Publications by authors named "Donghee Kim"

278 Publications

Trends in the Prevalence of Hepatitis C Virus Infection based on the Insurance Status in the United States from 2013 to 2018.

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United States.

Background & Aims: With the recent improvement in the treatment of hepatitis C virus (HCV) infection, a better understanding of the infection burden is needed. We aimed to (1) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (2) identify at-risk populations for HCV infection in the United States (US) general population.

Methods: Population-based analyses using the National Health and Nutrition Examination Survey (2013-2018) were performed with a focus on HCV infection. We analyzed the prevalence of HCV infection based on the health insurance status before the direct-acting antiviral (DAA) era (2013-2014) and during the DAA era (2015-2018).

Results: The age-adjusted prevalence of active HCV infection (HCV RNA [+]) was 0.92% (95% confidence interval [CI], 0.71%-1.19%) in the US non-institutionalized civilian population. While the prevalence of active HCV infection has remained stable, the prevalence of resolved HCV infection has increased after the introduction of DAA. In terms of health insurance coverage, the prevalence of active HCV infection decreased, and the prevalence of resolved HCV infection increased among individuals who had health insurance, especially private health insurance. The independent risk factors of active HCV infection were 40-69 years group, male, less than high school education, unmarried, below poverty status, being born in the US, history of blood transfusion, and not having private health insurance.

Conclusion: The burden of active HCV infection has decreased among individuals who had health insurance, especially private health insurance, during the DAA era.
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http://dx.doi.org/10.1111/liv.15113DOI Listing
November 2021

Sex-specific Risk Factors and Health Disparity Among Hepatitis C Positive Patients Receiving Pharmacotherapy for Opioid Use Disorder: Findings From a Propensity Matched Analysis.

J Addict Med 2021 Nov 18. Epub 2021 Nov 18.

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada (BBD, LJM, AW, TO); Department of Family Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada (LN); Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford University, CA (BBD, GC, DK, AA); Department of Medicine, University of British Columbia, Vancouver Costal Health, Vancouver, Canada (DA); Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada (NS, AH, CC, AD, BP, ZS); Department of Health Research Evaluation and Impact (Formerly Department of Clinical Epidemiology and Biostatistics), McMaster University, Hamilton, ON, Canada (LN, AW, LT, ZS); Northern Ontario School of Medicine, Sudbury ON, Canada (DCM); Canadian Addiction Treatment Centres, Markham ON, Canada (DCM); Guys and St. Thomas Hospital NHS Trust, London, United Kingdom (MB); Centre for Evaluation of Medicine, Hamilton, ON, Canada (LT); System Linked Research Unit, Hamilton, ON, Canada (LT); Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada (ZS).

Background: The incidence of opioid-related fatality has reached unparalleled levels across North America. Patients with comorbid hepatitis C virus (HCV) remain the most vulnerable and difficult to treat. Considering the unique challenges associated with this population, we aimed to re-examine the impact of HCV on response to medication assistant treatment for opioid use disorder and establish sex-specific risk factors affecting care.

Methods: This study employs a multi-center prospective cohort design, with 1-year follow-up. Patients aged ≥18, receiving methadone for opioid use disorder were recruited from a network of out-patient opioid addiction treatment centers across Southern Ontario, Canada. Patients with ≥50% positive opioid urine screens over 1 year of follow-up were classified as poor responders. The prognostic impact of HCV on response was established using a propensity score matched analysis. Sex-specific regression models were constructed to evaluate risk factors for treatment response.

Results: Among participants eligible for inclusion (n = 1234), HCV was prevalent in 25% (n = 307). HCV patients exhibited significantly higher rates of high-risk opioid consumption patterns 35.29% (standard deviation 0.478). Sex-specific examination revealed females with HCV incur a 2 times increased risk for high-risk opioid consumption behaviors (female odds ratio: 1.95, 95% confidence interval 1.23, 3.10; P = 0.01).

Conclusions: Findings from this study establish the link between HCV and poor treatment response, with differentially higher risk among female patients. In light of the high potential for overdose among this population, concerted efforts are required for distinguishing the source for sex-based disparities, in addition to establishing trauma and gender informed treatment protocols.
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http://dx.doi.org/10.1097/ADM.0000000000000937DOI Listing
November 2021

Emergent Vertebral Artery Embolization during C12 Screw Fixation for Rheumatoid Arthritis.

Korean J Neurotrauma 2021 Oct 11;17(2):199-203. Epub 2021 Oct 11.

Department of Neurosurgery, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju, Korea.

The subaxial screw fixation technique is commonly used for fixation in a wide range of cervical diseases, including traumatic, degenerative, and neoplastic diseases, rheumatoid arthritis (RA), and spondyloarthropathy. Although it is regarded as a relatively safe procedure, several complications may be encountered during surgery, such as vertebral artery (VA) and nerve root injuries, facet violation, and mass fracture. We report a case of endovascular embolization after VA injury during a high cervical spinal surgery. A 48-year-old woman was scheduled for C-1-2-3 posterior fixation. Plain radiography of the cervical spine revealed a severely unstable state. During dissection around the C1 lateral mass on the right side, sudden brisk arterial bleeding was observed. On vertebral angiography, flow voiding was noted above the right V3 portion. After checking patent collateral flow from the contralateral VA, routine coil embolization was performed to pack the V3 segment. Iatrogenic vascular injuries due to spinal surgery are rare but serious complications. For patients with RA, we recommend careful preoperative evaluation before a high cervical surgical procedure to avoid iatrogenic VA injury and endovascular interventions that are safe and effective in the diagnosis and treatment of such vascular injuries.
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http://dx.doi.org/10.13004/kjnt.2021.17.e30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558018PMC
October 2021

Reply to: "NAFLD vs. MAFLD - It is not the name but the disease that decides the outcome in fatty liver".

J Hepatol 2021 Nov 5. Epub 2021 Nov 5.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, United States.

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http://dx.doi.org/10.1016/j.jhep.2021.10.023DOI Listing
November 2021

Extrahepatic causes of death in cirrhosis compared to other chronic conditions in the United States, 1999-2017.

Ann Hepatol 2021 Oct 30:100565. Epub 2021 Oct 30.

Baylor University Medical Center, Dallas, TX, USA. Electronic address:

Introduction And Objectives: Cirrhosis-related mortality is underestimated and is increasing; extrahepatic factors may contribute. We examined trends in cirrhosis mortality from 1999-2017 in the United States attributed to liver-related (varices, peritonitis, hepatorenal syndrome, hepatic encephalopathy, hepatocellular carcinoma, sepsis) or extrahepatic (cardiovascular disease, influenza and pneumonia, diabetes, malignancy) causes, and compared mortality trends with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) populations.

Materials And Methods: A national mortality database was used. Changes in age-standardized mortality over time were determined by joinpoint analysis. Average annual percentage change (AAPC) was estimated.

Results: Cirrhosis cohort: From 1999-2017, both liver-related (AAPC 1.3%; 95% confidence interval [CI] 0.7-1.9) and extrahepatic mortality (AAPC 1.0%; 95% CI 0.7-1.2) increased. Cirrhosis vs other chronic disease cohorts: changes in all-cause mortality were higher in cirrhosis (AAPC 1.0%; 95% CI 0.7-1.4) than CHF (AAPC 0.1%; 95% CI -0.5- 0.8) or COPD (AAPC -0.4%; 95% CI -0.6- -0.2). Sepsis mortality was highest in cirrhosis (AAPC 3.6%, 95% 3.2- 4.1) compared to CHF (AAPC 0.6%, 95% CI -0.5- 1.7) or COPD (AAPC 0.8%, 95% CI 0.5- 1.2). Cardiovascular mortality increased in cirrhosis (AAPC 1.3%, 95% CI 1.1- 1.5), declined in CHF (AAPC -2.0%, 95% CI -5.3- 1.3) and remained unchanged in COPD (AAPC 0.1%, 95% CI -0.2- 0.4). Extrahepatic mortality was higher among women, rural populations, and individuals >65 years with cirrhosis.

Conclusions: Extrahepatic causes of death are important drivers of mortality and differentially impact cirrhosis compared to other chronic diseases.
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http://dx.doi.org/10.1016/j.aohep.2021.100565DOI Listing
October 2021

Factors associated with rebleeding after coil embolization in patients with aneurysmal subarachnoid hemorrhage.

J Cerebrovasc Endovasc Neurosurg 2021 Oct 26. Epub 2021 Oct 26.

Department of Neurosurgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) has a high mortality rate, and hemorrhage amounts and perioperative rebleeding importantly determines prognosis. However, despite adequate treatment, prognosis is poor in many ruptured aneurysm cases. In this study, we identified and evaluated factors related to perioperative rebleeding in patients with aSAH.

Methods: The medical and surgical records of 166 patients that underwent endovascular embolization for a ruptured cerebral aneurysm at a single institution from 2014 to 2016 were retrospectively analyzed to identify risk factors of rebleeding. All patients were examined for risk factors and evaluated for increased hemorrhage by brain computed tomography at 3 days after surgery.

Results: This series included 54 men (32.5%) and 112 women (67.5%) of mean age 58.3±14.3 years. After procedures, 26 patients (15.7%) experienced rebleeding, and 1 of these (0.6%) experienced an intraoperative aneurysmal rupture. External ventricular drainage (EVD) (odds ratio [OR] 5.389, [95% confidence interval (CI) 1.171- 24.801]) and modified Fisher grade (OR 2.037, [95% CI 1.077-3.853]) were found to be independent risk factors of rebleeding, and perioperative rebleeding was strongly associated with patient outcomes (p<0.001).

Conclusions: We concluded the rebleeding risk after aSAH is greater in patients with large hemorrhage amounts and a high pre-operative modified Fisher grade, and thus, we caution neurosurgeons should take care in such cases.
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http://dx.doi.org/10.7461/jcen.2021.E2021.05.006DOI Listing
October 2021

Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway.

Int J Mol Sci 2021 Oct 5;22(19). Epub 2021 Oct 5.

Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.

Psoriasis is a chronic inflammatory skin disease. Recently, lysophosphatidic acid (LPA)/LPAR5 signaling has been reported to be involved in both NLRP3 inflammasome activation in macrophages and keratinocyte activation to produce inflammatory cytokines, contributing to psoriasis pathogenesis. However, the effect and molecular mechanisms of LPA/LPAR signaling in keratinocyte proliferation in psoriasis remain unclear. In this study, we investigated the effects of LPAR1/3 inhibition on imiquimod (IMQ)-induced psoriasis-like mice. Treatment with the LPAR1/3 antagonist, ki16425, alleviated skin symptoms in IMQ-induced psoriasis-like mouse models and decreased keratinocyte proliferation in the lesion. It also decreased LPA-induced cell proliferation and cell cycle progression via increased cyclin A2, cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 expression and decreased p27 expression in HaCaT cells. LPAR1 knockdown in HaCaT cells reduced LPA-induced proliferation, suppressed cyclin A2 and CDK2 expression, and restored p27 expression. LPA increased Rho-associated protein kinase 2 (ROCK2) expression and PI3K/AKT activation; moreover, the pharmacological inhibition of ROCK2 and PI3K/AKT signaling suppressed LPA-induced cell cycle progression. In conclusion, we demonstrated that LPAR1/3 antagonist alleviates IMQ-induced psoriasis-like symptoms in mice, and in particular, LPAR1 signaling is involved in cell cycle progression via ROCK2/PI3K/AKT pathways in keratinocytes.
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http://dx.doi.org/10.3390/ijms221910777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509620PMC
October 2021

Combination of PD98059 and TGF-β1 Efficiently Differentiates Human Urine-Derived Stem Cells into Smooth Muscle Cells.

Int J Mol Sci 2021 Sep 29;22(19). Epub 2021 Sep 29.

College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21999, Korea.

Pluripotent adult stem cells have potential applications in cell therapy and tissue engineering. Urine-derived stem cells (UDSCs) differentiate into various cell types. Here, we attempted to differentiate human UDSCs (hUDSCs) into smooth muscle cells (SMCs) using transforming growth factor-beta 1 (TGF-β1) and/or PD98059, an extracellular signal-regulated kinase (ERK) inhibitor. Both quantitative polymerase chain reaction (qPCR) and Western blot analysis showed that the expression of messenger ribonucleic acid (mRNA) and proteins for alpha-smooth muscle actin (α-SMA), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC), which are specific markers for SMCs, increased on day 9 after differentiation and again on day 14. The differentiated cells from human UDSCs (hUDSCs) with a combination of TGF-β1 and PD98059 showed the highest expression of SMC marker proteins. Immunocytochemical staining performed to assess the molecular expression revealed CNN and α-SMA colocalizing in the cytoplasm. The cells that differentiated from hUDSCs with a combination of TGF-β1 and PD98059 showed the strongest expression for CNN1, α-SMA, and SM-MHC. Functional testing of the differentiated cells revealed a stronger contractile capacity for the cells differentiated with a combination of PD98059 and TGF-β1 than those differentiated with a single factor. These results suggest the combination of PD98059 and TGF-β1 to be a more effective differentiation method and that differentiated SMCs could be used for restoring the functions of the sphincter muscle or bladder.
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http://dx.doi.org/10.3390/ijms221910532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508912PMC
September 2021

Current epidemiology in hepatocellular carcinoma.

Expert Rev Gastroenterol Hepatol 2021 Nov 22;15(11):1295-1307. Epub 2021 Oct 22.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

Introduction: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world.

Areas Covered: This review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity.

Expert Opinion: Interventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC.
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http://dx.doi.org/10.1080/17474124.2021.1991792DOI Listing
November 2021

Management of Cardiometabolic Complications in Patients With Nonalcoholic Fatty Liver Disease: A Review of the Literature With Recommendations.

J Clin Gastroenterol 2021 10;55(9):747-756

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver conditions characterized by significant lipid deposition within hepatocytes. As an overarching diagnosis, NAFLD contains a continuum of progressive liver diseases ranging from isolated liver steatosis to necroinflammatory states leading to end-stage liver disease. Nonalcoholic fatty liver and nonalcoholic steatohepatitis are distinguished by their histologic patterns, with the former exhibiting steatosis without fibrosis or inflammation. This important distinction provides clinicians a timeline within the NAFLD staging to target appropriate interventions against modifiable risk factors. NAFLD is likely formed in response to metabolic imbalances that damage the livers adaptive capacity. Metabolic conditions leading to steatosis mirror common cardiovascular risk factors, including dyslipidemia, diabetes mellitus, and obesity. Acknowledging the common risk factors for development and progression of NAFLD, it is unsurprising the first-line management focuses on the treatment of metabolic syndrome with an emphasis on weight reduction in obese populations. The purpose of this review is to provide a detailed summary of the literature as well as outline the current treatment recommendations for patients with NAFLD with a detailed focus on pharmacologic antiobesity interventions.
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http://dx.doi.org/10.1097/MCG.0000000000001555DOI Listing
October 2021

New hope for hepatitis C virus: Summary of global epidemiologic changes and novel innovations over 20 years.

World J Gastroenterol 2021 Aug;27(29):4818-4830

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, United States.

Hepatitis C virus (HCV) is a global health concern associated with significant morbidity and mortality. Before the approval of second-generation direct-acting antiviral agents (DAAs), interferon therapy and liver transplantation constituted the mainstay of treatment. The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95% cure rates. The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs. Despite the unparallel efficacy observed among these novel therapies, pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally. To reduce the burden of disease worldwide, essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies. Through transparent negotiations with the pharmaceutical industry, the consideration for compassionate release of medications to promote equitable division of care is paramount. Here we provide a literature review of HCV, changes in epidemiologic trends, access issues for current therapies, and global inequities in disease burden.
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http://dx.doi.org/10.3748/wjg.v27.i29.4818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371499PMC
August 2021

Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States.

J Hepatol 2021 Dec 8;75(6):1284-1291. Epub 2021 Aug 8.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, United States.

Background & Aims: Recently, international experts proposed redefining non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD), based on modified criteria. It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on all-cause and cause-specific mortality in US adults.

Methods: We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD, with adjustments for known risk factors.

Results: During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk of all-cause mortality (hazard ratio [HR] 1.17; 95% CI 1.04-1.32). Furthermore, MAFLD was associated with a higher risk of cardiovascular mortality. NAFLD per se did not increase the risk of all-cause mortality. Individuals who met both definitions had a higher risk of all-cause mortality (HR 1.13, 95% CI 1.00-1.26), while individuals who met the definition for MAFLD but not NAFLD had a 1.7-fold higher risk of all-cause mortality (HR 1.66, 95% CI 1.19-2.32). Estimates for all-cause mortality were higher for those with advanced fibrosis and MAFLD than for those with advanced fibrosis and NAFLD.

Conclusions: In this US population-based study, MAFLD was associated with an increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors.

Lay Summary: Our findings provide further support for the idea that non-alcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may help improve our understanding of predictors that increase the risk of death.
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http://dx.doi.org/10.1016/j.jhep.2021.07.035DOI Listing
December 2021

Impact of COVID-19 Pandemic on Liver Transplantation and Alcohol-Associated Liver Disease in the USA.

Hepatology 2021 Jul 26. Epub 2021 Jul 26.

Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX.

Background And Aims: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD.

Approach And Results: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30.

Conclusions: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.
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http://dx.doi.org/10.1002/hep.32067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426752PMC
July 2021

Mortality Trends in Chronic Liver Disease and Cirrhosis in the United States, Before and During COVID-19 Pandemic.

Clin Gastroenterol Hepatol 2021 12 10;19(12):2664-2666.e2. Epub 2021 Jul 10.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.

Chronic liver disease (CLD) and cirrhosis accounts for approximately 2 million deaths annually worldwide. CLD and cirrhosis-related mortality has increased steadily in the United States. With the global pandemic of coronavirus disease 2019 (COVID-19), patients with CLD and cirrhosis represent a vulnerable population at higher risk for complications and mortality. Although high mortality from COVID-19 among patients with CLD and cirrhosis have been reported, national trends in mortality related to CLD and cirrhosis before and during the COVID-19 pandemic have not been assessed. This study estimated the temporal quarterly trends in CLD and cirrhosis-related mortality in the United States from 2017 Q1 to 2020 Q3 using provisional data releases from the National Vital Statistics System..
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http://dx.doi.org/10.1016/j.cgh.2021.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271030PMC
December 2021

Current Trends in Liver Transplantation for Alcoholic Hepatitis.

Clin Liver Dis 2021 08 29;25(3):625-634. Epub 2021 May 29.

Baylor College of Medicine, Section of Gastroenterology and Hepatology, 6620 Main Street, Suite 1450, Houston, TX 77030, USA; Baylor College of Medicine, Division of Abdominal Transplantation, Houston, TX, USA. Electronic address:

Liver transplantation (LT) for alcohol-related or alcoholic hepatitis (AH) remains a controversial treatment option. However, recent studies have shown promising outcomes for LT in a subgroup of patients with AH. Considering these emerging data, LT as definitive therapy for severe AH refractory to medical management is gaining recognition. However, concerns of alcohol recidivism pose a significant barrier to perform LT for this indication. Predictive models can be utilized to develop a selection criterion to identify suitable candidates for LT. Hence, carefully selected patients with severe AH and low risk of alcohol relapse can be considered for LT.
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http://dx.doi.org/10.1016/j.cld.2021.04.002DOI Listing
August 2021

Physical Activity Is Associated With Nonalcoholic Fatty Liver Disease and Significant Fibrosis Measured by FibroScan.

Clin Gastroenterol Hepatol 2021 Jun 29. Epub 2021 Jun 29.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.

Background And Aims: Studies evaluating the association of 2018 Physical Activity Guidelines for Americans (PA Guidelines) with nonalcoholic fatty liver disease (NAFLD) and significant fibrosis or cirrhosis are needed. We evaluated the association of meeting PA Guidelines with NAFLD and significant fibrosis or cirrhosis by transient elastography in the United States.

Methods: A cross-sectional analysis was performed using the 2017-2018 U.S. National Health and Nutrition Examination Survey data. NAFLD and significant fibrosis or cirrhosis were defined by transient elastography in the absence of other causes of chronic liver disease. The detailed PA questionnaire assessed the leisure-time, occupation-related, and transportation-related PA. PA was categorized based on the PA Guidelines.

Results: Of the 4304 subjects, leisure-time PA, which met the PA Guidelines (≥150 min/wk), was associated with 44% lower risk of NAFLD (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.46-0.67). Subjects who reported 1-2 times (150-299 min/wk) or over 2 times (≥300 min/wk) the recommended amount of PA Guidelines had 40% (OR, 0.60; 95% CI, 0.41-0.90) and 49% (OR, 0.51; 95% CI, 0.40-0.65) lower odds of NAFLD, respectively. Over 8 hours of sitting time had a 44% higher risk of NAFLD (OR, 1.44; 95% CI, 1.01-2.05) when we considered leisure-time PA and sitting time simultaneously. Over 2 times (≥300 min/wk) the recommended amount of PA Guidelines for leisure-time PA had 59% (OR, 0.41; 95% CI, 0.22-0.74) lower risk for significant fibrosis and 63% (OR, 0.37; 95% CI, 0.21-0.64) lower odds of cirrhosis.

Conclusions: Meeting PA Guidelines for leisure-time PA has beneficial effects on NAFLD, and over 2 times the recommended amount of PA Guidelines had lower risk for significant fibrosis or cirrhosis.
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http://dx.doi.org/10.1016/j.cgh.2021.06.029DOI Listing
June 2021

Effect of charge storage engineering on the NO gas sensing properties of a WO FET-type gas sensor with a horizontal floating-gate.

Nanoscale 2021 May 11;13(19):9009-9017. Epub 2021 May 11.

Department of Electrical and Computer Engineering and Inter-university Semiconductor Research Center, Seoul National University, Seoul 08826, Republic of Korea.

In this paper, we investigate the effects of charge storage engineering (CSE) on the NO gas sensing properties such as response, recovery, and sensitivity of a FET-type gas sensor with a horizontal floating-gate (FG) having tungsten trioxide (WO) as a sensing layer. When the FET transducer is set at an erase state (ΔV = -2 V), the holes injected into the FG by Fowler-Nordheim (F-N) tunneling increase the electron concentration at the WO-passivation layer interface. Accordingly, an oxidizing gas, NO, can take more electrons from WO, which increases the change in the FG voltage (ΔV) by a factor of 2.4. Also, the recovery speed of the sensor in the erase state can be improved by applying pre-bias (V) which is larger than the read bias (V). As the carriers in the WO film that can interact with NO increase by the excess holes stored in the FG by the erase operation, the sensitivity of the sensor also increases 3.2 times. The effects of CSE on various sensing performances are explained using energy band diagrams.
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http://dx.doi.org/10.1039/d1nr00513hDOI Listing
May 2021

Association between Sarcopenic Obesity and Nonalcoholic Fatty Liver Disease and Fibrosis detected by Fibroscan.

J Gastrointestin Liver Dis 2021 06 18;30(2):227-232. Epub 2021 Jun 18.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) and sarcopenic obesity share several pathophysiologic backgrounds. No prior studies have determined a plausible association between sarcopenic obesity and NAFLD and NAFLD-associated fibrosis. We aim to investigate the association between sarcopenic obesity and NAFLD, and NAFLD-associated fibrosis detected by transient elastography.

Methods: In a cross-sectional study from the 2017-2018 National Health and Nutrition Examination Survey, 1,925 participants were identified. NAFLD was defined by controlled attenuation parameter (CAP) scores and significant fibrosis (≥F2)/cirrhosis by liver stiffness measurements on transient elastography. Sarcopenic obesity was defined by appendicular lean mass and body fat.

Results: Individuals with sarcopenic obesity had a significantly higher odds of having NAFLD [CAP score ≥263 dB/m, odds ratio (OR): 2.88, 95% confidence interval (CI): 1.82-4.57, and CAP score ≥285, OR: 3.71, 95%CI: 2.24-6.14] after adjusting for age, gender, and race/ethnicity. The association remained statistically significant after adjustment for socioeconomic status, lifestyle and behavioral risk factors, and metabolic conditions (CAP score ≥263, OR: 2.61, 95%CI: 1.51-4.50, and CAP score ≥285, OR: 3.31, 95%CI: 1.85-5.96). Sarcopenic obesity was also associated with higher odds of having NAFLD-associated significant fibrosis (OR 2.22, 95% CI: 1.03-4.80) in the multivariate model. While those with sarcopenic obesity had a higher prevalence of NAFLD-associated cirrhosis, this association did not reach statistical significance.

Conclusions: Sarcopenic obesity was independently associated with an increased risk of NAFLD and NAFLD- associated significant fibrosis independent of well-defined risk factors. Targeted interventions to improve sarcopenic obesity may reduce the risk of NAFLD and NAFLD-associated siginificant fibrosis.
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http://dx.doi.org/10.15403/jgld-3323DOI Listing
June 2021

Trends in the Mortality of Biliary Tract Cancers Based on Their Anatomical Site in the United States From 2009 to 2018.

Am J Gastroenterol 2021 05;116(5):1053-1062

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.

Introduction: Recent trends in the incidence and mortality of biliary tract cancers are unknown. We estimated the trends in biliary tract cancers-related incidence and mortality stratified by anatomical site, age, sex, and race/ethnicity in the US adults.

Methods: We performed a population-based trend analysis using the US national incidence (2009-2017) and mortality records (2009-2018). We identified age-standardized incidence and mortality from intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer using appropriate ICD-10 code. Temporal mortality was calculated by joinpoint trend analysis with estimates of annual percentage change (APC) described as each trend segment.

Results: The incidence rates of ICC increased linearly (APC 8.9%, 95% confidence interval [CI] 7.8%-10.0%) while gallbladder cancer-related incidence rates remained stable early and decreased significantly later in the study (APC -2.8%, 95% CI -5.5% to -0.0% [2014-2017]). Age-standardized mortality from biliary tract cancers steadily increased with an annual increase of 2.0% (95% CI 1.6%-2.3%). Although there was a linear increase in the ICC-related mortality (APC 3.5%, 95% CI 3.1%-3.8%), extrahepatic cholangiocarcinoma-related mortality tended to remain stable earlier and increased later (APC 7.0%, 95% CI 4.6%-9.5% [2013-2018]). By contrast, gallbladder cancer-related mortality steadily decreased over 10 years (APC -1.6%, 95% CI -2.1% to -1.1%). Significant differences in mortality and changes in trends over time were observed in non-Hispanic blacks, Hispanics, and non-Hispanic Asians.

Discussion: In this analysis of nationally representative data, changing mortality trends in various biliary tract cancers was noted with a disproportionately higher burden of fatality in minorities.
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http://dx.doi.org/10.14309/ajg.0000000000001151DOI Listing
May 2021

Cudrania tricuspidata Root Extract Prevents Methylglyoxal-Induced Inflammation and Oxidative Stress via Regulation of the PKC-NOX4 Pathway in Human Kidney Cells.

Oxid Med Cell Longev 2021 30;2021:5511881. Epub 2021 Mar 30.

Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea.

Diabetic nephropathy is a microvascular complication induced by diabetes, and methylglyoxal (MGO) is a reactive carbonyl species causing oxidative stress that contributes to the induction of inflammatory response in kidney cells. (CT), cultivated in Northeast Asia, has been used as traditional medicine for treating various diseases, including neuritis, liver damage, and cancer. In this study, we determined whether a CT root extract (CTRE) can prevent MGO-induced reactive oxygen species (ROS) production and inflammation and assessed underlying mechanisms using a kidney epithelial cell line, HK-2. We observed that CTRE inhibited MGO-induced ROS production. Additionally, CTRE ameliorated the activation of MGO-induced inflammatory signaling pathways such as p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-JUN N-terminal kinase (JNK). Consistent with these results, expressions of p-nuclear factor-kappa B (NFB) and inflammatory cytokines, tumor necrosis factor-, interleukin- (IL-) 1, and IL-6, were decreased when compared with MGO-only exposed HK-2 cells. CTRE alleviated the MGO-induced decrease in nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and antioxidant enzyme mRNA expressions. MGO induced the expression of NADPH oxidase 4 (NOX4); CTRE pretreatment inhibited this induction. Further studies revealed that the NOX4 expression was inhibited owing to the suppression of MGO-induced protein kinase C (PKC) activation following CTRE treatment. Collectively, our data suggest that CTRE attenuates MGO-induced inflammation and oxidative stress via inhibition of PKC activation and NOX4 expression, as well as upregulating the Nrf2-antioxidant enzyme pathway in HK-2 cells.
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http://dx.doi.org/10.1155/2021/5511881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026309PMC
June 2021

Identification and Kinetic Characterization of Serum- and Glucocorticoid-Regulated Kinase Inhibitors Using a Fluorescence Polarization-Based Assay.

SLAS Discov 2021 06 30;26(5):655-662. Epub 2021 Mar 30.

Department of Chemistry, College of Natural Sciences, Keimyung University, Daegu, Republic of Korea.

The serum- and glucocorticoid-regulated kinase (SGK) family consists of three isoforms (SGK1, SGK2, and SGK3) that have been implicated in the regulation of tumor growth, metastasis, autophagy, and epithelial ion transport. SGK1 and SGK3 play essential roles in protein kinase B (AKT or PKB)-independent phosphoinositide 3-kinases (PI3K)-mediated tumorigenesis, as evidenced by the significantly elevated expression levels of SGK1 and SGK3 in many cancers, including prostate cancer, colorectal carcinoma, estrogen-dependent breast cancer, and glioblastoma. Therefore, SGK is a potential target for anticancer therapy. A small kinase-focused library comprising 160 compounds was screened against SGK1 using a fluorescence polarization-based kinase assay that yielded a Z'-factor of 0.82. Among the 39 compounds obtained as initial hits in a primary screen, 12 compounds contained the thiazolidine-2,4-dione scaffold. The inhibitory mechanisms of the most potent hit, KMU010402, were further investigated using kinetic analyses, followed by determination of the inhibition constants for SGK1, SGK2, and SGK3. Molecular modeling was used to propose a potential binding mode of KMU010402 to SGK1.
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http://dx.doi.org/10.1177/24725552211002465DOI Listing
June 2021

Prevalence of Nonalcoholic Fatty Liver Disease and Hepatic Fibrosis Among US Adults with Prediabetes and Diabetes, NHANES 2017-2018.

J Gen Intern Med 2021 Mar 5. Epub 2021 Mar 5.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

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http://dx.doi.org/10.1007/s11606-021-06677-wDOI Listing
March 2021

Sarcopenia in nonalcoholic fatty liver disease and all-cause and cause-specific mortality in the United States.

Liver Int 2021 08 11;41(8):1832-1840. Epub 2021 Mar 11.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has been associated with sarcopenia. However, mortality in the setting of NAFLD-related sarcopenia remains undefined. We aim to determine the all-cause and cause-specific mortality from sarcopenia among adults with NAFLD in the USA.

Methods: 11 065 individuals in the Third National Health and Nutrition Examination Survey were studied and linked mortality through 2015 was analysed. NAFLD was diagnosed based on presence of ultrasonographic hepatic steatosis without other known liver diseases. Sarcopenia was defined as skeletal muscle index determined by bioelectrical impedance analysis. The Cox proportional hazard model was used to assess all-cause mortality and cause-specific mortality, and hazard ratio (HR) adjusted for known risk factors.

Results: During a median follow-up of 23 years or more, sarcopenia was associated with increased all-cause mortality (HR 1.27, 95% confidence interval [CI] 1.11-1.44). Only in individuals with NAFLD, sarcopenia was associated with a higher risk for all-cause mortality, while this association was absent in those without NAFLD. Individuals with both sarcopenia and NAFLD had a higher risk for all-cause mortality (HR 1.28 95% CI 1.06-1.55) compared with those without sarcopenia and NAFLD. Furthermore, sarcopenia was associated with a higher risk for cancer- and diabetes-related mortality among those with NAFLD. This association was not noted in those without NAFLD.

Conclusion: In this nationally representative sample of US adults, sarcopenia was associated with a higher risk for all-cause, cancer- and diabetes-related mortality in individuals with NAFLD.
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http://dx.doi.org/10.1111/liv.14852DOI Listing
August 2021

Evaluation and management of extrahepatic manifestations of nonalcoholic fatty liver disease.

Clin Mol Hepatol 2021 Apr 3;27(2):221-235. Epub 2020 Dec 3.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease and a rapidly growing cause of chronic liver disease in children and adults worldwide. Diagnosis and management of extrahepatic manifestations of NAFLD, including cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, obstructive sleep apnea, polycystic ovarian syndrome, hypothyroidism, psoriasis, and extrahepatic malignancy are crucial for the treatment of patients with NAFLD. The leading cause of death in NAFLD is primarily from CVD, followed by liver-related mortality, extrahepatic cancer, liver cancer, and diabetes-related mortality. Therefore, clinicians need to identify high-risk patients earlier in the disease course and be aware of the extrahepatic manifestations of NAFLD to improve liver disease outcomes. In this review, we focus on the monitoring and management of the extrahepatic manifestations of NAFLD.
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http://dx.doi.org/10.3350/cmh.2020.0239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046623PMC
April 2021

Increasing changes in visceral adiposity is associated with higher risk for colorectal adenoma: Multilevel analysis in a prospective cohort.

J Gastroenterol Hepatol 2021 Jul 6;36(7):1836-1842. Epub 2021 Jan 6.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background And Aim: While many studies demonstrated an association between visceral adiposity and colorectal adenoma (CRA), the effect of longitudinal changes in body fat composition on CRA is unclear. We investigated the longitudinal association between changes in visceral adiposity and CRA occurrence.

Methods: Between 2006 and 2018, 732 (62.8%) of the 1165 subjects in a prospective cohort voluntarily underwent follow-up abdominal fat computed tomography and colonoscopy. We defined incident and recurrent CRA as adenoma detected at follow-up colonoscopy from negative and positive adenoma at baseline colonoscopy, respectively. Multilevel survival analysis examined the longitudinal association between changes in visceral fat and CRA.

Results: During a median follow-up of 7.4 years, 400 (54.6%) subjects developed CRA. In multivariable analysis, increasing changes in visceral adipose tissue (VAT) area were associated with higher risk of incident adenoma (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.00-1.46 for change per 10 cm increase; HR 1.79, 95% CI 1.08-2.97 for highest vs lowest quartile, P values for trend = 0.045). Likewise, increasing changes in VAT area were independently associated with a higher risk of recurrent adenoma (HR 1.35, 95% CI 1.13-1.62 for change per 10 cm increase; HR 1.62, 95% CI 1.04-2.52 for highest vs lowest quartile, P values for trend = 0.001). Changes in subcutaneous adipose tissue area were not independently associated with CRA.

Conclusion: Increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent CRA, independent of risk factors, suggesting that visceral adiposity may be an important target in CRA prevention.
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http://dx.doi.org/10.1111/jgh.15364DOI Listing
July 2021

Comparison of the Effects of Liraglutide on Islet Graft Survival Between Local and Systemic Delivery.

Cell Transplant 2020 Jan-Dec;29:963689720971245

College of Pharmacy and Gachon Institute Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon, Korea.

Islet transplantation has emerged as a promising treatment for type 1 diabetes mellitus. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, protects beta cells after islet transplantation by improving glycemic control through several mechanisms. In this study, we compared the effects of local pretreatment and systemic treatment with liraglutide on islet transplantation in a diabetic mouse model. Streptozotocin (STZ)-induced diabetic C57BL/6 mice were transplanted with syngeneic islets under the kidney capsule. Isolated islets were either locally treated with liraglutide before transplantation or mice were treated systemically by intraperitoneal injection after islet transplantation. Local pretreatment of islets with liraglutide was more effective in increasing body weight, decreasing hemoglobin A1c levels, and lowering blood glucose levels in STZ-diabetic mice transplanted with islets. Local pretreatment was also more effective in increasing insulin secretion and islet survival in STZ-diabetic mice. Histological analysis of the transplantation site revealed fewer apoptotic cells following local pretreatment compared with systemic injection of liraglutide. These findings indicate that liraglutide administered once locally before transplantation might have superior effects on islet preservation than systemic administration.
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http://dx.doi.org/10.1177/0963689720971245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784585PMC
July 2021

Trends in mortality in hepatitis C infection and alcoholic liver disease based on drug overdose in the United States.

J Viral Hepat 2021 02 18;28(2):436-439. Epub 2020 Nov 18.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

We examined trends in mortality from hepatitis C virus (HCV) infection and alcoholic liver disease (ALD) in the setting of drug overdose. Using US Census and national mortality records (2009-2018), we identified deaths with HCV infection, ALD and drug overdose. HCV-related mortality without drug overdose increased up to 2014, followed by a marked decrease. Mortality from HCV and drug overdose increased significantly. Whereas ALD-related mortality without drug overdose continued to rise, no significant trend from ALD with drug overdose was noted. HCV-related mortalities reduced after the introduction of DAA agents, while drug overdose-related mortality in HCV was constantly increased.
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http://dx.doi.org/10.1111/jvh.13435DOI Listing
February 2021

Patients with hepatocellular carcinoma from more rural and lower-income households have more advanced tumor stage at diagnosis and significantly higher mortality.

Cancer 2020 01 26;127(1):45-55. Epub 2020 Oct 26.

Division of Gastroenterology and Hepatology, University of South Dakota, Sioux Falls, South Dakota.

Background: Patients from rural and low-income households may have suboptimal access to liver disease care, which may translate into worse HCC outcomes. The authors provide a comprehensive update of HCC incidence and outcomes among US adults, focusing on the effect of rural geography and household income on tumor stage and mortality.

Methods: The authors retrospectively evaluated adults with HCC using Surveillance, Epidemiology, and End Results data from 2004 to 2017. HCC incidence was reported per 100,000 persons and was compared using z-statistics. Tumor stage at diagnosis used the Surveillance, Epidemiology, and End Results staging system and was evaluated with multivariate logistic regression. HCC mortality was evaluated using Kaplan-Meier and multivariate Cox proportional hazards methods.

Results: HCC incidence plateaued for most groups, with the exception of American Indians/Alaska Natives (2004-2017: APC, 4.17%; P < .05) and patients in the lowest household income category (<$40,000; 2006-2017: APC, 2.80%; P < .05). Compared with patients who had HCC in large metropolitan areas with a population >1 million, patients in more rural regions had higher odds of advanced-stage HCC at diagnosis (odds ratio, 1.10; 95% CI, 1.00-1.20; P = .04) and higher mortality (hazard ratio, 1.05; 95% CI, 1.01-1.08; P = .02). Compared with the highest income group (≥$70,000), patients with HCC who earned <$40,000 annually had higher odds of advanced-stage HCC (odds ratio, 1.15; 95% CI, 1.01-1.32; P = .03) and higher mortality (hazard ratio, 1.23; 95% CI, 1.16-1.31; P < .001).

Conclusions: Patients from rural regions and lower-income households had more advanced tumor stage at diagnosis and significantly higher HCC mortality. These disparities likely reflect suboptimal access to consistent high-quality liver disease care, including HCC surveillance.
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http://dx.doi.org/10.1002/cncr.33211DOI Listing
January 2020

Proposition of deposition and bias conditions for optimal signal-to-noise-ratio in resistor- and FET-type gas sensors.

Nanoscale 2020 Oct 23;12(38):19768-19775. Epub 2020 Sep 23.

Department of Electrical and Computer Engineering and Inter-university Semiconductor Research Center, Seoul National University, Seoul 08826, Republic of Korea.

In the field of gas sensor studies, most researchers are focusing on improving the response of the sensors to detect a low concentration of gas. However, factors that make a large response, such as abundant or strong adsorption sites, also work as a source of noise, resulting in a trade-off between response and noise. Thus, the response alone cannot fully evaluate the performance of sensors, and the signal-to-noise-ratio (SNR) should additionally be considered to design gas sensors with optimal performance. In this regard, thin-film-type sensing materials are good candidates thanks to their moderate response and noise level. In this paper, we investigate the effects of radio frequency (RF) sputtering power for deposition of sensing materials on the SNR of resistor- and field-effect transistor (FET)-type gas sensors fabricated on the same Si wafer. In the case of resistor-type gas sensors, the deposition conditions that improve the response also worsen the noise either by increasing the scattering at the bulk or damaging the interface of the sensing material. Among resistor-type gas sensors with sensing materials deposited with different RF powers, a sensor with low noise shows the largest SNR despite its small response. However, the noise of FET-type gas sensors is not affected by changes in RF power and thus there is no trade-off between response and noise. The results reveal different noise sources depending on the deposition conditions of the sensing material, and provide design guidelines for resistor- and FET-type gas sensors considering noise for optimal performance.
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http://dx.doi.org/10.1039/d0nr04406gDOI Listing
October 2020

Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study.

Clin Gastroenterol Hepatol 2021 Jul 17;19(7):1469-1479.e19. Epub 2020 Sep 17.

Stanford University, Stanford, California.

Background & Aims: Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19).

Methods: We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD.

Results: Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19.

Conclusions: The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.
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http://dx.doi.org/10.1016/j.cgh.2020.09.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497795PMC
July 2021
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