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Purpose To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial. Materials and Methods Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients. Results Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACE-DEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACE-DEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms. Conclusions In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.

Table S3. Natural logarithm transformed data for NAFLD stages analysis. (DOCX 12 kb)

Figure S1. PR3 concentrations measured in plasma samples versus serum samples. (PPTX 65 kb)

Contains fulltext : 220051.pdf (Publisher’s version ) (Closed access) Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.

Goals and background Spontaneous rupture is a rare complication of hepatocellular carcinoma (HCC). Treatment options consist of transcatheter arterial embolization (TAE), hepatic resection, and conservative therapy. The best approach is under debate. Study This study presents a review of clinical data of patients with a ruptured HCC admitted to a European tertiary care center. Results Eleven patients were included; six (55%) had underlying cirrhosis. The majority of patients (73%) had no previous history of HCC. Spontaneous HCC rupture was diagnosed using abdominal computed tomography with or without a diagnostic paracentesis. Computed tomography showed one or two tumors in eight (73%) patients; the other patients had multiple tumors or diffuse infiltrative HCC. Seven (64%) patients were initially treated by TAE and one (9%) patient underwent hepatic resection. The remaining three (27%) patients, all of whom had liver cirrhosis, received conservative therapy. Two patients initially treated by TAE underwent a delayed resection and ultimately received systemic therapy. Overall, at the end of the follow`-up period, three patients were still alive at 84, 991, and 1026 days after the initial presentation. Eight (73%) patients had died after a median of 88 days (range 7-417). One year after presentation, none of the conservatively treated patients was alive compared with three out of seven (43%) patients treated with TAE with or without delayed resection. Conclusion Patients with a spontaneously ruptured HCC have a poor prognosis. In selected patients, however, prolonged survival is possible using TAE as initial therapy with or without a delayed resection and systemic therapy. Eur J Gastroenterol Hepatol 28:963-966 Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

Natural killer cells (NK) are one of the key players in the eradication and control of viral infections. Infections with the hepatitis B virus (HBV) may lead to persistence in a subgroup of patients, and impaired NK cell functions have been observed in these patients. Crosstalk with other immune cells has been shown to modulate the function of NK cells. We studied the functional crosstalk between NK cells and plasmacytoid dendritic cell (pDC) and its modulation by HBV. Healthy human peripheral bloodderived NK cells and pDC were purified and cocultured in the presence or absence of HepG2.2.15-derived HBV under various in vitro conditions. The functionality of NK cells was assessed by evaluation of activation markers, cytokine production and cytotoxicity of carboxyfluorescein succinimidyl ester-labelled K562 target cells by flow cytometry or immunoassays. Additionally, the crosstalk was examined using NK and pDC from patients with chronic HBV. The activation of NK cells in cocultures with pDC, as demonstrated by CD69, CD25 and HLA-DR, was not affected by the presence of HBV. Similarly, when cocultured with pDC, the cytotoxic potential of NK cells was not influenced by HBV. However, HBV significantly inhibited pDC-induced IFN-? production by NK cells both in the presence and in the absence of CpG. As HBV did not affect cytokine-induced IFN-? production by NK cells cultured alone, the suppressive effect of HBV on NK cell function was mediated via interference with pDCNK cell interaction. In contrast to other viruses, HBV does not activate pDCNK cell interaction but inhibits pDC-induced NK cell function. In parallel with NK cells of patients with chronic HBV, which show diminished cytokine production with normal cytotoxicity, HBV specifically suppressed pDC-induced IFN-? production by NK cells without affecting their cytolytic ability. These data demonstrate that HBV modulates pDCNK cell crosstalk, which may contribute to HBV persistence.

Table S4. Natural logarithm transformed data in our type 2 diabetes cohort analysis. (DOCX 12 kb)

Figure S2. Levels in patients at risk to develop NAFLD or ALD. (PPTX 270 kb)

Table S2. Linear regression analysis for NSPs and hsCRP. (DOCX 12 kb)

Table S1. Natural logarithm transformed data in our four groups of patients and controls. (DOCX 13 kb)

Table S4. Natural logarithm transformed data in our type 2 diabetes cohort analysis. (DOCX 12 kb)

Figure S2. Levels in patients at risk to develop NAFLD or ALD. (PPTX 270 kb)

Table S2. Linear regression analysis for NSPs and hsCRP. (DOCX 12 kb)

Table S1. Natural logarithm transformed data in our four groups of patients and controls. (DOCX 13 kb)