Publications by authors named "Rohit Loomba"

518 Publications

Oximetry titrated care: This is the way.

Paediatr Anaesth 2021 Dec 5. Epub 2021 Dec 5.

Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pan.14350DOI Listing
December 2021

Comparative diagnostic performance of ultrasound shear wave elastography and magnetic resonance elastography for classifying fibrosis stage in adults with biopsy-proven nonalcoholic fatty liver disease.

Eur Radiol 2021 Dec 2. Epub 2021 Dec 2.

Liver Imaging Group, Altman Clinical and Translational Research Institute, Department of Radiology, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA, 92037, USA.

Objectives: To compare the diagnostic accuracy of US shear wave elastography (SWE) and magnetic resonance elastography (MRE) for classifying fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: Patients from a prospective single-center cohort with clinical liver biopsy for known or suspected NAFLD underwent contemporaneous SWE and MRE. AUCs for classifying biopsy-determined liver fibrosis stages ≥ 1, ≥ 2, ≥ 3, and = 4, and their respective performance parameters at cutoffs providing ≥ 90% sensitivity or specificity were compared between SWE and MRE.

Results: In total, 100 patients (mean age, 51.8 ± 12.9 years; 46% males; mean BMI 31.6 ± 4.7 kg/m) with fibrosis stage distribution (stage 0/1/2/3/4) of 43, 36, 5, 10, and 6%, respectively, were included. AUCs (and 95% CIs) for SWE and MRE were 0.65 (0.54-0.76) and 0.81 (0.72-0.89), 0.81 (0.71-0.91) and 0.94 (0.89-1.00), 0.85 (0.74-0.96) and 0.95 (0.89-1.00), and 0.91 (0.79-1.00) and 0.92 (0.83-1.00), for detecting fibrosis stage ≥ 1, ≥ 2, ≥ 3, and = 4, respectively. The differences were significant for detecting fibrosis stage ≥ 1 and ≥ 2 (p < 0.01) but not otherwise. At ≥ 90% sensitivity cutoff, MRE yielded higher specificity than SWE at diagnosing fibrosis stage ≥ 1, ≥ 2, and ≥ 3. At ≥ 90% specificity cutoff, MRE yielded higher sensitivity than SWE at diagnosing fibrosis stage ≥ 1 and ≥ 2.

Conclusions: In adults with NAFLD, MRE was more accurate than SWE in diagnosing stage ≥ 1 and ≥ 2 fibrosis, but not stage ≥ 3 or 4 fibrosis.

Key Points: • For detecting any fibrosis or mild fibrosis, MR elastography was significantly more accurate than shear wave elastography. • For detecting advanced fibrosis and cirrhosis, MRE and SWE did not differ significantly in accuracy. • For excluding advanced fibrosis and potentially ruling out the need for biopsy, SWE and MRE did not differ significantly in negative predictive value. • Neither SWE nor MRE had sufficiently high positive predictive value to rule in advanced fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-021-08369-9DOI Listing
December 2021

Expert Panel Review to Compare FDA and EMA Guidance on Drug Development and Endpoints in Nonalcoholic Steatohepatitis.

Gastroenterology 2021 Nov 22. Epub 2021 Nov 22.

Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Medical Director, Pinnacle Clinical Research, San Antonio, TX, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.10.051DOI Listing
November 2021

Non-invasive methods for imaging hepatic steatosis and their clinical importance in NAFLD.

Nat Rev Endocrinol 2021 Nov 23. Epub 2021 Nov 23.

NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Hepatic steatosis is a key histological feature of nonalcoholic fatty liver disease (NAFLD). The non-invasive quantification of liver fat is now possible due to advances in imaging modalities. Emerging data suggest that high levels of liver fat and its temporal change, as measured by quantitative non-invasive methods, might be associated with NAFLD progression. Ultrasound-based modalities have moderate diagnostic accuracy for liver fat content and are suitable for screening. However, of the non-invasive imaging modalities, MRI-derived proton density fat fraction (MRI-PDFF) has the highest diagnostic accuracy and is used for trial enrolment and to evaluate therapeutic effects in early-phase clinical trials in nonalcoholic steatohepatitis (NASH). In patients with NAFLD without advanced fibrosis, high levels of liver fat are associated with rapid disease progression. Furthermore, changes on MRI-PDFF (≥30% decline relative to baseline) are associated with NAFLD activity score improvement and fibrosis regression. However, an inverse association exists between liver fat and complications of cirrhosis. Liver fat decreases as liver fibrosis progresses towards cirrhosis, and the clinical importance of quantitative measurements of liver fat differs by NAFLD status. As such, patients with NAFLD should be stratified by fibrosis severity to investigate the utility of quantitative measurements of liver fat for assessing NAFLD progression and prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41574-021-00584-0DOI Listing
November 2021

Evaluating Outcomes Related to Donor and Recipient Metabolic Environment: Macrosteatotic Allograft and Nonalcoholic Steatohepatitis.

Liver Transpl 2021 Nov 22. Epub 2021 Nov 22.

Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla.

The pressing need for available organs is growing as the field of liver transplantation evolves and responds with expanding criteria and utilization of marginal allografts for certain recipients (1). Over the past 15 years, patient and graft outcomes of marginal allografts including donation after cardiac death, advanced age donors, and macrosteatoic allograft have improved (2). Altshuler and colleagues contribute further to clinically useful insights into increased organ availability utilizing macrosteatotic allografts in recipients with nonalcoholic steatohepatitis (NASH) cirrhosis (1).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.26371DOI Listing
November 2021

Non-invasive evaluation of response to obeticholic acid in patients with NASH: Results from the REGENERATE study.

J Hepatol 2021 Nov 15. Epub 2021 Nov 15.

Department of Hepatology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié - Salpêtrière, Institute for Cardiometabolism and Nutrition, Paris, France. Electronic address:

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic, progressive fibrotic liver disease that can lead to cirrhosis. While liver biopsy is considered the reference standard for histologic diagnosis of NASH and staging of fibrosis, use in clinical practice is limited. Noninvasive tests (NITs) are increasingly being used to identify and stage liver fibrosis in patients with NASH, and several can assess liver-related outcomes. We report changes in various NITs in patients treated with obeticholic acid (OCA) or placebo in the phase 3 REGENERATE study.

Methods: Patients with NASH and fibrosis stage F2 or F3 (N = 931) were randomized (1:1:1) to receive placebo, OCA 10 mg, or OCA 25 mg once daily. Various NITs based on clinical chemistry and/or imaging were evaluated at baseline and throughout the study.

Results: Rapid, sustained reductions from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels, as well as in FIB-4, FibroTest, FibroMeter, and FibroScan-AST scores were observed in OCA-treated patients versus placebo. Reduction in liver stiffness by vibration-controlled transient elastography (VCTE) was observed in the OCA 25 mg group versus placebo group at Month 18. NIT changes were associated with shifts in histologic fibrosis stage. The greatest improvements were observed in patients with ≥1-stage fibrosis improvement; however, improvements in ALT, AST, FIB-4, and FibroTest were also observed in OCA-treated patients whose histologic fibrosis remained stable.

Conclusions: Based on the REGENERATE Month 18 interim analysis, rapid and sustained improvements in various NITs were observed with OCA treatment. Dynamic changes in selected NITs separated histologic responders from non-responders. These results suggest that NITs may be useful in assessing histologic response to OCA therapy.

Lay Summary: Nonalcoholic steatohepatitis (NASH) is a chronic, progressive liver disease that can lead to cirrhosis. To diagnose and assess liver fibrosis (scarring) in patients with NASH, noninvasive tests (NITs) are increasingly being used rather than liver biopsy, which is invasive, expensive, and can be risky. In the REGENERATE study evaluating the effects of obeticholic acid versus placebo in patients with NASH, various NITs were evaluated as well. This analysis shows that improvements in levels of certain blood components, as well as favorable results of ultrasound imaging and proprietary tests of liver function, were associated with improvements in liver fibrosis after treatment with obeticholic acid, suggesting that NITs may be useful alternatives to liver biopsy in assessing NASH patients' response to therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.10.029DOI Listing
November 2021

Non-invasive Risk Stratification for NAFLD Among Living Liver Donor Candidates: A Proposed Algorithm.

Liver Transpl 2021 Nov 9. Epub 2021 Nov 9.

NAFLD Research Center, Department of Medicine, La Jolla, California; Division of Gastroenterology, Department of Medicine, La Jolla, California; Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, California, MD, USA.

To reduce waitlist mortality, living donor liver transplantation (LDLT) has increased over the past decade in US, however, not at a rate sufficient to completely mitigate organ shortage. As a result, there are ongoing efforts to expand the living liver donor pool. Simultaneously, the prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) in the general population has increased, which has significant implications on the pool of potential living liver donors. As such, a clinical assessment algorithm that exhaustively evaluates for NAFLD and fibrosis is critical to the safe expansion of LDLT. An ideal algorithm would employ safe and non-invasive methods, relying on liver biopsy only when necessary. While exclusion of NAFLD and fibrosis by non-invasive means is widely studied within the general population, there are no well-accepted guidelines for evaluation of living donors using these modalities. Here we review the current literature regarding non-invasive NALFD and fibrosis evaluation and propose a potential algorithm to apply these modalities for the selection of living liver donors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.26365DOI Listing
November 2021

Editorial: evolution of GLP-1 receptor agonists as pharmacotherapy for NASH beyond diabetes mellitus and obesity - authors' reply.

Aliment Pharmacol Ther 2021 12;54(11-12):1498

University of California San Diego School of Medicine, San Diego, California, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16669DOI Listing
December 2021

Advancing the global public health agenda for NAFLD: a consensus statement.

Nat Rev Gastroenterol Hepatol 2021 Oct 27. Epub 2021 Oct 27.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41575-021-00523-4DOI Listing
October 2021

Hepatocellular Carcinoma Risk Assessment for Patients With Advanced Fibrosis After Eradication of Hepatitis C Virus.

Hepatol Commun 2021 Oct 22. Epub 2021 Oct 22.

Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase < 28 IU/L, alpha-fetoprotein < 4.0 ng/mL, and Fibrosis-4 Index < 4.28) were classified as low-risk and others were classified as high-risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low-risk patients (0.5-1.1 per 100 person-years in the derivation cohort and 0.9-1.1 per 100 person-years in the validation cohort) than in high-risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high-risk to low-risk (HCC incidence: 0.6 per 100 person-years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person-years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1833DOI Listing
October 2021

Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease.

N Engl J Med 2021 10;385(17):1559-1569

From the Virginia Commonwealth University School of Medicine, Richmond (A.J.S.); the Bloomberg School of Public Health, Johns Hopkins University, Baltimore (M.L.V.N., J.C., L.A.W., K.P.Y., P.B., M.L., J.T.), and the Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda (D.E.K.) - both in Maryland; Saint Louis University, St. Louis (B.A.N.-T.); Duke University, Durham, NC (A.M.D.); Cleveland Clinic, Cleveland (S.D.); the University of California, San Diego, School of Medicine, La Jolla (R.L., C.B.), and the University of California, San Francisco, School of Medicine, San Francisco (B.H.); Indiana University School of Medicine, Indianapolis (N.C.); and the Liver Institute Northwest, Seattle (K.K.).

Background: The prognoses with respect to mortality and hepatic and nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined.

Methods: We prospectively followed a multicenter patient population that included the full histologic spectrum of NAFLD. The incidences of death and other outcomes were compared across baseline histologic characteristics.

Results: A total of 1773 adults with NAFLD were followed for a median of 4 years. All-cause mortality increased with increasing fibrosis stages (0.32 deaths per 100 person-years for stage F0 to F2 [no, mild, or moderate fibrosis], 0.89 deaths per 100 persons-years for stage F3 [bridging fibrosis], and 1.76 deaths per 100 person-years for stage F4 [cirrhosis]). The incidence of liver-related complications per 100 person-years increased with fibrosis stage (F0 to F2 vs. F3 vs. F4) as follows: variceal hemorrhage (0.00 vs. 0.06 vs. 0.70), ascites (0.04 vs. 0.52 vs. 1.20), encephalopathy (0.02 vs. 0.75 vs. 2.39), and hepatocellular cancer (0.04 vs. 0.34 vs. 0.14). As compared with patients with stage F0 to F2 fibrosis, patients with stage F4 fibrosis also had a higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years) and a decrease of more than 40% in the estimated glomerular filtration rate (2.98 vs. 0.97 events per 100 person-years). The incidence of cardiac events and nonhepatic cancers were similar across fibrosis stages. After adjustment for age, sex, race, diabetes status, and baseline histologic severity, the incidence of any hepatic decompensation event (variceal hemorrhage, ascites, or encephalopathy) was associated with increased all-cause mortality (adjusted hazard ratio, 6.8; 95% confidence interval, 2.2 to 21.3).

Conclusions: In this prospective study involving patients with NAFLD, fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; NAFLD DB2 ClinicalTrials.gov number, NCT01030484.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2029349DOI Listing
October 2021

A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH.

N Engl J Med 2021 10;385(17):1547-1558

From Antwerp University Hospital and the Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp (S.M.F., L.V.), and Service d'Hépato-Gastroentérologie, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (N.L.) and Cliniques Universitaires de Bruxelles-Hôpital Erasme, Université Libre de Bruxelles (C.M.), Brussels - all in Belgium; the Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (P. Bedossa, Q.M.A.); Pitie-Salpétriêre Hospital, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris (V.R.), Centre Hospitalier Universitaire Rangueil, Toulouse (M.G.), and Inventiva Pharma, Daix (P.H.-M., M.B., M.-P.R., J.-L.A., P. Broqua, J.-L.J.) - all in France; the Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy (E.B.); Virginia Commonwealth University, Richmond (A.J.S.); the University of California San Diego, La Jolla (R.L.); Pinnacle Clinical Research, San Antonio, TX (S.A.H.); Acibadem City Clinic Tokuda Hospital (R.B.), University Hospital "St. Ivan Rilski," Medical University-Sofia (L.M.), and Diagnostic Consultation Center Alexandrovska (D.S.-P.) - all in Sofia, Bulgaria; Arizona Liver Health, Phoenix (N.A.); Metabolic Liver Research Program, Department of Medicine, University Medical Center, Mainz, Germany (J.M.S.); Cap Research, Quatre Bornes, Mauritius (R.R.); Monash Medical Centre, Clayton, VIC, Australia (A.H.); Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain (M.R.-G.); and Duke University Medical Center, Durham, NC (M.F.A.).

Background: Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator-activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH.

Methods: In this phase 2b, double-blind, randomized, placebo-controlled trial, patients with noncirrhotic, highly active NASH were randomly assigned in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo once daily for 24 weeks. The primary end point was a decrease of at least 2 points in the SAF-A score (the activity part of the Steatosis, Activity, Fibrosis [SAF] scoring system that incorporates scores for ballooning and inflammation) without worsening of fibrosis; SAF-A scores range from 0 to 4, with higher scores indicating more-severe disease activity. Secondary end points included resolution of NASH and regression of fibrosis.

Results: A total of 247 patients underwent randomization, of whom 103 (42%) had type 2 diabetes mellitus and 188 (76%) had significant (moderate) or advanced fibrosis. The percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher among those who received the 1200-mg dose, but not among those who received the 800-mg dose, of lanifibranor than among those who received placebo (1200-mg dose vs. placebo, 55% vs. 33%, P = 0.007; 800-mg dose vs. placebo, 48% vs. 33%, P = 0.07). The results favored both the 1200-mg and 800-mg doses of lanifibranor over placebo for resolution of NASH without worsening of fibrosis (49% and 39%, respectively, vs. 22%), improvement in fibrosis stage of at least 1 without worsening of NASH (48% and 34%, respectively, vs. 29%), and resolution of NASH plus improvement in fibrosis stage of at least 1 (35% and 25%, respectively, vs. 9%). Liver enzyme levels decreased and the levels of the majority of lipid, inflammatory, and fibrosis biomarkers improved in the lanifibranor groups. The dropout rate for adverse events was less than 5% and was similar across the trial groups. Diarrhea, nausea, peripheral edema, anemia, and weight gain occurred more frequently with lanifibranor than with placebo.

Conclusions: In this phase 2b trial involving patients with active NASH, the percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher with the 1200-mg dose of lanifibranor than with placebo. These findings support further assessment of lanifibranor in phase 3 trials. (Funded by Inventiva Pharma; NATIVE ClinicalTrials.gov number, NCT03008070.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2036205DOI Listing
October 2021

Hemodynamic Response to Calcium Chloride Boluses in Single-Ventricle Patients with Parallel Circulation.

Pediatr Cardiol 2021 Oct 15. Epub 2021 Oct 15.

Department of Pediatrics, Divisions of Critical Care Medicine and Cardiology, Texas Children's Hospital and Baylor College of Medicine, Lester A. Smith Legacy Tower, 6651 Main Street, 14th floor, Houston, TX, 77030, USA.

The purpose of this study is to assess the effect of calcium bolus in response to a hypotensive episode by assessing high-fidelity hemodynamic data obtained from children with single-ventricle physiology with parallel circulation. Single-center, retrospective analysis of hemodynamic data after calcium bolus administrations within the first 2 weeks post-surgery. Time intervals were the baseline (- 60 to - 10 min); the hypotensive episode (- 10 to 0 min); time point zero at the bolus administration; and the response (0 to 60 min). The main responses assessed were the peak increase in mean blood pressure (mBP), duration of the response after the bolus, and markers of oximetric effects. These analyses included 128 boluses in 63 patients. Of the total boluses analyzed, 80% increased the mBP by 5 mmHg or higher with the effect lasting at least 10 min, whereas 10% of the boluses analyzed increased the mBP by 20 mmHg or higher with the effect lasting at least 50 min. The boluses induced a significant increase in arterial oxygen saturation and an upward trend in pulmonary-to-systemic flow ratio, without increasing renal or cerebral oxygen extraction ratios. Calcium chloride boluses are an effective rescue medication for hypotensive episodes in children with parallel circulation. They lead to an improvement in mBP, as well as an increase in pulmonary-to-systemic blood flow ratio. More importantly, these boluses do not compromise systemic oxygen delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-021-02754-3DOI Listing
October 2021

Diagnostic accuracy of two-dimensional shear wave elastography and transient elastography in nonalcoholic fatty liver disease.

Therap Adv Gastroenterol 2021 8;14:17562848211050436. Epub 2021 Oct 8.

Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, 9500 Gilman Drive, ACTRI Building, 2W202, La Jolla, CA 92093-0887, USA.

Introduction: Two-dimensional shear wave elastography (2D-SWE) and vibration-controlled transient elastography (VCTE) provide noninvasive assessment of hepatic fibrosis. We compared performance of 2D-SWE and VCTE for fibrosis detection in nonalcoholic fatty liver disease (NAFLD).

Methods: We performed a prospective study of adults with NAFLD who underwent 2D-SWE, VCTE, and liver biopsy analysis (using Nonalcoholic Steatohepatitis Clinical Research Network scoring system). The primary outcome was hepatic fibrosis (stage ⩾ 1); secondary outcomes included dichotomized fibrosis stages. Area under receiver operating characteristic curve (AUROC) analyses were used to compare 2D-SWE and VCTE performance.

Results: A total of 114 adults with a median BMI of 31.2 kg/m were included. The VCTE was better than 2D-SWE for the detection of fibrosis (AUROC: 0.81 0.72,  = 0.03). The VCTE detected fibrosis stage 2, 3, or 4 with AUROCs of 0.86 (95% CI, 0.80-0.93), 0.91 (95% CI, 0.82-0.99), and 0.96 (95% CI, 0.91-1.00). The 2D-SWE detected fibrosis stage 2, 3, or 4 with AUROCs of 0.84 (95% CI, 0.76-0.92), 0.88 (95% CI, 0.81-0.96), and 0.93 (95% CI, 0.86-0.99).

Conclusion: In a prospective study including more than 100 adults with NAFLD, we found VCTE to be more accurate than 2D-SWE in detecting fibrosis; these modalities, however, are comparable in assessing for higher stages of fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/17562848211050436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504217PMC
October 2021

Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease.

Gastroenterology 2021 Nov 20;161(5):1657-1669. Epub 2021 Sep 20.

University of Florida, Gainesville, Florida; Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida. Electronic address:

Find AGA's NASH Clinical Care Pathway App for iOS and Android mobile devices at nash.gastro.org. Scan this QR code to be taken directly to the website.Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common, currently affecting approximately 37% of US adults. NAFLD is most often managed in primary care or endocrine clinics, where clinicians must determine which patients might benefit from secondary care to address hepatic manifestations, comorbid metabolic traits, and cardiovascular risks of the disease. Because NAFLD is largely asymptomatic, and because optimal timing of treatment depends on accurate staging of fibrosis risk, screening at the primary care level is critical, together with consistent, timely, evidence-based, widely accessible, and testable management processes. To achieve these goals, the American Gastroenterological Association assembled a multidisciplinary panel of experts to develop a Clinical Care Pathway providing explicit guidance on the screening, diagnosis, and treatment of NAFLD. This article describes the NAFLD Clinical Care Pathway they developed and provides a rationale supporting proposed steps to assist clinicians in diagnosing and managing NAFLD with clinically significant fibrosis (stage F2-F4) based on the best available evidence. This Pathway is intended to be applicable in any setting where care for patients with NAFLD is provided, including primary care, endocrine, obesity medicine, and gastroenterology practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.07.049DOI Listing
November 2021

Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging.

Aliment Pharmacol Ther 2021 11 27;54(9):1150-1161. Epub 2021 Sep 27.

Profil, Mainz, Germany.

Background: Glucagon-like peptide-1 receptor agonists may be a treatment option in patients with non-alcoholic fatty liver disease (NAFLD).

Aims: To investigate the effects of semaglutide on liver stiffness and liver fat in subjects with NAFLD using non-invasive magnetic resonance imaging (MRI) methods.

Methods: This randomised, double-blind, placebo-controlled trial enrolled subjects with liver stiffness 2.50-4.63 kPa by magnetic resonance elastography (MRE) and liver steatosis ≥10% by MRI proton density fat fraction (MRI-PDFF). The primary endpoint was change from baseline to week 48 in liver stiffness assessed by MRE.

Results: Sixty-seven subjects were randomised to once-daily subcutaneous semaglutide 0.4 mg (n = 34) or placebo (n = 33). Change from baseline in liver stiffness was not significantly different between semaglutide and placebo at week 48 (estimated treatment ratio 0.96 (95% CI 0.89, 1.03; P = 0.2798); significant differences in liver stiffness were not observed at weeks 24 or 72. Reductions in liver steatosis were significantly greater with semaglutide (estimated treatment ratios: 0.70 [0.59, 0.84], P = 0.0002; 0.47 [0.36, 0.60], P < 0.0001; and 0.50 [0.39, 0.66], P < 0.0001) and more subjects achieved a ≥ 30% reduction in liver fat content with semaglutide at weeks 24, 48 and 72, (all P < 0.001). Decreases in liver enzymes, body weight and HbA were also observed with semaglutide.

Conclusions: The change in liver stiffness in subjects with NAFLD was not significantly different between semaglutide and placebo. However, semaglutide significantly reduced liver steatosis compared with placebo which, together with improvements in liver enzymes and metabolic parameters, suggests a positive impact on disease activity and metabolic profile. ClinicalTrials.gov identifier: NCT03357380.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16608DOI Listing
November 2021

The Acute Effect of Packed Red Blood Cell Transfusion in Mechanically Ventilated Children after the Norwood Operation.

Pediatr Cardiol 2021 Sep 21. Epub 2021 Sep 21.

Division of Cardiology, Advocate Children's Hospital, Chicago, IL, USA.

Packed red blood cell (PRBC) transfusions are commonly administered in pediatric patients following the Norwood operation. This study was conducted to determine the effect of PRBC transfusions on hemodynamic parameters in pediatric patients with single-ventricle physiology and parallel circulation. A single-center, retrospective chart review was conducted. Pediatric patients admitted to the cardiac intensive care unit after Norwood operation between 2017 and 2018 were identified. Hemodynamic parameters were collected within a four-hour period before and after a PRBC transfusion. Univariate analyses using paired t tests were conducted to compare blood gas values before and after PRBC transfusion. Next, multivariate regression analyses were conducted to model the impact of transfusion volume, change in hemoglobin levels, and change in FiO2 on the change in PaO2 and PaCO2. These analyses included data from 33 eligible patients who received a PRBC transfusion following a Norwood operation. The hemoglobin levels (p < 0.01) and the PaO2/FiO2 ratio (p = 0.04) were significantly increased, while arterial lactate levels (p = 0.03) were significantly decreased following the transfusion. Transfusion for a pre-transfusion hemoglobin of 12.4 g/dL appears to provide greatest reduction in lactate, used as a surrogate marker for systemic oxygen delivery. No significant changes were found in arterial pH, PaO2, and PaCO2. PRBC transfusions following the Norwood operation may be a useful intervention to increase systemic oxygen delivery, improving PaO2/FiO2 ratio and improving serum lactate. The benefits of PRBC transfusions must be weighed against previously identified risks on a patient-specific basis. Further studies are warranted to further delineate the effects of such transfusions in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-021-02735-6DOI Listing
September 2021

Heterotaxy - Res ipsos loquitur.

Cardiol Young 2021 Oct 21;31(10):1712-1714. Epub 2021 Sep 21.

Heart Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

The essence of so-called heterotaxy is the potential disharmony between the arrangement of the bronchuses, abdominal organs, and the atrial appendages. Accurate description of the heart, however, can only be provided by specific description of these features, all of which are readily discernible in the clinical setting. We argue that, when accurate description of the atrial and visceral arrangement is provided, along with appropriate description of the intracardiac findings, no further accuracy is gained by suggesting that an individual heart is "heterotaxic".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951121003814DOI Listing
October 2021

Alpha-blockade during congenital heart surgery admissions: analysis from national database.

Cardiol Young 2021 Sep 17:1-7. Epub 2021 Sep 17.

Cardiology, Advocate Children's Hospital, Chicago, IL, USA.

Introduction: The effects of alpha-blockade on haemodynamics during and following congenital heart surgery are well documented, but data on patient outcomes, mortality, and hospital charges are limited. The purpose of this study was to characterise the use of alpha-blockade during congenital heart surgery admissions and to determine its association with common clinical outcomes.

Materials And Methods: A cross-sectional study was conducted using the Pediatric Health Information System database. De-identified data for patients under 18 years of age with a cardiac diagnosis who underwent congenital heart surgery were obtained from 2004 to 2015. Patients were subdivided on the basis of receiving alpha-blockade with either phenoxybenzamine or phentolamine during admission or not. Continuous and categorical variables were analysed using Mann−Whitney U-tests and Fisher exact tests, respectively. Characteristics between subgroups were compared using univariate analysis. Regression analyses were conducted to determine the impact of alpha-blockade on ICU length of stay, hospital length of stay, billed charges, and mortality.

Results: Of the 81,313 admissions, 4309 (5.3%) utilised alpha-blockade. Phentolamine was utilised in 4290 admissions. In univariate analysis, ICU length of stay, total length of stay, inpatient mortality, and billed charges were all significantly higher in the alpha-blockade admissions. However, regression analyses demonstrated that other factors were behind these increased. Alpha-blockade was significantly, independently associated with a 1.5 days reduction in ICU length of stay (p < 0.01) and a 3.5 days reduction in total length of stay (p < 0.01). Alpha-blockade was significantly, independently associated with a reduction in mortality (odds ratio 0.8, 95% confidence interval 0.7−0.9). Alpha-blockade was not independently associated with any significant change in billed charges.

Conclusions: Alpha-blockade is used in a subset of paediatric cardiac surgeries and is independently associated with significant reductions in ICU length of stay, hospital length of stay, and mortality without significantly altering billed charges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951121003875DOI Listing
September 2021

Venous blood gases in pediatric patients: a lost art?

Minerva Pediatr (Torino) 2021 Sep 16. Epub 2021 Sep 16.

Medicine, Chicago Medical School/Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

Blood oximetry provides a fundamental approach to blood gases for inpatients. Arterial blood gases (ABG) have been considered the gold standard for blood oximetry assessment. Venous blood gas (VBG) evaluation is frequently available and provides a source of a more comfortable method for the assessment of blood oximetry in pediatric patients. Some data provided by the venous blood gas can be additive and offer insights apart from the arterial blood gas. The purpose of this review is to provide an assessment of the performance of VBG in pediatric patients. The study concludes that VBG are helpful tools in assessing oxygenation and ventilation in critically ill children and can be used as a marker of adequacy of systemic oxygen delivery. In the setting of systemic oxygen delivery decrease or oxygen extraction increase, the partial pressure of oxygen on the VBG will decrease. Thus, the partial pressure of oxygen and the corresponding venous saturation can be a marker of systemic oxygen delivery in a variety of illnesses. Simultaneous ABG and VBG comparison can actually lend great insight to not only the respiratory status of a patient but provide an assessment of the adequacy of cardiac output and systemic oxygen delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S2724-5276.21.06464-8DOI Listing
September 2021

Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), versus placebo in patients with non-alcoholic fatty liver disease.

Aliment Pharmacol Ther 2021 11 16;54(10):1263-1277. Epub 2021 Sep 16.

NAFLD Research Center, Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA.

Background: Pemafibrate is a novel, selective peroxisome proliferator-activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non-alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT).

Aims: To evaluate the efficacy and safety of Pemafibrate in patients with high-risk, non-alcoholic fatty liver disease (NAFLD).

Methods: This double-blind, placebo-controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI-PDFF from baseline to week 24. The secondary endpoints included MRE-based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters.

Results: There was no significant difference between the groups in the primary endpoint (-5.3% vs -4.2%; treatment difference -1.0%, P = 0.85). However, MRE-based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference -5.7%, P = 0.036), and was maintained at week 72 (treatment difference -6.2%, P = 0.024), with significant reduction in ALT and LDL-C. Adverse events were comparable between the treatment groups and therapy was well tolerated.

Conclusions: Pemafibrate did not decrease liver fat content but had significant reduction in MRE-based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16596DOI Listing
November 2021

The effect of dexmedetomidine on renal function after surgery: A systematic review and meta-analysis.

J Clin Pharm Ther 2021 Sep 12. Epub 2021 Sep 12.

Section of Critical Care Medicine and Cardiology, Texas Children's Hospital, Houston, TX, USA.

What Is Known And Objective: Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree of renal protection in the perioperative stage. Such is the case of dexmedetomidine, a selective alpha-2 adrenergic agonist used in the intensive care unit (ICU) as a sedative agent. The primary objective of this meta-analysis was to characterize the use of dexmedetomidine and to evaluate its impact on renal markers and outcomes in patients after surgery.

Methods: A systematic review of manuscripts was performed to identify patients who received dexmedetomidine after surgery by searching the PubMed, Embase, and Cochrane databases. The following parameters were captured: blood urea nitrogen (BUN), serum creatinine, creatinine clearance, neutrophil gelatinase-associated lipoprotein (NGAL), cystatin C, urine output, duration of mechanical ventilation, ICU length of stay, AKI, need for dialysis, and mortality.

Results And Discussion: Nineteen studies with 3,395 patients were included in the analyses. The mean bolus and infusion dose of dexmedetomidine were 0.82 µg/kg and 0.54 mcg/kg/hr, respectively. There was a significant difference in creatinine clearance and NGAL in favour of the dexmedetomidine group. In addition, the dexmedetomidine group had a shorter ICU length of stay, and a lower risk of acute kidney injury and mortality compared to the control. There was no difference in the rest of the parameters.

What Is New And Conclusion: Dexmedetomidine appears to have postoperative renal protective effects. This is evidenced by lower NGAL levels and increased creatinine clearance in those who received dexmedetomidine. These effects are associated with decreases in ICU length of stay and risk of AKI and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpt.13527DOI Listing
September 2021

What Does the Future Hold for Patients With Nonalcoholic Steatohepatitis: Diagnostic Strategies and Treatment Options in 2021 and Beyond?

Hepatol Commun 2021 Nov 9;5(11):1810-1823. Epub 2021 Sep 9.

Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and its complications, including hepatocellular carcinoma. Given that the majority of patients with NASH are asymptomatic, developing screening strategies to identify those individuals at risk for progressive NASH remains a highly unmet need. Furthermore, noninvasive tests that accurately predict disease progression as part of the natural history of NASH or regression in response to treatment are urgently needed to decrease the reliance on repeat liver biopsies. To date, there are no US Food and Drug Administration (FDA)-approved medications for NASH that can resolve steatohepatitis and lead to fibrosis regression. The lack of FDA-approved therapy has led to apathy in diagnosis and referral for specialty care. However, several therapeutic agents are rapidly progressing through the different phases of clinical trials with several already in phase 3 programs. In this review, we provide a summary of recent developments in NASH diagnostics and therapeutics that are likely to shape the future management of this underdiagnosed and undertreated disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557311PMC
November 2021

MRE plus FIB-4 (MEFIB) versus FAST in detection of candidates for pharmacological treatment of NASH-related fibrosis.

Hepatology 2021 Sep 8. Epub 2021 Sep 8.

NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States.

Background And Aim: Nonalcoholic fatty liver disease (NAFLD) patients with significant hepatic fibrosis (stage ≥ 2) are at increased risk of liver-related morbidity and are candidates for pharmacologic therapies. In this study, we compared the diagnostic accuracy of MEFIB (the combination of magnetic resonance elastography [MRE] and FIB-4) and FAST (FibroScan-AST; combined liver stiffness measurement by vibration-controlled transient elastography, controlled attenuation parameter, and aspartate aminotransferase) for detecting significant fibrosis.

Approach And Results: This prospective cohort study included 234 consecutive NAFLD patients who underwent liver biopsy, MRE, and FibroScan at University of California San Diego [UCSD] Cohort, and an independent cohort (N=314) from Yokohama City University, Japan Cohort. The primary outcome was diagnostic accuracy for significant fibrosis (stage ≥ 2). The proportion of significant fibrosis in UCSD and Yokohama cohorts were 29.5% and 66.2%, respectively. Area under the receiver operating characteristic curve (95% confidence interval) of MEFIB (0.860 [0.81-0.91]) was significantly higher than FAST (0.757 [0.69-0.82]) in UCSD cohort (p = 0.005), with consistent results in the Yokohama cohort (AUROC: 0.899 [MEFIB] vs 0.724 [FAST], p < 0.001). When used as the rule-in criteria (MEFIB: MRE ≥ 3.3 kPa and FIB-4 ≥ 1.6, and FAST ≥ 0.67), the positive predictive value for significant fibrosis was 91.2-96.0% for MEFIB, and 74.2-89.2% for FAST. When used as the rule-out criteria (MEFIB: MRE < 3.3 kPa and FIB-4 < 1.6, and FAST ≤ 0.35), negative predictive value for significant fibrosis was 85.6-92.8% for MEFIB, and 57.8-88.3% for FAST.

Conclusions: MEFIB has higher diagnostic accuracy than FAST for significant fibrosis in NAFLD, and our results support the utility of a two-step strategy for detecting significant fibrosis in NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.32145DOI Listing
September 2021

Early Identification of Myocardial Reperfusion Injury After Cardiopulmonary Bypass: Toward the Final Frontier of Congenital Heart Surgery.

Pediatr Crit Care Med 2021 09;22(9):852-854

Division of Cardiology, Department of Pediatrics, Advocate Children's Hospital, Chicago, IL.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000002769DOI Listing
September 2021

Correlation of Near-Infrared Spectroscopy Oximetry and Corresponding Venous Oxygen Saturations in Children with Congenital Heart Disease.

Pediatr Cardiol 2021 Aug 30. Epub 2021 Aug 30.

Division of Critical Care, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA.

Invasive and non-invasive monitoring allow for early detection of hemodynamic compromise, facilitating timely intervention and avoidance of further decline. While venous oximetry is useful for assessing the adequacy of systemic oxygen delivery (DO), it is most often intermittent, invasive, and costly. Near-infrared spectroscopy (NIRS) oximetry allows for the non-invasive estimation of the adequacy of DO. We assessed the correlation between cerebral NIRS oximetry and superior vena cava (SVC) and jugular venous (JV) oxygen saturations and between renal NIRS oximetry and inferior vena cava (IVC) oxygen saturations. Systematic review of the literature was conducted to identify studies with data regarding near-infrared spectroscopy and venous saturation. The PubMed, EMBASE, Medline, and Cochrane databases were queried using the following terms in isolation and various combinations: "congenital heart disease," "near infrared spectroscopy," "venous saturation," and "pediatric." Pediatric studies in which simultaneous NIRS oximetry and corresponding venous oxygen saturations were simultaneously collected after cardiac surgery or catheterization were identified. Data were pooled from these studies to analyze the correlation between NIRS oximetry and the corresponding venous oxygen saturations. A total of 16 studies with 613 patients were included in the final analyses. Data were present to compare cerebral and renal NIRS oximetry with corresponding venous oxygen saturation. Cerebral NIRS and SVC and JV oxygen saturations and renal NIRS and IVC oxygen saturations demonstrated strong degrees of correlation (r-value 0.70 for each). However, cerebral NIRS and IVC oxygen saturation had a week degree of correlation (r-value of 0.38). Pooled analyses demonstrate that cerebral NIRS oximetry correlates strongly with SVC or JV oxygen saturation while renal NIRS oximetry correlates strongly with IVC oxygen saturations. A weak correlation was noted between cerebral NIRS oximetry and IVC oxygen saturations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-021-02718-7DOI Listing
August 2021

C-reactive protein and procalcitonin after congenital heart surgery utilizing cardiopulmonary bypass: When should we be worried?

J Card Surg 2021 Nov 29;36(11):4301-4307. Epub 2021 Aug 29.

Department of Pediatrics, Chicago Medical School/Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.

Introduction: To assess the efficacy of C-reactive protein (CRP) and procalcitonin (PCT) at identifying infection in children after congenital heart surgery (CHS) with cardiopulmonary bypass (CPB).

Materials And Methods: Systematic review of the literature was conducted to identify studies with data regarding CRP and/or PCT after CHS with CPB. The primary variables identified to be characterized were CRP and PCT at different timepoints. The main inclusion criteria were children who underwent CHS with CPB. Subset analyses for those with and without documented infection were conducted in similar fashion. A p value of less than .05 was considered statistically significant.

Results: A total of 21 studies were included for CRP with 1655 patients and a total of 9 studies were included for PCT with 882 patients. CRP peaked on postoperative Day 2. A significant difference was noted in those with infection only on postoperative Day 4 with a level of 53.60 mg/L in those with documented infection versus 29.68 mg/L in those without. PCT peaked on postoperative Day 2. A significant difference was noted in those with infection on postoperative Days 1, 2, and 3 with a level of 12.9 ng/ml in those with documented infection versus 5.6 ng/ml in those without.

Conclusions: Both CRP and PCT increase after CHS with CPB and peak on postoperative day 2. PCT has a greater statistically significant difference in those with documented infection when compared to CRP and a PCT of greater than 5.6 ng/ml should raise suspicion for infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.15952DOI Listing
November 2021

Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH.

Aliment Pharmacol Ther 2021 10 25;54(7):880-889. Epub 2021 Aug 25.

NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, San Diego, California, USA.

Background: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for the treatment of NASH.

Aim: To assess the relative rank-order of different pharmacological interventions in fibrosis improvement and NASH resolution.

Methods: A comprehensive search of several databases was conducted by an experienced librarian. We included randomised controlled-trials (RCTs) comparing pharmacological interventions in patients with biopsy-proven NASH. The primary outcome was ≥1 stage improvement in fibrosis. The secondary outcome was NASH resolution.

Results: A total of 26 RCTs with 23 interventions met the eligibility criteria. Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively. For NASH resolution, semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively. Lanifibranor, obeticholic acid, pioglitazone and vitamin E were significantly better than placebo in achieving ≥1 stage of fibrosis improvement. Conversely, semaglutide, liraglutide, vitamine E plus pioglitazone, pioglitazone, lanifibranor and obeticholic acid were significantly better than placebo in achieving NASH resolution.

Conclusion: These data provide relative rank-order efficacy of various NASH therapies in terms of their improvements in liver fibrosis and NASH resolution. Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16583DOI Listing
October 2021

Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature - The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11).

Cardiol Young 2021 Jul;31(7):1057-1188

Congenital Heart Surgery, Birmingham Women's and Children's Foundation Trust Hospital, University of Birmingham, Birmingham, UK.

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S104795112100281XDOI Listing
July 2021

Whither heterotaxy?

Cardiol Young 2021 07;31(7):1197-1199

Heart Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951121002821DOI Listing
July 2021
-->