Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome.

BACKGROUND: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe. METHODS: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons. RESULTS: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group. CONCLUSIONS: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.).

Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

A data processing pipeline for the AACR project GENIE biopharma collaborative data with the {genieBPC} R package.

MOTIVATION: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC) represent comprehensive clinical data linked to high-throughput sequencing data, providing a multi-institution, pan-cancer, publicly available data repository. GENIE BPC data provide detailed demographic, clinical, treatment, genomic and outcome data for patients with cancer. These data result in a unique observational database of molecularly characterized tumors with comprehensive clinical annotation that can be used for health outcomes and precision medicine research in oncology. Due to the inherently complex structure of the multiple phenomic and genomic datasets, the use of these data requires a robust process for data integration and preparation in order to build analytic models. RESULTS: We present the {genieBPC} package, a user-friendly data processing pipeline to facilitate the creation of analytic cohorts from the GENIE BPC data that are ready for clinico-genomic modeling and analyses. AVAILABILITY AND IMPLEMENTATION: {genieBPC} is available on CRAN and GitHub.

Decreased need for RRT in liver transplant recipients after pretransplant treatment of hepatorenal syndrome-type 1 with terlipressin.

Hepatorenal syndrome-acute kidney injury (HRS-AKI), a serious complication of decompensated cirrhosis, has limited therapeutic options and significant morbidity and mortality. Terlipressin improves renal function in some patients with HRS-1, while liver transplantation (LT) is a curative treatment for advanced chronic liver disease. Renal failure post-LT requiring renal replacement therapy (RRT) is a major risk factor for graft and patient survival. A post hoc analysis with a 12-month follow-up of LT recipients from a placebo-controlled trial of terlipressin (CONFIRM; NCT02770716) was conducted to evaluate the need for RRT and overall survival. Patients with HRS-1 were treated with terlipressin plus albumin or placebo plus albumin for up to 14 days. RRT was defined as any type of procedure that replaced kidney function. Outcomes compared between groups included the incidence of HRS-1 reversal, the need for RRT (pretransplant and posttransplant), and overall survival. Of the 300 patients in CONFIRM (terlipressin n = 199; placebo, n = 101), 70 (23%) underwent LT alone (terlipressin, n = 43; placebo, n = 27) and 5 had simultaneous liver-kidney transplant (terlipressin, n = 3, placebo, n = 2). The rate of HRS reversal was significantly higher in the terlipressin group compared with the placebo group (37%, n = 16 vs. 15%, n = 4; p = 0.033). The pretransplant need for RRT was significantly lower among those who received terlipressin ( p = 0.007). The posttransplant need for RRT, at 12 months, was significantly lower among those patients who received terlipressin and were alive at Day 365, compared to placebo ( p = 0.009). Pretransplant treatment with terlipressin plus albumin in patients with HRS-1 decreased the need for RRT pretransplant and posttransplant.

Treatment Patterns and Outcomes in Pancreatic Cancer: A Comparative Analysis of Ontario and the USA.

BACKGROUND: Comparative studies evaluating quality of care in different healthcare systems can guide reform initiatives. This study seeks to characterize best practices by comparing utilization and outcomes for patients with pancreatic cancer (PC) in the USA and Ontario, Canada. METHODS: Patients (age ≥ 66 years) with PC were identified from the Ontario Cancer Registry and SEER-Medicare databases from 2006 to 2015. Demographics and treatment (surgery, radiation, chemotherapy, or multimodality (surgery and chemotherapy)) were described. In resected patients, neoadjuvant therapy, readmission, and 30- and 90-day postoperative mortality rates were calculated. Survival was assessed using Kaplan-Meier curves. RESULTS: This study includes 38,858 and 11,512 patients with PC from the USA and Ontario, respectively. More female patients were identified in the USA (54.0%) versus Ontario (46.9%). In the entire cohort, US patients received more radiation in addition to other therapies (18.8% vs. 13.5% Ontario) and chemotherapy alone (34.3% vs. 19.0% Ontario). While rates of resection were similar (13.4% USA vs.12.5% Ontario), multimodality therapy was more common in the UAS (9.0% vs. 6.4%). Among resected patients, neoadjuvant chemotherapy was uncommon in both groups, although more frequent in the USA (12.0% vs. 3.2% Ontario). The 30- and 90-day postoperative mortality rates were lower in Ontario vs. the USA (30-day: 3.26% vs. 4.91%; 90-day: 7.08% vs. 10.96%), however, overall survival was similar between the USA and Ontario. CONCLUSIONS: We observed substantive differences in treatment and outcomes between PC patients in the USA and Ontario, which may reflect known differences in healthcare systems. Close evaluation of healthcare policies can inform initiatives to improve care quality.

Isolation, Oxidation, and Application of Crystalline-Pristine Cellulose: Natural Products That Could End Plastic Waste.

ConspectusGiven this special issue's efforts to highlight the research emanating from HBCUs (Historically Black Colleges and Universities) and the trials and tribulations associated with their research, the authors have presented work associated with the characterization and application of cellulosic materials as renewable products. Despite challenges, the research completed in this laboratory at Tuskegee, a HBCU, hinges upon the many investigations of cellulose as a carbon-neutral, biorenewable material that can potentially replace environmentally unfriendly and hazardous petroleum-based polymers. Although cellulose is one of the most promising candidates, overcoming the challenge of its incompatibility (i.e., lack of good dispersion, interfacial adhesion, etc.) with most hydrophobic polymers due to its hydrophilic nature is critical to usage in plastic products across industries. Chemical isolations via acid hydrolysis and surface functionalities have emerged as new approaches to modulate the surface chemistry of cellulose to improve its compatibility and physical performance within the polymer composites. Recently, we have explored the influence of (1) acid hydrolysis and (2) chemical modifications via surface oxidation to ketones and aldehydes on the resulting macrostructural arrangements and thermal performance and (3) the application of crystalline cellulose as reinforcement agents in ABS (acrylonitrile-butadiene-styrene) composites.XRD structural characterizations of crystalline cellulose isolated from wheat straw under dissimilar acid hydrolysis conditions showed induced alterations in the native cellulose polymorph (CI). Mixing of the native polymorph (CI) with CIII was observed and found to be more prominent under sulfuric acid isolation conditions which is one of the more commonly used methods of chemical isolation. Thermal evaluations using TGA confirmed that the introduction of the mixed polymorphs changed the thermal behavior of the isolated crystalline cellulose. Further, FTIR analysis and Tollens testing of chemically oxidized crystalline cellulose via the Albright-Goldman reaction revealed the transformation of surface OH groups to ketones and aldehydes, respectively. We observed similar macrostructural disruption behavior to that of acid hydrolysis processing (i.e., mixing of polymorphs) for oxidation of crystalline cellulose, which had no negative impacts on the thermal stability of the cellulosic structure. The application of acid-hydrolyzed pristine cellulose (PC) as reinforcement agents in ABS composites showed increased thermal-mechanical performance as revealed by TGA and thermal mechanical analysis (TMA). As the ratio of crystalline cellulose increased, the thermal stability of the ABS composite increased, and at extremely high ratios, increased dimensional stability (i.e., low coefficient of thermal expansion (CTE) value) was observed, expanding the application of ABS plastic products.

Highest 3-month international normalized ratio (INR): a predictor of bleeding following ultrasound-guided liver biopsy.

OBJECTIVES: To determine whether international normalized ratio (INR), bilirubin, and creatinine predict bleeding risk following percutaneous liver biopsy. METHODS: A total of 870 consecutive patients (age 53 ± 14 years; 53% (459/870) male) undergoing non-targeted, ultrasound-guided, percutaneous liver biopsy at a single tertiary center from 01/2016 to 12/2019 were retrospectively reviewed. Results were analyzed using descriptive statistics and logistic regression models to evaluate the relationship between individual and combined laboratory values, and post-biopsy bleeding risk. Receiver operating characteristic (ROC) curves and area under ROC (AUC) curves were constructed to evaluate predictive ability. RESULTS: Post-biopsy bleeding occurred in 2.0% (17/870) of patients, with 0.8% (7/870) requiring intervention. The highest INR within 3 months preceding biopsy demonstrated the best predictive ability for post-biopsy bleeding and was superior to the most recent INR (AUC = 0.79 vs 0.61, p = 0.003). Total bilirubin is an independent predictor of bleeding (AUC = 0.73) and better than the most recent INR (0.61). Multivariate regression analysis of the highest INR and total bilirubin together yielded no improvement in predictive performance compared to INR alone (0.80 vs 0.79). The MELD score calculated using the highest INR (AUC = 0.79) and most recent INR (AUC = 0.74) were similar in their predictive performance. Creatinine is a poor predictor of bleeding (AUC = 0.61). Threshold analyses demonstrate an INR of > 1.8 to have the highest predictive accuracy for bleeding. CONCLUSION: The highest INR in 3 months preceding ultrasound-guided percutaneous liver biopsy is associated with, and a better predictor for, post-procedural bleeding than the most recent INR and should be considered in patient risk stratification. CLINICAL RELEVANCE STATEMENT: Despite correction of coagulopathic indices, the highest international normalized ratio within the 3 months preceding percutaneous liver biopsy is associated with, and a better predictor for, bleeding and should considered in clinical decision-making and determining biopsy approach. KEY POINTS: • Bleeding occurred in 2% of patients following ultrasound-guided liver biopsy, and was non-trivial in 41% of those patients who needed additional intervention and had an associated 23% 30-day mortality rate. • The highest INR within 3 months preceding biopsy (AUC = 0.79) is a better predictor of bleeding than the most recent INR (AUC = 0.61). • The MELD score is associated with post-procedural bleeding, but with variable predictive performance largely driven by its individual laboratory components.

Association between Patient Experience Scores and Low Utilization of Hepatocellular Carcinoma Treatment in the United States: A Surveillance, Epidemiology, and End Results-Consumer Assessment of Healthcare Providers and Systems Analysis (SEER-CAHPS).

PURPOSE: To study the experiences of patients with hepatocellular carcinoma (HCC) contributing to treatment discrepancy in the United States. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results data from National Cancer Institute (NCI), Medicare (2002-2015) beneficiaries with HCC who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey were included. Six CAHPS items (3 global scores: global care rating [GCR], primary doctor rating [PDR], and specialist rating [SR]; 3 composite scores: getting needed care [GNC], getting care quickly [GCQ], and doctor communication [DC]) assessed patient experience. Covariates assessed between treated and nontreated groups included patient, disease, hospital, and CAHPS items. RESULTS: Among 548 patients with HCC, 211 (39%) received treatment and 337 (61%) did not receive treatment. Forty-two percent (GCR), 29% (PDR), 30% (SR), 36% (GNC), 78% (GCQ), and 35% (DC) of patients reported less-than-excellent experiences on the respective CAHPS items. Chronic liver disease (CLD) was present in 52% and liver decompensation (LD) in 60%. A minority of the hospitals were NCI-designated cancer centers (47%), transplant centers (27%), and referral centers (9%). On univariable analysis, patients with at least a high school degree (odds ratio [OR], 1.9), admittance to a ≥400-bed hospital (OR, 2.7), CLD (OR, 3.0), or LD (OR, 1.7) were more likely to receive treatment, whereas older patients (≥75 years) (OR, 0.5) were less likely to receive treatment. On multivariable, patients with CLD (OR, 6.8) and an excellent experience in GNC with a specialist (OR, 10.6) were more likely to receive treatment. CONCLUSIONS: HCC treatment discrepancy may be associated with patient-related factors, such as lack of specialist care (GNC), and disease-related factors, such as absence of underlying CLD.

Angiography with cone-beam CT versus contrast-enhanced MRI for living donor transplant imaging: Is MRI enough?

The purpose of this study is to compare the subjective and objective quality and confidence between conventional angiography with cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) for the preoperative evaluation of potential donors for living donor liver transplant. Seventeen patients undergoing preoperative donor evaluation for living donor liver transplantation that underwent angiography with CBCT and contrast-enhanced MRI for evaluation of hepatic vascular anatomy were included in the study. Four attending radiologists interpreted anonymized, randomized angiography with CBCT images and MRIs, rating the diagnostic quality and confidence of their interpretation (on a 3-point scale) for each element, as well as clinically relevant measurements. Overall, the readers rated the quality of angiography with CBCT to be higher than that of MRI (median [interquartile range] = 3 (2, 3) vs. 2 (1-3), p < 0.001) across all patients. Readers of angiography with CBCT had more confidence in their interpretations as an average of all elements evaluated than the MRI readers (3 (3) vs. 3 (2, 3), p < 0.001). When the same reader interpreted both MRI and CBCT, the right hepatic artery diameter (3.8 mm ± 0.72 mm vs. 4.5 mm ± 1.2 mm, p < 0.005) and proper hepatic artery diameter (4.43 mm ± 0.98 mm vs. 5.4 mm ± 1.05 mm, p < 0.003) were significantly different between MRI and CBCT. There was poor interrater reliability for determining segment IV arterial supply for both modalities (κ < 0.2). Angiography with CBCT provides higher subjective diagnostic quality and greater radiologist confidence than MRI. The difference in measurements between CBCT and MRI when the same reader reads both studies suggests CBCT adds additional information over MRI evaluation alone.

A Curious Case of Clear Cell Morphology in a Patient with Lung Cancer: Diagnostic Challenges.

An 82-year-old woman with COPD presented to the emergency department with cough, increasing sputum production, wheezing, and worsening shortness of breath for two weeks. On imaging studies, the patient was found to have a right upper lobe spiculated nodule and an endobronchial lesion with near total occlusion of the right lower lobe bronchus with sub-segmental atelectasis. Bronchoscopy with EBUS-TBNA of subcarinal and right hilar lymph nodes revealed lung cancer with clear cell phenotype. Given the predominance of clear cell morphology, the diagnosis of metastatic renal or ovarian cancer was entertained. However, there was no evidence of renal or ovarian lesions on the PET-CT scan, ruling out the possibility. Salivary gland type lung cancer (STLC), which is responsible for less than 1% of all lung cancer cases in adults, was also considered. The two distinct STLCs that may have similar morphologic appearances are hyalinizing clear cell carcinoma (HCCC) and mucoepidermoid carcinoma (MEC). The other type of tumour in the lung that demonstrates a clear cell phenotype is perivascular epithelioid cell neoplasms or PEComa, which are mesenchymal in origin. Immunohistochemical staining was strongly positive for p63, CK5/6, CK7, CK-LMW, and negative for TTF-1, Napsin A, p16, and CK20. Additional staining, including HMB-45, S-100, and mucicarmine, were also negative. Next-generation sequencing for the salivary gland fusion panel, including EWSR1-ATF1 fusion and EWSR1 gene rearrangement for HCCC and MAML2 gene rearrangements for MEC, was negative. She was diagnosed with non-small cell lung cancer favouring squamous cell carcinoma with clear cell phenotype, a rare entity.

Testosterone therapy and cancer risks among men in the SEER-Medicare linked database.

BACKGROUND: We examined associations between two forms of testosterone therapy (TT) and risks of seven cancers among men. METHODS: SEER-Medicare combines cancer registry data from the Surveillance, Epidemiology, and End Results programme with Medicare claims. Our population-based case-control study included incident cancer cases diagnosed between 1992-2015: prostate (n = 130,713), lung (n = 105,466), colorectal (n = 56,433), bladder (n = 38,873), non-Hodgkin lymphoma (n = 17,854), melanoma (n = 14,241), and oesophageal (n = 9116). We selected 100,000 controls from a 5% random sample of Medicare beneficiaries and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: TT was associated with lower risk of distant-stage prostate cancer (injection/implantation OR = 0.72, 95% CI: 0.60-0.86; topical OR = 0.50, 95% CI: 0.24-1.03). We also observed inverse associations for distant-stage colorectal cancer (injection/implantation OR = 0.75, 95% CI: 0.62-0.90; topical OR = 0.11, 95% CI: 0.05-0.24). Risks of distant-stage colorectal and prostate cancers decreased with time after initiating TT by injection/implantation. By contrast, TT was positively associated with distant-stage melanoma (injection/implantation OR = 1.70, 95% CI: 1.37-2.11). TT was not associated with bladder cancer, oesophageal cancer, lung cancer or non-Hodgkin lymphoma. CONCLUSION: TT was inversely associated with distant-stage prostate and colorectal cancers but was positively associated with distant-stage melanoma. These observations may suggest an aetiologic role for TT or the presence of residual confounding.

Pregnancy-associated breast cancer: does timing of presentation affect outcome?

PURPOSE: Pregnancy-associated breast cancer (PABC) comprises breast cancer diagnosed during the gestational period or within 12 months postpartum. While the incidence of PABC appears to be increasing, data regarding prognosis remain limited. METHODS: Here we evaluate clinicopathologic features, treatments, and clinical outcomes among women with stage 0-III PABC diagnosed between 1992 and 2020. Comparisons were made between women who were diagnosed with PABC during gestation and those who were diagnosed within 12 months postpartum. RESULTS: A total of 341 women were identified, with a median age of 36 years (range 25-46). The pregnancy group comprised 119 (35%) women, while 222 (65%) women made up the postpartum group. Clinicopathologic features were similar between groups, with most patients being parous and presenting with stage I and II disease. Treatment delays were uncommon, with a median time from histologic diagnosis to treatment of 4 weeks for both groups. Recurrence-free survival was similar between groups: 67% at 10 years for both. While 10-year overall survival appeared higher in the postpartum group (83% versus 78%, p = 0.02), only the presence of nodal metastases was associated with an increased risk of death (hazard ratio 5.61, 95% CI 2.20-14.3, p < 0.001), whereas timing of diagnosis and receptor profile did not reach statistical significance. CONCLUSION: Clinicopathologic features of women with PABC are similar regardless of timing of diagnosis. While 10-year recurrence-free survival is similar between groups, 10-year overall survival is higher among women diagnosed postpartum; however, timing of diagnosis may not be the driving factor in determining survival outcomes.

Liver transplantation in alcohol-associated liver disease: ensuring equity through new processes.

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients.

Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol-associated hepatitis.

BACKGROUND AND AIMS: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation. APPROACH AND RESULTS: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z. CONCLUSIONS: Impaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication.

Technical Feasibility of Suction Thrombectomy Using a Large-Bore Aspiration System in the Portomesenteric Venous System.

PURPOSE: To assess technical feasibility and safety of portal vein thrombectomy with suction thrombectomy using a large-bore thrombectomy device for portomesenteric venous thrombosis (PMVT). MATERIALS AND METHODS: After receiving approval from institutional review board, patients undergoing PMVT treatment using a large-bore aspiration thrombectomy device (Inari FlowTriever or ClotTriever) between July 2019 and June 2021 were identified at 2 medical centers. Charts were reviewed for demographic information, imaging findings, and procedural details. PMVT was categorized using the Yerdel grading system. The thrombectomy procedure was performed via transjugular access through the existing or a new transjugular intrahepatic portosystemic shunt (TIPS) or transsplenic or transhepatic approach. Technical success was defined as successful clot reduction and restoration of portal venous flow at the conclusion of the procedure. Patient outcomes based on clinical presentation, adverse events, and thrombectomy-associated adverse events were recorded. RESULTS: Twenty patients, with a median age of 58 years (range, 23-72 years), underwent large-bore aspiration thrombectomy, which was technically successful in 19 of 20 (95%) patients. In 9 of 20 (45%) patients, 9 of 20 (45%) patients, and 2 of 20 (10%) patients, the 20-F, 16-F, and 24-F devices were used, respectively. Fourteen patients had a pre-existing TIPS, and 6 patients had a TIPS created. In 5 of 20 (25%) patients, overnight lysis was performed in conjunction with Inari thrombectomy. Thrombus resolution with restoration of flow was achieved in 19 of 20 (95%) cases. There were no thrombectomy-associated adverse events. The mean follow-up time was 70 days (±113) at which time primary patency of the portal venous system was present in 16 of 20 (80%) patients. CONCLUSIONS: Large-bore aspiration portal vein thrombectomy is feasible for PMVT.

Transjugular Intrahepatic Portosystemic Shunt and Thrombectomy (TIPS-Thrombectomy) for Symptomatic Acute Noncirrhotic Portal Vein Thrombosis.

PURPOSE: To report the safety and effectiveness of transjugular intrahepatic portosystemic shunt and mechanical thrombectomy (TIPS-thrombectomy) for symptomatic acute noncirrhotic portal vein thrombosis (NC-PVT). MATERIALS AND METHODS: Patients with acute NC-PVT who underwent TIPS-thrombectomy between 2014 and 2021 at a single academic medical center were retrospectively reviewed. Thirty-two patients were included (men, 56%; median age, 51 years [range, 39-62 years]). The causes for PVT included idiopathic (n = 12), prothrombotic disorders (n = 11), postsurgical sequelae (n = 6), pancreatitis (n = 2), and Budd-Chiari syndrome (n = 1). The indications for TIPS-thrombectomy included refractory abdominal pain (n = 14), intestinal venous ischemia (n = 9), ascites (n = 4), high-risk varices (n = 3), and variceal bleeding (n = 2). Variables studied included patient, disease, and procedure characteristics. Patients were monitored over the course of 1-year follow-up. RESULTS: Successful recanalization of occluded portal venous vessels occurred in all 32 patients (100%). Compared with pretreatment patency, recanalization with TIPS-thrombectomy resulted in an increase in patent veins (main portal vein [28% vs 97%, P < .001], superior mesenteric vein [13% vs 94%, P < .001], and splenic vein [66% vs 91%, P < .001]). Three procedure-related adverse events occurred (Society of Interventional Radiology grade 2 moderate). Hepatic encephalopathy developed in 1 (3%) of 32 patients after TIPS placement. At 1-year follow-up, return of symptoms occurred in 3 (9%) of 32 patients: (a) ascites (n = 1), (b) variceal bleeding (n = 1), and (c) intestinal venous ischemia (n = 1). The intention-to-treat 1-year portal vein and TIPS primary and secondary patency rates were 78% (25/32) and 100% (32/32), respectively. Seven patients required additional procedures, and the 1-year mortality rate was 3% (1/32). CONCLUSIONS: TIPS-thrombectomy is a safe and effective method for treating patients with symptomatic acute NC-PVT.

Factors Associated With Complete Pathologic Necrosis of Hepatocellular Carcinoma on Explant Evaluation After Locoregional Therapy: A National Analysis Using the UNOS Database.

BACKGROUND. Complete pathologic necrosis (CPN) is associated with improved survival in patients who undergo liver transplant (LT) after locoregional therapy (LRT) for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to identify patient, HCC, and transplant center characteristics associated with rates of CPN on explant evaluation using a large national sample of patients undergoing LT after LRT for HCC measuring 3 cm or smaller. METHODS. This retrospective study used data from the United Network for Organ Sharing database. The study included 6265 adults (median age, 62 years; 1505 women, 4760 men) who underwent LT after a single type of LRT (either transarterial chemoembolization [TACE], thermal ablation, or transarterial radioembolization [TARE]) for HCCs measuring 3 cm or smaller at one of 118 U.S. transplant centers from April 12, 2012, to March 31, 2020. Patients were classified as having CPN if explant evaluation showed 100% necrosis of all HCCs. Associations with CPN were explored. Centers were categorized into tertiles on the basis of center-level CPN rates, and tertiles were compared. RESULTS. LRT was performed by TACE in 69.5% (4352/6265), thermal ablation in 19.4% (1217/6265), and TARE in 11.1% (696/6265) of patients. CPN rate was 18.5% (805/4352) after TACE, 35.8% (436/1217) after thermal ablation, 33.6% (234/696) after TARE, and 23.5% (1475/6265) overall. In multivariable analysis incorporating age, sex, model for end-stage liver disease score, α-fetoprotein level before LRT, wait list time, number of HCCs, HCC size, and the transplant center (as a random factor), use of thermal ablation (OR, 2.19; 95% CI, 1.86-2.57; p < .001) or TARE (OR, 1.92; 95% CI, 1.57-2.36; p < .001), with TACE as reference, independently predicted greater likelihood of CPN. Center-level CPN rates ranged from 0.0% to 50.0%. With centers stratified by CPN rates, ablation was performed more frequently than TACE in 5.0% of centers in the first, 15.4% in the second, and 23.1% in the third tertiles (p = .07). CONCLUSION. CPN rate on explant evaluation was low. Thermal ablation or TARE, rather than TACE, was associated with higher likelihood of CPN in patient-level and center-level analyses. CLINICAL IMPACT. Findings from this large national sample support a potential role of thermal ablation or TARE for achieving CPN of HCC measuring 3 cm or smaller.

Type 2 diabetes complications are associated with liver fibrosis independent of hemoglobin A1c.

INTRODUCTION AND OBJECTIVES: The association between type 2 diabetes, non-alcoholic fatty liver disease, and liver fibrosis is well established, but it is unknown whether complications of type 2 diabetes influence fibrosis levels. We defined the complications of type 2 diabetes by the presence of diabetic nephropathy, retinopathy, or neuropathy and aimed to evaluate their association with the degree of liver fibrosis measured by the fibrosis-4 (FIB-4) index. MATERIALS AND METHODS: This is a cross-sectional study evaluating the association of type 2 diabetes complications with liver fibrosis. A total of 2389 participants were evaluated from a primary care practice. FIB-4 was evaluated as a continuous and categorical measure using linear and ordinal logistic regression. RESULTS: Patients with complications were older, had higher hemoglobin A1c, and a higher median FIB-4 score (1.34 vs. 1.12, P<0.001). On adjusted analysis, type 2 diabetes complications were associated with higher fibrosis by continuous FIB-4 score (Beta-coefficient: 0.23, 95% confidence interval [CI]: 0.004-1.65) and demonstrated increased odds of fibrosis by categorical FIB-4 score (odds ratio [OR]: 4.48, 95% CI: 1.7-11.8, P=0.003), independent of hemoglobin A1c level. CONCLUSIONS: The presence of type 2 diabetes complications is associated with the degree of liver fibrosis, independent of hemoglobin A1c level.

Coronavirus Disease 2019 Messenger RNA Vaccine Immunogenicity in Immunosuppressed Individuals.

Individuals on immunosuppressive (IS) therapy have increased mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and delayed viral clearance may lead to new viral variants. IS therapy reduces antibody responses following coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination; however, a comprehensive assessment of vaccine immunogenicity is lacking. Here we show that IS therapy reduced neutralizing, binding, and nonneutralizing antibody functions in addition to CD4 and CD8 T-cell interferon-γ responses following COVID-19 mRNA vaccination compared to immunocompetent individuals. Moreover, IS therapy reduced cross-reactivity against SARS-CoV-2 variants. These data suggest that the standard COVID-19 mRNA vaccine regimens will likely not provide optimal protection in immunocompromised individuals.

Willingness of Kidney and Liver Transplant Candidates to Receive HCV-Infected Organs.

INTRODUCTION: Transplantation of organs exposed to hepatitis C virus (HCV) into uninfected patients has yielded excellent outcomes and more widespread adoption may lead to fewer discarded organs and more transplants. Patient perceptions may shed light on acceptability and likely the uptake of HCV+/HCV- transplantation, gaps in understanding, and perceived benefits/risks. METHODS: We surveyed 435 uninfected kidney and liver transplant candidates at four centers about their attitude towards HCV-infected organs. RESULTS: The percentage of patients willing to accept HCV-infected organs increased from 58% at baseline, to 86% following education about HCV, direct-acting antiviral agents (DAAs), and HCV+/HCV- transplantation benefits/risks. More willingness to accept an organ from an intravenous drug user (P < 0.001), age >50 y old (P = 0.02), longer waiting time (P = 0.02), more trust in the transplant system (P = 0.03), and previous awareness of DAAs (P = 0.04) were associated with higher willingness to accept an HCV-infected organ. The most important reasons for accepting an HCV-infected organ were a decrease in waiting time (65%), lower mortality and morbidity risk while on the waiting list (63%), effectiveness of DAAs (54%), and a quicker return to higher functional status (51%). CONCLUSIONS: Presenting patients with information about HCV+/HCV- transplantation in small doses that are calibrated to account for varying levels of health and numerical literacy is recommended.