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.

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.

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.

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.

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.

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.

Echocardiographic and Other Preprocedural Predictors of Heart Failure After TIPS Placement in Patients With Cirrhosis: A Single-Center 15-Year Analysis.

BACKGROUND. Heart failure (HF) is an uncommon complication after TIPS placement; its development represents a poor prognostic factor. OBJECTIVE. The purpose of our study was to evaluate the frequency, risk factors, and association with survival of HF developing within 90 days after TIPS placement in patients with cirrhosis. METHODS. This retrospective single-center study included patients with cirrhosis who underwent nonemergent covered-stent TIPS placement from June 2003 to December 2018 and who underwent echocardiography within 2 months before TIPS placement and had at least 90 days of post-TIPS follow-up. Development of HF within 90 days after TIPS was recorded. Frequency of TIPS reduction for post-TIPS HF was determined. Univariable logistic regression analysis and ROC curve analysis were performed to assess potential risk factors for post-TIPS HF. Association of post-TIPS HF and 1-year survival was assessed by the log rank test. RESULTS. The study sample included 107 patients (71 men and 36 women; median age, 58 years). Post-TIPS HF developed in 11 of 107 (10%) patients; median time to development of HF was 16 days (range, 2-62 days). Of these 11 patients, three (27%) required TIPS reduction to achieve resolution of HF symptoms after unsuccessful diuretic therapy. Pre-TIPS right atrium size (odds ratio [OR], 3.26 [95% CI, 1.22-10.16]; p = .03], left ventricle (LV) end-systolic dimension (OR, 5.43 [95% CI, 1.44-24.50], p = .02), LV end-diastolic dimension (OR, 4.12 [95% CI, 1.51-13.47]; p = .009), and estimated peak pulmonary artery systolic pressure (PASP) (OR, 1.27 [95% CI, 1.12-1.50]; p = .001) were associated with post-TIPS HF. AUC of right atrium size, LV end-systolic dimension, LV end-diastolic dimension, and estimated peak PASP for development of post-TIPS HF were 0.71, 0.74, 0.72, and 0.83, respectively. At a cutoff of 31 mm Hg, PASP achieved sensitivity of 70% and specificity of 86% for post-TIPS HF. Patients with post-TIPS HF and those without post-TIPS HF had 1-year survival of 46% versus 73% (p = .06). CONCLUSION. Multiple pre-TIPS echocardiographic variables predict the development of post-TIPS HF in patients with cirrhosis. CLINICAL IMPACT. Preprocedural echocardiography may guide risk stratification in patients with cirrhosis being considered for TIPS placement.

Introduction of a standardized protocol for cardiac risk assessment in candidates for liver transplant - A retrospective cohort analysis.

INTRODUCTION: Recommendations on non-invasive imaging to assess pre-operative cardiac risk among liver transplant candidates vary amongst societal guidelines and individual institutional practices. In 2018, a standardized pre-transplant coronary evaluation protocol was established at Beth Israel Deaconess Medical Center, Boston MA, to ensure appropriate and consistent pre-operative testing was performed. METHODS: All patients who underwent liver transplant evaluation between January 1st, 2016 and December 31st, 2019, were retrospectively analyzed and divided into three cohorts; before the introduction of the protocol (prior to 2018), initial protocol favoring invasive coronary angiography (ICA) (2018), and amended protocol favoring coronary computed tomography angiography (CCTA) (post-2018). We described clinical characteristics, candidacy for transplant, and cardiovascular complications during follow-up. As an unadjusted exploratory analysis, the Cochran-Armitage Exact Trend Test was used to examine univariate differences across time. RESULTS: A total of 462 patients underwent liver transplant evaluation during the study period. Among these, 218 (47.2%) patients underwent stress test, 50 (10.8%) underwent CCTA, and 68 (14.8%) underwent ICA. Across the three time periods, there was an increase in the proportion of CCTAs performed (3%, 6.3%, and 26.3% respectively; p <0.001) and proportion of patients diagnosed with obstructive CAD using CCTA (0%, 30%, and 51.4% respectively; p = 0.04). There was no significant difference in post-transplant cardiac complications among patients evaluated before 2018, during 2018, and after 2018 (5.9% vs. 5.6 vs. 6.0%; p=1.0). CONCLUSION: Our findings suggest it is reasonable to shift practice to a less invasive approach utilizing CCTA or nuclear stress testing when assessing liver transplant candidates at increased cardiovascular risk.

Multicenter, Double-Blind, Randomized Trial of Emricasan in Hepatitis C-Treated Liver Transplant Recipients With Residual Fibrosis or Cirrhosis.

Despite achieving sustained virologic response (SVR) to hepatitis C virus (HCV) therapy, there remains a post liver transplantation population with advanced fibrosis/cirrhosis. Emricasan is an orally active, pan-caspase inhibitor that suppresses apoptosis and inflammation, potentially decreasing hepatic inflammation and fibrosis. We aimed to determine the safety and efficacy of emricasan (IDN-6556-07) in a double-blind, randomized, placebo-controlled, multicenter study in reducing or preventing the progression of hepatic fibrosis in HCV liver transplant recipients with residual fibrosis or cirrhosis after achieving SVR. A total of 64 participants were randomly assigned to receive 25 mg twice daily of emricasan or placebo in a 2:1 ratio for 24 months. 41 participants were randomly assigned to emricasan and 23 to placebo; 32 participants in the emricasan group (78.0%) and 19 who took a placebo (82.6%) completed the study. There was no difference in the primary endpoint (Ishak fibrosis stages F2-F5, improvement in fibrosis or stability; Ishak fibrosis stage F6, improvement) between the emricasan (77.1%) and placebo groups (74.1%); P = NS. There was no difference between the emricasan (54.5%) and placebo (60.7%) arms in the rate of fibrosis improvement alone. However, those in the prespecified F3 to F5 subgroup had higher rates of stability or improvement in fibrosis in the emricasan group (95.2%) compared with placebo (54.6%) (P = 0.01). The tolerability and safety profiles were similar in both groups. In conclusion, overall stability in the Ishak fibrosis stage was similar between emricasan and placebo groups at 24 months. However, there was improvement and/or stability in fibrosis stage in the prespecified F3 to F5 subgroup with emricasan versus placebo, suggesting that patients with moderate fibrosis may benefit with emricasan.

Fresh frozen plasma transfusion in acute variceal haemorrhage: Results from a multicentre cohort study.

BACKGROUND: Fresh frozen plasma (FFP) transfusion is often used in the management of acute variceal haemorrhage (AVH) despite best practice advice suggesting otherwise. OBJECTIVE: We investigated if FFP transfusion affects clinical outcomes in AVH. DESIGN, SETTING AND PATIENTS: We performed a retrospective cohort study of 244 consecutive, eligible patients admitted to five tertiary health care centres between 2013 and 2018 with AVH. MAIN OUTCOME MEASUREMENTS: Multivariable regression analyses were used to study the association of FFP transfusion with mortality at 42 days (primary outcome) and failure to control bleeding at 5 days and length of stay (secondary outcomes). RESULTS: Patients who received FFP transfusion (n = 100) had higher mean Model for End Stage Liver Disease (MELD) score and more severe variceal bleeding than those who did not received FFP transfusion (n = 144). Multivariable analysis showed that FFP transfusion was associated with increased odds of mortality at 42 days (odds ratio [OR] 9.41, 95% confidence interval [CI] 3.71-23.90). FFP transfusion was also associated with failure to control bleeding at 5 days (OR 3.87, 95% CI 1.28-11.70) and length of stay >7 days (adjusted OR 1.88, 95% CI 1.03-3.42). The independent association of FFP transfusion with mortality at 42 days persisted when the cohort was restricted to high-risk patients and in patients without active bleeding. LIMITATIONS AND CONCLUSIONS: Fresh frozen plasma transfusion in AVH is independently associated with poor clinical outcomes. As this an observational study, there may be residual bias due to confounding; however, we demonstrate no benefit and potential harm with FFP transfusions in AVH.

Neoadjuvant Yttrium-90 Transarterial Radioembolization with Resin Microspheres Prescribed Using the Medical Internal Radiation Dose Model for Intrahepatic Cholangiocarcinoma.

PURPOSE: To evaluate outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing neoadjuvant yttrium-90 (90Y) transarterial radioembolization (TARE) with resin microspheres prescribed using the Medical Internal Radiation Dose (MIRD) model. MATERIALS AND METHODS: This retrospective institutional review board-approved study included 37 patients with iCCA treated with 90Y-TARE from October 2015 to September 2020. The primary outcome was overall survival (OS) from 90Y-TARE. The secondary outcomes were progression-free survival (PFS), Response Evaluation Criteria In Solid Tumors 1.1 imaging response, and downstaging to resection. Patients with tumor proximity to the middle hepatic vein (<1 cm) and/or insufficient future liver remnant were treated with neoadjuvant intent (n = 21). Patients were censored at the time of surgery or at the last follow-up for the Kaplan-Meier survival analysis. RESULTS: For 31 patients (69 years; interquartile range, 64-74 years; 20 men [65%]) included in the study, the first-line therapy was 90Y-TARE for 23 (74%) patients. Imaging assessment at 6 months showed a disease control rate of 86%. The median PFS was 5.4 months (95% confidence interval [CI], 3-not reached). The PFS was higher after first-line 90Y-TARE (7.4 months [95% CI, 5.3-not reached]) than that after subsequent 90Y-TARE (2.7 months [95% CI, 2-not reached]) (P = .007). The median OS was 22 months (95% CI, 7.3-not reached). The 1- and 2-year OS rates were 60% (95% CI, 41%-86%) and 40% (95% CI, 19.5%-81%). In patients treated with neoadjuvant intent, 11 of 21 patients (52%) underwent resections. The resection margins were R0 and R1 in 8 (73%) and 3 (27%) of 11 patients, respectively. On histological review in 10 patients, necrosis of ≥90% tumor was achieved in 7 of 10 patients (70%). CONCLUSIONS: First-line 90Y-TARE prescribed using the MIRD model as neoadjuvant therapy for iCCA results in good survival outcome and R0 resection for unresectable patients.

The presence of diabetes impacts liver fibrosis and steatosis by transient elastography in a primary care population.

INTRODUCTION AND OBJECTIVES: Noninvasive liver assessment in type 2 diabetes (T2DM) in a primary care population identifies higher risk non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association of T2DM with liver fibrosis and steatosis by transient elastography (TE). MATERIALS AND METHODS: This is a retrospective study of a TE referral program where primary care physicians were able to order TE. Patients with alcohol abuse were excluded. TE and Controlled Attenuation Parameter (CAP) scores were obtained. Multivariable linear and logistic regression models were used to adjust for confounders. RESULTS: 28% had T2DM. The mean TE score in T2DM patients was 8.3 (±6) kilopascal (kPa) and 6.4 (±3.7) kPa in those without T2DM (p = 0.0001). Those with T2DM had a higher CAP (322 ± 51 dB/m vs. 296 ± 57 dB/m, p < 0.0001). In multivariable analysis, T2DM was associated with TE score (ß: 1.9, 95% confidence interval [CI]: 0.74-3.1, p = 0.001) and CAP (ß: 2.8, 95% CI: 9.3-36.2, p = 0.001). Patients with T2DM had higher-risk TE scores and more steatosis by CAP. CONCLUSION: T2DM is associated with liver fibrosis and steatosis by TE within a primary care population. A TE referral pathway may be utilized for T2DM patients who are at higher risk of NAFLD and its complications.

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

BACKGROUND: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options. METHODS: We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. RESULTS: In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower. CONCLUSIONS: Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247 .).

Baseline Factors Associated With Improvements in Decompensated Cirrhosis After Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection.

BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce Model for End-Stage Liver Disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus. However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials on the effects of sofosbuvir-based therapy in patients with hepatitis C virus-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C). In these trials, patients were given 12 or 24 weeks of treatment with ledipasvir, sofosbuvir, and ribavirin or velpatasvir, sofosbuvir, and/or ribavirin, or 48 weeks of treatment with sofosbuvir and ribavirin. We collected demographic, clinical, treatment response, and laboratory data from patients and tested their associations with patient outcomes at 36 weeks. The primary outcome was factors associated with reduction of CPT score to class A. RESULTS: The presence of ascites or encephalopathy, serum level of albumin <3.5 g/dL or alanine aminotransferase <60 U/L, and body mass index >25 kg/m2 were associated with an increased risk of not achieving a reduction in CPT to class A, independent of sustained viral response to therapy. Serum level of albumin <2.8 g/dL and abnormal level of bilirubin were associated with an increased risk of liver transplantation or death. We developed a scoring system based on 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated significantly with patient outcomes, which we called the "BE3A score." For patients with scores of 4-5, the hazard ratio for reduction of CPT score to class A was 52.3 (95% confidence interval, 15.2-179.7). CONCLUSIONS: We identified 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated with a reduction of CPT score to class A in patients with hepatitis C virus-associated decompensated cirrhosis receiving DAA therapy. We developed a predictive score using these factors, called the BE3A score, which can be used as a shared decision-making tool, quantifying the potential benefits of DAA therapy for patients with decompensated cirrhosis.