Impact of Sarcopenia on the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib.

BACKGROUND AND AIMS: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. METHODS: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. RESULTS: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment.

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment.

AIM: This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. METHODS: 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. RESULTS: In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treatments progressively decreased as the SMD worsened. Consequently, overall survival was better in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). CONCLUSIONS: Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival.

The changing scenario of hepatocellular carcinoma in Italy: an update.

BACKGROUND AND AIMS: Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, management and prognosis of HCC in Italy during the last 15 years. METHODS: Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004-2008, 2009-2013 and 2014-2018). RESULTS: The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non-viral cases and, particularly, of 'metabolic' and 'metabolic + alcohol' HCCs; (iii) a slightly decline of cases diagnosed under surveillance, but with an incremental use of the semiannual schedule; (iv) a favourable cancer stage migration; (v) an increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) an improved overall survival (adjusted for the lead time in surveyed patients) in the last calendar period, particularly in viral patients; (viii) a large gap between the number of potential candidates (according to oncologic criteria and age) to liver transplant and that of transplanted patients. CONCLUSIONS: During the last 15 years several aspects of HCC scenario have changed, as well as its management. The improvement in patient survival observed in the last period was likely because of a larger use of thermal ablation with respect to the less effective alcohol injection and to an improved management of intermediate stage patients.

More than a "monstrous obesity"! Time to overcome the "anti-fat" bias.

A 54-years-old woman complained of unintentional important body weight gain associated with abdominal bloating. For this reason, she had consulted many different diet and nutritional professionals, general practitioners and a gastroenterology specialist, but no one went beyond a simple diagnosis of "monstrous obesity". At our hospital division, based on physical examination, a computed tomography (CT) of the abdomen and pelvis was performed. It showed a voluminous intraperitoneal mass occupying the most part of the abdomen. The patient underwent laparotomy with resection of the abdomino-pelvic mass, originating from the left ovary, measuring 60 x 45 cm and weighing 46 kg. Histopathology examination revealed a tumor composed of three different areas, including a well-differentiated adenocarcinoma of intestinal-type. It is emblematic of a grotesque misdiagnosis generated by a non-comprehensive patient assessment and consequently by a too quick judgement related to the "anti-fat bias".

Radiomics of cholangiocarcinoma on pretreatment CT can identify patients who would best respond to radioembolisation.

OBJECTIVES: Results after trans-arterial radioembolisation (TARE) for intrahepatic cholangiocarcinoma (iCC) depend on the architecture of the tumour. This latter can be quantified through computed tomography (CT) texture analysis. The aims of the present study were to analyse relationships between CT textural features prior to TARE and objective response (OR), progression-free survival (PFS), and overall survival (OS). METHODS: Texture analysis was retrospectively applied to 55 pre-TARE CT scans of iCCs, focusing attention on the histogram-based features and the grey-level co-occurrence matrix (GLCM). Texture features were harmonised using the ComBat procedure. Objective response was assessed using the Response Evaluation Criteria In Solid Tumours 1.1. The least absolute shrinkage and selection operator (LASSO) method was applied to select the most useful textural features related to OR. RESULTS: Of the 55 patients, 53 had post-TARE imaging available, showing OR in 56.6% of cases. Texture analysis showed that iCCs showing OR after TARE had a higher uptake of iodine contrast in the arterial phase (higher mean histogram values, p < 0.001) and more homogeneous distribution (lower kurtosis, p = 0.043; GLCM contrast, p = 0.004; GLCM dissimilarity, p = 0.005, and higher GLCM homogeneity, p = 0.005; and GLCM correlation p = 0.030) at the pre-TARE CT scan. A favourable radiomic signature was calculated and observed in 15 of the 55 patients. The median PFS of these 15 patients was 12.1 months and that of the remaining 40 patients was 5.1 months (p = 0.008). CONCLUSIONS: Texture analysis of pre-TARE CT scans can quantify vascularisation and homogeneity of iCC architecture, providing clinical information useful in identifying ideal TARE candidates. KEY POINTS: • Hypervascular tumours with a more homogeneous uptake of iodine contrast in the arterial phase were those most likely to be effectively treated by TARE. • The arterial phase was observed to be the best acquisition phase for providing information regarding the "sensitivity" of the tumour to TARE. • Patients with favourable radiomic signature showed a median progression-free survival of 12.1 months versus 5.1 months of patients with an unfavourable signature (p = 0.008).

Survival and Tolerability of Transarterial Chemoembolization in Greater Versus less than 70 Years of Age Patients with Unresectable Hepatocellular Carcinoma: A Propensity Score Analysis.

BACKGROUND: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is progressively increasing. The aim of this study was to determine the safety and efficacy of conventional transarterial chemoembolization (TACE) in elderly HCC patients compared with younger adults. METHODS: A consecutive cohort of unresectable HCC patients treated with TACE as a first-line treatment was retrospectively analyzed. Patients were categorized into "elderly" (≥ 70 years, 80 patients) and "younger" (< 70 years, 145 patients). Liver-related death and progression-free survival after TACE were compared before and after propensity score matching. A competing risk regression analysis was used for univariate/multivariate survival data analysis. RESULTS: cTACE was well tolerated in both groups. The cumulative risk of both liver-related death and progression-free survival after cTACE was comparable between "elderly" and "younger" (death: 73.8% vs 69.4%, P = 0.505; progression-free survival: 48.2% vs 44.8%, P = 0.0668). Propensity model matched 61 patients in each group for gender and Barcelona Clinic Liver Cancer staging. Even after matching, the cumulative risk of liver-related death and of progression-free survival did not differ between the two groups. At multivariate analysis, Child-Pugh class, tumor gross pathology and alpha-fetoprotein were independently associated with the liver-related mortality risk. CONCLUSIONS: This study confirms that TACE is well tolerated and effective in patients aged 70 years or more with unresectable HCC as it is for their younger counterparts (< 70 years). Liver-related mortality was not associated with age ≥ 70 years and primarily predicted by tumor multifocality, Child-Pugh class B and an increased alpha-fetoprotein value (> 31 ng/ml).

Computed Tomography-Colonography With Intravenous Contrast Medium and Urographic Phase for the Evaluation of Pelvic Deep Infiltrating Endometriosis of Intestinal and Urinary Tract.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of a specific protocol of computed tomography-colonography with intravenous contrast medium and urographic phase, which combined simultaneously the study of the intestinal and urinary tract, in the preoperative evaluation of women with deep infiltrating endometriosis (DIE) of anterior and posterior pelvic compartments. METHODS: We retrospectively analyzed 73 women who underwent 74 computed tomography-colonography with intravenous contrast medium and urographic phase examinations for strong clinical suspicion of DIE. All the women had surgical confirmation. RESULTS: Computed tomography-colonography with intravenous contrast medium and urographic phase in detecting DIE rectosigmoid involvement had a sensitivity of 82.3% and a specificity of 66.7%, while in detecting DIE urinary tract involvement had a sensitivity of 45.9% and a specificity of 78.4%. CONCLUSIONS: Computed tomography-colonography with intravenous contrast medium and urographic phase is a useful technique for the preoperative planning of selected women with DIE, in particular, for the detection of sigmoid colon and bladder lesions especially when performed with a dose reduction protocol.

Development and Validation of a Scoring System That Includes Corrected QT Interval for Risk Analysis of Patients With Cirrhosis and Gastrointestinal Bleeding.

BACKGROUND & AIMS: The electrocardiographic QT interval frequently is prolonged in patients with cirrhosis. Acute gastrointestinal bleeding further prolongs corrected QT (QTc) in patients with cirrhosis, which has been associated with an increased risk of death within 6 weeks. We aimed to confirm these findings and develop a mortality risk index that incorporates QTc. METHODS: We collected data from 274 patients with cirrhosis and acute gastrointestinal bleeding from any cause admitted to a hospital in Bologna, Italy, from January 2001 through December 2012 (training set). We used logistic regression analysis to identify patient factors associated with death within 6 weeks (6-week mortality). We validated our findings by using data from 200 patients with cirrhosis and gastrointestinal bleeding treated at 2 separate hospitals in Italy, from 2001 through 2016 and 2007 through 2012. Our primary aim was to confirm the prognostic effects of prolonged QTc in a large population of patients and develop a 6-week mortality risk score for acute gastrointestinal bleeding from any cause that incorporates the QTc interval. RESULTS: In the training set, QTc greater than 456 ms, the model for end-stage liver disease-sodium (MELD-Na) score, previous bleeding, and serum albumin concentration were associated independently with 6-week mortality. We combined these parameters to create a risk scoring system that we named MELD-Na acute gastrointestinal bleeding (MELDNa-AGIB). In the validation set, the MELDNa-AGIB identified patients who died within 6 weeks with an area under the receiver operating characteristic curve (AUROC) of 0.888; this value was higher than that of the MELD score (AUROC, 0.838; P = .031), MELD score with updated calibration (AUROC, 0.837; P = .029), Child-Turcotte-Pugh score (AUROC, 0.789; P = .004), D'Amico score (AUROC, 0.761; P = .003), and Augustin score (AUROC, 0.792; P = .001), with a net reclassification improvement better than the MELD-Na score (0.266; P = .045). In calibration, the MELDNa-AGIB produced a high score in the Hosmer-Lemeshow test (P = .947), which was superior to that of MELD-Na (P = .146). In the training set, only 6.3% of patients with MELDNa-AGIB scores of 4 or less died within 6 weeks. Among patients with a scores of 9, 16, and 25 or higher, 15.5%, 41.5%, and 81% or more patients died within 6 weeks, respectively. The probability of survival progressively and significantly decreased with increasing scores in the training and validation sets. CONCLUSIONS: We confirmed QTc as an independent predictor of 6-week mortality in a large population of patients with cirrhosis and acute gastrointestinal bleeding. The combination of QTc, MELD-Na, previous bleeding, and serum albumin (the MELDNa-AGIB score) accurately determines the risk of 6-week mortality, providing timely identification of patients at very high risk of death.

Trans-arterial radioembolization for intermediate-advanced hepatocellular carcinoma: a budget impact analysis.

BACKGROUND: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management of hepatocellular carcinoma (HCC). TARE may compete with systemic chemotherapy, sorafenib, in intermediate stage patients with prior chemoembolization failure or advanced patients with tumoral macrovascular invasion with no extra-hepatic spread and good liver function. We performed a budget impact analysis (BIA) evaluating the expected changes in the expenditure for the Italian Healthcare Service within scenarios of increased utilization of TARE in place of sorafenib over the next five years. METHODS: Starting from patient level data from three oncology centres in Italy, a Markov model was developed to project on a lifetime horizon survivals and costs associated to matched cohorts of intermediate-advanced HCC patients treated with TARE or sorafenib. The initial model has been integrated with epidemiological data to perform a BIA comparing the current scenario with 20 and 80% utilization rates for TARE and sorafenib, respectively, with increasing utilization rates of TARE of 30, 40 and 50% over the next 1, 3 and 5 years. RESULTS: Compared to the current scenario, progressively increasing utilization rates of TARE over sorafenib in the next 5 years is expected to save globally about 7 million Euros. CONCLUSIONS: Radioembolization can be considered a valuable treatment option for patients with intermediate-advanced HCC. These findings enrich the evidence about the economic sustainability of TARE in comparison to standard systemic chemotherapy within the context of a national healthcare service.

Yttrium-90 microsphere radioembolization in unresectable intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is increasing in frequency worldwide, but radical surgical treatment is practicable in 30-40% of cases. The median survival without therapy is about 8 months, increased to 12 months in combination with systemic chemotherapy. Therefore, locoregional therapies, such as, radiofrequency ablation or transarterial chemoembolization have been employed. Radioembolization with yttrium-90 microspheres (90Y-TARE) is a novel intrarterial treatment which could be included in the armamentarium of treatment options, having shown higher median survival (up to 22 months) and low complication rates. Evidence-based algorithms for staging and allocation to treatment should be defined in the future, after robust results obtained through randomized controlled trials, thus establishing the exact role and timing of 90Y-TARE in the treatment protocol of unresectable intrahepatic cholangiocarcinoma.

Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma.

BACKGROUND & AIMS: The Barcelona Clinic Liver Cancer intermediate stage (BCLC-B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumour burden and liver function. Transarterial-chemoembolization (TACE) is the first-line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC-B patients and its outcome. METHODS: Retrospective analysis of 485 consecutive BCLC-B patients from the ITA.LI.CA database diagnosed with naïve HCC after 1999. Patients were stratified by treatment. RESULTS: 29 patients (6%) were lost to follow-up before receiving treatment. Treatment distribution was: TACE (233, 51.1%), curative treatments (145 patients, 31.8%), sorafenib (18, 3.9%), other (39, 8.5%), best supportive care (BSC) (21, 4.6%). Median survival (95% CI) was 45 months (37.4-52.7) for curative treatments, 30 (24.7-35.3) for TACE, 14 (10.5-17.5) for sorafenib, 14 (5.2-22.7) for other treatments and 10 (6.0-14.2) for BSC (P<.0001). Independent prognosticators were gender and treatment. Curative treatments reduced mortality (HR 0.197, 95%CI: 0.098-0.395) more than TACE (HR 0.408, 95%CI: 0.211-0.789) (P<.0001) as compared with BSC. Propensity score matching confirmed the superiority of curative therapies over TACE. CONCLUSIONS: In everyday practice TACE represents the first-line therapy in an half of patients with naïve BCLC-B HCC since treatment choice is driven not only by liver function and nodule characteristics, but also by contraindications to procedures, comorbidities, age and patient opinion. The treatment type is an independent prognostic factor in BCLC-B patients and curative options offer the best outcome.

The HEART score with high-sensitive troponin T at presentation: ruling out patients with chest pain in the emergency room.

The HEART score is a simple scoring system, ranging from 0 to 10, specifically developed for risk stratification of patients with undifferentiated chest pain. It has been validated for the conventional troponin, but not for high-sensitive troponin. We assess a modified version of the HEART score using a single high-sensitivity troponin T dosage at presentation, regardless of symptom duration, and with different ECG criteria to evaluate if the patients with a low HEART score could be safely discharged early. The secondary aim was to confirm a statistically significant difference in each HEART score group (low 0-3, intermediate 4-6, high 7-10) in the occurrence of major adverse cardiac events at 30 and 180 days. We retrospectively analyzed the HEART score of 1597 consecutive patients admitted to the Emergency Department of our Hospital for chest pain between January 1 and June 30, 2014. Of these, 190 did not meet the inclusion criteria and 29 were lost to follow-up. None of the 512 (37.2 %) patients with a low HEART score had an event within 180 days. The difference between the cumulative incidences of events in the three HEART score groups was statistically significant (P < 0.0001). We demonstrate that it might be possible to safely discharge Emergency Department chest pain patients with a low modified HEART score after an initial determination of high-sensitive troponin T, without a prolonged observation period or an additional cardiac testing.

Probiotics History.

Gut microbiota promotes healthy effects on the host and prevents diseases. Probiotic (probios, for life) are defined as "live microorganisms which when administered in adequate amounts confer a health benefit on the host." At the beginning of 1900s Louis Pasteur identified the microorganisms responsible for the process of fermentation, whereas E. Metchnikoff associated the enhanced longevity of Bulgarian rural people to the regular consumption of fermented dairy products such as yogurt. He suggested that lactobacilli might counteract the putrefactive effects of gastrointestinal metabolism that contributed to illness and aging. Hippocrates declared, 2000 years earlier, that "death sits in the bowels." Metchnikoff considered the lactobacilli as probiotics ("probios," conducive to life of the host as opposed to antibiotics); probiotics could have a positive influence on health and prevent aging. During the neolitic period of the age of the stone, the domestication of animals occurred and man began to get fermented food. Probably serendipitous contaminations in favorable environments played a major role. Fecal microbiota transplantation dates to a fourth-century Chinese handbook for food poisoning or severe diarrhea. To date fecal transplant cures Clostridium difficile infections with more efficacy than vancomycin, and prevents recurrence.

Yttrium-90 radioembolization for unresectable/recurrent intrahepatic cholangiocarcinoma: a survival, efficacy and safety study.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a rapidly progressing malignancy; only a minority of the tumours can be resected and the palliative regimens have shown limited success. The aim of this study was to assess overall survival (OS), tumour response and the safety of radioembolization with yttrium-90 ((90)Y-TARE) in patients with unresectable/recurrent ICC. METHODS: Survival was calculated from the date of the (90)Y-TARE procedure. Target and overall Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) and European Association for the Study of the Liver (EASL)-measuring delayed-phase contrast enhancement-treatment responses were assessed at 3 months. RESULTS: The overall median survival was 17.9 months (95% CI: 14.3-21.4 months). Significantly longer survival was obtained in naive patients as compared with patients in whom TARE was preceded by other treatments, including surgery (52 vs 16 months, P=0.009). Significantly prolonged OS was recorded for patients with a response based on mRECIST and the EASL criteria while RECIST responses were not found to be associated with survival. Treatment was well-tolerated, and no mortality was reported within 30 days. CONCLUSIONS: In unresectable ICC, (90)Y-TARE is safe and offers a survival benefit in naive patients, as well as in responders.

Biomarkers for the early diagnosis of bacterial infection and the surveillance of hepatocellular carcinoma in cirrhosis.

The early detection of bacterial infections and hepatocellular carcinoma (HCC) could ameliorate the prognosis of cirrhosis. C-reactive protein and procalcitonin are under investigation in the setting of cirrhosis as markers of sepsis. In the attempt to discriminate bacterial infection from systemic inflammation, the role of novel biomarkers such as lypopolysaccharide binding-protein, mid-regional fragment of pro-adrenomedullin and delta neutrophil index are currently in development. Concerning HCC, many studies attempted to evaluate biomarkers in the hope of ameliorating the accuracy of the surveillance based on ultrasound. The use of α-fetoprotein (AFP) has been extensively investigated, as well as other biomarkers expressed in the serum of HCC patients like lens culinaris agglutinin-reactive fraction of AFP, des-γ-carboxy prothrombin, glypican-3, α-l-fucosidase and their combined use.

Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis.

BACKGROUND & AIMS: Sorafenib and transarterial (90) Y-radioembolization (TARE) are possible treatments for Barcelona Clinic Liver Cancer (BCLC) intermediate-advanced stage hepatocellular carcinoma (HCC). No study directly comparing sorafenib and TARE is currently available. This single-centre retrospective study compares the outcomes achieved with sorafenib and TARE in HCC patients potentially amenable to either therapy. METHODS: Seventy-four sorafenib (71 ± 10 years, male 87%, BCLC B/C 53%/47%) and 63 TARE HCC patients (66 ± 9 years, male 79%, BCLC B/C 41%/59%) were included based on the following criteria: Child-Pugh class A/B, performance status ≤1, HCC unfit for other effective therapies, no metastases and no previous systemic chemotherapy. RESULTS: Median overall survivals of the two groups were comparable, being 14.4 months (95% CI: 4.3-24.5) in sorafenib and 13.2 months (95% CI: 6.1-20.2) in TARE patients, with 1-, 2- and 3-year survival rates of 52.1%, 29.3% and 14.7% vs 51.8%, 27.8% and 21.6% respectively. Two TARE patients underwent liver transplantation after successful down-staging. To minimize the impact of confounding factors on survival analysis, propensity model matched 32 patients of each group for median age, tumour gross pathology and the independent prognostic factors (portal vein thrombosis, performance status, Model for End Liver Disease). Even after matching, the median survival did not differ between sorafenib (13.1 months; 95% CI: 1.2-25.9) and TARE patients (11.2 months; 95% CI: 6.7-15.7), with comparable 1-, 2- and 3-year survival rates. CONCLUSIONS: In cirrhotic patients with intermediate-advanced or not-otherwise-treatable HCC, sorafenib and TARE provide similar survivals. Down-staging allowing liver transplantation only occurred after TARE.

A new prognostic model to predict dropout from the waiting list in cirrhotic candidates for liver transplantation with MELD score <18.

BACKGROUND & AIMS: The model for end-stage liver disease (MELD) is used for organ allocation in liver transplantation (LT), but its prognostic performance is less accurate in patients with low score. We assess the outcome of patients with MELD < 18 awaiting LT, finding prognostic variables to identify a high dropout risk. METHODS: Training set consisted of 277 patients and validation cohort of 292 patients. Competing risk regression analysis, taking into account LT, was used for univariate/multivariate analysis. RESULTS: Ascites, sodium, bilirubin, albumin and glomerular filtration rate were independently associated with a 12-month dropout risk in the training set. Combining these five prognostic parameters, we calculated a new score named liver-renal-risk (LIRER). In the validation set, the 12-month LIRER concordance index showed a discrimination power [0.798, 95% confidence interval (95% CI) 0.793-0.803] better than MELD (0.582, 95% CI 0.575-0.588), Child-Turcotte-Pugh (0.687, 95% CI 0.681-0.693), MELD-sodium (0.721, 95% CI 0.715-0.727) and MELD-ascites-sodium (0.729, 95% CI 0.724-0.735), with a remarkable calibration (Hosmer-Lemeshow test: P = 0.91; R(2) = 0.911). Considering all study patients, the risk of wait list dropout increased with the rise in LIRER. The survival benefit analysis comparing the wait list dropout risk with the mortality of the 216 transplanted patients with same LIRER showed an important benefit for LT in patients with LIRER > 15.9. CONCLUSIONS: In patients with low MELD (<18), combination of ascites, sodium, albumin, bilirubin and renal function in a new score (LIRER) discriminates patients at high risk of medium-term adverse outcome from those in whom LT may be safely deferred.

Hepatitis C virus reinfection after liver transplantation: is there a role for direct antiviral agents?

Recurrence of hepatitis C virus (HCV) infection following liver transplantation (LT) is almost universal and can accelerate graft cirrhosis in up to 30% of patients. The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge, considering the shortage of donor organs and the accelerated progression of HCV in LT recipients. Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients, even though the combination is not as effective as it is in immunocompetent patients. A sustained virological response in the setting of LT improves patient and graft survival, but this is only achieved in 30%-45% of patients and the treatment is poorly tolerated. To improve the efficacy of pre- and post-transplant antiviral therapy, a new class of potent direct-acting antiviral agents (DAAs) has been developed. The aim of this review is to summarize the use of DAAs in LT HCV patients. PubMed, Cochrane Library, MEDLINE, EMBASE, Web of Science and clinical trial databases were searched for this purpose. To date, only three clinical studies on the topic have been published and most of the available data are in abstract form. Although a moderately successful early virological response has been reported, DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness. Moreover, the ongoing nature of data, the lack of randomized studies, the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable. In conclusion, large well-designed clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.