scholarly journals Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; a Call for Development of Targeted Therapeutics

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3316
Author(s):  
Anthony J. Pellicano ◽  
Kiera Spahn ◽  
Ping Zhou ◽  
Itzhak D. Goldberg ◽  
Prakash Narayan
Keyword(s):  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Collagen Type ◽  
Microscopic Analysis ◽  
Collagen Type I ◽  
Hepatic Tissue ◽  
Type I ◽  
Nonalcoholic Fatty Liver ◽  
End Stage ◽  
Modified Diet

Left untreated, nonalcoholic fatty liver disease can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and end-stage liver disease. To date, few if any therapies have proven effective against NASH with fibrosis. Quantification and qualification of hepatic scar might enable development of more effective targeted therapies. In a murine model of NASH induced by diet, we characterized fibrillar collagen deposition within the hepatic parenchyma. At harvest, livers from the modified diet cohort exhibited NASH with fibrosis. Transcriptomic analysis of hepatic tissue revealed increased col1a1, col1a2, and col3a1, each of which correlated directly with hepatic hydroxyproline content. Circular polarized microscopic analysis of Picrosirius red-stained liver sections revealed deposition of collagen type I within the parenchyma. Development of therapeutics designed to mitigate collagen type I accumulation might prove effective in NASH with fibrosis.

scholarly journals Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 730
Author(s):  
Moritz Peiseler ◽  
Frank Tacke
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Disease Progression ◽  
Immune Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Adaptive Immune System ◽  
Nonalcoholic Fatty Liver ◽  
Inflammatory Processes ◽  
New Treatment ◽  
End Stage

Nonalcoholic fatty liver disease (NAFLD) is a rising chronic liver disease and comprises a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to end-stage cirrhosis and risk of hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. In this review, we highlight some of the emerging paradigms, including macrophage heterogeneity, contributions of nonclassical immune cells, the role of the adaptive immune system, interorgan crosstalk with adipose tissue and gut microbiota. Furthermore, we summarize recent advances in preclinical and clinical studies aimed at modulating the inflammatory cascade and discuss how these novel therapeutic avenues may help in preventing or combating NAFLD-associated HCC.

scholarly journals Multidisciplinary Approach for Liver Transplantation in Patients with Nonalcoholic Steatohepatitis: It Takes a Village

2020 ◽  
Vol 04 (01) ◽  
pp. 019-030
Author(s):  
Eugenia Tsai ◽  
Ronit Patnaik ◽  
Naim Alkhouri
Keyword(s):  
Bariatric Surgery ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
De Novo ◽  
Management Strategies ◽  
Genetic Determinants ◽  
Nonalcoholic Fatty Liver ◽  
Short And Long Term ◽  
End Stage

AbstractNonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in Western countries, and its aggressive form, nonalcoholic steatohepatitis (NASH), is a leading cause of cirrhosis and end-stage liver disease. The total number of new liver transplantation waitlist registrants with NASH continues to increase rapidly, making NASH the second most common indication for liver transplantation. Compared with recipients for other etiologies, patients with NASH often have higher rates of obesity, diabetes, dyslipidemia, hypertension, kidney disease, and cardiac disease. Many of these medical comorbidities are independently associated with increased preoperative risk and both short- and long-term complications. The presence of these particular risk factors necessitates the need for early detection, medical optimization, and careful preoperative care. Bariatric surgery is an effective strategy for weight loss and ultimately reducing obesity-related medical complications. In select patients, bariatric surgery—before, during, or after liver transplantation—may be useful to help improve posttransplant outcomes. NAFLD/NASH can present after liver transplantation and occurs as either recurrent or de novo disease. Posttransplant NAFLD occurs in the setting of metabolic syndrome, immunosuppression use, and genetic determinants. Future studies and efforts should focus on optimizing medical management strategies to further improve transplant outcomes in patients with NAFLD.

Nonalcoholic Fatty Liver Disease

2018 ◽  
Author(s):  
Michael Fuchs ◽  
Puneet Puri
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Daily Intake ◽  
Clinical Manifestations ◽  
Nonalcoholic Fatty Liver ◽  
End Stage

Nonalcoholic fatty liver disease (NAFLD) is defined by the pathologic accumulation of fat in more than 5% of hepatocytes in the absence of significant alcohol consumption (daily intake < 20 g in women and < 30 g in men) and by excluding secondary causes of hepatic steatosis. NAFLD can be categorized into two principal phenotypes: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is defined by the presence of macrovesicular steatosis without inflammation, whereas NASH sees inflammation and hepatocyte ballooning injury, is associated with varying degrees of fibrosis, and can progress to cirrhosis and end-stage liver disease. This review addresses the epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis of NAFLD. Figures show the spectrum of fatty liver disease, hepatic consequences of insulin resistance, role of liver biopsy in evaluation of NAFLD, histologic features of NASH, and principles of NAFLD. Tables list risk factors and clinical manifestations for NAFLD, physical examination findings in NAFLD, comparison of imaging modalities, and noninvasive fibrosis markers. This review contains 6 figures, 5 tables and 166 references Key words: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, non-invasive assessment, vibration controlled transient elastography, magnetic resonance elastography, diet and lifestyle treatment

Nonalcoholic Fatty Liver Disease

2018 ◽  
Author(s):  
Michael Fuchs ◽  
Puneet Puri
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Daily Intake ◽  
Clinical Manifestations ◽  
Nonalcoholic Fatty Liver ◽  
End Stage

Nonalcoholic fatty liver disease (NAFLD) is defined by the pathologic accumulation of fat in more than 5% of hepatocytes in the absence of significant alcohol consumption (daily intake < 20 g in women and < 30 g in men) and by excluding secondary causes of hepatic steatosis. NAFLD can be categorized into two principal phenotypes: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is defined by the presence of macrovesicular steatosis without inflammation, whereas NASH sees inflammation and hepatocyte ballooning injury, is associated with varying degrees of fibrosis, and can progress to cirrhosis and end-stage liver disease. This review addresses the epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis of NAFLD. Figures show the spectrum of fatty liver disease, hepatic consequences of insulin resistance, role of liver biopsy in evaluation of NAFLD, histologic features of NASH, and principles of NAFLD. Tables list risk factors and clinical manifestations for NAFLD, physical examination findings in NAFLD, comparison of imaging modalities, and noninvasive fibrosis markers. This review contains 6 figures, 5 tables and 166 references Key words: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, non-invasive assessment, vibration controlled transient elastography, magnetic resonance elastography, diet and lifestyle treatment

Nonalcoholic Fatty Liver Disease

2018 ◽  
Author(s):  
Michael Fuchs ◽  
Puneet Puri
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Daily Intake ◽  
Clinical Manifestations ◽  
Nonalcoholic Fatty Liver ◽  
End Stage

Nonalcoholic fatty liver disease (NAFLD) is defined by the pathologic accumulation of fat in more than 5% of hepatocytes in the absence of significant alcohol consumption (daily intake < 20 g in women and < 30 g in men) and by excluding secondary causes of hepatic steatosis. NAFLD can be categorized into two principal phenotypes: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is defined by the presence of macrovesicular steatosis without inflammation, whereas NASH sees inflammation and hepatocyte ballooning injury, is associated with varying degrees of fibrosis, and can progress to cirrhosis and end-stage liver disease. This review addresses the epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis of NAFLD. Figures show the spectrum of fatty liver disease, hepatic consequences of insulin resistance, role of liver biopsy in evaluation of NAFLD, histologic features of NASH, and principles of NAFLD. Tables list risk factors and clinical manifestations for NAFLD, physical examination findings in NAFLD, comparison of imaging modalities, and noninvasive fibrosis markers. This review contains 6 figures, 5 tables and 166 references Key words: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, non-invasive assessment, vibration controlled transient elastography, magnetic resonance elastography, diet and lifestyle treatment

scholarly journals Emerging Pharmacological Treatment in Nonalcoholic Steatohepatitis

2020 ◽  
Vol 36 (5) ◽  
pp. 411-416
Author(s):  
Jörn M. Schattenberg
Keyword(s):  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Advanced Disease ◽  
Treatment Success ◽  
Lifestyle Changes ◽  
Current Response ◽  
Nonalcoholic Fatty Liver ◽  
End Stage Liver Disease ◽  
End Stage ◽  
Metabolic Treatment

<b><i>Background:</i></b> The increasing prevalence of nonalcoholic ­fatty liver disease has led to a strong demand for an optimal therapeutic approach. At present, guidelines recommend lifestyle changes, but it has become apparent that pharmacotherapy will be required in patients with advanced disease to prevent the progression to end-stage liver disease and potentially improve extrahepatic outcomes. <b><i>Summary:</i></b> This review discusses current pharmacological approaches focusing on substances studied in pivotal trials and selected phase 2 trials in patients with nonalcoholic steatohepatitis (NASH) and fibrosis. <b><i>Key Message:</i></b> Currently, several compounds are subjected to clinical testing to explore predominantly anti-inflammatory, anti-fibrotic, and metabolic treatment for NASH. With current response rates around 20%, the combination of several drugs targeting more than one pathway could lead to increased treatment success in the future.

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