Publications by authors named "George Cholankeril"

111 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

Clinical factors associated with lack of serological response to SARS-CoV-2 mRNA vaccine in liver transplant recipients.

Liver Transpl 2021 Nov 1. Epub 2021 Nov 1.

Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas, USA.

Recent preliminary data report lower serological response to SARS-CoV-2 mRNA vaccines in solid organ transplant (SOT) recipients (1, 2). There are no data on factors associated with lack of serological response in SOT recipients - information that could guide recommendations regarding booster dose and closer follow up. We evaluated the serological response to SARS-CoV-2 vaccination in liver transplant (LT) recipients.
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http://dx.doi.org/10.1002/lt.26351DOI Listing
November 2021

Gastrointestinal manifestations of coronavirus disease 2019.

Curr Opin Infect Dis 2021 10;34(5):471-476

Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery.

Purpose Of Review: The ubiquitous expression of angiotensin-converting enzyme-2 receptors and its significance as the origin of viral entry have assisted in comprehending the pathophysiology of extrapulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we focus on the clinical significance of gastrointestinal manifestations.

Recent Findings: The global pandemic, a result of the widespread implications of SARS-CoV-2, remains a significant burden to current healthcare systems. Fever, dyspnea, and tussive symptoms have primarily been recognized as the most common presenting signs/symptoms. During the past one year our scope of practice has transcended beyond the management of the respiratory system to incorporate other varying systemic manifestations such as anorexia, nausea, vomiting, diarrhea, and abdominal pain. The outcomes reported by recent studies suggest an association between the presence of gastrointestinal symptoms and important clinical factors such as delay in presentation, disease severity, and mortality.

Summary: We provide a summarization of the most recent in-depth investigations of coronavirus disease 2019 with gastrointestinal manifestations and their conclusions. Although the pathophysiology remains an area of evolving interest, a better understanding of this disease process may allow for early recognition, efficient triage, and improved prognostication for those presenting with gastrointestinal manifestations of SARS-CoV-2.
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http://dx.doi.org/10.1097/QCO.0000000000000760DOI Listing
October 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

Practical Consideration for Drug Monitoring of Tacrolimus in Liver Transplantation Recipients with SARS-CoV-2 Infection.

Liver Transpl 2021 Aug 20. Epub 2021 Aug 20.

Liver Center, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX.

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http://dx.doi.org/10.1002/lt.26278DOI Listing
August 2021

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

Hepatology 2021 Dec 28;74(6):3316-3329. Epub 2021 Sep 28.

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
December 2021

The impact of alteration in gut microbiome in the pathogenesis of nonalcoholic fatty liver disease.

Curr Opin Infect Dis 2021 Oct;34(5):477-482

Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine.

Purpose Of Review: We have increasing evidence that alterations of the intestinal microbiome have a strong influence on human health. Previous work has demonstrated the association between changes in the microbiome and metabolic risk factors. One related area of interest is the relationship between dysbiosis and nonalcoholic fatty liver disease (NAFLD), as the global prevalence of NAFLD, and its resultant complications, increases.

Recent Findings: In this review, we summarize the hypothesized pathophysiology of dysbiosis-mediated progression of NAFLD, including promotion of an inflammatory intestinal environment, increased intestinal permeability, endogenous ethanol production, short-chain fatty acid production, secondary bile acid metabolism, and choline depletion. We also review potential therapeutic interventions of the microbiome to slow or prevent NAFLD progression, including antibiotics, probiotics, prebiotics, fecal microbiota transplant, and farnesoid × receptor agonism.

Summary: Much of the evidence supporting dysbiosis-mediated NAFLD progression has been gathered in high-quality animal trials. There remains a need for additional observational and randomized controlled trials in humans to establish causality between the suspected factors and pathogenesis of NAFLD.
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http://dx.doi.org/10.1097/QCO.0000000000000759DOI Listing
October 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

Elevated serum sodium in recipients of liver transplantation has a substantial impact on outcomes.

Transpl Int 2021 Oct 14;34(10):1971-1983. Epub 2021 Sep 14.

Division of Abdominal Transplant, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.

Dysnatremias are a rare but significant event in liver transplantation. While recipient pre-transplant hypernatremia has been demonstrated to increase post-transplant mortality, the degree of hypernatremia and the impact of its resolution have been less well characterized. Here, we used multivariate Cox regression with a comprehensive list of donor and recipient factors in order to conduct a robust multivariate retrospective database study of 54,311 United Network for Organ Sharing (UNOS) liver transplant patients to analyze the effect of pre-transplant serum sodium on post-transplant mortality, post-transplant length of hospitalization, and post-transplant graft survival. Mortality and graft failure increased in a stepwise fashion with increasing pre-transplant hypernatremia: 145 -150 mEq/L (HR = 1.118 and HR = 1.113), 150-155 mEq/L (HR = 1.324 and HR = 1.306), and > 155 mEq/L (HR = 1.623 and HR = 1.661). Pre-transplant hypo- and hypernatremia also increased length of post-transplant hospitalization: < 125 mEq/L (HR = 1.098), 125-130 mEq/L (HR = 1.060), 145 -150 mEq/L (HR = 1.140), and 150-155 mEq/L (HR = 1.358). Resolution of hypernatremia showed no significant difference in mortality compared with normonatremia, while unresolved hypernatremia significantly increased mortality (HR = 1.254), including a durable long-term increased mortality risk for patients with creatinine < 2 mg/dL and MELD < 25. Pre-transplant hypernatremia serves as a morbid prognostic indicator for post-transplant morbidity and mortality.
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http://dx.doi.org/10.1111/tri.13968DOI Listing
October 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

NAFLD and HCC: Time to Bridge the Gap.

Hepatology 2021 Nov 30;74(5):2336-2338. Epub 2021 Aug 30.

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

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http://dx.doi.org/10.1002/hep.32025DOI Listing
November 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

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

Association of Anti-TNF Therapy With Increased Risk of Acute Cholangitis in Patients With Primary Sclerosing Cholangitis.

Inflamm Bowel Dis 2021 10;27(10):1602-1609

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA.

Background: Patients with primary sclerosing cholangitis (PSC) are at increased risk of developing acute cholangitis. The majority of patients with PSC have comorbid inflammatory bowel disease, and many take immunosuppressive medications. The epidemiological risks for the development of acute cholangitis in patients with PSC, including the impact of immunosuppressive therapy, are unknown.

Methods: We conducted a 2-center, retrospective cohort study using data from 228 patients at Stanford University Medical Center and Santa Clara Valley Medical Center (CA), a county health care system. Patient demographics, medications, PSC disease severity, and inflammatory bowel disease status were extracted. Using stepwise variable selection, we included demographic and covariate predictors in the multiple logistic regression model assessing risk factors for cholangitis. Time-to-event analysis was performed to evaluate specific immunosuppressive medications and development of cholangitis.

Results: Thirty-one percent of patients had at least 1 episode of acute cholangitis (n = 72). Anti-tumor necrosis factor (TNF) therapy was associated with increased odds of acute cholangitis (odds ratio, 7.29; 95% confidence interval, 2.63-12.43), but immunomodulator use was protective against acute cholangitis (odds ratio, 0.23; 95% confidence interval, 0.05-0.76). Anti-TNF therapy was associated with decreased time-to-cholangitis, with a median time of 28.4 months; in contrast, only 11.1% of patients who were prescribed immunomodulators developed cholangitis over the same time period (P < 0.001).

Conclusions: Our observations suggest that classes of immunosuppressive medications differentially modify the odds of acute cholangitis. Biologic therapy, ie, anti-TNF therapy, was shown to have significantly higher odds for patients developing acute cholangitis whereas immunomodulator therapy was shown to have a potential protective effect. These findings may help guide physicians in decision-making for determining appropriate immunosuppressive therapy.
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http://dx.doi.org/10.1093/ibd/izaa317DOI Listing
October 2021

Nationwide Evolution of Pediatric Endoscopic Retrograde Cholangiopancreatography Indications, Utilization, and Readmissions over Time.

J Pediatr 2021 05 14;232:159-165.e1. Epub 2020 Nov 14.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Lucille Packard Children's Hospital at Stanford University Medical Centerr, Stanford, CA. Electronic address:

Objectives: To analyze outcome and utilization trends over time of pediatric endoscopic retrograde cholangiopancreatography (ERCP) in an all-capture US population-level study.

Study Design: Using the National Inpatient Sample (2005-2014) and National Readmission Database (2010-2014), we identified pediatric (age <20 years) hospitalizations during which ERCP was performed and assessed ERCP-associated readmissions. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify hospitalization diagnoses, comorbidities, and patient/hospital characteristics. Multivariate logistic regression analyses were performed to determine significant predictors (P < .05) of 30-day readmission.

Results: A total of 11 060 hospitalized pediatric patients underwent ERCP between 2005 and 2014. Most were female (n = 8859; 81%), aged 14-20 years (n = 9342; 84%), and white (n = 4230; 45%). Most (85%) of ERCPs were therapeutic, and leading indications were biliary (n = 5350; 48%) and pancreatitis (n = 3218; 29%). Thirteen pecent of patients were readmitted post-ERCP. Odds for 30-day readmission were highest for patients with a history of liver transplantation, age 0-4 years, male sex, and obesity (P < .001 for each). Patients in both urban teaching and urban hospitals had much lower odds than those in rural hospitals for prolonged length of stay associated with ERCP.

Conclusions: These data represent a comprehensive study of nationwide trends in age-specific volumes and outcomes following ERCP in the pediatric population and provide important insights into trends in pediatric pancreaticobiliary disease management, as well as practice setting, patient characteristics, and patient comorbidities associated with pediatric post-ERCP outcomes, including readmission and length of stay.
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http://dx.doi.org/10.1016/j.jpeds.2020.11.019DOI Listing
May 2021

Are Proton Pump Inhibitors Contributing to SARS-COV-2 Infection?

Am J Gastroenterol 2020 11;115(11):1920-1921

Division of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA.

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http://dx.doi.org/10.14309/ajg.0000000000000933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505035PMC
November 2020

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

Prevalence of Fatty Liver Disease and Fibrosis Detected by Transient Elastography in Adults in the United States, 2017-2018.

Clin Gastroenterol Hepatol 2021 07 12;19(7):1499-1501.e2. Epub 2020 Aug 12.

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

Fatty liver disease is a clinicopathologic spectrum that encompasses simple steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Transient elastography has evolved as an accurate technique and noninvasive tool for assessing hepatic fibrosis in clinical practice. The controlled attenuation parameter (CAP) score has been added to elastography, which computes ultrasound attenuation related to hepatic steatosis and improves the measurement of hepatic steatosis. Given the unmet need to reckon the current burden of disease, it is essential to estimate the recent prevalence of fatty liver disease and fibrosis assessed by transient elastography in the United States. We investigated the sex-, race/ethnicity-, and body mass index-based prevalence of fatty liver disease and hepatic fibrosis by CAP-enhanced transient elastography in the United States.
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http://dx.doi.org/10.1016/j.cgh.2020.08.017DOI Listing
July 2021

Physical Activity, Measured Objectively, Is Associated With Lower Mortality in Patients With Nonalcoholic Fatty Liver Disease.

Clin Gastroenterol Hepatol 2021 06 16;19(6):1240-1247.e5. Epub 2020 Jul 16.

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

Background & Aims: The association between physical activity (PA) and all-cause and cause-specific mortality from nonalcoholic fatty liver disease (NAFLD) requires investigation. We studied whether PA, measured by accelerometer, is associated with all-cause and cause-specific mortality among individuals with NAFLD.

Methods: We performed a longitudinal analysis using the 2003 to 2006 US National Health and Nutrition Examination Survey data of adults (age, ≥20 y) and collecting mortality data through December 2015. NAFLD was defined based on the hepatic steatosis index or US fatty liver index scores, in the absence of other causes of chronic liver disease. PA was measured from participants who wore accelerometers 10 h/d for a minimum of 4 days over a 7-day period and were classified as total PA, moderate to vigorous PA (MVPA), and sedentary behavior.

Results: Over an average follow-up period of 10.6 years, increasing the duration of total PA was associated with a reduced risk of death, from any cause, in an age- and sex-adjusted model (hazard ratio [HR], 0.52; 95% CI, 0.32-0.86 for highest quartile vs lowest quartile; P for trend = .001) and multivariable model (HR, 0.46; 95% CI, 0.28-0.75; P for trend < .001) among individuals with NAFLD. Increasing the duration of MVPA was associated with a lower risk of death from any cause in individuals with NAFLD. Furthermore, longer total PA was associated with a lower risk for cardiovascular disease-related death in individuals with NAFLD (HR, 0.28; 95% CI, 0.08-0.98 for highest quartile vs lowest quartile; P for trend = .007). We did not find this association for cancer-related mortality in individuals with NAFLD. Increasing the duration of sedentary behavior did not affect all-cause or cause-specific mortality in individuals with NAFLD.

Conclusions: Longer total PA and MVPA, measured by accelerometers over a 7-day period, are associated with lower all-cause and cardiovascular mortality in individuals with NAFLD.
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http://dx.doi.org/10.1016/j.cgh.2020.07.023DOI Listing
June 2021

Early Impact of COVID-19 on Solid Organ Transplantation in the United States.

Transplantation 2020 11;104(11):2221-2224

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

Background: The regional impact of coronavirus disease 2019 on solid organ transplantation in the United States has not been fully evaluated.

Methods: A retrospective analysis of month-to-month trends on waitlist additions, waitlist deaths, and transplant surgeries between all United Network for Organ Sharing (UNOS) regions was performed. A linear regression model trained on historical data was used to estimate anticipated transplantation volume.

Results: All UNOS regions reported a decrease in total waitlist additions and transplant surgeries. The largest decreases in total transplants were identified in regions 1, 2, 6, and 9, with regions 2, 7, 8, and 9 noting the largest decrease in waitlist additions. Six of the 11 regions noted increases in waitlist deaths, with UNOS regions 9, 1, and 2, all located within the Northeast, noting the highest percent increase in waitlist deaths at 170%, 89%, and 54%, respectively. The largest reductions in solid organ transplantation and waitlist deaths were seen in kidney and lung transplantation. Current transplantation volume is significantly lower than the low range of the 95% confidence interval derived from the linear regression model (2182 versus 3110; P < 0.05).

Conclusions: Significant decreases in total waitlist additions and transplant surgeries with increases in waitlist deaths were noted in the majority of US transplant domains. The impact was especially prevalent in areas with high burden of coronavirus disease 2019 infection. National and regional strategies aimed at minimizing disruptions in transplantation are needed.
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http://dx.doi.org/10.1097/TP.0000000000003391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406203PMC
November 2020

Association of Digestive Symptoms and Hospitalization in Patients With SARS-CoV-2 Infection.

Am J Gastroenterol 2020 07;115(7):1129-1132

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

Introduction: High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established.

Methods: This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild.

Results: In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68-13.94).

Discussion: The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.
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http://dx.doi.org/10.14309/ajg.0000000000000712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302101PMC
July 2020

Implementation and Impact of Universal Preprocedure Testing of Patients for COVID-19 Before Endoscopy.

Gastroenterology 2020 Oct 17;159(4):1586-1588.e4. Epub 2020 Jun 17.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Stanford University School of Medicine, Stanford, California. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833582PMC
October 2020

Gender and Racial Differences in Hospitalizations for Primary Biliary Cholangitis in the USA.

Dig Dis Sci 2021 05 13;66(5):1461-1476. Epub 2020 Jun 13.

Department of Medicine, St. Luke's Hospital, St. Louis, MO, USA.

Background/aim: The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear.

Method: We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations.

Result: There were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09-1.16]), 53% lower in Blacks (RR: 0.47 [0.45-0.49]) and 5% lower among other racial minorities (0.95 [0.91-0.99]). The rate was higher among females (RR:4.02 [3.93-4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03-2.10] and 1.33 [0.96-1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites.

Conclusion: The hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.
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http://dx.doi.org/10.1007/s10620-020-06402-3DOI Listing
May 2021

Association of Digestive Symptoms and Hospitalization in Patients with SARS-CoV-2 Infection.

medRxiv 2020 Apr 28. Epub 2020 Apr 28.

Background: High rates of concurrent gastrointestinal manifestations have been noted in patients with COVID- 19, however the association between these digestive manifestations and need for hospitalization has not been established.

Methods: Following expedited approval from our Institutional Review Board, we analyzed retrospectively collected data from consecutive patients with confirmed COVID-19 based on a positive polymerase chain reaction testing at our institution from March 03, 2020 to April 7, 2020. Baseline demographic, clinical, laboratory and patient-reported symptom data were collected at presentation in the emergency room. Multivariable logistic regression analyses were performed to evaluate the association between hospitalization and presence of gastrointestinal symptoms.

Results: During this study period, we identified 207 consecutive patients with confirmed COVID-19. 34.5% noted concurrent gastrointestinal symptoms; of which 90% of gastrointestinal symptoms were mild. In a multivariate regression model controlled for demographics and disease severity, an increased risk for hospitalization was noted in patients with any gastrointestinal symptom (adjusted OR 4.84 95% CI: 1.68-13.94]. Diarrhea was associated with a seven-fold higher likelihood for hospitalization (adjusted OR=7.58, 95% CI: 2.49-20.02, P <0.001) and nausea or vomiting had a four times higher odds (adjusted OR 4.39, 95% CI: 1.61-11.4, P = 0.005).

Conclusion: We demonstrate that a significant portion of COVID19 patients have concurrent mild gastrointestinal symptoms and that the presence of these digestive symptoms is associated with a need for hospitalization. With the current focus on streamlining triaging efforts, first responders and frontline providers should consider assessing for digestive symptoms in their initial clinical evaluation and decision-making.
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http://dx.doi.org/10.1101/2020.04.23.20076935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276990PMC
April 2020

Low Thyroid Function in Nonalcoholic Fatty Liver Disease Is an Independent Predictor of All-Cause and Cardiovascular Mortality.

Am J Gastroenterol 2020 09;115(9):1496-1504

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

Introduction: Higher levels of thyroid-stimulating hormone (TSH) in the euthyroid state can negatively affect the metabolic health, including nonalcoholic fatty liver disease (NAFLD). We studied the effect of TSH levels in the setting of normal levels of thyroid hormone on all-cause and cause-specific mortality stratified by NAFLD status.

Methods: The National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and NHANES III-linked mortality data through 2015 were used. NAFLD was defined as ultrasonographically diagnosed hepatic steatosis without coexisting liver diseases. Subclinical hypothyroidism was defined as a TSH level over 4.5 mIU/L and "low-normal" thyroid function as higher TSH level (2.5-4.5 mIU/L) within the euthyroid reference range. The Cox proportional hazard model analyzed the all-cause mortality and cause-specific mortality.

Results: In a multivariate logistic regression analysis, individuals with low thyroid function demonstrated an association with NAFLD in a dose-dependent manner. During a median follow-up of 23 years, low thyroid function was associated with increased all-cause mortality only in the univariate model. Low thyroid function was associated with a higher risk for all-cause mortality in individuals with NAFLD and not in those without NAFLD. Furthermore, low thyroid function was associated with a higher risk for cardiovascular mortality in the entire population and among those with NAFLD but demonstrated no association with the non-NAFLD group.

Discussion: In this large nationally representative sample of American adults, low thyroid function was associated with NAFLD and a predictor of higher risk for all-cause and cardiovascular mortality in individuals with NAFLD.
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http://dx.doi.org/10.14309/ajg.0000000000000654DOI Listing
September 2020

Decline in Annual Mortality of Hepatitis C Virus-Related Hepatocellular Carcinoma in the United States, From 2009 to 2018.

Gastroenterology 2020 10 8;159(4):1558-1560.e2. Epub 2020 May 8.

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

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http://dx.doi.org/10.1053/j.gastro.2020.05.007DOI Listing
October 2020

Accuracy of Noninvasive Fibrosis Scoring Systems in African American and White Patients With Nonalcoholic Fatty Liver Disease.

Clin Transl Gastroenterol 2020 04;11(4):e00165

Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA.

Objectives: Nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) score, and AST-alanine aminotransferase (ALT) ratio are noninvasive fibrosis scoring systems for the staging of liver fibrosis in patients with chronic liver disease.

Methods: In a large cohort of patients with nonalcoholic fatty liver disease, we compared AST-ALT ratio, NFS, FIB-4 score, and APRI score in predicting advanced fibrosis (defined as fibrosis stage ≥ 3) in histologically confirmed African American (AA) and white patients. We identified 907 patients: 677 (74.6%) white and 230 (25.3%) AA patients with nonalcoholic fatty liver disease.

Results: Of the 907 patients, 115 (12.8%) patients had advanced fibrosis (stages 3 and 4) in the total cohort: 6 (2.6%) AAs, and 109 (16.2%) whites. In AAs, the area under the receiver operating characteristic (area under the curve) for predicting advanced fibrosis was 0.58 by NFS, 0.86 by APRI score, 0.77 by FIB-4 score, and 0.65 by AST-ALT ratio. In whites, the area under the receiver operating characteristic for predicting advanced fibrosis was 0.82 by NFS, 0.82 by APRI score, 0.88 by FIB-4 score, and 0.76 by AST-ALT ratio. In the AA population, NFS > 0.675, FIB-4 score > 2.67, and APRI score > 1.5 each has a negative predictive value of 98%, whereas the negative predictive values in whites are 91%, 88%, and 85%, respectively.

Discussion: Noninvasive fibrosis scoring systems can reliably exclude advanced fibrosis in both AAs and whites and have acceptable discriminatory ability to predict advanced fibrosis in whites. The utility of noninvasive fibrosis scoring systems in predicting advanced fibrosis in AAs needs further validation in a larger multicenter cohort.
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http://dx.doi.org/10.14309/ctg.0000000000000165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263664PMC
April 2020
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