Advanced Cirrhosis Research Articles

Magnetic resonance elastography is useful to determine the severity of liver fibrosis according to liver biopsy in post-fontan patients.

The reliability of various modalities for assessing and monitoring Fontan-associated liver disease compared to liver biopsy remains an intriguing subject of inquiry. Our objective was to assess the efficacy of multiple modalities in comparison to liver histology for evaluating liver fibrosis in post-Fontan patients. We conducted a cross-sectional study involving Fontan patients without known liver disease. Eligible patients underwent cardiac and hepatic evaluations, including ultrasound liver elastography, magnetic resonance elastography (MRE) of the liver, computerized tomography (CT) scan of the upper abdomen, echocardiography, cardiac catheterization, and liver biopsy. The severity of liver fibrosis was categorized using the METAVIR score derived from liver biopsy results: F0/F1 indicated no or mild fibrosis, F2 indicated significant fibrosis, F3 indicated advanced fibrosis and F4 indicated cirrhosis. A total of 38 patients (mean age 21 ± 6.5 years, 52.6% female) were included in the cross-sectional study, with a mean time elapsed since the Fontan operation of 13 years. Parameters obtained from echocardiography, ultrasound liver elastography, and CT scan of the upper abdomen did not exhibit significant differences among the groups. Notably, liver biopsy revealed advanced cirrhosis in 23 out of 38 patients and none were diagnosed with hepatocellular carcinoma. Multivariate logistic regression analysis demonstrated that the factor significantly associated with significant liver fibrosis or cirrhosis in post-Fontan patients was liver stiffness with MRE > 4.4kPa [OR 13.5 (95% CI 1.2-152.2)]. Our findings suggest that post-Fontan patients with liver stiffness of MRE > 4.4kPa should undergo further investigation. These results contribute to understanding the liver fibrosis assessment in post-Fontan patients and highlight the importance of MRE in predicting significant liver disease.

Adiponectin as a biomarker in liver cirrhosis-A systematic review and meta-analysis.

Adiponectin, a key adipokine, shows promise as a non-invasive biomarker for liver cirrhosis by reflecting inflammation and metabolic changes, but conflicting findings highlight the need for a systematic review and meta-analysis to clarify its role. Our study aimed to evaluate adiponectin levels across various stages of liver cirrhosis, compare them with other chronic liver diseases (CLD) and hepatocellular carcinoma (HCC), and assess its potential as a diagnostic and prognostic biomarker. Our systematic search was conducted on September 2023 using PubMed, EMBASE and Scopus, searching for observational studies evaluating serum and plasma adiponectin levels in liver cirrhosis. Inclusion and exclusion criteria were applied, and study quality was assessed using the Newcastle-Ottawa Scale. To evaluate the overall effect size, we utilized a random-effects model along with a mean difference (MD) analysis. The principal summary outcome was the MD in adiponectin levels. We included 16 articles involving 2617 subjects in our qualitative and quantitative synthesis. We found significantly higher adiponectin levels in liver cirrhosis patients (8.181 [95% CI 3.676, 12.686]), especially in Child-Pugh B individuals (13.294 [95% CI 4.955, 21.634]), compared to controls. Child-Pugh A patients did not show significant differences compared to controls. In addition, adiponectin levels were significantly elevated in primary biliary cholangitis (PBC) patients compared to controls (8.669 [95% CI .291, 17.047]), as well as in liver cirrhosis compared to other CLD patients (4.805 [95% CI 1.247, 8.363]), including non-alcoholic fatty liver disease (NAFLD) (8.532 [95% CI 3.422, 13.641]), but not viral hepatitis. No significant MD was observed between liver cirrhosis and HCC patients. Adiponectin levels are significantly elevated in liver cirrhosis, especially in advanced stages, potentially serving as a biomarker for advanced cirrhosis. Adiponectin also differentiates cirrhosis from other CLD, including NAFLD. However, its role in distinguishing cirrhosis from viral hepatitis and HCC is limited.

Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study.

Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5years after successful HCV treatment) in persons with HIV/HCV coinfection. We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.

Treatment variants in hepatorenal syndrome. Systematic review

Introduction: hepatorenal syndrome (HRS) is a form of acute renal failure that occurs in patients with advanced cirrhosis and presents high mortality.Objective: to describe the therapeutic alternatives in hepatorenal syndrome. Methods: a search for information was carried out using the PubMed, TripDatabase and Cochrane databases; MeSH terms were used. Initially, 1749 articles were obtained; subsequently, 5 articles used in this systematic review were selected through the use of filters, review of titles, and elimination of duplicates. Results: 548 patients were included. 325 patients received Terlipressin and 223 patients received Placebo. A reversal of SHR was evidenced in 35,8 % in patients receiving Terlipressin vs. 12,1 % placebo. Overall survival without liver transplantation was 36,7 % for the Terlipressin group and 21,1 % placebo. Adverse events were higher in the Terlipressin group. Conclusion: Terlipressin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1 (HRS-1). However, its use is associated with serious adverse events, such as respiratory failure. The combined treatment of terlipressin and albumin shows a greater improvement in renal function compared to the use of albumin alone. Further studies are needed to determine whether the improvement in renal function translates into a survival benefit for patients. Liver transplantation remains the most definitive treatment, and should be considered early in the course of the disease

CT/MRI technical pitfalls for diagnosis and treatment response assessment using LI-RADS and how to optimize.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is a significant global health burden. Accurate imaging is crucial for diagnosis and treatment response assessment, often eliminating the need for biopsy. The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation and reporting of liver imaging for diagnosis and treatment response assessment, categorizing observations using defined categories that are based on the probability of malignancy or post-treatment tumor viability. Optimized imaging protocols are essential for accurate visualization and characterization of liver findings by LI-RADS. Common technical pitfalls, such as suboptimal postcontrast phase timing, and MRI-specific challenges like subtraction misregistration artifacts, can significantly reduce image quality and diagnostic accuracy. The use of hepatobiliary contrast agents introduces additional challenges including arterial phase degradation and suboptimal uptake in advanced cirrhosis. This review provides radiologists with comprehensive insights into the technical aspects of liver imaging for LI-RADS. We discuss common pitfalls encountered in routine clinical practice and offer practical solutions to optimize imaging techniques. We also highlight technical advances in liver imaging, including multi-arterial MR acquisition and compressed sensing. By understanding and addressing these technical aspects, radiologists can improve accuracy and confidence in the diagnosis and treatment response assessment for hepatocellular carcinoma.

Non-alcohlic Fatty Liver Disease (NAFLD): Is it a Dormant Volcano or Tip of an Iceberg?

Non-alcoholic fatty liver disease (NAFLD), a major cause of chronic liver disease, is known to affect a quarter of the global adults. Natural history of NAFLD shows interindividual variation, traditionally it progresses from simple steatosis to steatohepatitis to fibrosis/cirrhosis and finally yet rarely to hepatocellular carcinoma. It is largely a lifestyle-related disease and is often labeled as the hepatic manifestation of metabolic syndrome. Both prevention and control of NAFLD include controlling risk factors (obesity, diabetes mellitus, hypertension and dyslipidemia), through lifestyle modification and medications. Drug therapy for NAFLD per se is still evolving and till date, no drugs are approved. It is clinically silent, especially in the early stages, and is a diagnosis of exclusion. Certain easily calculated indices can stratify cases into high or low risk for advanced fibrosis, thereby dictating appropriate monitoring and treatment measures. In addition to complications specific to liver disease in those who do progress to advanced fibrosis or cirrhosis, an increased risk of nonliver disease-related morbidity and mortality is also present. Challenges are manifold and include rising burden due to ever-growing epidemic of diabetes and obesity, low public awareness, fragmented healthcare, no approved drugs, and dearth of data on magnitude and epidemiology of the disease. The recent integration of NAFLD into the National Program for Prevention and Control of Non-Communicable Diseases (NPCDCS) by the Ministry of Health and Family Welfare of India is a welcome step in this direction as the contributory factors are mostly the same for all diseases and controlling any one or all of them will have a desired impact on the prevalence of all the diseases under this program.

Liver cirrhosis is a risk-factor for Pneumocystis jirovecii associated mortality.

Pneumocystis jirovecci pneumonia (PCP) is a life threating disease in immunodeficient patients. Liver cirrhosis itself can lead to immunodefiency, however little is known if Pneumocystis jirovecci infection affects the outcome of patients with liver cirrhosis. We aimed to assess the predictors for Pneumocystis jirovecci-associated mortality in patients with Pneumocystis jirovecci infection treated at intensive care units. A total of 151 patients hospitalized between January 2013 and November 2019 with a PCR-confirmed Pneumocystis jirovecci infection were retrospectively included in this study and analysed for clinical predictors for PCJ associated mortality. The overall mortality in our patient cohort was 60%. Out of 151 patients included in the analysis, 67 (44%) patients suffered from liver cirrhosis. Patients with an advanced liver cirrhosis (Child-Pugh class C) showed the highest mortality rate of 84.7%. The presence of a liver cirrhosis was associated with a significant increased risk of mortality (OR: 4.809) ([95%-CI: 2.32-9.97]; p < 0.001). There was a significant correlation of Meld score and mortality (r = 0.612, p < 0.001). To our knowledge, this study represents the largest evaluation of Pneumocystis jirovecci infection in patients with advanced liver cirrhosis. Cirrhosis associated immune dysfunction (CAID) describes the spectrum of immunological disturbances in patients with cirrhosis, which is linked to a heightened vulnerability to bacterial infections. Our data indicate a heightened susceptibility to fungal infections. Understanding the phenotypic manifestations of CAID could lead to immune-targeted therapies aimed at reducing infection susceptibility and decreasing CAID-associated mortality in cirrhosis patients.

Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the ‘CAVARLY TRIAL’

ObjectivesBeta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk...

7247 Adrenal Insufficiency In Advanced Cirrhosis: A ‘Shocky’ Clinical Dilemma

Abstract Disclosure: L. Aboishava: None. A. Pareek: None. A. Mertens: None. A. Erokhin: None. Background: In patients with advanced cirrhosis, profound hypoproteinemia can complicate the laboratory assessment of the hypothalamic-pituitary-adrenal axis, but a clinical phenotype of persistent hypotension and suboptimal cortisol response to ACTH stimulation raises the question of whether adrenal insufficiency could also be a contributing factor. Clinical Case: A 65-year-old man with a history of cirrhosis complicated by esophageal varices, ascites, encephalopathy and hepatorenal syndrome was admitted to the ICU with worsening fatigue, profound hypotension, and respiratory arrest. He was started on pressors, antibiotics and was also intubated for a short time. A broad workup was negative for cardiac or infectious causes of shock and showed decreased total protein and albumin (1.6 g/dl (3.5-5.2), with normal serum sodium and potassium. The patient had no previous history of adrenal disease or corticosteroid use. Workup for adrenal insufficiency was initiated and showed decreased morning blood serum cortisol (10.6 ug/dl (2.5-19.5)) and ACTH (&amp;lt;5.0 pg/ml (7.2-63)), as well as suboptimal cortisol response on ACTH stimulation testing (12.5 ug/dl initially, 16.7 ug/dl after stimulation). Head CT on admission was negative for intracranial pathology, and lab results showed normal TSH and mildly increased prolactin of 36.2 ng/ml (4.0-15.0). Pt was started on IV hydrocortisone 50 mg TID. Glucocorticoid therapy didn’t improve his state significantly but was continued with a gradual tapering down of the dose. After intense treatment in the ICU the patient’s state was stabilized. Unfortunately, an endoscopy performed for worsening anemia and blood in stools showed gastric cancer. The patient was transferred to comfort care after a discussion of goals of treatment and died within the next 24 hours. Conclusion: The nature of decreased cortisol levels in patients with cirrhosis is most likely multifactorial, due to impaired hepatic synthetic function, dysregulation of hormone-binding protein balance, abnormal ACTH secretion, and other factors. Impaired corticosteroid-binding globulin synthesis might affect the ratio of globulin-bound and free hormone fractions and alter the accuracy of cortisol assays. Whether adrenal insufficiency is truly one of the complications of advanced cirrhosis contributing to persistent hypotension, or a mere laboratory finding is difficult to answer. It is also yet to be determined whether patients with advanced cirrhosis might benefit from screening and treatment of adrenal insufficiency in circumstances of persistent hypotension, and studies are needed to decide on optimal diagnostic tests to recognize the disease and develop treatment algorithms. Presentation: 6/3/2024

Oral-gut microbiome interactions in advanced cirrhosis: characterisation of pathogenic enterotypes and salivatypes, virulence factors and antimicrobial resistance

Background & AimsCirrhosis complications are often triggered by bacterial infections with multidrug-resistant organisms. Alterations in the gut and oral microbiome in decompensated cirrhosis (DC) influence clinical outcomes. We interrogated: (i) gut and oral microbiome community structures, (ii) virulence factors (VFs) and antimicrobial resistance genes (ARGs) and (iii) oral-gut microbial overlap in patients with differing cirrhosis severity. Methods15 healthy controls (HC), 26 stable cirrhosis (SC), 46 DC, 14 acute-on-chronic liver failure (ACLF) and 14 with severe infection without cirrhosis (NLS) participated. Metagenomic sequencing was undertaken on paired saliva (S) and faecal (F) samples. ‘Salivatypes’ and ‘enterotypes’ based on genera clustering were assessed against cirrhosis severity and clinical parameters. VFs and ARGs were evaluated in oral and gut niches, and distinct resistotypes identified. ResultsSalivatypes and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity and hyperammonaemia. Increasing overlap between oral and gut microbiome communities was observed in DC and ACLF vs SC and HCs, independent of antimicrobial, beta-blocker and acid suppressant therapies. Two distinct gut microbiome clusters [ENT2/ENT3] harboured genes encoding for the phosphoenolpyruvate:sugar phosphotransferase system (PTS) system and other VFs in DC and ACLF. Substantial ARGs (oral: 1,218 and gut: 672) were detected [575 common to both sites]. The cirrhosis resistome was distinct, with three oral and four gut resistotypes identified, respectively. DiscussionThe degree of oral-gut microbial community overlap, frequency of VFs and ARGs all increment significantly with cirrhosis severity, with progressive dominance of pathobionts and loss of commensals. Despite similar antimicrobial exposure, patients with DC and ACLF have reduced microbial richness compared to NLS, supporting the additive pathobiological effect of cirrhosis. Impact and implicationsThis research underscores the crucial role of microbiome alterations in the progression of cirrhosis in an era of escalating multidrug resistant infections, highlighting the association and potential impact of increased oral-gut microbial overlap, virulence factors, and antimicrobial resistance genes on clinical outcomes. These findings are particularly significant for patients with decompensated cirrhosis and acute-on-chronic liver failure, as they reveal the intricate relationship between microbiome alterations and cirrhosis complications. This is relevant in the context of multidrug-resistant organisms and reduced oral-gut microbial diversity that exacerbate cirrhosis severity, drive hepatic decompensation and complicate treatment. For practical applications, these insights could guide for cirrhosis patients the development of targeted microbiome-based therapeutics and personalised antimicrobial regimens to mitigate infectious complications to improve their clinical outcomes.

Endoscopic Ultrasound Shear Wave Elastography for Fibrosis Screening in Patients with Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Pilot Study (With Video)

Background and AimsLiver fibrosis staging is challenging in patients with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Liver biopsies are invasive, whereas non-invasive tests such as vibration-controlled transient elastography (VCTE) can be inaccurate in patients with obesity. We hypothesized that endoscopic ultrasound shear wave elastography (EUS-SWE) is more accurate for liver fibrosis staging in patients with MASLD and obesity, and in this pilot study we aimed to test this hypothesis and establish optimal fibrosis stage cutoffs for EUS-SWE. MethodsThis was a multicenter, cross-sectional study from prospectively collected data. Consecutive patients who underwent EUS-SWE with subsequent liver biopsy were included. EUS-SWE was compared to Fibrosis-4 Index (FIB-4) and VCTE. Area under the receiver operator characteristic (AUROC) curve analysis was performed, and 90% sensitivity and specific cutoffs were calculated to determine optimal cutoffs. Results62 patients were included. Mean body mass index was 40.74kg/m2. EUS-SWE was superior to FIB-4 in discriminating significant fibrosis (F2; AUROC 0.87 vs 0.61, p<0.0048) and advanced fibrosis (F3; AUROC 0.93 vs 0.63 p<0.0001), but not cirrhosis (F4; AUROC 0.95 vs 0.81, p=0.099). EUS-SWE was superior to VCTE in predicting advanced fibrosis and cirrhosis (p=0.0067 and 0.0022 respectively). 90% sensitivity cutoffs for EUS-SWE were 7.50, 8.48, and 11.30 for F2-F4 respectively, and 90% specificity cutoffs were 9.82, 10.20, and 14.60 respectively. ConclusionsIn this pilot study, EUS-SWE was superior to FIB-4 and VCTE for liver fibrosis staging in patients with MASLD and obesity (Clinical trial registration number: NCT05728697).

Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: A systematic review and meta-analysis.

Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of vibration-controlled transient elastography (VCTE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine VCTE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment VCTE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. VCTE >8.4-11 kPa and FIB-4 >3.25 measured after SVR maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment VCTE. That of VCTE measured after the SVR was 11.2 kPa. VCTE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

Predictors of Inpatients Mortality in Patients with Liver Cirrhosis with Hepatic Encephalopathy

Background Hepatic encephalopathy has high risk of recurrence and is associated with advanced cirrhosis of liver. It features a spectrum of reversible neuropsychiatric abnormalities. The purpose of the research was to study the inpatients mortality and its predictors among cirrhotic patients with hepatic encephalopathy. MethodsA cross-sectional, hospital-based study comprising of 182 cirrhotic patients with hepatic encephalopathy were evaluated. West Haven Classification (Grade I to IV) was used for grading of hepatic encephalopathy. The data analysis was done using SPSS version 20 and p-value of ≤0.05 was considered significant. ResultsMajority of patients (39.6%) presented with Grade II encephalopathy followed by Grade III (26.4%). Inpatient mortality was 22.5%. Mortality was seen in 95% patients with HE of grade IV. Univariate analysis showed male sex [p-value=0.01, OR-0.37, CI (0.17-0.820)], shock at presentation [p-value=0.0001, OR-42, CI (16.05 -109.9)], CTP [p-value=0.03, OR-3.8, CI (1.1-13.3)], presence of more than two precipitating factors [P=0.0001, OR-48, CI (10.3-216.3)], presence of SBP [p-value=0.0001, OR-23.4, CI (9.1-60.4)] as statistically significant predictive factors. Multivariate analysis showed shock [P=0.0001, OR-85.3, CI (12.7-571.7)], presence of more than two precipitating factors [p-value=0.0001, OR-101.8, CI (3.32-3119.32)] and SBP [p-value=0.0001, OR-44.7, CI (6.49-309.5)] as statistically significant predictive factors for mortality in patients with liver cirrhosis with hepatic encephalopathy. Conclusions Inpatient mortality was high with increasing grades of encephalopathy among cirrhotic patients. Initial presentation with shock, presence of more than two precipitating factors and SBP were independent predictors of inpatient mortality in patients with liver cirrhosis with hepatic encephalopathy.

Prognostic Accuracy of Transient Elastography-Based Predictors in Diabetes and Obesity: A Multicenter International Cohort Study.

Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is recommended for risk stratification of patients with nonalcoholic fatty liver disease (NAFLD). More recently, AGILE3 + and AGILE4 have combined LSM with clinical parameters to identify patients with advanced fibrosis and cirrhosis, respectively. However, there are limited data on prognostic performance of these scores in key at-risk subgroups such as those with diabetes and obesity compared to LSM alone. This is a retrospective cohort study including 1903 adult patients with NAFLD from tertiary care centers in the United States and Singapore undergoing VCTE between 2015 and 2022. Primary predictors were FAST, LSM, AGILE3 + , and AGILE4 scores and the primary outcome was liver-related events (LRE). Patients were further stratified by diabetes and obesity status. Prognostic performance was measured using the time-dependent area under the receiver operating characteristic curve (tAUC) at 5years. In total, 25 LRE occurred and the overall incidence rate of LRE was 4.4 per 1000 person-years. tAUC for predicting LRE in the overall group was significantly higher with AGILE3 + (0.94 [95% CI: 0.90-0.98]) and AGILE4 (0.94 [95% CI: 0.90-0.98]) compared to LSM (0.87 [95% CI: 0.80-0.94]) (p = 0.001 and 0.009, respectively) and FAST (0.73 [95% CI: 0.59-0.86]) (p < 0.001 for both). Similarly, tAUC was significantly higher in those with T2D for AGILE3 + compared to LSM (0.92 vs 0.86, respectively) (p = 0.015) and FAST (0.92 vs 0.73, respectively) (p = 0.008). Among people with obesity, tAUC was significantly higher for AGILE3 + compared to LSM (0.95 vs 0.89, respectively) (p = 0.005) and FAST (0.95 vs 0.76, respectively) (p = 0.0035). Though AGILE4 had a higher tAUC in these subgroups compared to LSM, it did not reach statistical significance. AGILE3 + significantly outperforms LSM and FAST for predicting LRE in patients with NAFLD including in those with diabetes or obesity.

Diagnostic performance of new BAST score versus FIB-4 index in predicating of the liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease

Background and aimMetabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common liver condition globally. The FIB-4 test is used to detect fibrosis in fatty liver disease but has limited accuracy in predicting liver stiffness, resulting in high rates of false positives and negatives. The new BAST scoring system, incorporating waist circumference, AST, and BMI, has been developed to assess the presence of fibrosis in NAFLD patients. This study compares the effectiveness of BAST and FIB-4 in predicting liver fibrosis in MASLD patients.Patients and methodsThe study included 140 non-diabetic MASLD patients who underwent transient elastography measurement. BAST score and FIB-4 were calculated for each patient. Patients were grouped based on fibrosis severity; F1, F2, and F3–F4. The sensitivity and specificity of the BAST score and FIB-4 were assessed using receiver operating characteristic curves.ResultsThe BAST score increased significantly with fibrosis progression from F1 to F3–F4. In differentiating advanced fibrosis (F2–F3) from mild/moderate fibrosis (F1–F2), the BAST score at cutoff ≤ − 0.451 showed better diagnostic performance with 90.70% sensitivity, 74.07% specificity, 84.8% PPV and 83.3% NPV compared to FIB-4 that had 60.47% sensitivity, 50.0% specificity, 65.8% PPV and 44.3% NPV. Similarly, for differentiating between F1 and F2 fibrosis, the BAST score at cutoff ≤ − 1.11 outperformed FIB-4, with 80.23% sensitivity, 79.49% specificity, 89.6% PPV and 64.6% NPV, while FIB-4 had 59.30% sensitivity, 51.28% specificity, 72.9% PPV and 36% NPV.ConclusionsThe BAST score is a better predictor of liver fibrosis in MASLD compared to FIB-4, especially in cases of advanced fibrosis or cirrhosis.

Bulevirtide improves liver function in candidates for liver transplant with advanced HDV cirrhosis and severe portal hypertension.

Bulevirtide improves liver function in candidates for liver transplant with advanced HDV cirrhosis and severe portal hypertension.

Validation of a Primary Biliary Cholangitis-Specific Version of Chronic Liver Disease Questionnaire: CLDQ-PBC.

Primary biliary cholangitis (PBC) is a chronic liver disease, leading to cirrhosis and impairment of patient-reported outcomes. We aimed to develop a PBC-specific version of the Chronic Liver Disease Questionnaire (CLDQ) instrument to assess health-related quality of life of patients with PBC. From our Liver Database, we included patients with PBC who had CLDQ, clinicolaboratory data, and completed Short Form-36 and The Functional Assessment of Chronic Illness Therapy-Fatigue. The 29 items of CLDQ were subjected to item reduction, exploratory factor analysis, and fed into a standard instrument validation pipeline. Data were available for 108 patients with PBC: 57 ± 11 years, 7% male, 58% cirrhosis, and 24% decompensated cirrhosis (Child B and C). Of 29 CLDQ items, none met the exclusion criteria. Exploratory factor analysis (95% of variance) returned 7 factors. Based on evaluation of factor loadings and face validity, those factors yielded 7 domains (Diet, Emotion, Fatigue, Itch, Symptoms, Sleep, and Worry). Good to excellent internal consistency (Cronbach's α 0.85-0.93) was observed for 5/7 domains. For the remaining 2 domains (Diet and Itch), additional items obtained from patients, experts, and review of the literature were included. For 5 domains, known-group validity tests discriminated between patients with PBC with and without cirrhosis, advanced cirrhosis, and depression ( P < 0.05 for 3-5 domains). The CLDQ-PBC domains were correlated with relevant domains of Short Form-36, CLDQ-PBC Fatigue correlated with Fatigue Scale of Functional Assessment of Chronic Illness Therapy-Fatigue (rho = +0.85), and CLDQ-PBC Worry domain negatively correlated with alkaline phosphatase (rho = -0.38, P = 0.0082). The CLDQ-PBC has been developed based on the original CLDQ. The new instrument has evidence for internal consistency and validity and is being fully validated using an external cohort.

Continuous enteral feeding at home and continuous infusion of terlipressin: two antipodean controlled trials aimed at improving the vigor of patients with advanced cirrhosis

Continuous enteral feeding at home and continuous infusion of terlipressin: two antipodean controlled trials aimed at improving the vigor of patients with advanced cirrhosis

Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D15]octanoate to deuterated water and detection with deuterium magnetic resonance methods. Perfused livers from a mouse model of MASLD reveal dysregulated hepatic β-oxidation, findings that corroborate invivo imaging. The high-fat-diet-induced MASLD mouse studies indicate that decreased β-oxidative efficiency in the fatty liver could serve as an indicator of MASLD progression. Furthermore, our method provides a clinically translatable imaging approach for determining hepatic β-oxidation efficiency.

Strategy and Outcomes of Cardiac Surgery in Patients With Cirrhosis: Comprehensive Approach With Liver Transplant Program.

Cardiac surgery is considered a contraindication in patients with advanced liver cirrhosis (LC) due to increased mortality and morbidity. There are limited data on the treatment strategy and management of this population. We aimed to present our strategy and evaluate the clinical outcome of cardiac surgery in patients with LC. Our strategy was (i) to list patients for liver transplant (LT) at the time of cardiac surgery; (ii) to maintain high cardiopulmonary bypass (CPB) flow (index up to 3.0 L/min/m2) based on hyper-dynamic states due to LC; and (iii) to proceed to LT if patients' liver function deteriorated with an increasing model for end-stage liver disease Na (MELD-Na) score after cardiac surgery. Thirteen patients (12 male and 1 female [mean age, 63.0]) with LC who underwent cardiac surgery between 2017 and 2024 were retrospectively analyzed. Six patients were listed for LT. Indications for cardiac surgery included coronary artery disease (N=7), endocarditis (N=2), and tricuspid regurgitation (N=1), tricuspid stenosis (N=1), mitral regurgitation (N=1), and hypertrophic obstructive cardiomyopathy (N=1). The Child-Pugh score was A in five, B in six, and C in one patient. The procedure included coronary artery bypass grafting (N=6), single valve surgery (mitral valve [N=2] and tricuspid valve [N=1]), concomitant aortic and tricuspid valve surgery (N=2), and septal myectomy (N=1). Two patients had a history of previous sternotomy. The perfusion index during CPB was 3.1±0.5 L/min/m2. Postoperative complications include pleural effusion (N=6), bleeding events (N=3), acute kidney injury (N=1), respiratory failure requiring tracheostomy (N=2), tamponade (N=1), and sternal infection (N=1). There was no in-hospital death. There was one remote death due to COVID-19 complication. Preoperative and postoperative highest MELD-Na score among listed patients was 15.8±5.1 and 19.3±5.3, respectively. Five patients underwent LT (1, 5, 8, 16, and 24 months following cardiac surgery) and one patient remains on the list. Survival rates at 1 and 3 years are 100% and 75.0%, respectively. Cardiac surgery maintaining high CPB flow with LT backup is a feasible strategy in an otherwise inoperable patient population with an acceptable early and midterm survival when performed in a center with an experienced cardiac surgery and LT program.