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Introduction: Lung ultrasound (LUS) has become the first diagnostic imaging approach to assess lung involvement in COVID-19. While LUS proved to be safe, reliable, and accurate, not many primary care physicians (PCP) are capable to employ this instrument in the first evaluation of COVID-19 outpatients. The aim of this study was to determine the effectiveness of a brief training program in LUS for PCP.Methods: Italian local authorities promoted a training program in LUS for PCP engaged in COVID-19 outpatients' evaluation. The course took place in a COVID-19 unit and included a hands-on practice on real COVID-19 patients. We conducted a qualitative and quantitative analysis of the results of the training program.Results: A total of 32 PCP completed the training. About 100% of participants reported an increase in competence and confidence in the use of LUS after the training. Self-reported confidence in detecting major COVID-19 LUS abnormalities was high (B-lines 8/10, pleural abnormalities 6.5/10). B-lines were accurately identified with a reliability of 81%, with a sensitivity of 96%, and a negative predictive value of 98%. Trainees were some less accurate in detecting pleural abnormalities (reliability 63%) but with a high specificity (99%).Conclusions: This study showed that a short training program, but comprising a hands-on practice, is capable to bring even almost novices to achieve a high overall accuracy and reliability in detecting lung involvement in COVID-19. This may result in a significant improvement of the performances of PCP involved in the first evaluation of COVID-19 cases in primary care facilities. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a globally relevant medical problem. Fortunately, risk factors for this tumor have been identified, and surveillance protocols developed. Patients with liver cirrhosis have the highest risk of developing HCC and have historically been included in surveillance programs. Special categories have also emerged in recent years, especially patients with eradicated HCV infection or nonalcoholic fatty liver disease. Novel serum biomarkers and magnetic resonance imaging protocols are currently being proposed to refine existing surveillance protocols. We discuss the rationale of surveillance programs for HCC and report the most recent recommendations from international guidelines about this topic. Gray areas, such as nonalcoholic fatty liver disease and the role of intrahepatic cholangiocellular carcinoma, are also discussed. Surveillance is recognized as a tool to favor early diagnosis of HCC, access to curative treatment, and increase survival, even if the supporting evidence is mainly based on observational studies. As new randomized clinical trials are difficult to propose, future challenges will include optimizing implementation in the primary care setting and a more personalized approach, balancing the opportunities and risks of overdiagnosis of novel techniques and biomarkers. Not long after its development, ultrasound (US) has been used to identify liver cancer in patients with liver cirrhosis. Consequently, US-based semiannual surveillance programs have been implemented in recent decades to facilitate an early diagnosis of liver cancer and increase chances of successful radical treatment. The efficacy of these protocols has been recognized in observational studies and clinical trials. However, recent years have shown the appearance of new categories of patients with chronic liver disease. Also, imaging innovations and putative novel biomarkers appeared on the stage. This review discusses the current knowledge and future perspective of these surveillance programs for liver cancer. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate imaging features of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) developed after direct-acting antiviral (DAA) therapy in HCV-related cirrhosis.Methods: Retrospective cohort study on 344 consecutive patients with HCV-related cirrhosis treated with DAA and followed for 48-74 weeks. Using established imaging criteria for MVI, HCC features were analysed and compared with those in nodules not occurring after DAA.Results: After DAA, HCC developed in 29 patients (single nodule, 18 and multinodular, 11). Median interval between therapy end and HCC diagnosis was 82 days (0-318). Forty-one HCC nodules were detected (14 de novo, 27 recurrent): maximum diameter was 10-20 mm in 27, 20-50 mm in 13, and > 50 mm in 1. Imaging features of MVI were present in 29/41 nodules (70.7%, CI: 54-84), even in 17/29 nodules with 10-20 mm diameter (58.6%, CI: 39-76). MVI was present in only 17/51 HCC nodules that occurred before DAA treatment (33.3%, CI: 22-47) (p= 0.0007). MVI did not correlate with history of previous HCC.Conclusions: HCC occurs rapidly after DAA therapy, and aggressive features of MVI characterise most neoplastic nodules. Close imaging evaluations are needed after DAA in cirrhotic patients.Key Points: • In HCV cirrhosis, hepatocellular carcinoma develops soon after direct-acting antiviral therapy. • HCC presents imaging features of microvascular invasion, predictive of more aggressive progression. • Cirrhotic patients need aggressive and close monitoring after direct-acting antiviral therapy. [ABSTRACT FROM AUTHOR]

Objectives Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur during systemic lupus erythematosus (SLE). Data on MAS in adult SLE patients are very limited. The aim of this study is to describe the clinical characteristics, laboratory findings, treatments, and outcomes of a large series of SLE-associated MAS. Methods We conducted a retrospective study that included 103 episodes of MAS in 89 adult patients with SLE. Results 103 episodes in 89 adult patients were analyzed. Median age at first MAS episode was 32 (18–80) years. MAS was inaugural in 41 patients (46%).Thirteen patients relapsed. Patients had the following features: fever (100% episodes), increased serum levels of AST (94.7%), LDH (92.3%), CRP (84.5%), ferritin (96%), procalcitonin (41/49 cases). Complications included myocarditis (n = 22), acute lung injury (n = 15) and seizures (n = 11). In 33 episodes, patients required hospitalization in an ICU and 5 died. Thrombocytopenia and high CRP levels were associated independently with an increased risk for ICU admission. High dose steroids alone as first line therapy induced remission in 37/57 cases (65%). Additional medications as first or second line therapies included IV immunoglobulins (n = 22), cyclophosphamide (n = 23), etoposide (n = 11), rituximab (n = 3). Etoposide and cyclophosphamide-based regimens had the best efficacy. Conclusion MAS is a severe complication and is often inaugural. High fever and high levels of AST, LDH, CRP, ferritin and PCT should be considered as red flags for early diagnosis. High dose steroids lead to remission in two third of cases. Cyclophosphamide or etoposide should be considered for uncontrolled/severe forms. [ABSTRACT FROM AUTHOR]

Background: Lung ultrasound (LU) is becoming an increasingly important diagnostic tool in detecting lung involvement in Corona Virus Disease 2019 (COVID-19). The aim of this study was to ascertain the likelihood of finding LU abnormalities; mimicking lung involvement; in COVID-19 negative healthy individuals. Methods: We performed LU on 265 healthcare workers; not presenting COVID-19 major symptoms and in good health; during the course of a serological screening program for COVID-19 in our General Hospital. LU results were reported as total Lung Ultrasound Score (LUS) using a 12-zone method of reporting. Results: 250/265 subjects were included in the COVID-19 negative group. LU was not completely normal (LUS ≠ 0) in 65/250 COVID-19 negative subjects (26%) and in 12/15 (80%) poorly symptomatic COVID-19 positive subjects; with a multifocal pattern in 12.7% vs. 66.7% of cases respectively. Age and COVID-19 positivity were independent predictors of total LUS. A total LUS ≥ 2 had a sensitivity of 66.67% and a specificity of 85.60% in detecting COVID-19 positivity. Conclusions: A slightly altered LU can be quite frequent in healthy COVID-19 negative subjects. LU can have a role in confirming but not screening COVID-19 poorly symptomatic cases. [ABSTRACT FROM AUTHOR]

An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47–6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23–7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05–3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08–4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35–6.09; p = 0.006) were associated with HCC recurrence. An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC. • The study focuses on the risk of developing de novo or recurrent HCC after DAA treatment in patients with HCV cirrhosis. • An early peak of HCC incidence was observed in DAA-treated patients. • Undefined non-malignant nodules, ascites and AFP were independently associated with the incidence of de novo HCC. • History of alcohol abuse and history of previous HCC recurrence were associated with HCC recurrence. • No evidence of increased tumour aggressiveness was reported in de novo or recurrent HCC. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic teleangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is the most common cause of hepatic vascular malformations in adults. Different vascular shunts (arteriovenous, arterioportal or portovenous) lead to different clinical manifestations. Even though no hepatic-related symptoms are reported in the majority of cases, the severity of liver disease could lead to refractory medical conditions, in some cases requiring liver transplantation. The aim of this manuscript is to provide an updated overview of the current evidence regarding the diagnosis and treatment of HHT liver involvement and liver-related complications., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: Fabio Piscaglia declares the following COI: Esaote, Bracco, Bayer, Samsung (lecturing or consultant or advisory board honoraria). All other authors have no COI to declare.

Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and HEV) can evolve in chronic infections, whereas hepatitis A virus (HAV) frequently produces acute self-limiting hepatitis. In the last years, different studies have been performed to introduce new antiviral therapies. The most important goal in the treatment of viral hepatitis is to avoid chronic liver disease and complications. This review analyzes currently available therapies, in particular for viruses associated with chronic liver disease. The focus is especially on HBV and HCV therapies, investigating new drugs already introduced in clinical practice and clinical trials. We also describe new entry inhibitors, developed for the treatment of chronic HDV and HBV and currently available treatments for HEV. The last drugs introduced have shown important efficacy in HCV, with achievable target HCV elimination by 2030. Concurrently, renewed interest in curative HBV therapies has been registered; current nucleotide/nucleoside analogs positively impact liver-related complications, ensuring high safety and tolerability. Novel approaches to HBV cure are based on new antivirals, targeting different steps of the HBV life cycle and immune modulators. The improved knowledge of the HDV life cycle has facilitated the development of some direct-acting agents, as bulevirtide, the first drug conditionally approved in Europe for HDV associated compensated liver disease. Further studies are required to identify a new therapeutic approach in hepatitis E, especially in immunosuppressed patients., Competing Interests: Conflict-of-interest statement: All authors has nothing to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The advent of directly acting antivirals (DAA) has determined a showy change in the management of hepatitis C virus (HCV) infection, the most common cause of hepatocellular carcinoma (HCC) in many countries. It was demonstrated that the achievement of sustained virologic response (SVR) with interferon (IFN) reduces the incidence of HCC. Recently, published data in the literature suggested an increased risk of HCC after IFN free treatments. The mechanism evoked to explain this trend is the deregulation of antitumor response, following the sudden decrease of HCV viral load, due to immune subversion which could favour the progressive development of pre-existing neoplastic clones. The lack of randomised controlled trials (RCTs) with control groups of patients and the fact that majority of studies are limited by retrospective settings, recruitment bias and lack of clinical goals scheduled at the start of treatment make difficult an adequate analysis of data. Main evidence seems to confirm that DAA therapy has not a carcinogenic effect per se but can lead to the earlier manifestation of latent tumours still present but underestimated. At present patients with HCV infection should be encouraged initiating DAA therapy to prevent cirrhosis and HCC but intensive screening is necessary to exclude HCC before initiating DAA. Curing HCV infection does not eliminate the possibility of ongoing liver disease and HCC, as such an adequate monitoring should continue for an indefinite period after SVR., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.04.01). The series “Primary Liver Cancer” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk factors such as obesity, type2-diabetes mellitus, and dyslipidemia has led to a worldwide diffusion of NAFLD. In parallel to the increased availability of effective anti-viral agents, NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries in the next years. This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis, management, and treatment of NAFLD. Different scientific societies from Europe, America, and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD. These guidelines are consistent with the key elements in the management of NAFLD, but still, show significant difference about some critical points. We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences. We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions. Differences were noted in: the definition of NAFLD, the opportunity of NAFLD screening in high-risk patients, the non-invasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis, in the follow-up protocols and, finally, in the treatment strategy (especially in the proposed pharmacological management). These difference have been discussed in the light of the possible evolution of the scenario of NAFLD in the next years., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.

Contrast-enhanced ultrasound (CEUS) is a sure, noninvasive, repeatable imaging technique widely used in the characterization of benign and malignant liver lesions. The European Federation of Societies for Ultrasound in Medicine and Biology guidelines suggest the typical CEUS features of liver lesions as criteria for the noninvasive diagnosis in cirrhotic and not-cirrhotic patients. The clinical application of CEUS in the liver study is summarized in this review; the contrast-enhanced patterns of the most frequent liver lesions are described (hepatocellular and cholangiocellular carcinoma, liver metastases, hemangioma, focal nodular hyperplasia, adenoma). The role of this imaging technique in the diagnostic algorithm of liver malignancy is illustrated and the CEUS application in hepatologic and oncological settings is depicted., Competing Interests: Financial & competing interests disclosure L Bolondi receives consulting and speakers fees from Bayer, Bracco and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.