This retrospective study aimed to confirm the safety and long-term efficacy of a single-session combined treatment approach with transcatheter arterial embolization (TAE) and microwave ablation (MWA) for inoperable small—to intermediate-sized hepatocellular carcinomas (HCC), focusing on their combined benefits for improving local control. All consecutive patients with up to 2 small-to-intermediate HCC lesions (≤ 5 cm) treated with a combined single-session MWA-TAE approach were enrolled between April 2020 and October 2023. All procedures were performed in two stages: TAE and MWA. Clinical and radiological follow-up was performed 3, 6, and 12 months after treatment. In the 21 enrolled patients (15 males, mean age 75.9 years), post-procedural contrast-enhanced CT scans confirmed a satisfactory ablation zone in all patients (100

BACKGROUND AND AIMS:Management of ultrasound (US)-guided percutaneous liver biopsy (PLB) lacks standardisation. Despite the low risk of major complications (< 1%), repeated blood counts and up to 4 h of in-hospital observation are typically recommended. We aimed to assess complication rates and predictors in a large cohort of patients undergoing US-PLB across three Italian tertiary centres. We included all patients undergoing US-PLB from January 2018 to December 2023. We collected clinical, biochemical and procedural features (needle type, insertions number, observation time and antiplatelet/anticoagulant regimens). Safety was assessed by the incidence of pain and major complications, including vasovagal reaction, bleeding, pneumothorax, shock, hospitalisation and death. APPROACH AND RESULTS:Among 1838 patients (mean age 55.1 years, 46.1% females, mean BMI 25.1 kg/m2, 74% parenchymal PLB), few were on anticoagulant/antiplatelet therapy (4.2%/16.2%); mean platelet count and PT INR were 209.7 × 103/mm3 and 1.04; 17 patients (0.9%) received prophylactic therapy (blood components, thrombopoietin receptor agonists or vitamin K). Needle aspiration was predominant (92%). During a mean time of observation of 5.4 ± 2.0 h, 134/1838 patients reported pain (7.4%). Major complications were few (26, 1.4%), with 14 episodes of transient hypotension (0.8%); 10 bleeding events (0.5%); 1 pneumothorax; 1 abscess formation; 1 haemobilia; and 1 episode of chest pain. Hospitalisation was rare (12, 0.7%), primarily for bleeding management. No fatalities were recorded. Pain was the sole significant independent predictor of major complications (18/26, HR 30.6, p < 0.05), particularly when reported within the first hour post-procedure (15/18, 83.3%). CONCLUSIONS:Major complications following US-PLB are few and strongly associated with early post-procedural pain. In the absence of pain within the first hour, extended monitoring may be unnecessary, allowing for earlier patient discharge.

The occurrence of decompensation due to portal hypertension (PH) in patients with hepatocellular carcinoma (HCC) could preclude the access to treatment. To date, non-invasive methods to predicts PH failed their application in HCC patients. Reiniš, J(JHep,2023) proposed a new non-invasive method developed through machine learning models, called the 3P model, using as reference the invasive measurement of hepatic venous pressure gradient. The model considers three laboratory parameters (platelet count, bilirubin, international normalized ratio) and held promising results in predicting the presence of PH in cACLD (compensated advanced chronic liver disease). The aim of our study is to verify reliability of 3P model in a cohort of patients with HCC.We retrospectively included all consecutive patients discussed in multidisciplinary HCC team consultation from 2018 to 2022 at our Academic Hospital. 3P score was calculated using the original formula and cut-off (0.332) and compared with baseline endoscopy.Data from 240 cACLD patients with HCC were collected. 146 patients performed endoscopy at baseline and were included in statistical analysis. Main etiology of cirrhosis was viral infection (64/146,44%) followed by metabolic disease (44/146,30%). The HCC stage was classified using the Barcelona clinic liver cancer (BCLC) system: BCLC-0 22 patients (15.7%), BCLC-A 76(52.5%), BCLC-B 46(31.51%), BCLC-C 2(1.37%). A total of 42 patients (28.77%) had varices at endoscopy. Applying the 3P score with 0.332 cutoff in our cohort we obtained a sensitivity of 40% and specificity of 89% (AUC 0.65). Based on our data, another cut-off (0.15) was calculated for prediction of presence of varices at endoscopy reaching a sensitivity of 80% and specificity of 44%, with a negative predictive value of 83.7%.3P model could be a rapid and non-invasive model to predict the absence of severe PH at diagnosis of HCC. More data are necessary to validate our proposed cut off in HCC setting.

IntroductionFirst decompensation event in patients with cirrhosis is associated with worse clinical outcomes and requires prompt referral to transplantation. Little is known about impact of etiology of liver disease in type of decompensation, survival and occurrence of further events.Material and methodsWe consecutively analyzed data from patients admitted to ER from January 2019 to December 2022 for the first episode of decompensation, defined as ascites, hepatic encephalopathy, jaundice and upper digestive bleeding. Patients with previous or active HCC were excluded. We collected baseline features and survival rates, occurrence of further decompensation, transplantation and TIPS placement rates during follow-up.ResultsWe included 105 patients, 70 males (66.6%), with median age of 65 years (range 35-94). Among them 65 (61.9%) were unaware of underlying liver disease. The majority of patients (58, 55.2%) had alcoholic liver disease (ALD), followed by metabolic (17, 16%) and viral etiologies (11, 10%). Ascites was the most frequent event (60.9%), followed by jaundice (19%) and digestive bleeding (14.3%). Median survival was 17 months. After first decompensation only 32 patients (30%) didn't experience further liver events, 7 (6.6%) underwent liver transplantation and in 5 patients (4.7%) TIPS was placed. 53 patients died during the follow-up period. A lower rate of further decompensation, even if not statistically significant, was observed in ALD (45%) when compared to other etiologies (79% in metabolic liver disease, p=0.36).ConclusionsDuring last decades, active control of viral infections has deeply changed natural history of cirrhosis, with alcohol and metabolic disease progressively emerging as major causes of liver disease. Impressively, in our cohort, more than half of patients were unaware of their condition. First decompensation still significantly impacts on survival: therefore, more efforts are needed to increase specialist referral to improve early diagnosis and prevent decompensation.

PurposeIn cases of perihilar focal liver lesions, distinguishing between benign strictures and malignancies is critical to prevent unnecessary surgery. Although the use of contrast-enhanced CT or MRI in combination with clinical and laboratory findings can aid in diagnosis, histologic examination is often necessary. Histologic specimens can be obtained through various techniques, including ERCP-guided brush cytology or intraductal biopsy, cholangioscopy-directed biopsy or endoscopic ultrasound (EUS). However, these methods have been associated with suboptimal sensitivity and specificity, sometimes leading to inconclusive results. Therefore, ultrasound-guided percutaneous biopsy (US-guided PB) may play a crucial role, but data is lacking for perihilar lesions. The objective of our study was to assess the technical feasibility and safety of US-guided PB for perihilar lesions.MethodsWe included 20 consecutive patients who underwent US-guided PB of perihilar liver lesions that were not suitable for surgery between June 2018 and October 2023.ResultsAll samples were obtained using a Menghini needle 20G and were adequate for histological examination, with a mean diameter of 12.3 mm (range 3-40 mm). Out of the 20 patients, 11 were diagnosed with malignancy while the remaining 9 had inflammatory or fibrotic tissue samples. No adverse events related to the procedure were reported.ConclusionUS-guided PB of perihilar liver lesions is a valuable and safe diagnostic approach to consider for patients who are not suitable for surgery.

Focal nodular hyperplasia (FNH) is a common benign lesion of the liver of uncertain pathogenesis that is more common in women. Lesions are often asymptomatic and diagnosed incidentally. Magnetic resonance imaging with liver-specific contrast allows non-invasive and accurate diagnosis. Most FNHs remain stable over long periods of follow-up. However, some rare cases of partial or complete spontaneous regression have been described in the literature. In this report, we discuss the case of a 38-year-old female patient who experienced not only complete regression of two liver lesions compatible with FNH, but also the appearance of a similar lesion in a different liver segment. To our knowledge, no similar cases have been reported.

Background: Previous studies on oocyte extract supplementation showed benefits in patients with liver tumours. In this trial, we hypothesized that the oocyte extract supplement impacted the QoL after hepatectomy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Methods: This was a multicentre, double-blind, randomized clinical trial designed to assess the QoL of patients receiving a supplement of oocyte extract or placebo postoperatively. QoL was assessed using the Short Form-36 questionnaire in participants randomly assigned to treatment (Synchrolevels) or placebo. All study personnel and participants were masked to treatment assignment. The endpoint was the change in the QoL score. Results: Between June 2018 and September 2022, 66 of 128 expected patients were considered as per interim analysis, of which 33 were assigned to the treatment and 33 to the placebo group. Baseline and clinicopathological characteristics were similar between the two groups. In the treatment group, the health, mental and psychological status improved for many of the items considered, reaching statistical significance, while in the placebo group, those items either did not change or were impaired in comparison with the corresponding baseline. Conclusions: Supplementation with oocyte extract modifies QoL after liver surgery by enhancing functional recovery. Further in-depth studies are required to confirm this evidence.

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug–drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. We retrospectively analyzed a cohort of 151 cirrhotic patients with unresectable hepatocellular carcinoma (HCC) who underwent their first trans-arterial embolization (TAE) between 1 March 2011 and 1 July 2019 at our Institution. Clinical and biochemical data were collected. Sarcopenia was assessed using the L3-SMI method while myosteatosis with a dedicated segmentation suite (3D Slicer), using a single slice at an axial plane located at L3 and calculating the IMAC (Intramuscular Adipose Tissue Content Index). The sex-specific cut-off values for defining myosteatosis were IMAC > −0.44 in males and >−0.31 in females. In our cohort, 115 (76%) patients were included in the myosteatosis group; 128 (85%) patients had a coexistent diagnosis of sarcopenia. Patients with myosteatosis were significantly older and showed higher BMI than patients without myosteatosis. In addition, male gender and alcoholic- or metabolic-related cirrhosis were most represented in the myosteatosis group. Myosteatosis was not associated with a different HCC burden, length of hospitalization, complication rate, and readmission in the first 30 days after discharge. Overall survival was not influenced by the presence of myosteatosis.

Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15–55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.

patient-derived organoids.Organoids and primary tissues were characterized through: (i) RT-qPCR to analyze the mutation status; (ii) immunofluorescence analysis to evaluate the expression of HB biomarkers; (iii) transcriptmic studies by performing total-and small-RNA sequencing.Results: Fourteen stable organoid lines have been successfully generated from T and NT tissues using a specific isolation protocol and have been grown in expansion media enriched in growth factors.T-and NT-organoids present differences in morphology and doubling time, with T organoids growing slower and in darker small structures compared to the NT organoids.Moreover, the T-organoids present the same mutations of the primary tissues.Additionally, T-and NTorganoids show different gene and protein expression of markers associated with hepatocyte-(HNF4) and progenitor-phenotype (KRT19, EpCAM), as well as HB-related genes, such as DLK1; and cytoplasmic localization of both GS and β-catenin.Interestingly, principal component analysis of total RNA and small RNA transcriptome revealed that HB organoids maintain general features of the tumor of origin.Finally, functional analysis has revealed conserved pathways between T-and NT-primary tissues and T-and NTorganoids, among them epigenetic regulation, proliferation, Wnt activaction and altered metabolism, indicating the maintenance of tumor features by organoids. Conclusion:In conclusion, we have developed a new patient-derived ex vivo 3D system mimicking HB features, including specific gene and protein expression.Specifically, these data suggest that HB-derived organoids are a reliable model to investigate this poorly understood pediatric tumor towards the development of personalized treatments.

Liver InternationalVolume 41, Issue 6 p. 1421-1422 LIVER INTERNATIONAL IMAGES Portal hypertension determined by von Hippel Lindau syndrome Antonio Capogreco, Corresponding Author Antonio Capogreco antonio.capogreco@humanitas.it orcid.org/0000-0002-2212-2266 Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Milan, Italy Correspondence Antonio Capogreco, MD, Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Via Alessandro Manzoni 56, Rozzano, 20089 Milan, Italy. Email: antonio.capogreco@humanitas.itSearch for more papers by this authorVittorio Pedicini, Vittorio Pedicini Unit of Interventional Radiology, Humanitas Research Hospital IRCCS, Milan, ItalySearch for more papers by this authorChiara Masetti, Chiara Masetti Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Milan, ItalySearch for more papers by this authorRoberto Ceriani, Roberto Ceriani Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Milan, ItalySearch for more papers by this author Antonio Capogreco, Corresponding Author Antonio Capogreco antonio.capogreco@humanitas.it orcid.org/0000-0002-2212-2266 Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Milan, Italy Correspondence Antonio Capogreco, MD, Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Via Alessandro Manzoni 56, Rozzano, 20089 Milan, Italy. Email: antonio.capogreco@humanitas.itSearch for more papers by this authorVittorio Pedicini, Vittorio Pedicini Unit of Interventional Radiology, Humanitas Research Hospital IRCCS, Milan, ItalySearch for more papers by this authorChiara Masetti, Chiara Masetti Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Milan, ItalySearch for more papers by this authorRoberto Ceriani, Roberto Ceriani Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Milan, ItalySearch for more papers by this author First published: 04 January 2021 https://doi.org/10.1111/liv.14783 Handling editor: Luca Valent Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume41, Issue6June 2021Pages 1421-1422 RelatedInformation