Search Results (371)

Nonalcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated steatotic liver disease (MASLD), is a liver condition that is linked to overweight, obesity, diabetes mellitus, and metabolic syndrome. Nonalcoholic steatohepatitis (NASH), or metabolic dysfunction-associated steatohepatitis (MASH), is a form of NAFLD/MASLD that progresses over time. While steatosis is a prominent histological characteristic and recognizable grossly and microscopically, liver biopsies of individuals with NASH/MASH may exhibit several other abnormalities, such as mononuclear inflammation in the portal and lobular regions, hepatocellular damage characterized by ballooning and programmed cell death (apoptosis), misfolded hepatocytic protein inclusions (Mallory–Denk bodies, MDBs), megamitochondria as hyaline inclusions, and fibrosis. Ballooning hepatocellular damage remains the defining feature of NASH/MASH. The fibrosis pattern is characterized by the initial expression of perisinusoidal fibrosis (“chicken wire”) and fibrosis surrounding the central veins. Children may have an alternative form of progressive NAFLD/MASLD characterized by steatosis, inflammation, and fibrosis, mainly in Rappaport zone 1 of the liver acinus. To identify, synthesize, and analyze the scientific knowledge produced regarding the implications of using a score for evaluating NAFLD/MASLD in a comprehensive narrative review. The search for articles was conducted between 1 January 2000 and 31 December 2023, on the PubMed/MEDLINE, Scopus, Web of Science, and Cochrane databases. This search was complemented by a gray search, including internet browsers (e.g., Google) and textbooks. The following research question guided the study: “What are the basic data on using a score for evaluating NAFLD/MASLD?” All stages of the selection process were carried out by the single author. Of the 1783 articles found, 75 were included in the sample for analysis, which was implemented with an additional 25 articles from references and gray literature. The studies analyzed indicated the beneficial effects of scoring liver biopsies. Although similarity between alcoholic steatohepatitis (ASH) and NASH/MASH occurs, some patterns of hepatocellular damage seen in alcoholic disease of the liver do not happen in NASH/MASH, including cholestatic featuring steatohepatitis, alcoholic foamy degeneration, and sclerosing predominant hyaline necrosis. Generally, neutrophilic-rich cellular infiltrates, prominent hyaline inclusions and MDBs, cholestasis, and obvious pericellular sinusoidal fibrosis should favor the diagnosis of alcohol-induced hepatocellular injury over NASH/MASH. Multiple grading and staging methods are available for implementation in investigations and clinical trials, each possessing merits and drawbacks. The systems primarily used are the Brunt, the NASH CRN (NASH Clinical Research Network), and the SAF (steatosis, activity, and fibrosis) systems. Clinical investigations have utilized several approaches to link laboratory and demographic observations with histology findings with optimal platforms for clinical trials of rapidly commercialized drugs. It is promising that machine learning procedures (artificial intelligence) may be critical for developing new platforms to evaluate the benefits of current and future drug formulations. Full article

Background: Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2’s impact on hemostasis in compensated patients with cirrhosis. Methods: We analyzed the US Collaborative Network, which comprises 63 HCOs in the U.S.A. Compensated cirrhosis patients were split into two groups: SARS-CoV-2-positive and -negative. Patients’ baseline characteristics were used in a 1:1 propensity score-matched module to create comparable cohorts. We compared the risk of portal vein thrombosis (PVT), deep venous thrombosis (DVT), and pulmonary embolism (PE) at 6 months, and 1 and 3 years. Results: Of 330,521 patients, 27% tested positive and 73% remained negative. After PSM, both cohorts included 74,738 patients. Patients with SARS-CoV-2 had a higher rate of PVT compared to those without at 6 months (0.63% vs 0.5%, p < 0.05), 1 year (0.8% vs 0.6%, p < 0.05), and 3 years (1% vs. 0.7%, p < 0.05), a higher rate of DVT at 6 months (0.8% vs. 0.4%, p < 0.05), 1 year (1% vs. 0.5%, p < 0.05), and 3 years (1.4% vs. 0.8%, p < 0.05), and a higher rate of PE at 6 months (0.6% vs. 0.3%, p < 0.05), 1 year (0.7% vs. 0.4%, p < 0.05), and 3 years (1% vs. 0.6%, p < 0.05). Conclusions: The presence of SARS-CoV-2 infection in patients with compensated cirrhosis was associated with a higher rate of PVT, DVT, and PE at 6 months, and 1 and 3 years. Full article

Vascular invasion of hepatocellular carcinoma involves tumor plugs in the main trunk of the portal vein, bile ducts, and veins, and it indicates poor prognosis. It is often associated with portal hypertension, which requires evaluation and management. Treatment includes hepatic resection, systemic pharmacotherapy, hepatic arterial infusion chemotherapy, and radiation therapy. Recurrence rates post-hepatic resection are high, and systemic drug therapy often has limited therapeutic potential in patients with a poor hepatic reserve. Single therapies are generally inadequate, necessitating combining multiple therapies with adjuvant and systemic pharmacotherapy before and after hepatectomy. This narrative review will provide an overview of the treatment of hepatocellular carcinoma with vascular invasion. Full article

Background and Objectives: Preoperative right portal vein embolization (RPVE) is often attempted before right hepatectomy for liver tumors to increase the future remnant liver volume (FRLV). Although many factors affecting FRLV have been discussed, few studies have focused on the ratio of the cross-sectional area of the right portal vein to that of the left portal vein (RPVA/LPVA). The aim of the present study was to evaluate the effect of RPVA/LPVA on predicting FRLV increase after RPVE. Materials and Methods: The data of 65 patients who had undergone RPVE to increase FRLV between 2004 and 2021 were investigated retrospectively. Using computed tomography scans, we measured the total liver volume (TLV), FRLV, the proportion of FRLV relative to TLV (FRLV%), the increase in FRLV% (ΔFRLV%), and RPVA/LPVA twice, immediately before and 2–3 weeks after RPVE; we analyzed the correlations among those variables, and determined prognostic factors for sufficient ΔFRLV%. Results: Fifty-four patients underwent hepatectomy. Based on the cut-off value of RPVA/LPVA, the patients were divided into low (RPVA/LPVA ≤ 1.20, N = 30) and high groups (RPVA/LPVA > 1.20, N = 35). The ΔFRLV% was significantly greater in the high group than in the low group (9.52% and 15.34%, respectively, p < 0.001). In a multivariable analysis, RPVA/LPVA (HR = 20.368, p < 0.001) was the most significant prognostic factor for sufficient ΔFRLV%. Conclusions: RPVE was more effective in patients with higher RPVA/LPVA, which is an easily accessible predictive factor for sufficient ΔFRLV%. Full article

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the “Club Epatologi Ospedalieri” (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000–44,000/μL) to 58,000 (49,000–82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04–1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug. Full article

Portal vein thrombosis (PVT) represents a restriction or occlusion of the portal vein by a blood clot, which can appear in liver cirrhosis, inherited or acquired thrombophilia, malignancies, abdominal infection, abdominal inflammation, and injury to the portal vein; it can evolve to local venous extension, recanalization, or portal cavernoma (PC). This research represents an observational study of patients admitted with a diagnosis of PVT between January 2018 and December 2022. We assessed the rate of and risk factors for PC. In total, 189 patients with PVT were included; the rate of PC was 14.8%. In univariate and multivariate analysis, the main risk factors for the presence of PC were etiology (thrombophilia, myeloproliferative disorders, local inflammatory diseases, and idiopathic causes), prior PVT, and complete versus incomplete or single-branch portal obstruction. In patients with superior mesenteric vein (SMV) thrombosis, distal obstruction was more prone to PC than proximal obstruction. The main predictive factors were etiology, prior PVT, complete PVT obstruction, and no prior non-selective beta-blocker (NSBB) use; in patients with SMV thrombosis, the distal extension was more significantly associated with the risk of PC. We propose a composite score for the prediction of PC which includes etiology, prior diagnosis of PVT, prior NSBB use, complete versus incomplete PVT, and distal versus proximal SMV thrombosis, with good accuracy (AUC 0.822) and an estimated sensitivity of 76.92% and specificity of 82.39% at a cut-off value of 4. Full article

Portal vein arterialization (PVA) is a surgical procedure that plays a crucial role in hepatic vascular salvage when hepatic artery flow restoration remains elusive. Dedicated diagnostic vascular imaging and the timely management of PVA shunts are paramount to preventing complications, such as portal hypertension and thrombosis. Regrettably, a lack of standardized postoperative management protocols for PVA has increased morbidity and mortality rates post-procedure. In response to this challenge, we developed a PVA standard operating procedure (SOP) tailored to the needs of interventional radiologists. This SOP is designed to harmonize postoperative care, fostering scientific comparability across cases. This concise brief report aims to offer radiologists valuable insights into the PVA technique and considerations for post-PVA care and foster effective interdisciplinary collaboration. Full article

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-β, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification. Full article

Portal hypertension from chronic liver disease leads to the formation of collateral blood vessels called spontaneous portosystemic shunts (SPSS). These shunts may form from existing vessels or through neo-angiogenesis. Their location affects clinical outcomes due to varying risks and complications. This review summarizes current knowledge on SPSS, covering their clinical impact and management strategies. Recent data suggest that SPSS increases the risk of variceal bleeding, regardless of shunt size. The size of the shunt is crucial in the rising incidence of hepatic encephalopathy (HE) linked to SPSS. It also increases the risk of portopulmonary hypertension and portal vein thrombosis. Detecting and assessing SPSS rely on computed tomography (CT) and magnetic resonance imaging. CT enables precise measurements and the prediction of cirrhosis progression. Management focuses on liver disease progression and SPSS-related complications, like HE, variceal bleeding, and portopulmonary hypertension. Interventional radiology techniques such as balloon-occluded, plug-assisted, and coil-assisted retrograde transvenous obliteration play a pivotal role. Surgical options are rare but are considered when other methods fail. Liver transplantation (LT) often resolves SPSS. Intraoperative SPSS ligation is still recommended in patients at high risk for developing HE or graft hypoperfusion. Full article

The “vein definition” for locally advanced pancreatic ductal adenocarcinoma (LA PDAC) assumes portal-to-superior mesenteric vein (PV/SMV) unreconstructability due to tumor involvement or occlusion. Radical pancreatectomies with SMV resection without PV/SMV reconstruction are scarcely discussed in the literature. Retrospective analysis of 19 radical pancreatectomies for “low” LA PDAC with SMV and all its tributaries resection without PV/SMV reconstruction has shown zero mortality; overall morbidity—56%; Dindo–Clavien—3–10.5%; R0—rate—82%; mean operative procedure time—355 ± 154 min; mean blood loss—330 ± 170 mL; delayed gastric emptying—25%; and clinically relevant postoperative pancreatic fistula—8%. In three cases, surgery was associated with superior mesenteric (n2) and common hepatic artery (n1) resection. Surgery was completed without vein reconstruction (n13) and with inferior mesenteric-to-splenic anastomosis (n6). There were no cases of liver, gastric, or intestinal ischemia. A specific complication of the SMV resection without reconstruction was 2–3 days-long intestinal edema (48%). Median overall survival was 25 months, and median progression-free survival was 18 months. All the relapses, except two, were distant. The possibility of successful SMV resection without PV/SMV reconstruction can be predicted before surgery by CT-based reconstructions. The mandatory anatomical conditions for the procedure were as follows: (1) preserved SMV-SV confluence; (2) occluded SMV for any reason (tumor or thrombus); (3) well-developed inferior mesenteric vein collaterals with dilated intestinal veins; (4) no right-sided vein collaterals; and (5) no varices in the upper abdomen. Conclusion: “Low” LA PDACs involving SMV with all its tributaries can be radically and safely resected in highly and specifically selected cases without PV/SMV reconstruction with an acceptable survival rate. Full article

Hepatic arterio-portal venous fistula (HAPVF) is a rare, abnormal connection between the hepatic artery and portal vein. HAPVFs are usually caused by trauma or hepatobiliary instrumentation. Fistulas can expand and produce symptoms of severe portal hypertension. The decision to embolize should be based on fistula location, size, and symptoms. We report a case of HAPVF in a liver transplant recipient presenting with worsening ascites and variceal hemorrhage after several prior liver biopsies. Given the extensive nature of the fistula and hepatic decompensation, the HAPVF was successfully embolized, resulting in clinical improvement and obviating the need for re-transplantation. Full article

Background: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival. Methods: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan–Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox’s proportional hazard model. Results: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion. Conclusion: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion. Full article

The clinical use of photon-counting CT (PCCT) allows for the generation of virtual non-contrast (VNC) series from contrast-enhanced images. In routine clinical practice, specific issues such as ruling out acute bleeding require non-contrast images. The aim of this study is to evaluate the use of PCCT-derived VNC reconstructions in abdominal imaging. PCCT scans of 17 patients including early arterial, portal venous and native sequences were enrolled. VNC reconstructions have been calculated. In every sequence and VNC reconstruction, 10 ROIs were measured (portal vein, descending aorta, inferior vena cava, liver parenchyma, spleen parenchyma, erector spinae muscle, subcutaneous adipose tissue, first lumbar vertebral body, air, and psoas muscle) and density values were compared. The VNC reconstructions show significant changes in density compared to the contrast-enhanced images. However, there were no significant differences present between the true non-contrast (TNC) and any VNC reconstructions in the observed organs and vessels. Significant differences (p < 0.05) between the measured mean density values in the TNC versus VNC reconstructions were found in fat and bone tissue. The PCCT-derived VNC reconstructions seemed to be comparable to the TNC images, despite some deviations shown in the adipose tissue and bone structures. However, the further benefits in terms of specific clinical issues need to be evaluated. Full article

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has a poor prognosis and is generally not indicated for surgery. Proton beam therapy (PBT) may offer an alternative treatment. In this study, long-term outcomes were examined in 116 patients (median age 66 years, 100 males) with HCC with advanced PVTT (Vp3 or Vp4) who received PBT from April 2008 to March 2018. Of these patients, 63 received PBT as definitive treatment and 53 as palliative treatment. The representative dose was 72.6 Gy (RBE) in 22 fractions. Eight patients died in follow-up, including 72 due to tumor progression. The 5-year overall survival (OS) rate was 18.0% (95% CI 9.8–26.2%) and the 5-year local control (LC) rate was 86.1% (74.9–97.3%). In multivariate analyses, performance status and treatment strategy were significantly associated with OS. The median follow-up period for survivors with definitive treatment was 33.5 (2–129) months, and the 5-year OS rate was 25.1% (12.9–37.3%) in these cases. The median survival time after definitive irradiation was >20 months. The 5-year OS rate was 9.1% (0–19.7%) for palliative irradiation. These results compare favorably with those of other therapies and suggest that PBT is a useful option for cases of HCC with advanced PVTT that cannot undergo surgery, with an expected survival benefit and good local control. Determining the optimal indication for this treatment is a future challenge. Full article

Background: Liver venous deprivation (LVD) is a recent radiological technique that has shown promising results on Future Remnant Liver (FRL) hypertrophy. The aim of this retrospective study is to compare the segmentary hypertrophy of the FRL after LVD and after portal vein embolization (PVE). Methods: Patients undergoing PVE or LVD between April 2015 and April 2020 were included. The segmentary volumes (seg 4, seg2+3 and seg1) were assessed before and after the radiological procedure. Results: Forty-four patients were included: 26 undergoing PVE, 10 LVD and 8 eLVD. Volume gain of both segment 1 and segments 2+3 was significantly higher after LVD and eLVD than after PVE (segment 1: 27.33 ± 35.37 after PVE vs. 38.73% ± 13.47 after LVD and 79.13% ± 41.23 after eLVD, p = 0.0080; segments 2+3: 40.73% ± 40.53 after PVE vs. 45.02% ± 21.53 after LVD and 85.49% ± 45.51 after eLVD, p = 0.0137), while this was not true for segment 4. FRL hypertrophy was confirmed to be higher after LVD and eLVD than after PVE (33.53% ± 21.22 vs. 68.63% ± 42.03 vs. 28.11% ± 28.33, respectively, p = 0.0280). Conclusions: LVD and eLVD may induce greater hypertrophy of segment 1 and segments 2+3 when compared to PVE. Full article