Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis.

BACKGROUND: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. METHODS: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients' sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. RESULTS: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2-deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, ß and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. CONCLUSIONS: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare benign focal liver lesion, part I.

Improved detection and characterization of common focal liver lesions (FLL) are the main topics of the World Federation for Ultrasound in Medicine and Biology (WFUMB) guidelines on the use of contrast-enhanced ultrasound (CEUS). On stateof-the-art CEUS imaging, to create a library of rare FLL, especially concerning their atypical imaging characteristics, might be helpful for improving clinical diagnostic efficiency. In this review, we aim to summarize the ultrasound and CEUS features of rare benign FLL. Currently there are limited reports and images published.

Lactobacillus rhamnosus probiotic treatment modulates gut and liver inflammatory pathways in a hepatocellular carcinoma murine model. A preliminary study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a growing global concern with an increasing incidence rate. The intestinal microbiota has been identified as a potential culprit in modulating the effects of antitumoral drugs. We aimed to assess the impact of adding Lactobacillus rhamnosus probiotic to regorafenib in mice with HCC. METHODS: Cirrhosis and HCCs were induced in 56 male Swiss mice via diethylnitrosamine injection and carbon tetrachloride administration. Mice were divided into four groups: treated with vehicle (VC), regorafenib (Rego), L. rhamnosus probiotic, and a combination of regorafenib and probiotic (Rego-Pro). After 3 weeks of treatment, liver and intestinal fragments were collected for analysis. RESULTS: Regorafenib elevated gut permeability, an effect mitigated by probiotic intervention, which exhibited a notable correlation with reduced inflammation (p < 0.01). iNOS levels were also reduced by adding the probiotic with respect to the mice treated with regorafenib only (p < 0.001). Notably, regorafenib substantially increased IL-6, TNF-a and TLR4 in intestinal fragments (p < 0.01). The administration of the probiotic effectively restored IL-6 to its initial levels (p < 0.001). CONCLUSION: Reducing systemic and intestinal inflammation by administering L. rhamnosus probiotic may alleviate tumoral resistance and systemic adverse effects.

Role of Metabolomics in Pathogenesis and Prompt Diagnosis of Gastric Cancer Metastasis-A Systematic Review.

INTRODUCTION: Gastric cancer is the fourth most frequently diagnosed form of cancer and the third leading cause of cancer-related mortality worldwide. The aim of this review is to identify individual metabolic biomarkers and their association with accurate diagnostic values, which can predict gastric cancer metastasis. MATERIALS AND METHODS: After searching the keywords, 83 articles were found over a period of 13 years. One was eliminated because it was not written in English, and two were published outside the selected period. Seven scientific papers were qualified for this investigation after eliminating duplicates, non-related articles, systematic reviews, and restricted access studies. RESULTS: New metabolic biomarkers with predictive value for gastric cancer metastasis and for elucidating metabolic pathways of the metastatic process have been found. The pathogenic processes can be outlined as follows: pro-oxidant capacity, T-cell inactivation, cell cycle arrest, energy production and mitochondrial enzyme impairment, cell viability and pro-apoptotic effect, enhanced degradation of collagen extracellular matrix, migration, invasion, structural protein synthesis, and tumoral angiogenesis. CONCLUSION: Metabolic biomarkers have been recognized as independent risk factors in the molecular process of gastric cancer metastasis, with good diagnostic and prognostic value.

Don't Judge a Book by Its Cover: The Role of Statins in Liver Cancer.

Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin's type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-tumorigenic attributes, such as its role in immune response activation, cellular senescence induction, and tumor surveillance. Through a comprehensive exploration of the intricate interactions between IL-6 and the tumor microenvironment, this review highlights the need for a nuanced comprehension of IL-6 signaling in HCC. It underscores the importance of tailored therapeutic strategies that consider the dynamic stages and diverse surroundings within the tumor microenvironment. Future research directions aimed at unraveling the multifaceted mechanisms of IL-6 in HCC hold promise for developing more effective treatment strategies and improving patient outcomes.

Refining Liver Biopsy in Hepatocellular Carcinoma: An In-Depth Exploration of Shifting Diagnostic and Therapeutic Applications.

The field of hepatocellular carcinoma (HCC) has faced significant change on multiple levels in the past few years. The increasing emphasis on the various HCC phenotypes and the emergence of novel, specific therapies have slowly paved the way for a personalized approach to primary liver cancer. In this light, the role of percutaneous liver biopsy of focal lesions has shifted from a purely confirmatory method to a technique capable of providing an in-depth characterization of any nodule. Cancer subtype, gene expression, the mutational profile, and tissue biomarkers might soon become widely available through biopsy. However, indications, expectations, and techniques might suffer changes as the aim of the biopsy evolves from providing minimal proof of the disease to high-quality specimens for extensive analysis. Consequently, a revamped position of tissue biopsy is expected in HCC, following the reign of non-invasive imaging-only diagnosis. Moreover, given the advances in techniques that have recently reached the spotlight, such as liquid biopsy, concomitant use of all the available methods might gather just enough data to improve therapy selection and, ultimately, outcomes. The current review aims to discuss the changing role of liver biopsy and provide an evidence-based rationale for its use in the era of precision medicine in HCC.

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare benign focal liver lesion, part II.

It is important to be familiar with the typical imaging features of the uncommon or even extremely rare focal liver lesions (FLL). Current guidelines of the World Federation for Ultrasound in Medicine and Biology (WFUMB) is aimed at assessing the usefulness of contrast enhanced ultrasound (CEUS) in the management of various FLL. In this review, we aim to summarize the ultrasound and CEUS characteristics with literature review of some extremely rare benign FLL, which might be helpful for improving diagnostic efficiency clinically.

Overlap syndrome of autoimmune hepatitis and primary biliary cholangitis complicated with atypical hepatocellular carcinoma: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary tumor of the liver. The majority of HCCs are associated most frequently with chronic B or C viral hepatitis, alcohol intake or aflatoxin exposure. Cirrhosis is a strong risk factor associated with HCC. The causes of liver cirrhosis are chronic viral hepatitis, alcohol intake, metabolic diseases (NAFLD), hemocromathosis, alfa 1 antitrypsisn deficiency. All aetiologic forms of cirrhosis are at risk to be complicated by HCC development, but the risk is higher for patients diagnosed with chronic viral hepatitis. Comparing to the above-mentioned causes, PBC and AIH are less associated with the risk of HCC development. A 71-year old Caucasian female previously diagnosed with overlap syndrome (AIH type 1 and PBC-ANA, SMA and AMA antibodies positive), liver cirrhosis, a nodule in the VI/VIIth hepatic segment, systemic sclerosis sine scleroderma, Hashimoto's thyroiditis, antiphospholipid syndrome, gastric antral vascular ectasia (GAVE) (with 2 previous sessions of argon plasma coagulation), cholecystectomy, arterial hypertension and nephro-angiosclerosis presented to the 2nd Department of Internal Medicine in Cluj-Napoca for a follow-up. The patient was following treatment with UDCA (Ursodeoxycholic acid), azathioprine, Plaquenil, calcium channel blockers, angiotensin-converting-enzyme inhibitor, calcium and vitamin D supplementation. The abdominal ultrasound showed a subcapsular hypoechoic nodule with a diameter of 29 mm (at the moment of the diagnosis the diameter was 9/10 mm) in the VI/VIIth hepatic segment. The contrast-enhanced ultrasound (CEUS) characterised the nodule as specific for hepatocellular carcinoma (LI-RADS 5). On MRI with gadoxetate disodium the nodule was hypovascular, non-specific, being classified as LI-RADS 3. An atypical resection of the VIIth hepatic segment was performed and the histohistological examination and imunohistochemistry (Hep Par-a positive, Glypican3 positive, CD34 positive) revealed a moderately differentiated hepatocellular carcinoma (G2), pT2 N0 M0 L0 V1 R0. CONCLUSION: Autoimmune hepatitis, PBC and the overlap syndrome are less associated with the development of liver cirrhosis and HCC than other chronic liver diseases, especially if other risk factors are not associated. This case highlights the importance of a proper surveillance of cirrhotic patients every 6 months including abdominal ultrasound and AFP levels is crucial for an early diagnosis of a HCC.

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare focal liver lesions - non-infectious, non-neoplastic.

In this series of papers on comments and illustrations of the World Federation for Medicine and Biology (WFUMB) guidelines on contrast enhanced ultrasound (CEUS) the topics of non-infectious and non-neoplastic focal liver lesions (FLL) are discussed. Improved detection and characterization of common FLL are the main topics of these guidelines but detailed and illustrating information is missing. The focus in this paper is on non-infectious and non-neoplastic FLL and their appearance on B-mode, Doppler ultrasound and CEUS features. Knowledge of these data should help to raise awareness of these rarer findings, to think of these clinical pictures in the corresponding clinical situation, to interpret the ultrasound images correctly and thus to initiate the appropriate diagnostic and therapeutic steps in time.

Enhanced diagnosis and prognosis of severe alcoholic hepatitis using novel metabolomic biomarkers.

AIM: Differentiating alcoholic hepatitis (AH) from acute decompensation of alcoholic cirrhosis (DC) is challenging, as the presentation and biochemistry are similar. We aimed to identify potential metabolomic biomarkers to differentiate between AH and DC, and to predict short-term mortality. METHODS: We included consecutive biopsy proven AH and DC patients, which were managed according to current guidelines and followed up until the end of the study. Untargeted metabolomics was assessed in all patients at baseline. Specific analyses were successively performed to identify potential biomarkers, which were further semi-quantitatively analysed against relevant clinical endpoints. RESULTS: Thirty-four patients with AH and 37 with DC were included. UHPLC-MS analysis identified 83 molecules potentially differentiating between AH and DC. C16-Sphinganine-1P (S1P) was the most increased, whereas Prostaglandin E2 (PGE2) was the most decreased. The PGE2/S1P ratio < 1.03 excellently discriminates between AH and DC: AUC 0.965 (p < 0.001), Se 90%, Sp 100%, PPV 0.91, NPV 1, and diagnostic accuracy 95%. This ratio is not influenced by the presence of infection (AUC 0.967 vs. 0.962), correlates with the Lille score at 7 days (r = -0.60; P = 0.022) and tends to be lower in corticosteroid non-responders as compared with patients who responded [0.85(±0.02) vs. 0.89(±0.05), P = 0.069]. Additionally, decreased ursodeoxycholic acid levels are correlated with MELD and Maddrey scores and predict mortality with a 77.27% accuracy (NPV = 100%). CONCLUSION: This study suggests the PGE2 (decreased)/S1P (increased) ratio as a biomarker to differentiate AH from DC. The study also finds that low levels of ursodeoxycholic acid could predict increased mortality in AH.

The Role of Immunohistochemistry in the Differential Diagnosis between Intrahepatic Cholangiocarcinoma, Hepatocellular Carcinoma and Liver Metastasis, as Well as Its Prognostic Value.

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.

Presence of Hepatocellular Carcinoma Does Not Affect Course and Response to Anticoagulation of Bland Portal Vein Thrombosis in Cirrhotic Patients.

Background: Malignancies are generally considered a risk factor for deep vein thrombosis and may hamper the recanalisation of thrombosed veins. Aim: We investigate whether the natural course and response to anticoagulant treatment of bland portal vein thrombosis (PVT) in patients with cirrhosis complicated by hepatocellular carcinoma (HCC) differ from those without HCC. Methods: Retrospective study in two hepatology referral centres, in Italy and Romania where patients with a diagnosis of PVT on cirrhosis and follow-up of at least 3 months with repeated imaging were included. Results: A total of 162 patients with PVT and matching inclusion and exclusion criteria were identified: 30 with HCC were compared to 132 without HCC. Etiologies, Child-Pugh Score (7 vs 7) and MELD scores (11 vs 12, p=0.3679) did not differ. Anticoagulation was administered to 43% HCC vs 42% nonHCC. The extension of PVT in the main portal trunk was similar: partial/total involvement was 73.3/6.7% in HCC vs 67.4/6.1% in nonHCC, p=0.760. The remainder had intrahepatic PVT. The recanalization rate was 61.5% and 60.7% in HCC/nonHCC in anticoagulated patients (p=1). Overall PVT recanalisation, including treated and untreated patients, was observed in 30% of HCC vs 37.9% of nonHCC, p=0.530. Major bleeding incidence was almost identical (3.3% vs 3.8%, p=1). Progression of PVT after stopping anticoagulation did not differ (10% vs 15.9%, respectively, HCC/nHCC, p=0.109). Conclusion: The course of bland non-malignant PVT in cirrhosis is not affected by the presence of active HCC. Treatment with anticoagulation in patients with active HCC is safe and as effective as in nonHCC patients, this can potentially allow us to use otherwise contraindicated therapies (ie TACE) if a complete recanalization is achieved with anticoagulation.

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for patients with intrahepatic cholangiocarcinoma.

Cholangiocarcinoma, the second most common liver malignancy, after hepatocarcinoma is highly aggressive and usually diagnosed in advanced cases. In the era of personalized medicine, targeted therapy protocols are limited for cholangiocarcinoma and the only potential curative treatment, surgical resection, is seldom applicable.This retrospective study included all cases with pathology-confirmed intrahepatic cholangiocarcinoma admitted in a tertiary healthcare facility during a 10-year timeframe. Clinical information, laboratory values, imaging studies, and survival data were retrieved, and PD-L1 immunostaining was performed on representative pathology slides, for each case. From the total of 136 included cases (49 surgical resections and 87 liver biopsies), 38.97% showed PD-L1 positivity on tumoral cells, 34.8% on tumor infiltrating immune cells, 10.11% on epithelial cells within the peritumoral area and 15.95% on immune cells from the peritumoral area. Overall survival was significantly higher in the first two scenarios. However, after adjusting for age, tumor number, tumor size, and tumor differentiation in a multivariate analysis, only PD-L1 positivity on tumor infiltrating immune cells remained a favorable prognostic for survival. High immune cell counts also correlated with increased overall survival.Our study demonstrated that PD-1/PD-L1 checkpoint pathway in the microenvironment of intrahepatic cholangiocarcinoma bears prognostic significance. PD-L1 expression on immune cells, in both resection and biopsy specimens, might be a strong independent predictor for a favorable outcome.

Clinical Utility of the Contrast-Enhanced Endoscopic Ultrasound Guided Fine Needle Aspiration in the Diagnosis of Pancreatic Cyst.

Endoscopic ultrasound fine needle aspiration (EUS-FNA) cytology from an intracystic fluid is useful in the differentiation of pancreatic cysts, with low sensitivity, which increases when the solid component is targeted. The clinical utility of contrast-enhanced guided EUS-FNA (CH-EUS-FNA) in the solid component is not known. We aimed to assess the diagnostic value of CH-EUS-FNA in enhanced mural nodules and discrimination between different cysts using contrast-enhanced endoscopic ultrasound (CH-EUS). The prospective study recruited patients with pancreatic cysts with an unclear diagnosis. The CH-EUS was followed by CH-EUS-FNA. The final diagnosis was based on surgery or the correlation between clinical history, cross-sectional imaging, echoendoscopic morphology, cystic fluid analysis, and follow-up. Fifty-eight patients with pancreatic cysts were evaluated. The mucinous cysts had wall arterial enhancement more often than non- mucinous cysts (p < 0.0001), with 90.2% sensitivity and 70.6% specificity. The CH-EUS-FNA from cystic fluid and mural nodules identified mucinous cysts and malignancy with 82.4% and 84.2% sensitivity and 92% and 100% specificity. Twenty-one cysts had solid components, but only 13 were enhanced mural nodules on EUS assessment with conclusive cytology in all cases and malignancy in 76.9%. Contrast-enhanced endoscopic ultrasound should be completed in all PCN with solid components in order to avoid unnecessary EUS-FNA and to guide FNA for the identification of malignant cysts.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy versus Fine-Needle Aspiration in the Diagnosis of Focal Liver Lesions: Prospective Head-to-Head Comparison.

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) or fine-needle aspiration (EUS-FNA) from focal liver lesions are indicated in selected cases, but there has been no previous comparison of needle types of the same size. The aim of our study was to compare the histologic diagnostic accuracy and adequacy of cores obtained with EUS-FNB needles in contrast to those obtained with FNA needles in focal liver lesions. This prospective one-center study included patients with left lobe hepatic focal lesions with contraindications for percutaneous liver biopsy or need for EUS for concomitant lesions. Each patient had one pass of 22G EUS-FNB (Franseen) needle and one pass of 22G EUS-FNA in a crossover manner, without macroscopic on-site evaluation. Each sample was analyzed separately for histologic adequacy and diagnosis. The final diagnosis was based on histology results or on imaging follow-up in the case of negative biopsies. The EUS-FNB samples (n = 30) were found to be more adequate for histologic analysis, with more cellularity and longer tissue aggregates than the EUS-FNA samples (n = 30). The accuracy of EUS-FNB was 100%, whereas that of EUS-FNA was 86.7% (p = 0.039). No post-procedure complications were noted. The 22G EUS-FNB needle proved superior to 22G EUS-FNA in terms of tissue acquisition diagnostic accuracy and histologic adequacy in focal liver lesions.

Pulmonary complications of portal hypertension: The overlooked decompensation.

The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.

Novel approaches in search for biomarkers of cholangiocarcinoma.

Cholangiocarcinoma (CCA) arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic CCA) or more commonly from the extrahepatic bile ducts (extrahepatic CCA). This disease has a poor prognosis and a growing worldwide prevalence. The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging, especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA, or distal CCA and pancreatic head adenocarcinoma. Most patients present with an advanced disease, unresectable disease, and there is a lack in non-surgical therapeutic modalities. Not least, there is an acute lack of prognostic biomarkers which further complicates disease management. Therefore, there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result, either singlehandedly or combined with other methods. In the "-omics" era, this goal can be attained by various means, as it has been successfully demonstrated in other primary tumors. Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins, metabolites, extracellular vesicles, and ultimately circulating tumor cells. However, given the relatively heterogeneous data, extracting clinical meaning from the inconsequential noise might become a tall task. The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

Contrast enhanced endoscopic ultrasound in the diagnosis of pancreatic metastases.

AIM: Less than 5% of pancreatic masses represent metastases and differentiation from primitive tumors using endo-scopic ultrasound (EUS) is difficult. The aim of our work was to assess the diagnostic value of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) for pancreatic metastases. MATERIAL AND METHODS: We retrospectively analyzed patients with pancreatic metastasis identified during a 8 year period in a tertiary medical center. RESULTS: We included in the study 20 patients evaluated with EUS and CH-EUS. The primary tumor was localized in the kidney (6 cases), lung (5 cases), colon (3 cases), skin (2 patients) and stomach, breast, ovary and liver (1 patient each). Only 11 patients (55%) (kidney, lung, liver, ovary or skin metastases), presented hypervascularity at EUS and arterial hyperenhancement on CH-EUS, with similar diag-nostic value. All renal metastases were hyperenhanced (the negative predictive value 100%) and the stomach, colon and ovary metastases were hypoenhanced. The fast wash-out of contrast substance was encountered in all cases or renal, pulmonary and digestive metastases, but with 53.3-64.3% specificity for the different origin of pancreatic metastases. CONCLUSIONS: The vascularity assessments on conventional EUS or CH-EUS are similar for pancreatic metastases of different origin. EUS tissue acquisition remains mandatory for the diagnosis.