Contrast-Enhanced Ultrasound Findings in Patients with Rare Solitary Necrotic Nodule of the Liver - a Multicenter Report.

PURPOSE: This multicenter retrospective study highlights the contrast-enhanced ultrasound (CEUS) findings in a series of histologically proven solitary necrotic nodules (SNN) of the liver, a poorly understood pathologic entity of uncertain origin that mimics malignancy. MATERIALS AND METHODS: 22 patients (M/F 13/9; mean age 59.4 years, SD ±â€Š10.7, range 35-81) with histological diagnosis of SNN and CEUS were selected from clinical, imaging, and pathological archives of 7 US interventional centers, each of which provided 1 to 6 cases (mean 2.8). Pathological diagnosis was made on 20 US-guided biopsies and 2 surgical specimens. 2 patients had 2 SNNs with identical CEUS findings so that imaging analysis was carried out on 24 nodules. RESULTS: SNN was an incidental finding in healthy people in 10 cases (45.5 %), and it was discovered during follow-up for either known extrahepatic malignancies (9 cases = 41 %) or chronic liver disease (3 cases = 13.5 %). SNNs had a mean size of 19.3 mm (SD ±â€Š6.5, range 9-40). On B-mode US, SNNs appeared hypoechoic in 14 cases (66.7 %), "target-like" in 7 cases (29.2 %), and homogeneously hyperechoic in 1 case (4.1 %). On CEUS, all lesions appeared devoid of contrast enhancement ("punched out" aspect) in the arterial, portal venous, and late phases after US contrast agent injection. A uniformly thin, hyperenhancing ring in the early arterial phase and isoenhanced with the surrounding parenchyma in the portal venous and late phases was found in 10 nodules (41.6 %). Clinical and imaging follow-up (mean duration 42.2 months, SD ±â€Š34.9, range 2-108) was available in 15 patients with 16 SNNs: no changes in size and echostructure were seen. CONCLUSION: CEUS can contribute to the diagnosis of SNN when a "punched out" appearance in all vascular phases with or without thin rim enhancement in the very early arterial phase is present in healthy subjects in whom a focal liver lesion is incidentally found. In patients with a history of chronic liver disease or malignancy, US-guided biopsy represents the unavoidable first-line diagnostic modality.

Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis.

BACKGROUND: For compensated advanced chronic liver disease (cACLD) patients, the first decompensation represents a dramatically worsening prognostic event. Based on the first decompensation event (DE), the transition to decompensated advanced chronic liver disease (dACLD) can occur through two modalities referred to as acute decompensation (AD) and non-AD (NAD), respectively. Clinically Significant Portal Hypertension (CSPH) is considered the strongest predictor of decompensation in these patients. However, due to its invasiveness and costs, CSPH is almost never evaluated in clinical practice. Therefore, recognizing non-invasively predicting tools still have more appeal across healthcare systems. The red cell distribution width to platelet ratio (RPR) has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). However, its predictive role for the decompensation has never been explored. AIM: In this observational study, we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients. METHODS: Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up (FUP) semiannually for 3 years. At baseline, biochemical, clinical, and Liver Stiffness Measurement (LSM), Child-Pugh (CP), Model for End-Stage Liver Disease (MELD), aspartate aminotransferase/platelet count ratio index (APRI), Fibrosis-4 (FIB-4), Albumin-Bilirubin (ALBI), ALBI-FIB-4, and RPR were collected. During FUP, DEs (timing and modaities) were recorded. CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines. RESULTS: Of 150 MASLD-related cACLD patients, 43 (28.6%) progressed to dACLD at a median time of 28.9 months (29 NAD and 14 AD). Baseline RPR values were significantly higher in cACLD in comparison to controls, as well as MELD, CP, APRI, FIB-4, ALBI, ALBI-FIB-4, and LSM in dACLD-progressing compared to cACLD individuals [all P < 0.0001, except for FIB-4 (P: 0.007) and ALBI (P: 0.011)]. Receiving operator curve analysis revealed RPR > 0.472 and > 0.894 as the best cut-offs in the prediction respectively of 3-year first DE, as well as its superiority compared to the other non-invasive tools examined. RPR (P: 0.02) and the presence of baseline-CSPH (P: 0.04) were significantly and independently associated with the DE. Patients presenting baseline-CSPH and RPR > 0.472 showed higher risk of decompensation (P: 0.0023). CONCLUSION: Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.

"Starry liver" - Von Meyenburg complex clinical case presentation and differential diagnosis discussion: A case report.

BACKGROUND: Von Meyenburg complex (VMC) (i.e., biliary hamartoma) is a rare congenital disorder characterized by multiple dilated cystic bile ducts, without clear trends in sex or age predominance. Due to the low number of published cases and the lack of recognized guidelines, the management of such patients remains a clinical challenge. CASE SUMMARY: We present a case of symptomatic VMC that was diagnosed after imaging and histopathological examinations. Considering the patient's condition, a conservative treatment strategy was chosen. Instrumental, laboratory, and clinical follow-up demonstrated the stable condition of the patient receiving conservative treatment. CONCLUSION: VMC is a potentially non-life threatening condition, but its recognition is crucial for the management of patients.

Asymptomatic portal vein aneurysm: Three case reports.

BACKGROUND: Portal vein aneurysm (PVA) is an uncommon vascular dilatation, showing no clear trend in sex or age predominance. Due to the low number of published cases and the lack of management guidelines, treatment of this condition remains a clinical challenge. CASE SUMMARY: We present three cases of asymptomatic PVA; the first and second involve an extrahepatic manifestation, of 48 mm and 42.3 mm diameter respectively, and the third involves an intrahepatic PVA of 27 mm. All were diagnosed incidentally during routine check-up, upon ultrasonography scan. Since all patients were asymptomatic, a conservative treatment strategy was chosen. Follow-up imaging demonstrated no progression in the aneurysm dimension for any case. CONCLUSION: As PVA remains asymptomatic in many cases, recognition of its imaging features is key to favourable outcomes.

How Immunotherapy Has Changed the Continuum of Care in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of death worldwide. The use of local treatment, such as surgical resection, liver transplant, and local ablation, has improved the survival of patients with HCC detected at an early stage. Until recently, the treatment of patients with metastatic disease was limited to the use of the multikinase inhibitor (MKI) sorafenib with a marginal effect on survival outcome. New target approaches, such as the oral MKI lenvatinib in first-line treatment and regorafenib, ramucirumab, and cabozantinib in later lines of therapy, have demonstrated efficacy in patients with preserved liver function (Child-Pugh class A) and good performance status. On the other hand, the implementation of immune checkpoint inhibitors directed against PD-1 (nivolumab and pembrolizumab), PD-L1 (atezolizumab), and anti-CTLA4 (ipilimumab) in the management of advanced HCC has strongly changed the continuum of care of HCC. Future research should include the evaluation of molecular biomarkers that can help patient selection and provide new insight on potential combined approaches. In this review, we provide an overview of the clinical evidence of the use of immune checkpoint inhibitors in HCC, and discuss how immunotherapy has been implemented into the continuum of HCC care.

Interaction of alcohol intake and cofactors on the risk of cirrhosis.

OBJECTIVE: Evaluation of the interaction between alcohol intake and cofactors [hepatitis B virus (HBV), hepatitis C virus (HCV), body mass index] and coffee consumption on the risk of cirrhosis. DESIGN: Seven hundred and forty-nine consecutive patients with chronic liver disease referring to units for liver or alcohol diseases in Italy during a 6-months period. Teetotalers were excluded. The odds ratios (OR) for cirrhosis were evaluated using chronic hepatitis cases as the control group. RESULTS: An alcohol intake of more than 3 units/day resulted associated with the likelihood of cirrhosis both in males (OR 4.3; 95% CI=2.5-7.3) and in females (OR 5.7; 95% CI=2.3-14.5). A multiplicative interaction on the risk of cirrhosis between risky alcohol intake and HBsAg or HCV-Ab/HCV-RNA positivity was observed. A reduction of cirrhosis risk was observed in subjects consuming more than 3 alcohol units/day with increasing coffee intake. The OR for the association with cirrhosis decreased from 2.3 (95% CI=1.2-4.4) in subjects drinking 0-2 cups of coffee/day to 1.4 (95% CI=0.6-3.6) in those drinking more than 2 cups/day. CONCLUSIONS: In subjects with an alcohol intake >3 units/day the coexistence of HBV or HCV multiplies the risk of cirrhosis. Coffee represents a modulator of alcoholic cirrhosis risk.

Emerging drugs for non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging relevance that includes different forms of chronic liver damage, from a simple fatty infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma. OBJECTIVE: To discuss therapeutic management of NAFLD. Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. Differentiation between steatosis and NASH currently requires a liver biopsy. METHODS: We discuss different therapeutic approaches proposed in literature for patients with NAFLD. RESULTS: The treatment of associated conditions leads to an improvement of NAFLD and NASH. No specific drug is actually present to treat liver steatosis or NASH. CONCLUSIONS: The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercise may be considered a basal universal approach. Future research will discover possible specific liver drugs.

Optimized contrast-enhanced ultrasonography for characterization of focal liver lesions in cirrhosis: A single-center retrospective study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial. AIMS: To evaluate whether, by selecting an appropriate 'time to wash-out' cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced. METHODS: We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best 'time to wash-out' cut-off values were selected. RESULTS: HISTOLOGICAL DIAGNOSIS OF FLLS WAS AS FOLLOWS: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out > 55 s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to wash-out ≤ 55 s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%). CONCLUSIONS: CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55 s is chosen as a reference value.

Ultrasound-guided percutaneous biopsy for diagnosis of gastrointestinal lesions.

BACKGROUND AND AIMS: Endoscopical examination is not always sufficient for the diagnosis of gastrointestinal masses. This study assessed the diagnostic accuracy and safety of ultrasound-guided percutaneous biopsy of gastrointestinal lesions. METHODS: This retrospective study evaluated 114 patients who underwent ultrasound-guided biopsy of gastrointestinal masses with a 18G needle. Thirty-two of these patients underwent a 22G fine-needle biopsy for cytology. Histology was compared with a composite standard of reference for diagnosis (i.e. post-surgery histological evaluation in 73 cases and computed tomography or magnetic resonance scan findings, together with a compatible clinical follow-up for at least 24 months, in the remaining 41 cases). Safety was assessed by recording side effects for up to 4h after the procedure. RESULTS: Of the 114 lesions evaluated, 112 were malignant (98.2%) and 2 benign (1.8%). Specimens were adequate for histology in all but one case. Specimens were obtained from the stomach (n=38; 33.3%), small bowel (n=36; 31.6%) and colon (n=40; 35.1%). Diagnosis was correct in 113/114 cases (99.1%). Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 99.1%, 100%, 100%, 66%, and 99%, respectively. One of the 114 patients (0.9%) bled from a gastric GIST. CONCLUSIONS: Ultrasound-guided percutaneous biopsy of gastrointestinal lesions is a valid alternative when diagnosis of a gastrointestinal mass cannot be obtained with an endoscopical procedure.

The effect of a silybin-vitamin e-phospholipid complex on nonalcoholic fatty liver disease: a pilot study.

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-beta, tumor necrosis factor-alpha, degree of steatosis, and gamma-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.