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.

Atezolizumab and bevacizumab for non-resectable or metastatic combined hepatocellular-cholangiocarcinoma: A multicentric retrospective study.

BACKGROUNDS: The efficacy of atezolizumab/bevacizumab has never been reported in patients with metastatic/unresectable combined hepatocellular-cholangiocarcinoma (cHCC-CCA). PATIENTS AND METHODS: We retrospectively included patients with a histological diagnosis of unresectable/metastatic cHCC-CCA and treated with atezolizumab/bevacizumab (2020-2022) in 7 centers. Clinical and radiological features were collected at the beginning of atezolizumab/bevacizumab. We reported the radiological response using RECIST criteria, overall survival (OS) and progression-free survival (PFS). RESULTS: Sixteen patients with cHCC-CCA were included and were predominantly male (75%) with advanced fibrosis/cirrhosis (69%). Nine patients received atezolizumab/bevacizumab as a first-line systemic treatment, 5 as a second line, 1 as a third line and 1 as a fifth line. Severe digestive bleeding occurred in 2 patients. Among the 9 patients treated in the first line, 4 experienced radiological progression, 3 partial response and 1 had stable disease. Patients treated with atezolizumab/bevacizumab in the first line had a median OS of 13 months and a median PFS of 3 months. Among the 7 patients receiving atezolizumab/bevacizumab as a second line or more, 4 patients harbored a stable disease, 2 a partial response, and 1 a progressive disease. CONCLUSIONS: The combination of atezolizumab and bevacizumab showed signs of anti-tumor efficacy in patients with unresectable/metastatic cHCC-CCA.

MALDI Imaging, a Powerful Multiplex Approach to Decipher Intratumoral Heterogeneity: Combined Hepato-Cholangiocarcinomas as Proof of Concept.

Combined hepato-cholangiocarcinomas (cHCC-CCA) belong to the spectrum of primary liver carcinomas, which include hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (iCCA) at both ends of the spectrum. Mainly due to the high intratumor heterogeneity of cHCC-CCA, its diagnosis and pathological description remain challenging. Taking advantage of in situ non-targeted molecular mapping provided by MALDI (Matrix Assisted Laser Desorption Ionization) imaging, we sought to develop a multiscale and multiparametric morphological approach, integrating molecular and conventional pathological analysis. MALDI imaging was applied to five representative cases of resected cHCC-CCA. Principal component analysis and segmentations with MALDI imaging techniques identified areas related to either iCCA or HCC and also hidden tumor areas not visible microscopically. In addition, the overlap between MALDI segmentation and immunostaining provided a comprehensive description of cHCC-CCA tumor heterogeneity by identifying transitional and micro-metastatic areas. Moreover, a list of peptides derived from in silico digestion was obtained for each immunohistochemical marker and was matched within the peptide peak list acquired by MALDI. Comparison of immunostaining images with ions from in silico digestion revealed an accurate identification of iCCA and HCC areas. Our study provides further evidence on the performance of MALDI imaging in exploring intratumor heterogeneity and offering virtual multiplex immunostaining through a single acquisition.

Imaging and histological features of tumor biopsy sample predict aggressive intrasegmental recurrence of hepatocellular carcinoma after radiofrequency ablation.

Aggressive intrasegmental recurrence (AIR) is a form of local recurrence associated with a dismal prognosis and defined by multiple nodules or by an infiltrative mass with a tumor thrombus, occurring in the treated segment, after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to identify radiological and/or histological characteristics of tumor biopsy predictive of AIR. We retrospectively analyzed patients treated by No-Touch multi-bipolar RFA (mbpRFA) for a first HCC with a systematic per-procedural tumor biopsy positive for diagnosis of HCC. The first recurrence was classified as non-aggressive local recurrence, AIR or intrahepatic distant recurrence. 212 patients were included (168 men; mean age 67.1 years; mean tumor size 28.6 mm, 181 cirrhosis). AIR occurred in 21/212 patients (10%) and was associated with a higher risk of death (57% in patients with AIR vs 30% without AIR, p = 0.0001). Non-smooth tumor margins, observed in 21% of the patients and macro-trabecular massive histological subtype, observed in 12% of the patients were independently related to a higher risk of AIR (HR: 3.7[1.57;9.06], p = 0.002 and HR:3.8[2.47;10], p = 0.005 respectively). Non smooth margins at imaging and macro-trabecular massive histological subtype are associated with AIR and could be considered as aggressive features useful to stratify therapeutic strategy.

Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization.

BACKGROUND: At the diagnosis of hepatocellular carcinoma (HCC), more than 90% of HCC patients present cirrhosis, a clinical condition often associated to malnutrition. Sarcopenia is an indirect marker of malnutrition assessable on computed tomography (CT). AIM: To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial (chemo)-embolization. METHODS: Patients with HCC treated by a first session of trans-arterial (chemo)embolization and an available CT scan before treatment were included. Sarcopenia was assessed using skeletal muscle index at baseline and at the first radiological assessment. Radiological response was recorded after the first session of treatment using mRECIST. RESULTS: Of 225 patients treated by trans-arterial bland embolization (n = 71) or trans-arterial chemoembolization (n = 154) for HCC between 2007 and 2013, Barcelona Clinic of Liver Cancer stage was A, B, and C in 27.5%, 55%, and 16.8% of cases, respectively. Sarcopenia was present in 57.7% of the patients. Patients with sarcopenia presented a higher rate of progressive disease (19% vs 8%, P = 0.0236), a shorter progression-free survival (8.3 vs 13.2 mo, P = 0.0035), and a shorter median overall survival (19.4 mo vs 35.5 mo, P = 0.0149) compared with non-sarcopenic patients. Finally, patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis (P = 0.0004). CONCLUSION: Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial (chemo)-embolization for HCC.

Predicting bleeding after liver biopsy using comprehensive clinical and laboratory investigations: A prospective analysis of 302 procedures.

BACKGROUND: Liver biopsy carries a small risk of bleeding complications. No validated clinical or laboratory tool helps predict liver biopsy-related bleeding. OBJECTIVES: To determine whether global hemostasis tests and/or a clinical questionnaire could identify patients at risk of liver biopsy-related bleeding. PATIENTS/METHODS: Consecutive patients scheduled for liver biopsy with an overnight hospital stay were prospectively included. Before liver biopsy, routine hemostasis tests, Platelet Function Analyzer 100, thromboelastometry, thrombin generation assay, plasma clot lysis time, and a clinical questionnaire were performed. Bleeding was defined as a liver hematoma or new free fluid on a systematic ultrasound performed 24 h after liver biopsy or a decrease in hemoglobin level of 2 g/dL or more in patients with pre-existing free fluid in the abdominal cavity. RESULTS: Three hundred two patients were included: 173 underwent percutaneous and 129 transjugular liver biopsy. There were 21 bleeding episodes (7%); 20 based on ultrasonographic criteria, 1 on laboratory criteria. None of the hemostasis tests and no item of the clinical questionnaire were associated with liver biopsy-related bleeding in the overall study group. Same results were obtained in subgroup analyses focusing on patients who underwent percutaneous liver biopsy, transjugular liver biopsy, or on patients with cirrhosis. Pain 2 h after liver biopsy was more frequent in patients with liver biopsy-related bleeding (55% vs. 23% p = .002). CONCLUSIONS: An extensive hemostasis workup, including global hemostasis assays, does not improve prediction of liver biopsy-related bleeding. Pain 2 h after liver biopsy should alert the clinician to the possibility of procedure-related bleeding.

Systemic Treatments with Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy in Patients with Unresectable or Metastatic Hepatocholangiocarcinoma.

Backgrounds and Aims: Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA. Patients and Methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n = 117) and with intrahepatic cholangiocarcinoma (iCCA, n = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator. Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (p < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (p < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (p = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37-1.22, p = 0.189 and HR = 0.66, 95% CI: 0.43-1.02, p = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23-3.76; p = 0.009), ascites (HR = 3.45, 95% CI: 1.31-9.03, p = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08-4.87, p = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (p = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27-3.15, p = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44-3.49, p = 0.67). Conclusions: First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.

Percutaneous ablation for locally advanced hepatocellular carcinoma with tumor portal invasion.

INTRODUCTION: We aim to assess the outcomes of percutaneous ablation of locally advanced HCC in a tertiary center, which is usually not indicated. We compared to sorafenib or trans-arterial radioembolization (TARE). METHODS: We included 272 patients with HCC and tumor portal invasion treated by percutaneous ablation (n = 44) assessed retrospectively from one center compared to a control group from the SARAH trial including patients treated with sorafenib (n = 123) or TARE (n = 105). A propensity-score matching was performed in a subgroup of patients with similar baselines characteristics. RESULTS: 84% of patients treated by ablation were male with a unique nodule (median size 50 mm) in 72.7% of the case. Complete tumor ablation was achieved in 75% of the patients with 20% Dindo-Clavien III-V adverse events including 6.8% of 90-days mortality. Sum of tumor size ≥70 mm was associated with incomplete ablation (p = 0.0239) and a higher risk of death (p = 0.0375). Patients in control group had a higher tumor burden, and more Vp3/4 compared to ablation group. Median overall survival was similar in the ablation and in the control group (16.4 and 14.0 months respectively, p = 0.48). The median progression-free survival was 6.6 months in ablation group compared to 4.2 months in the control group (p = 0.12). CONCLUSION: Percutaneous ablation for locally advanced HCC was feasible and associated with similar long-term outcomes to sorafenib or TARE.

New insights into the pathophysiology and clinical care of rare primary liver cancers.

Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.

Similar performance of liver stiffness measurement and liver surface nodularity for the detection of portal hypertension in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: We compare the performance of liver surface nodularity (LSN) and liver stiffness measurements (LSM) using transient elastography (TE) for the detection of clinically significant portal hypertension (CSPH) in patients with cirrhosis and hepatocellular carcinoma (HCC). METHODS: All patients with cirrhosis and HCC who underwent computed tomography, LSM and hepatic venous pressure gradient (HVPG) measurements within 30 days between 2015 and 2018 were included. The estimation of CSPH by LSN and LSM, and the LSM-spleen-size-to-platelet ratio score (LSPS) were evaluated and compared. RESULTS: In total, 140 patients were included (109 men [78%], mean age 63 ± 9 years old), including 39 (28%) with CSPH. LSN measurements were valid in 130 patients (93%) and significantly correlated with HVPG (r = 0.68; p <0.001). Patients with CSPH had higher LSN measurements compared with those without [3.1 ± 0.4 vs. 2.5 ± 0.3, p <0.001; area under the receiver operating characteristic (AUROC): 0.87 ± 0.31]. LSM and LSPS were valid in 132 patients (94%) and significantly correlated with HVPG (r = 0.75, p <0.001; AUROC 0.87 ± 0.04 and r = 0.68, p <0.001; AUROC 0.851 ± 0.04, respectively). There was no significant difference in the diagnostic performance between LSN and LSM-LSPS (DeLong, p = 0.28, 0.37, and 0.65, respectively) in patients with both valid tests (n = 122). LSN <2.50 had a 100% negative predictive value for CSPH. A 2-step algorithm combining LSN and LSPS for the diagnosis of CSPH classified 108/140 patients (77%) with an 8% error. CONCLUSIONS: The diagnostic performance and feasibility of LSN measurements were similar to those of LSM for the detection of CSPH in patients with compensated cirrhosis and HCC. Combining LSN and LSPS accurately detected CSPH in >75% of patients. Such a combination could be useful in centres where the HVPG measurement is unavailable. LAY SUMMARY: The diagnostic performance and feasibility of liver surface nodularity was similar to that of liver stiffness measurement (LSM) for the detection of clinically significant portal hypertension in patients with compensated cirrhosis. Thus, liver surface nodularity could be an option for the preoperative detection of clinically significant portal hypertension in patients with hepatocellular carcinoma. Combining liver surface nodularity with LSM-spleen-size-to-platelet ratio score resulted in the accurate detection of clinically significant portal hypertension in >75% of patients, thus limiting the need for HVPG measurements.

Hepatocellular carcinoma in the context of non-alcoholic steatohepatitis (NASH): recent advances in the pathogenic mechanisms.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is particularly aggressive and is one of the leading causes of cancer mortality. In recent decades, the epidemiological landscape of HCC has undergone significant changes. While chronic viral hepatitis and excessive alcohol consumption have long been identified as the main risk factors for HCC, non-alcoholic steatohepatitis (NASH), paralleling the worldwide epidemic of obesity and type 2 diabetes, has become a growing cause of HCC in the US and Europe. Here, we review the recent advances in epidemiological, genetic, epigenetic and pathogenic mechanisms as well as experimental mouse models that have improved the understanding of NASH progression toward HCC. We also discuss the clinical management of patients with NASH-related HCC and possible therapeutic approaches.

Combining imaging and tumour biopsy improves the diagnosis of combined hepatocellular-cholangiocarcinoma.

BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is by definition a highly heterogeneous tumour, which significantly impacts its diagnosis. The aim of the study was to evaluate the diagnostic performance of imaging using computed tomography and/or magnetic resonance (MR) and biopsy for the diagnosis of cHCC-CCA. METHODS: cHCC-CCA resected between December 2006 and April 2017 with available pre-operative imaging and tumour biopsy were retrospectively included. cHCC-CCA diagnosis was based on morphological and immunophenotypical features. A total of 21 cHCC-CCA were compared to 21 intrahepatic cholangiocarcinoma (iCCA) as controls. All biopsies were reviewed. Two radiologists reviewed the cases and classified tumours into four patterns (type 1 [progressive enhancement of the entire lesion, iCCA type], type 2 [arterial enhancement with washout, HCC type], type 3 [mixed pattern with combinations of 1, 2 and 4] and type 4 [atypical pattern, areas of arterial enhancement without washout and/or hypovascular]). RESULTS: The presence of a type 3 pattern at imaging had a 48% sensitivity and 81% specificity for cHCC-CCA diagnosis. The initial diagnosis performed on biopsy was cHCC-CCA in 8/21 patients (38%). After reviewing and including immunophenotypical markers, two more cases were diagnosed as cHCC-CCA (48% sensibility, 100% specificity). When either imaging or biopsy suggested the diagnosis of cHCC-CCA, the sensitivity and specificity were 60% and 82% respectively. CONCLUSIONS: We showed that a two-step strategy combining imaging as the first step and biopsy as the second step improved the diagnostic performance of cHCC-CCA.

Proteomic Landscape of Cholangiocarcinomas Reveals Three Different Subgroups According to Their Localization and the Aspect of Non-Tumor Liver.

PURPOSE: Cholangiocarcinomas (CCs) define a heterogeneous entity based upon their anatomic localization (intra versus extrahepatic) and, for the intrahepatic CCs, the aspect of background liver (normal versus cirrhosis). The aim of the study was to characterize the molecular heterogeneity of CCs by a global proteomic approach. EXPERIMENTAL DESIGN: Thirty-three tumor samples from 17 intrahepatic CCs (iCC) (9 developed on normal (iCCN ) and 8 developed in cirrhotic liver (iCCC )); 5 hilar CCs (CCH ); 5 pancreatic CCs (CCP ) and 6 hepatocellular carcinomas (HCC), were submitted to label-free quantitative proteomic analysis. Differential proteins were analyzed by immunohistochemistry in a validation set of 30 CCs. RESULTS: Unsupervised analysis revealed two main clusters: cluster 1 contained most of the iCCC while cluster 2 was divided in 2 subgroups, one containing most of the iCCN and the other regrouping CCH and CCP . Compared to iCCN , iCCC displayed upregulation of molecules involved in cell adhesion, motility and angiogenesis. Epithelial markers associated with secretory pathway and fibroblast markers were overexpressed in CCH compared to iCCN CONCLUSION AND CLINICAL RELEVANCE: This study demonstrated that iCCC is a specific entity, suggesting a major impact of the background liver on tumor biology, and confirmed that extrahepatic CCs define a homogeneous subgroup.

Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment.

BACKGROUND: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours. OBJECTIVE: Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image. RESULTS: Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31-87) versus 72 years (30-84), p = 0.04], with no difference in other baseline characteristics. The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26-50) versus 61 (95% CI 47-77) weeks (p = 0,01)) and shorter time on treatment (12.3 (95% CI 8-19) versus 25.9 (95% CI 15-33) weeks (p = 0.0044)). At multivariate analysis, sarcopenia was independently associated to reduced OS (p = 0.03) and reduced time on treatment (p = 0.001). CONCLUSION: Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy.

Sarcopenia Predicts Reduced Survival in Patients with Hepatocellular Carcinoma at First Diagnosis

Abstract: Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. Aim. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Material and methods. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. Results. Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). Conclusions. This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

 Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. AIM: To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. MATERIAL AND METHODS: Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. RESULTS: Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). CONCLUSIONS: This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

Liver biopsy: Analysis of results of two specialist teams.

AIM: To analyze the safety and the adequacy of a sample of liver biopsies (LB) obtained by gastroenterologist (G) and interventional radiologist (IR) teams. METHODS: Medical records of consecutive patients evaluated at our GI unit from 01/01/2004 to 31/12/2010 for whom LB was considered necessary to diagnose and/or stage liver disease, both in the setting of day hospital and regular admission (RA) care, were retrieved and the data entered in a database. Patients were divided into two groups: one undergoing an ultrasonography (US)-assisted procedure by the G team and one undergoing US-guided biopsy by the IR team. For the first group, an intercostal approach (US-assisted) and a Menghini modified type needle 16 G (length 90 mm) were used. The IR team used a subcostal approach (US-guided) and a semiautomatic modified Menghini type needle 18 G (length 150 mm). All the biopsies were evaluated for appropriateness according to the current guidelines. The number of portal tracts present in each biopsy was assessed by a revision performed by a single pathologist unaware of the previous pathology report. Clinical, laboratory and demographic patient characteristics, the adverse events rate and the diagnostic adequacy of LB were analyzed. RESULTS: During the study period, 226 patients, 126 males (56%) and 100 females (44%), underwent LB: 167 (74%) were carried out by the G team, whereas 59 (26%) by the IR team. LB was mostly performed in a day hospital setting by the G team, while IR completed more procedures on inpatients (P < 0.0001). The groups did not differ in median age, body mass index (BMI), presence of comorbidities and coagulation parameters. Complications occurred in 26 patients (16 G team vs 10 IR team, P = 0.15). Most gross samples obtained were considered suitable for basal histological evaluation, with no difference among the two teams (96.4% G team vs 91.5% IR, P = 0.16). However, the samples obtained by the G team had a higher mean number of portal tracts (G team 9.5 ± 4.8; range 1-29 vs IR team 7.8 ± 4.1; range 1-20) (P = 0.0192) and a longer mean length (G team 22 mm ± 8.8 vs IR team 15 ± 6.5 mm) (P = 0.0001). CONCLUSION: LB can be performed with similar outcomes both by G and IR. Use of larger dimension needles allows obtaining better samples, with a similar rate of adverse events.

Perception of hepatitis B virus infection reactivation-related issues among specialists managing hematologic malignancies: result of an Italian survey.

Hepatitis B virus (HBV) reactivation strongly affects the practice of physicians dealing with hematological malignancies. In this respect, in collaboration with the Italian Lymphoma Foundation we developed a descriptive study of the real-life approach of physicians caring for patients with these diseases. A questionnaire was designed to explore the perception of HBV reactivation-related issues. Fifty-nine Italian Lymphoma Foundation-affiliated institutions participated, and 504 questionnaires were sent out. Forty institutions (67.8%) returned 154 (30.5%) completed questionnaires. The largest majority (91.5%, 141/154) were aware of possible HBV reactivation as a consequence of immunosuppression. Most of the participants providing an answer (93.3%; 126/135) performed universal screening, and were aware of strategies for managing reactivation (96.4%, 132/137). Specialists treating lymphoma show a high level of awareness concerning the management of HBV reactivation under immunosuppression. However, uncertainties regarding the issue of HBV reactivation still emerge in this setting, and thus continuing collaborative effort between hepatologists and hematologists is necessary.

'Les liaisons dangereuses': Hepatitis C, Rituximab and B-cell non-Hodgkin's lymphomas.

Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin's lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy.