scholarly journals An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia

2021 ◽  
Vol 22 (5) ◽  
pp. 2604
Author(s):  
Young Joo Yang ◽  
Dong Joon Kim
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Musculoskeletal Disorders ◽  
Molecular Mechanisms ◽  
Chronic Liver ◽  
Pathophysiological Mechanism ◽  
Alcoholic Fatty Liver ◽  
Receptor Activator ◽  
Branched Chain ◽  
Prevalence Of Osteoporosis

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, β-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/β-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.

scholarly journals Translational Control in Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexandra Balvey ◽  
Mercedes Fernandez
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Translational Control ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Chronic Liver ◽  
Obese People ◽  
Alcoholic Fatty Liver ◽  
New Strategies

Chronic liver disease is one of the biggest threats to public health worldwide. Worryingly, the incidence of liver disease is dramatically rising due to the aging of the population and the global epidemics of obesity. Both are major risk factors for chronic liver disease and adverse prognostic factors, causing an increase in mortality rate. It is of great concern that 80–95% of obese people have non-alcoholic fatty liver disease, the major precursor for liver failure and a global health challenge. Currently, the only curative treatment for advanced chronic liver disease is liver transplantation, which is, however, hampered by high treatment costs and the scarcity of donor organs. New strategies are therefore urgently needed to prevent and reverse chronic liver disease. And for that it is essential to understand better the molecular mechanisms underlying human disease. This review focuses on the abnormalities in the regulation of translation by RNA-binding proteins during chronic liver disease and their pathological impact on portal hypertension, fibrosis, steatosis, neovascularization, and cancer development.

scholarly journals Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maryam Moini ◽  
Fernanda Onofrio ◽  
Bettina E. Hansen ◽  
Oyedele Adeyi ◽  
Korosh Khalili ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Transient Elastography ◽  
Area Under The Curve ◽  
High Specificity ◽  
Serum Markers ◽  
Chronic Liver ◽  
Alcoholic Fatty Liver ◽  
Advanced Liver Fibrosis ◽  
Independent Association

AbstractReliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4.

scholarly journals Notch Inhibition Promotes Differentiation of Liver Progenitor Cells into Hepatocytes via sox9b Repression in Zebrafish

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jacquelyn O. Russell ◽  
Sungjin Ko ◽  
Satdarshan P. Monga ◽  
Donghun Shin
Keyword(s):  
Liver Disease ◽  
Liver Regeneration ◽  
Notch Signaling ◽  
Chronic Liver Disease ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Chronic Liver ◽  
Hepatocyte Proliferation ◽  
Hepatocyte Differentiation

Liver regeneration after most forms of injury is mediated through the proliferation of hepatocytes. However, when hepatocyte proliferation is impaired, such as during chronic liver disease, liver progenitor cells (LPCs) arising from the biliary epithelial cell (BEC) compartment can give rise to hepatocytes to mediate hepatic repair. Promotion of LPC-to-hepatocyte differentiation in patients with chronic liver disease could serve as a potentially new therapeutic option, but first requires the identification of the molecular mechanisms driving this process. Notch signaling has been identified as an important signaling pathway promoting the BEC fate during development and has also been implicated in regulating LPC differentiation during regeneration. SRY-related HMG box transcription factor 9 (Sox9) is a direct target of Notch signaling in the liver, and Sox9 has also been shown to promote the BEC fate during development. We have recently shown in a zebrafish model of LPC-driven liver regeneration that inhibition of Hdac1 activity through MS-275 treatment enhances sox9b expression in LPCs and impairs LPC-to-hepatocyte differentiation. Therefore, we hypothesized that inhibition of Notch signaling would promote LPC-to-hepatocyte differentiation by repressing sox9b expression in zebrafish. We ablated the hepatocytes of Tg(fabp10a:CFP-NTR) larvae and blocked Notch activation during liver regeneration through treatment with γ-secretase inhibitor LY411575 and demonstrated enhanced induction of Hnf4a in LPCs. Alternatively, enhancing Notch signaling via Notch3 intracellular domain (N3ICD) overexpression impaired Hnf4a induction. Hepatocyte ablation in sox9b heterozygous mutant embryos enhanced Hnf4a induction, while BEC-specific Sox9b overexpression impaired LPC-to-hepatocyte differentiation. Our results establish the Notch-Sox9b signaling axis as inhibitory to LPC-to-hepatocyte differentiation in a well-established in vivo LPC-driven liver regeneration model.

scholarly journals Trends in the prevalence of chronic liver disease in the Korean adult population, 1998–2017

2020 ◽  
Vol 26 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Seung Ha Park ◽  
Lindsay D. Plank ◽  
Ki Tae Suk ◽  
Yong Eun Park ◽  
Jin Lee ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Adult Population ◽  
Chronic Liver ◽  
Excessive Alcohol Consumption ◽  
Alcoholic Fatty Liver ◽  
Future Burden ◽  
Definition Of ◽  
Hepatic Steatosis Index

Data on the trends in the prevalence of chronic liver disease (CLD) in Korea are scarce. This study aimed to evaluate whether the CLD prevalence changed between 1998–2001 and 2016–2017. Data were extracted from the Korea National Health and Nutrition Examination Survey (1998–2001 to 2016–2017; n=25,893). Non-alcoholic fatty liver disease (NAFLD) was defined as a hepatic steatosis index >36 in the absence of any other evidence of CLD. The definition of alcoholrelated liver disease (ALD) was excessive alcohol consumption (≥210 g/week for men and ≥140 g/week for women) and an ALD/NAFLD index >0. The prevalence of NAFLD increased from 18.6% (95% confidence interval [CI], 17.8–19.5%) in 1998–2001 to 21.5% (95% CI, 20.6–22.6%) in 2016–2017. During the same time period, increases were observed in the prevalence of obesity (27.0 vs. 35.1%), central obesity (29.4 vs. 36.0%), diabetes (7.5 vs. 10.6%), and excessive drinking (7.3 vs. 10.5%). ALD prevalence also increased from 3.8% (95% CI, 3.4–4.2%) to 7.0% (95% CI, 6.4–7.6%). In contrast, chronic hepatitis B decreased from 5.1% (95% CI, 4.6–5.5%) to 3.4% (95% CI, 3.0–3.8%). The prevalence of chronic hepatitis C was approximately 0.3% in 2016–2017. The prevalence of NAFLD and ALD increase among Korean adults. Our results suggest potential targets for interventions to reduce the future burden of CLD.

scholarly journals Characteristics of opioid prescribing to outpatients with chronic liver diseases: A call for action

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261377
Author(s):  
Olufunso M. Agbalajobi ◽  
Theresa Gmelin ◽  
Andrew M. Moon ◽  
Wheytnie Alexandre ◽  
Grace Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
High Risk ◽  
Chronic Liver Disease ◽  
Medical Center ◽  
Chronic Liver ◽  
Prescribing Patterns ◽  
Prescription Opioid ◽  
Alcoholic Fatty Liver ◽  
Opioid Prescribing ◽  
One Year

Background Chronic liver disease (CLD) is among the strongest risk factors for adverse prescription opioid-related events. Yet, the current prevalence and factors associated with high-risk opioid prescribing in patients with chronic liver disease (CLD) remain unclear, making it challenging to address opioid safety in this population. Therefore, we aimed to characterize opioid prescribing patterns among patients with CLD. Methods This retrospective cohort study included patients with CLD identified at a single medical center and followed for one year from 10/1/2015-9/30/2016. Multivariable, multinomial regression was used identify the patient characteristics, including demographics, medical conditions, and liver-related factors, that were associated with opioid prescriptions and high-risk prescriptions (≥90mg morphine equivalents per day [MME/day] or co-prescribed with benzodiazepines). Results Nearly half (47%) of 12,425 patients with CLD were prescribed opioids over a one-year period, with 17% of these receiving high-risk prescriptions. The baseline factors significantly associated with high-risk opioid prescriptions included female gender (adjusted incident rate ratio, AIRR = 1.32, 95% CI = 1.14–1.53), Medicaid insurance (AIRR = 1.68, 95% CI = 1.36–2.06), cirrhosis (AIRR = 1.22, 95% CI = 1.04–1.43) and baseline chronic pain (AIRR = 3.40, 95% CI = 2.94–4.01), depression (AIRR = 1.93, 95% CI = 1.60–2.32), anxiety (AIRR = 1.84, 95% CI = 1.53–2.22), substance use disorder (AIRR = 2.16, 95% CI = 1.67–2.79), and Charlson comorbidity score (AIRR = 1.27, 95% CI = 1.22–1.32). Non-alcoholic fatty liver disease was associated with decreased high-risk opioid prescriptions (AIRR = 0.56, 95% CI = 0.47–0.66). Conclusion Opioid medications continue to be prescribed to nearly half of patients with CLD, despite efforts to curtail opioid prescribing due to known adverse events in this population.

scholarly journals Peran Terlipressin pada Penyakit Hati Kronik

2021 ◽  
Vol 3 (1) ◽  
pp. 24
Author(s):  
Decky Andrea ◽  
Luciana Rotty
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Chronic Liver Disease ◽  
Variceal Bleeding ◽  
Hepatorenal Syndrome ◽  
Chronic Liver ◽  
Refractory Ascites ◽  
Esophageal Variceal ◽  
Alcoholic Fatty Liver ◽  
Esophageal Variceal Bleeding

Abstract: Chronic liver disease is a progressive impairment of liver function. It is caused by non-alcoholic fatty liver, viral infection of the liver, excessive alcohol consumption, metabolic diseases such as galactosemia, autoimmune disease, and the influence of chemicals. Complications that are often found are esophageal variceal bleeding, hepatorenal syndrome, and refractory ascites. Terlipressin, which is a vasopressin analogue, is currently widely used in developed countries because it has been shown to improve survival of patients with esophageal varices, hepatorenal syndrome, and refractory ascites. Terlipressin is the current standard therapy for esophageal variceal bleeding in countries where it is available.Keywords: chronic liver disease; terlipressin  Abstrak: Penyakit hati kronis (PHK) adalah gangguan fungsi hati yang terjadi secara progresif. Peyakit hati kronis di sebabkan oleh non-alcoholic fatty liver, infeksi virus pada hati, konsumsi alkohol berlebihan, peyakit metabolik seperti galaktosemia, penyakit autoimun, dan pengaruh bahan kimia. Komplikasi yang sering ditemukan pada PHK ialah perdarahan varises esofagus, sindrom hepatorenal, dan asites refrakter. Terlipressin yang merupakan analog vasopressin saat ini banyak di pakai di negara maju karena terbukti dapat meningkatkan kelangsungan hidup pasien perdarahan varises esofagus, sindrom hepatorenal, dan asites refrakter. Dewasa ini terlipressin telah menjadi terapi standar perdarahan varises esofagus di negara-negara di mana obat ini tersedia.Kata kunci: penyakit hati kronik; terlipressin

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