Faculty Bibliography
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Biliary Tract Injury in Patients With COVID-19: A Review of the Current Literature
Multiple studies and extensive clinical experience have shown that COVID-19 can impact the hepatobiliary system, with most reports describing primarily hepatocellular injury with elevations of aspartate aminotransferase and alanine aminotransferase. In addition to hepatocellular injury, recent literature has described a pattern of severe biliary tract injury resulting in patients with COVID-19. This novel syndrome, termed COVID-19 cholangiopathy, may have severe consequences for affected patients. This article will examine the literature describing this novel entity, its relationship to secondary sclerosing cholangitis, clinical outcomes, and proposed mechanisms underlying this form of biliary injury.
PMCID:9666809
PMID: 36397771
ISSN: 1554-7914
CID: 5384972
Letter to the editor: Both universal screening and vaccination are essential components of a multipronged approach to hepatitis B elimination [Letter]
PMID: 35092080
ISSN: 1527-3350
CID: 5155002
High Sustained Virologic Response Rates of Glecaprevir/Pibrentasvir in Patients With Dosing Interruption or Suboptimal Adherence
INTRODUCTION:Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment. METHODS:Data were pooled from 10 phase 3 clinical trials of treatment-naive patients with HCV genotype 1-6 without cirrhosis/with compensated cirrhosis (treatment adherence analysis) and 13 phase 3 clinical trials of all patients with HCV (interruption analysis). RESULTS:Among 2,149 patients included, overall mean adherence was 99.4%. Over the treatment duration, adherence decreased (weeks 0-4: 100%; weeks 5-8: 98.3%; and weeks 9-12: 97.1%) and the percentage of patients with ≥80% or ≥90% adherence declined. SVR12 rate in the intention-to-treat (ITT) population was 97.7% (modified ITT SVR12 99.3%) and remained high in nonadherent patients in the modified ITT population (<90%: 94.4%-100%; <80%: 83.3%-100%). Psychiatric disorders were associated with <80% adherence, and shorter treatment duration was associated with ≥80% adherence. Among 2,902 patients in the interruption analysis, 33 (1.1%) had a G/P treatment interruption of ≥1 day, with an SVR12 rate of 93.9% (31/33). No virologic failures occurred. DISCUSSION:These findings support the impact of treatment duration on adherence rates and further reinforce the concept of "treatment forgiveness" with direct-acting antivirals.
PMCID:8389353
PMID: 34465693
ISSN: 1572-0241
CID: 5011252
Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications
INTRODUCTION/BACKGROUND:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS:We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS:Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION/CONCLUSIONS:Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.
PMID: 33993134
ISSN: 1572-0241
CID: 4876442
Safety of Patients with Hepatitis C Virus Treated with Glecaprevir/Pibrentasvir from Clinical Trials and Real-World Cohorts
INTRODUCTION/BACKGROUND:More than 70 million people are estimated to be infected with hepatitis C virus (HCV) globally. If left untreated, HCV infection can lead to complications such as extensive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Evolution of treatments has resulted in highly effective and well-tolerated all-oral direct-acting antivirals. The pangenotypic regimen of glecaprevir/pibrentasvir is approved for treating HCV for patients without cirrhosis or with compensated cirrhosis (CC). Guidelines have evolved to simplify treatment to enable non-specialists to manage and treat HCV-infected patients. Simultaneously, such treatment algorithms provide guidance on the pretreatment identification of small subsets of patients who may require specialist treatment and long-term follow-up for advanced liver disease, including those at risk of developing HCC. This study describes the safety profile of glecaprevir/pibrentasvir in patients identified using previously described noninvasive laboratory measures who may be eligible for treatment by non-liver specialists. METHODS:This post hoc analysis of glecaprevir/pibrentasvir in patients, identified by noninvasive laboratory measures, intended to exclude patients with advanced liver disease and severe renal impairment, who can be managed within non-liver specialist settings. Patients were included from clinical trials and real-world studies of glecaprevir/pibrentasvir for HCV treatment. Baseline demographics, clinical characteristics, and safety assessments, including adverse events and laboratory abnormalities, were summarized. RESULTS:Data across these large-scale studies confirm that glecaprevir/pibrentasvir is well tolerated across different patient populations, with fewer than 0.1% of patients experiencing a serious adverse event related to treatment drugs, and few patients developing HCC during or after treatment. CONCLUSION/CONCLUSIONS:The safety profile of glecaprevir/pibrentasvir enhances the confidence of non-liver specialists to treat the majority of HCV-infected patients, and provides an opportunity to expand the treater pool, potentially increasing diagnosis and treatment rates for HCV, contributing to elimination of HCV.
PMID: 34021887
ISSN: 1865-8652
CID: 4894932
Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment
BACKGROUND:There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. METHODS:This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6-9 months) and late follow-up (9-16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. RESULTS:= 0.007). No bleeding complications attributable to anticoagulation were observed. CONCLUSION/CONCLUSIONS:TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.
PMID: 34073236
ISSN: 2077-0383
CID: 4891422
The case for simplifying and using absolute targets for viral hepatitis elimination goals
The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries' progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.
PMID: 32979881
ISSN: 1365-2893
CID: 4679282
Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2
PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.55 µM. PT150 is a member of an extended platform of novel glucocorticoid receptor (GR) and androgen receptor (AR) modulating molecules. In vivo, their predominant net effect is one of systemic glucocorticoid antagonism, but they also show direct downregulation of AR and minor GR agonism at the cellular level. We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol.
PMCID:7738205
PMID: 33305659
ISSN: 1551-4005
CID: 4735512
Prevalence of Chronic Hepatitis B Virus Infection in the United States
Chronic hepatitis B virus (HBV) infection represents a major global health problem, affecting an estimated 257-291 million persons worldwide and is associated with substantial morbidity and mortality because of clinical complications, such as liver cirrhosis and hepatocellular carcinoma. Despite existing resources for vaccination, screening, and treatment, the burden of chronic HBV remains significant within the United States (US). Both the World Health Organization (WHO) and US Department of Health and Human Services (DHHS) have articulated formal hepatitis elimination plans, although an updated assessment of the epidemiology and prevalence of chronic HBV is needed to inform these initiatives. The Chronic Liver Disease Foundation (CLDF), a nonprofit 501(c)(3) educational organization dedicated to raising awareness of liver disease, partnered with a panel of leading US hepatologists to conduct an updated literature review to develop a contemporary HBV prevalence range estimate. Panel members researched and evaluated the peer-reviewed literature on HBV prevalence and, in May 2019, discussed their findings during a live HBV epidemiology workshop. The panel proposed an overall estimated prevalence for chronic HBV infection in the US of 1.59 million persons (range 1.25-2.49 million). This review provides a summary of the workshop findings and conclusions, which may serve to inform future initiatives focused on HBV screening and prevention in the US.
PMID: 32483003
ISSN: 1572-0241
CID: 4480922
Clinical assessment for high-risk patients with non-alcoholic fatty liver disease in primary care and diabetology practices
BACKGROUND:Primary care practitioners (PCPs) and diabetologists are at the frontline of potentially encountering patients with NASH. Identification of those at high risk for adverse outcomes is important. AIM/OBJECTIVE:To provide practical guidance to providers on how to identify these patients and link them to specialty care. METHODS:US members of the Global Council on NASH evaluated the evidence about NASH and non-invasive tests and developed a simple algorithm to identify high-risk NASH patients for diabetologists and primary care providers. These tools can assist frontline providers in decision-making and referral to gastroenterology/hepatology practices for additional assessments. RESULTS:The presence of NASH-related advanced fibrosis is an independent predictor of adverse outcomes. These patients with NASH are considered high risk and referral to specialists is warranted. Given that staging of fibrosis requires a liver biopsy, non-invasive tests for fibrosis would be preferred. Consensus recommendation from the group is to risk-stratify patients based on metabolic risk factors using the FIB-4 as the initial non-invasive test due to its simplicity and ease of use. A FIB-4 score ≥1.3 can be used for further assessment and linkage to specialty care where additional technology to assess liver stiffness or serum fibrosis test will be available. CONCLUSION/CONCLUSIONS:Due to the growing burden of NAFLD and NASH, PCPs and diabetologists are faced with increased patient encounters in their clinical practices necessitating referral decisions. To assist in identifying high-risk NASH patients requiring specialty care, we provide a simple and easy to use algorithm.
PMID: 32598051
ISSN: 1365-2036
CID: 4526802
