Search

Background and Aims: Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension., Approach and Results: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value. In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% negative predictive value., Conclusions: This study gathering a total of 309 patients with PSVD showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes., Patients and Methods: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey., Results: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model., Conclusions: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution., Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients., Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% ( p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm 2 , p <0.001)., Conclusions: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased., Impact and Implications: There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop., Competing Interests: JG has received consulting fees from Boehringer Ingelheim and speaking fees from Echosens. MS-T has received consulting fees from Grifols. AK has served as speaker for Novo Nordisk, Norgine, Siemens and Nordic Bioscience and participated in advisory boards for Norgine, Siemens, Resalis Therapeutics, Boehringer Ingelheim and Novo Nordisk, all outside the submitted work. Research support Norgine, Siemens, Nordic Bioscience, Astra, Echosense. Consulting Takeda, Resalis Therapeutics, Zealand Pharma, Novo Nordisk, Boehringer Ingelheim. Board member and co-founder Evido. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4 + T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4 + T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4 + T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders ( p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits ( p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels ( p < 0.01), and low circulating RBP4 concentrations were related to a low CD4 + T-cell gain ( p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4 + T cells at 144 weeks ( p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.

Background: The underlying mechanisms of incomplete immune reconstitution in treated HIV-positive patients are very complex and may be multifactorial, but perturbation of chemokine secretion could play a key role in CD4 + T-cell turnover., Methods: We evaluated the circulating baseline and 48-week follow-up concentrations of SDF-1/CXCL12, fractalkine/CX3CL1, MCP-1/CCL2, MIP-α/CCL3, MIP-β/CCL4 and RANTES/CCL5, and we estimated their association with CXCL12, CX3CR1, CCR2, CCL5 and CCR5 single nucleotide polymorphisms (SNPs) to investigate multiple chemokine-chemokine receptor signatures associated with immune dysregulation preceding poor immune recovery., Findings: The circulating concentrations and gene expression patterns of SDF-1/CXCL12 (CXCL12 rs1801157) and MCP-1/CCL2 (CCR2 rs1799864&#95;814) were associated with immune recovery status. CCR2 rs1799864&#95;814 and CCR5 rs333&#95;814 (Δ32) determine the baseline plasma RANTES and MIP-α concentrations, respectively, in participants with poor immune response., Interpretation: SDF-1/CXCL12 and MCP-1/CCL2 could be considered prognostic markers of immune failure despite suppressive antiretroviral therapy. The strong linkage disequilibrium (LD) between CCR2 rs1799864&#95;814 and CCR5 rs1800024 indicated that the alleles of each gene are inherited together more often than would be expected by chance., Funding: This work was supported by Fondo de Investigacion Sanitaria and SPANISH AIDS Research Network (ISCIII-FEDER); AGAUR and Gilead Fellowship. FV and YMP are supported by grants from the Programa de Intensificación (ISCIII) and Servicio Andaluz de Salud, respectively. JVG,EY and LR are supported by the Instituto de Salud Carlos III (ISCIII). AR is supported by Departament de Salut, Generalitat de Catalunya and by the Instituto de Salud Carlos III (ISCIII)., Competing Interests: Declaration of Competing interest All authors declare they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is the most important primary malignant liver disease. A large proportion of patients with advanced HCC have macrovascular invasion. HCC tends to infiltrate vascular structures, particularly the portal vein and its branches, and more rarely, the hepatic veins. The intravascular tumor thrombus can affect the inferior vena cava (IVC) or even the right atrium (RA), the latter having a poor prognosis., Case Summary: HCC is one of the most aggressive malignant tumors. Tumor thrombus (TT) formation in advanced HCC stages is common and usually involves the hepatic or portal veins. Herein, we report a 69-year-old woman who presented with dyspnea to the emergency department. A ventilation/perfusion lung scan was performed, ruling out pulmonary embolism. Hepatopulmonary syndrome and portopulmonary hypertension were discarded with contrasted echocardiography, but a mass in the RA was detected and confirmed by cardiac magnetic resonance imaging. Abdominal computed tomography showed a liver mass with a dynamic enhancement pattern compatible with HCC and an intraluminal IVC mass extending from the hepatic vein into the RA. HCC with TT expansion to IVC and RA is rare and indicates poor prognosis., Conclusion: HCC with TT expansion to IVC and RA is rare and indicates poor prognosis. There is no consensus about anticoagulation or other interventions in these patients., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Portal hypertension is the main consequence of liver cirrhosis, leading to severe complications such as variceal hemorrhage, ascites or hepatic encephalopathy. As an attempt to decompress the portal venous system, portal flow is derived into the systemic venous system through spontaneous portosystemic shunts (SPSSs), bypassing the liver. In this review, we aim to provide an overview of the published reports in relation to the prevalence and physiopathology behind the appearance of SPSS in liver cirrhosis, as well as the complications derived from its formation and its management. The role of SPSS embolization is specifically discussed, as SPSSs have been assessed as a therapeutic target, mainly for patients with recurrent/persistent hepatic encephalopathy and preserved liver function. Furthermore, different aspects of the role of SPSS in liver transplantation, as well as in candidates for transjugular intrahepatic portosystemic shunt are reviewed. In these settings, SPSS occlusion has been proposed to minimize possible deleterious effects, but results are so far inconclusive., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background & Aims: Check point inhibitors (CPI) have improved survival of oncology patients but adverse effects that mimic autoimmune disorders have been reported. Our aim was describe the characteristics of immune-related hepatitis (irH) and prognosis, and compared them to those of patients with autoimmune hepatitis (AIH)., Methods: This is a retrospective study including all grade ≥ 3 (severe) irH diagnosed among 414 patients treated with CPI from 2016 to 2018., Results: Twenty-eight cases of severe irH were recorded: 10 on anti-CTLA-4 ± anti-PD1/PD-L1 and 18 on anti-PD1/PD-L1. Half were female, age 63 years, median time on CPI three cycles. Four (14.3%) presented acute liver injury or failure and one (3.6%) died as consequence. 94% presented normal immunoglobulin G (IgG). Six (21.4%) patients were retreated with CPI and none presented relapse or new immune-related adverse events after a median cycles of 11 (range 6-36). Subjects with irH were older and had lower IgG values than a cohort of AIH (N = 38). Presentation tended to be more severe in AIH. Twenty-five percent of irH and 84% AIH presented ANAs ≥ 1:80 (P = .001). In irH Initial dose of corticosteroids was higher (60 vs 30 mg, P < .001) but duration shorter (2.3 vs 7 months, P < .001) and frequently in monotherapy (41.7% vs 91.3%, P < .001)., Conclusions: Immune-related hepatitis can lead to acute liver failure, with absence of increased values of IgG and ANAs. In contrast to autoimmune hepatitis, initial corticosteroids dose were higher, duration shorter with few requiring additional immunosuppression. Retreatment with CPI was not associated with recurrence., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis., Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint., Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm 2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA., Conclusion: This study suggests that TSA >83 mm 2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis., Lay Summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS., Competing Interests: Conflict of Interest MP Sponsored lectures: Gore; AZ Sponsored lectures: Gilead, Abbvie, Norgine, Grifols, Bayer, Gore, BMS; AD Sponsored lectures: Bayer; WL Grants: Boston Scientific, Consultant: Boston Scientific, Abbvie, Gilead, Norgine, Gore; VLM Grants: Gilead Sciences research Scholar Program, Consultant: Gore, Sponsored lectures (National or International): Gore, Abbvie, Alfa-sigma; CR Grant: Schweine Stiftung; VHG Sponsored lectures (National or International): GORE; TR Grants: Abbvie, Boehringer Ingelheim, Gilead, MSD, Philips Healthcare, Gore; Consultant: Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; Sponsored lectures (National or International): Abbvie, Gilead, Gore, Intercept, Roche, MSD; AA Grants: Gilead Sciences, Consultant: AbbVie, Gilead Sciences, Gore, Griffols, Intercept Pharmaceuticals, Pfizer and Merck & Co., Sponsored lectures (National or International): AbbVie, Gilead Sciences, Gore, Griffols, Intercept Pharmaceuticals, Pfizer and Merck & Co.; EAT Consultant: Pfizer, Intercept, Gilead, Promethera, Astra Zeneca; JT Grants: Gore, Consultant: Martins Pharma, Ironwood, Gore, Alexion, BMS, Grifols, Sequana Medicals, Versantis, Sponsored lectures (National or International): Gilead, Gore, Alexion, BMS, Grifols, Sequana Medicals, Norgine, Intercept. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

HIV and antiretroviral therapy affect lipid metabolism. Lipidomics quantifies several individual species that are overlooked using conventional biochemical analyses, outperforming traditional risk equations. We aimed to compare the plasma lipidomic profile of HIV patients taking efavirenz (EFV) or rilpivirine (RPV). Patients ≥ 18 years old on EFV co-formulated with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with HIV-RNA < 50 copies/mL for ≥6 months were randomized to continue EFV/FTC/TDF (n = 14) or switch to RPV/FTC/TDF (n =15). Lipidomic analyses conducted by mass spectrometry (MS) were performed at baseline and after 12 and 24 weeks. OWLiver ® Care and OWLiver ® tests were performed to estimate the presence of fatty liver disease (NAFLD). No significant differences (83% male, median age 44 years, 6 years receiving EFV/FTC/TDF, CD4 + count 740 cells/mm 3 , TC 207 [57 HDL-C/133 LDL-C] mg/dL, TG 117 mg/dL) were observed between the groups at baseline. Significant reductions in plasma lipids and lipoproteins but increased circulating bilirubin concentrations were observed in patients who switched to RPV/FTC/TDF. Patients on RPV/FTC/TDF showed a decrease in the global amount of storage lipids (-0.137 log 2 [fold-change] EFV vs. 0.059 log 2 [fold-change] RPV) but an increase in lysophosphatidylcholines (LPCs) and total steroids. Compared with EFV, RPV increased metabolites with anti-inflammatory properties and reduced the repository of specific lipotoxic lipids.