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1.
Front Cell Infect Microbiol ; 12: 726263, 2022.
Article in English | MEDLINE | ID: covidwho-2198679

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction. Discussion: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver. Conclusion: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Gastrointestinal Diseases , Liver Neoplasms , Aged , COVID-19/complications , Humans , Liver/pathology , Liver Neoplasms/pathology , Pandemics , SARS-CoV-2
2.
Lipids Health Dis ; 20(1): 126, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-2196306

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Chemical and Drug Induced Liver Injury/complications , Hypoxia/complications , Liver/metabolism , Non-alcoholic Fatty Liver Disease/complications , SARS-CoV-2/pathogenicity , Age Factors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/virology , Cytokines/genetics , Cytokines/metabolism , Dipeptides/therapeutic use , Gene Expression Regulation , Glucose/metabolism , Glycyrrhizic Acid/therapeutic use , Humans , Hypoxia/drug therapy , Hypoxia/pathology , Hypoxia/virology , Liver/drug effects , Liver/pathology , Liver/virology , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung/virology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/virology , Receptors, Virus/genetics , Receptors, Virus/metabolism , Severity of Illness Index
3.
Nutrients ; 14(17)2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-1997734

ABSTRACT

BACKGROUND: COVID-19 lockdowns had a significant impact on people's health, triggering levels of anxiety, perceived stress, and changes in food and nutritional status. OBJECTIVES: To assess the changes in dietary habits, metabolic syndrome (MetS) and liver parameters before and after the COVID-19 lockdown according to changes in intrahepatic fat content in adults with non-alcoholic fatty liver disease (NAFLD) and MetS. DESIGN: Pre- and post-lockdown observation of the COVID-19 lockdown on fifty-nine 40-60-year-old participants with MetS and NAFLD, in a parallel group, randomised experiment intended to treat NAFLD. METHODS: Anthropometrics, liver and MetS biochemical parameters, intrahepatic fat content by abdominal magnetic resonance imaging, and dietary assessment using a validated 148-item Food Frequency Questionnaire were collected pre-COVID-19 lockdown and post-lockdown. RESULTS: COVID-19 lockdown led to negative changes in the liver of patients with NAFLD and MetS, with weight gain and increases in glycemia, ALT and intrahepatic fat content post lockdown. Participants with worsened liver status had low consumption of fibre, cheese, nuts and coffee, and high consumption of sweets and pastries. Participants who improved liver status ameliorated ALT values, waist circumference, and intrahepatic fat content, assessed by magnetic resonance imaging post-lockdown. CONCLUSIONS: The maintenance of healthy lifestyle habits is vital, especially for populations with NAFLD and MetS, to reduce unhealthy lifestyle patterns displayed during lockdown.


Subject(s)
Body Fat Distribution , COVID-19 , Liver , Metabolic Syndrome , Non-alcoholic Fatty Liver Disease , Adult , COVID-19/prevention & control , Communicable Disease Control , Feeding Behavior , Humans , Liver/diagnostic imaging , Liver/pathology , Magnetic Resonance Imaging , Metabolic Syndrome/complications , Metabolic Syndrome/diagnostic imaging , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging
4.
Am J Case Rep ; 23: e936250, 2022 Aug 18.
Article in English | MEDLINE | ID: covidwho-1994516

ABSTRACT

BACKGROUND The incidence of abnormal liver function, mainly aspartate aminotransferase and alanine aminotransferase elevations, in patients with COVID-19 is not uncommon, but persistent liver damage after the acute phase of the disease is uncommon and has been recently recognized as a new entity named post-COVID-19 cholangiopathy. CASE REPORT We report a clinical case with progressive cholestatic disease following severe COVID-19. AST and ALT peaked at hospital admission and while its serum concentration went down, bilirubin and cholestatic liver enzymes started to increase, reaching the maximum at day 122. Magnetic resonance imaging (MRI) revealed a diffuse irregularity of intra- and extrahepatic bile ducts, with multiple focal strictures alternating with mild focal dilations of the biliary tree, suggesting a sclerosing cholangiopathy. A transjugular liver biopsy showed a prominent bile ductular reaction, cholangiocyte injury, inflammatory infiltrate rich in neutrophils, biliary infarctions, marked cholestasis, and portal fibrosis, suggesting the diagnosis of post-Covid-19 secondary sclerosing cholangitis. The patient evolved with a continuous deterioration of liver functions, but liver transplantation was not performed due to his poor clinical condition. CONCLUSIONS Post-COVID-19 SSC is a severe disease with no effective clinical treatment and has liver transplantation as the only treatment for a few selected patients.


Subject(s)
Bile Ducts, Extrahepatic , COVID-19 , Cholangitis, Sclerosing , Liver Transplantation , Bile Ducts, Extrahepatic/pathology , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/diagnosis , Humans , Liver/pathology , Liver Transplantation/adverse effects
6.
J Pediatr Gastroenterol Nutr ; 75(3): 244-251, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-1891183

ABSTRACT

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. METHODS: This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. RESULTS: We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. CONCLUSIONS: We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.


Subject(s)
COVID-19 , Liver Failure, Acute , Adolescent , COVID-19/complications , Child , Humans , Infant , Liver/pathology , Liver Failure, Acute/pathology , Retrospective Studies , SARS-CoV-2
7.
Hepatol Commun ; 6(9): 2513-2522, 2022 09.
Article in English | MEDLINE | ID: covidwho-1819362

ABSTRACT

Immune-mediated liver injury (ILI) following coronavirus disease 2019 (COVID-19) vaccination is not well-characterized. Therefore, we systematically reviewed the literature on ILI after COVID-19 vaccination. We searched PubMed, Cochrane, Ovid, Embase, and gray literature to include articles describing ILI following COVID-19 vaccination. Reports without confirmatory evidence from liver biopsy were excluded. Descriptive analysis, and study quality were reported as appropriate. Of the 1,048 articles found, 13 (good/fair quality; 23 patients) were included. Studies were primarily from Europe (n = 8), America (n = 2), Asia (n = 2), or Australia (n = 1). Patients were predominantly females (62.5%) of age 55.3 years (49.1-61.4), with an antecedent exposure to Moderna messenger RNA (mRNA)-1273 (47.8%), Pfizer-BioNTech BNT162b2 mRNA (39.2%), or ChAdOx1 nCoV-19 vaccine (13%). Pre-existing comorbidities (69.6%) were common, including liver disease in 26.1% and thyroid disorders in 13% of patients. About two-thirds of the patients were on concurrent medications (paracetamol, levothyroxine, statins, and non-steroidal anti-inflammatory drugs). Jaundice was the most common symptom (78.3%). Peak bilirubin, alanine aminotransferase, and alkaline phosphatase levels were 10.8 (6.8-14.8) mg/dl, 1,106.5 (757.0-1,702.5) U/L, and 229 (174.6-259.6) U/L, respectively. Histological findings were intense portal lymphoplasmacytic infiltrate with interface hepatitis. Steroids were used in 86.9% of patients, and complete response, recovering course, and death were reported in 56.5%, 39.1%, and 4.3% of patients, respectively. ILI following COVID-19 vaccination is rare. The diagnosis is established on temporal correlation, biochemical findings, and histopathology. Prognosis is excellent with corticosteroids. Causality establishment remains a challenge.


Subject(s)
COVID-19 Vaccines , COVID-19 , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Female , Humans , Liver/pathology , Male , Middle Aged , RNA, Messenger , Vaccination
8.
Malays J Pathol ; 44(1): 83-92, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1812960

ABSTRACT

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.


Subject(s)
COVID-19 , Pneumonia, Necrotizing , Pneumonia , Aged , Aged, 80 and over , Biopsy, Needle , Humans , Liver/pathology , Lung/pathology , Middle Aged , Pneumonia/pathology , Pneumonia, Necrotizing/pathology , SARS-CoV-2
14.
Nat Metab ; 4(1): 29-43, 2022 01.
Article in English | MEDLINE | ID: covidwho-1612214

ABSTRACT

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.


Subject(s)
COVID-19/complications , COVID-19/virology , Glucose/metabolism , Hyperglycemia/etiology , Hyperglycemia/metabolism , Membrane Proteins/metabolism , SARS-CoV-2 , Animals , Biomarkers , Cyclic AMP-Dependent Protein Kinases/metabolism , Diet, High-Fat , Disease Models, Animal , Fasting , Gene Expression , Gluconeogenesis/drug effects , Gluconeogenesis/genetics , Host-Pathogen Interactions , Humans , Hyperglycemia/blood , Liver/metabolism , Liver/pathology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/blood , Membrane Proteins/genetics , Mice , Mice, Knockout , Organ Specificity/genetics
15.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1867(2): 159070, 2022 02.
Article in English | MEDLINE | ID: covidwho-1596012

ABSTRACT

N-[4-hydroxyphenyl]retinamide, commonly known as fenretinide, a synthetic retinoid with pleiotropic benefits for human health, is currently utilized in clinical trials for cancer, cystic fibrosis, and COVID-19. However, fenretinide reduces plasma vitamin A levels by interacting with retinol-binding protein 4 (RBP4), which often results in reversible night blindness in patients. Cell culture and in vitro studies show that fenretinide binds and inhibits the activity of ß-carotene oxygenase 1 (BCO1), the enzyme responsible for endogenous vitamin A formation. Whether fenretinide inhibits vitamin A synthesis in mammals, however, remains unknown. The goal of this study was to determine if the inhibition of BCO1 by fenretinide affects vitamin A formation in mice fed ß-carotene. Our results show that wild-type mice treated with fenretinide for ten days had a reduction in tissue vitamin A stores accompanied by a two-fold increase in ß-carotene in plasma (P < 0.01) and several tissues. These effects persisted in RBP4-deficient mice and were independent of changes in intestinal ß-carotene absorption, suggesting that fenretinide inhibits vitamin A synthesis in mice. Using Bco1-/- and Bco2-/- mice we also show that fenretinide regulates intestinal carotenoid and vitamin E uptake by activating vitamin A signaling during short-term vitamin A deficiency. This study provides a deeper understanding of the impact of fenretinide on vitamin A, carotenoid, and vitamin E homeostasis, which is crucial for the pharmacological utilization of this retinoid.


Subject(s)
Fenretinide/pharmacology , Vitamin A/pharmacology , beta Carotene/metabolism , Animals , Body Weight/drug effects , Dioxygenases/metabolism , Intestinal Absorption/drug effects , Intestines/drug effects , Liver/drug effects , Liver/pathology , Mice, Inbred C57BL , Models, Biological , Retinol-Binding Proteins, Plasma/deficiency , Retinol-Binding Proteins, Plasma/metabolism , Vitamin A/blood , Vitamin A Deficiency/blood , Vitamin A Deficiency/pathology , Vitamin E/blood , Vitamin E/metabolism , beta Carotene/blood
16.
Front Public Health ; 9: 778340, 2021.
Article in English | MEDLINE | ID: covidwho-1595542

ABSTRACT

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.


Subject(s)
COVID-19 , Interleukin-6 , Liver/pathology , Receptors, Interleukin-2/blood , COVID-19/diagnosis , Humans , Interleukin-6/blood , Pandemics
17.
Viruses ; 13(12)2021 12 14.
Article in English | MEDLINE | ID: covidwho-1572667

ABSTRACT

Pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of COVID-19. Chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a Western Diet. For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome. We observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, and edema, delayed viral clearance and functional lung recovery, and prolonged viral shedding. This was accompanied by an altered, but not significantly different, systemic IL-10 and IL-6 profile, as well as a dysregulated serum lipid response dominated by polyunsaturated fatty acid-containing phosphatidylethanolamine, partially recapitulating cytokine and lipid responses associated with severe human COVID-19. Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19.


Subject(s)
COVID-19 , Diet, High-Fat/adverse effects , Dietary Carbohydrates/adverse effects , Lipid Metabolism , Severity of Illness Index , Animals , COVID-19/pathology , Cricetinae , Cytokines/blood , Disease Models, Animal , Edema , Fibrin , Hemorrhage , Humans , Interleukin-10 , Interleukin-6 , Lipidomics , Lipids/blood , Liver/pathology , Lung/pathology , Male , Mesocricetus , Obesity , SARS-CoV-2 , Sugars , Vasculitis/pathology , Virus Shedding
18.
Arch Pathol Lab Med ; 146(8): 940-946, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1555658

ABSTRACT

CONTEXT.­: Nonalcoholic fatty liver disease (NAFLD) encompasses steatosis and steatohepatitis. The cause may be multifactorial, and diagnosis requires correlation with clinical information and laboratory results. OBJECTIVE.­: To provide an overview of the status of histology diagnosis of steatosis, steatohepatitis, and associated conditions. DATA SOURCES.­: A literature search was performed using the PubMed search engine. The terms ''steatosis,'' ''steatohepatitis,'' ''nonalcoholic fatty liver disease (NAFLD),'' ''nonalcoholic steatohepatitis (NASH),'' "alcoholic steatohepatitis (ASH)," ''type 2 diabetes (T2DM),'' "cryptogenic cirrhosis," "drug-induced liver injury (DILI)," "immune checkpoint inhibitor therapy," and "COVID-19 and liver" were used. CONCLUSIONS.­: Nonalcoholic fatty liver disease has become the most common chronic liver disease in the United States. NASH is the progressive form of nonalcoholic fatty liver disease. The hallmarks of steatohepatitis are steatosis, ballooned hepatocytes, and lobular inflammation. NASH and alcoholic steatohepatitis share similar histologic features, but some subtle differences may help their distinction. NASH is commonly seen in patients with metabolic dysfunction but can also be caused by other etiologies. Examples are medications including newly developed immune checkpoint inhibitors and viral infections such as coronavirus disease 2019 (COVID-19). NASH is also a common cause of cryptogenic cirrhosis but can be reversed. The results from recent clinical trials for NASH treatment are promising in reducing the severity of steatosis, ballooning, and fibrosis.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Fatty Liver, Alcoholic , Non-alcoholic Fatty Liver Disease , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Fatty Liver, Alcoholic/complications , Fatty Liver, Alcoholic/pathology , Humans , Liver/pathology , Liver Cirrhosis/congenital , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology
19.
Nat Med ; 27(7): 1262-1271, 2021 07.
Article in English | MEDLINE | ID: covidwho-1550325

ABSTRACT

Preclinical and clinical data suggest that fibroblast growth factor 21 (FGF21) is anti-fibrotic, improves metabolic status and has potential to treat non-alcoholic steatohepatitis (NASH). We assessed the safety and efficacy of efruxifermin, a long-acting Fc-FGF21 fusion protein, for the treatment of NASH. BALANCED was a randomized, placebo-controlled study in patients with NASH conducted at 27 centers in the United States (ClinicalTrials.gov NCT03976401 ). Eighty patients, stratified by hepatic fat fraction (HFF) and fibrosis stage, were randomized using a centrally administered minimization algorithm 1:1:1:1 to receive placebo (n = 21) or efruxifermin 28 mg (n = 19), efruxifermin 50 mg (n = 20) or efruxifermin 70 mg (n = 20) via weekly subcutaneous injection for 16 weeks. The primary endpoint-absolute change from baseline in HFF measured as magnetic resonance imaging-proton density fat fraction at week 12-was met. For the full analysis set, the least squares mean absolute changes (one-sided 97.5% confidence interval) from baseline in HFF were -12.3% (-infinity (-inf), -10.3), -13.4% (-inf, -11.4) and -14.1% (-inf, -12.1) in the 28-, 50- and 70-mg groups, respectively, versus 0.3% (-inf, 1.6) in the placebo group, with statistically significant differences between efruxifermin groups and placebo (P < 0.0001 each). Overall, 70 of 79 patients who received the study drug (89%) experienced at least one treatment-emergent adverse event (TEAE), with the majority grade 1-2 (64 (81%)), five (6%) grade 3 and one grade 4. The most commonly reported drug-related TEAEs were grade 1-2 gastrointestinal (36 (46%)). Treatment with efruxifermin significantly reduced HFF in patients with F1-F3 stage NASH, with an acceptable safety profile.


Subject(s)
Fibroblast Growth Factors/therapeutic use , Immunoglobulin Fc Fragments/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Recombinant Fusion Proteins/therapeutic use , Body Mass Index , Double-Blind Method , Female , Humans , Liver/pathology , Liver Cirrhosis/drug therapy , Magnetic Resonance Imaging , Male , Middle Aged , Treatment Outcome
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