL28BCC was higher in HCV genotype 2 and 3 than in 1 (38.3 vs. 28.2) (P = 0.02). Levels of ALT higher in IL28BCC than in non-CC were observed regardless of HCV genotypes (P = 0.0014). Conclusions IL28BCC frequencies progressively decline from subjects with spontaneous HCV clearance to normal non-infected subjects and to chronically infected. This study suggests that patients with IL28BCC, if genotype 1, are able to clear HCV more often than if genotype 2 and 3 infected, and that CC genotype is associated with higher grade of necro-inflammation.

Background Triple therapy including Telaprevir or Boceprevir still represents in many European countries the standard of care for patients with Hepatitis C Virus genotype 1 infection. The number of patients who received this treatment resulted generally lower than expected. We investigated, among naive patients, number and characteristics of treatment candidates who were started on triple or dual therapy in comparison to those who were deferred. Patients and Methods 621 naive treatment candidates were prospectively evaluated at each center. Factors associated with decision to defer or treat with dual or triple therapy were investigated by univariate and multivariate analyses. Rates of Sustained Virological Response and safety profile were analysed. Results Of candidates to treatment, 33% did not received it. It was mostly due to high risk of Interferon-induced decompensation. Of 397 patients who were started on treatment, 266 (67%) received triple, 131 dual. Among patient receiving treatment, unfavorable IL28B, severe liver damage and higher albumin were independently associated with the physician decision to administer triple therapy. Sustained Virological Response after dual therapy was 66.4%, after triple 73.7% (p = 0.14). 142 patients received Telaprevir. The choice of Telaprevir-based therapy was associated with higher Body Mass Index and advanced liver disease. Sustained Virological Response rates were 71.1% after Telaprevir and 76.6% after Boceprevir. Conclusions Individualizing treatment with available regimens allows to maximize Sustained Virological Response and to reduce the number of patients who remain untreated. High proportion of patients with severe liver damage urgently need Interferon free treatment.

s / Digestive and Liver Disease 48S (2016) e1–e17 e5 eGFR was ≥60mL/min/1.73m2 in 92 patients (93.8%) and between45and59mL/min/1.73m2 in6patients (6.1%).Glomerular involvement was found in 19 patients (19.4%), tubular involvement in 31 (31.6%) and they co-occurred in 10 patients (p=0.034). Subjects with glomerular or tubular involvement, or both, showed significantly lower eGFRvalues (p=0.005). AROC curvewasdrafted and a cut point of 90ml/min predicted renal involvement (RI) (sensitivity 63%, specificity 75%), although it was unable to distinguish tubular vs glomerular involvement (p=0.914). Patients with RI were older, had higher ACR and 1MCR levels and exhibited a more severe KDIGO stage. No association was found between RI and: HCV-RNA levels, liver stiffness and liver function tests. L-FABP andKIM-1 levelswere significantlyhigher inpatientswithRI. Tubular involvement was significantly associated with increased levels of L-FABPandKIM-1,while glomerular involvementwas associated only with high L-FABP level. Conclusion: Tubular and/or glomerular involvement are quite frequent in HCV cirrhotic patients. The occurrence of eGFR

Background Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4). Method 267 naive HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n = 180) or current standard-of-care (SoC, n = 87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2 log10 at week 12 or detectable HCV-RNA at week 24 discontinued treatment. Results Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25 ± 15 vs. 36 ± 12.1 weeks], and for subgroups: G1 [35.3 ± 16.7 vs. 47.3 ± 2.6 weeks], G2 [18.3 ± 7.5 vs. 24 ± 2.8 weeks], G3 [15.2 ± 8.7 vs. 22.8 ± 3 weeks] and G4 [26.9 ± 13 vs. 48 weeks]. Conclusions In HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction.

A case of autoimmune liver hepatitis is reported: the onset was triggered by consumption of green tea infusion in a patient taking oral contraceptives and irbesartan. We hypothesize that our patient, carrying genetic variant of hepatic metabolism making her particularly susceptible to oxidative stress, developed an abnormal response to a mild toxic insult, afforded by a combination of agents (oral contraceptives+irbesartan+green tea) that normally would not be able to cause damage. Her particular hepatic metabolism further increased the drugs' concentration, favoring the haptenization of liver proteins, eventually leading to the development of an autoimmune hepatitis.

A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and fainting. A blood analysis revealed high levels of serum amylase and lipase, confirming a diagnosis of acute pancreatitis. The history showed that the patient had self-administered a single dose of pegylated interferon alfa-2b and ribavirin daily for 7 days for chronic hepatitis C. The medications were stopped and his condition gradually improved. In agreement with the literature and the Naranjo algorythm result, pegylated interferon alfa-2b is associated with acute pancreatitis. Identification of a few signs and symptoms is the first 'signal' in preventing a serious drug-induced adverse event.

Background & Aims: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-α-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. Methods: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-α-2b 1.5 μg/kg per week and ribavirin 1000–1200 mg/day for 48 weeks and followed up for 24 weeks. Results: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low γ-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6–79.6) and low viral load (OR, 3.8; 95% CI: 1.1–12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response ( P = .2) or with early response ( P = .3). Conclusions: Retreatment with pegylated IFN-α-2b and ribavirin of multiexperienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low γ-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.

AIM: To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis. METHODS: From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC-B) but unfit or unresponsive to other therapeutic strategies. Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo, and analyzed according to the modified Response Evaluation Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until radiological progression or occurrence of unacceptable adverse events (AEs). Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival. RESULTS: Forty-four patients were enrolled, 15 had intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment interruption in 19 patients (43%), and median treatment duration was shorter in this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40 wk, P = 0.015). No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years. After 16 wk of treatment, 18 patients (41%) had stable disease or partial response. Patients with viral infection or BCLC-C were at higher risk of disease progression. ECOG, extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival. CONCLUSION: In patients with cirrhosis and HCC treated with sorafenib, AEs are a common cause of early treatment withdrawal. Vascular invasion and extrahepatic spread condition early response to treatment and survival. Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.

s of the 46th A.I.S.F. Annual Meeting 2013 / Digestive and Liver Disease 45S (2013), S1–S48 S7 the increase of HRR. The analysis of survival benefit comparing the risk of waiting list drop-out with the mortality of the 170 transplanted patients with same HRR, showed an important benefit for LT in patients with HRR>16.3. Conclusions: In patients with MELD