NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States

Gadiparthi, Chiranjeevi; Spatz, Moshe; Greenberg, Simi; Iqbal, Umair; Kanna, Sowjanya; Broder, Arkady; Ahmed, Aijaz

doi:10.14218/jcth.2020.00014

Cited by 48 publications

(40 citation statements)

References 56 publications

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“…Currently, NAFLD already represents one of the most common conditions leading to liver transplantation in many developed countries. 4 5 Due to its initially asymptomatic course, NAFLD tends to be underdiagnosed. Patients are usually diagnosed at advanced stages and specific therapies by specialists are often initiated late.…”

Section: Introductionmentioning

confidence: 99%

Variables associated with increased incidence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes

Loosen

Demir

Kunstein

et al. 2021

BMJ Open Diab Res Care

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IntroductionType 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) show a rapidly increasing incidence worldwide. Although both diseases often occur in the same patient population, their mutual influence is not fully understood. We therefore aimed at analyzing the impact of T2D on the incidence of NAFLD in a large cohort of outpatients in Germany.Research design and methods32 201 patients with T2D diagnosed between 2012 and 2018 were identified in the IQVIA Disease Analyzer database. Probability of NAFLD was analyzed using Cox regression models.ResultsThe cumulative incidence of NAFLD within the 7-year observation period was 4.3%. The probability of NAFLD was significantly higher among patients with T2D with increased body mass index but not hemoglobin A1c. Prescriptions of sodium-glucose cotransporter-2 inhibitors (HR: 0.54, 95% CI 0.45 to 0.64), glucagon-like peptide-1 receptor antagonists (HR: 0.65, 95% CI 0.52 to 0.81), and insulin (HR: 0.72, 95% CI 0.62 to 0.8) were significantly associated with lower incidence of NAFLD.ConclusionOur data from a large population-based cohort of patients with T2D identified sociodemographic and therapeutic parameters associated with NAFLD incidence in patients with T2D which should be taken into account for novel therapeutic concepts.

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Section: Introductionmentioning

confidence: 99%

Variables associated with increased incidence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes

Loosen

Demir

Kunstein

et al. 2021

BMJ Open Diab Res Care

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“…Hepatitis and alcohol abuse were previously considered the leading risk factors for HCC, but at present, nonalcoholic fatty liver disease (NAFLD) is considered an increasing risk factor. 3 , 4 NAFLD represents a spectrum of liver pathologies that are strongly associated with metabolic disorder. 5 Metabolic dysregulation also contributes to the progression from NAFLD to HCC.…”

Section: Introductionmentioning

confidence: 99%

UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1β in hepatocellular carcinoma

Ruan

et al. 2021

Sig Transduct Target Ther

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The treatment for hepatocellular carcinoma (HCC) is promising in recent years, but still facing critical challenges. The first targeted therapy, sorafenib, prolonged the overall survival by months. However, resistance often occurs, largely limits its efficacy. Sorafenib was found to target the electron transport chain complexes, which results in the generation of reactive oxygen species (ROS). To maintain sorafenib resistance and further facilitate tumor progression, cancer cells develop strategies to overcome excessive ROS production and obtain resistance to oxidative stress-induced cell death. In the present study, we investigated the roles of ROS in sorafenib resistance, and found suppressed ROS levels and reductive redox states in sorafenib-resistant HCC cells. Mitochondria in sorafenib-resistant cells maintained greater functional and morphological integrity under the treatment of sorafenib. However, cellular oxygen consumption rate and mitochondria DNA content analyses revealed fewer numbers of mitochondria in sorafenib-resistant cells. Further investigation attributed this finding to decreased mitochondrial biogenesis, likely caused by the accelerated degradation of peroxisome proliferator-activated receptor γ coactivator 1β (PGC1β). Mechanistic dissection showed that upregulated UBQLN1 induced PGC1β degradation in a ubiquitination-independent manner to attenuate mitochondrial biogenesis and ROS production in sorafenib-resistant cells under sorafenib treatment. Furthermore, clinical investigations further indicated that the patients with higher UBQLN1 levels experienced worse recurrence-free survival. In conclusion, we propose a novel mechanism involving mitochondrial biogenesis and ROS homeostasis in sorafenib resistance, which may offer new therapeutic targets and strategies for HCC patients.

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“…While NASH is the second leading indication for liver transplantation (LT), it is expected that NASH will overtake hepatitis C virus (HCV) as the leading cause, given the efficacy of direct-acting antiviral therapy[ 3 ]. A recent epidemiological study has already confirmed a downward trend for HCV-related LT in the United States[ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Non-alcoholic fatty liver and chronic kidney disease: Retrospect, introspect, and prospect

Heda¹,

Yazawa²,

Shi³

et al. 2021

WJG

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With the growing prevalence of obesity and diabetes in the United States and across the world, a rise in the overall incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is expected. The risk factors for NAFLD are also associated with the development of chronic kidney disease (CKD). We review the epidemiology, risk factors, genetics, implications of gut dysbiosis, and specific pathogenic mechanisms linking NAFLD to CKD. Mechanisms such as ectopic lipid accumulation, cellular signaling abnormalities, and the interplay between fructose consumption and uric acid accumulation have led to the emergence of potential therapeutic implications for this patient population. Transplant evaluation in the setting of both NAFLD and CKD is also reviewed. Potential strategies for surveillance and management include the monitoring of comorbidities, the use of non-invasive fibrosis scoring systems, and the measurement of laboratory markers. Lastly, we discuss the management of patients with NAFLD and CKD, from preventative measures to experimental interventions.

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NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States

Cited by 48 publications

References 56 publications

Variables associated with increased incidence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes

Variables associated with increased incidence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes

UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1β in hepatocellular carcinoma

Non-alcoholic fatty liver and chronic kidney disease: Retrospect, introspect, and prospect

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