Hepatology Commons^™

Identifying Gaps In Interpretive Services To Improve Patient Care: A Root Cause Analysis, Christiane Phillips, Reed Ritterbusch, Ken Scott, Jenny Wickens

Articles, Abstracts, and Reports

No abstract provided.

Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian

Articles, Abstracts, and Reports

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression …

Primary Sclerosing Cholangitis: Epidemiology, Genetics, Diagnosis, And Current Management., Eric Gochanour, Channa Jayasekera, Kris V Kowdley

Articles, Abstracts, and Reports

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-gochanour a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-interview-kowdley an interview with the author.

Tumor Slice Culture As A Biologic Surrogate Of Human Cancer., Heidi L Kenerson, Kevin M Sullivan, Yongwoo D Seo, Kathryn M Stadeli, Cigdem Ussakli, Xiaowei Yan, Christopher G Lausted, Venu G Pillarisetty, James O Park, Kimberly J Riehle, Matthew Yeh, Qiang Tian, Raymond S Yeung

Articles, Abstracts, and Reports

Background: The tumor microenvironment (TME) is critical to every aspect of cancer biology. Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and

Methods: One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression …

Methylation Signatures In Peripheral Blood Are Associated With Marked Age Acceleration And Disease Progression In Patients With Primary Sclerosing Cholangitis., Michael Trauner, Yevgeniy Gindin, Zhaoshi Jiang, Chuhan Chung, G Mani Subramanian, Robert P Myers, Aliya Gulamhusein, Kris V Kowdley, Cynthia Levy, Zachary Goodman, Michael P Manns, Andrew J Muir, Christopher L Bowlus

Articles, Abstracts, and Reports

Background & Aims: A DNA methylation (DNAm) signature derived from 353 CpG sites (the Horvath clock) has been proposed as an epigenetic measure of chronological and biological age. This epigenetic signature is accelerated in diverse tissue types in various disorders, including non-alcoholic steatohepatitis, and is associated with mortality. Here, we assayed whole blood DNAm to explore age acceleration in patients with primary sclerosing cholangitis (PSC).

Methods: Using the MethylationEPIC BeadChip (850K) array, DNAm signatures in whole blood were analyzed in 36 patients with PSC enrolled in a 96-week trial of simtuzumab (Ishak F0-1, n = 13; F5-6, n = 23). …

A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response To Obeticholic Acid In Patients With Nash., Samer Gawrieh, Xiuqing Guo, Jingyi Tan, Marie Lauzon, Kent D Taylor, Rohit Loomba, Oscar W Cummings, Sreekumar Pillai, Pallav Bhatnagar, Kris V Kowdley, Katherine Yates, Laura A Wilson, Yii-Der Ida Chen, Jerome I Rotter, Naga Chalasani

Articles, Abstracts, and Reports

A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome-wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 …

Characterization Of Patients With Both Alcoholic And Nonalcoholic Fatty Liver Disease In A Large United States Cohort., George Khoudari, Amandeep Singh, Mazen Noureddin, Danielle Fritze, Rocio Lopez, Imad Asaad, Eric Lawitz, Fred Poordad, Kris V Kowdley, Naim Alkhouri

Articles, Abstracts, and Reports

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS) and is characterized by steatosis in the absence of significant alcohol consumption. However, MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.

AIM: To assess the clinical characteristics of patients with both alcoholic and NAFLD (BAFLD) in a large cohort in the United States.

METHODS: Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included. NAFLD was diagnosed based on elevated alanine aminotransferase (ALT) and being overweight or obese in the absence of other …

Association Of Histologic Disease Activity With Progression Of Nonalcoholic Fatty Liver Disease., David E Kleiner, Elizabeth M Brunt, Laura A Wilson, Cynthia Behling, Cynthia Guy, Melissa Contos, Oscar Cummings, Matthew Yeh, Ryan Gill, Naga Chalasani, Brent A Neuschwander-Tetri, Anna Mae Diehl, Srinivasan Dasarathy, Norah Terrault, Kris V Kowdley, Rohit Loomba, Patricia Belt, James Tonascia, Joel E Lavine, Arun J Sanyal

Articles, Abstracts, and Reports

Importance: The histologic evolution of the full spectrum of nonalcoholic fatty liver disease (NAFLD) and factors associated with progression or regression remain to be definitively established.

Objective: To evaluate the histologic evolution of NAFLD and the factors associated with changes in disease severity over time.

Design, Setting, and Participants: A prospective cohort substudy from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database study, a noninterventional registry, was performed at 8 university medical research centers. Masked assessment of liver histologic specimens was performed, using a prespecified protocol to score individual biopsies. Participants included 446 adults with NAFLD enrolled in …

Current Perspectives Into The Evaluation And Management Of Hepatitis B: A Review., Vignan Manne, Eric Gochanour, Kris V Kowdley

Articles, Abstracts, and Reports

Hepatitis B is a widespread disease which affects millions of people worldwide. Chronic hepatitis B (CHB) can lead to significant morbidity and mortality due to complications such as cirrhosis and hepatocellular carcinoma. The pathophysiology of hepatitis is critical to diagnosing CHB. Deciding which patients with CHB should be treated is an important decision as treatment can often lead to better outcomes in the appropriate patient population. The nucleos(t)ide analog inhibitors entecavir and tenofovir are currently the mainstay of treatment as they are able to successfully suppress the virus and lead to fewer complications. Novel therapies are currently being developed which …

Sofosbuvir, Velpatasvir, And Voxilaprevir For Treatment Of Recurrent Hepatitis C Virus Infection After Liver Transplantation., Maria G Cardona-Gonzalez, Jason D Goldman, Lawrence Narayan, Diana M Brainard, Kris V Kowdley

Articles, Abstracts, and Reports

There are limited data on direct-acting antiviral (DAA) treatment options for previously treated patients with recurrent genotype 3 (GT3) hepatitis C virus (HCV) after liver transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is currently approved for treatment of HCV in patients with prior treatment with DAAs. We report the first published experience using SOF/VEL/VOX after liver transplantation for a DAA-experienced patient with severe hepatitis due to early recurrent GT3 HCV. The patient was treated with SOF/VEL/VOX that was extended to a total duration of 16 weeks and was intensified with ribavirin (RBV) starting at week 8 due to persistent viremia during treatment. Sustained virologic …

Complement Factor D Protects Mice From Ethanol-Induced Inflammation And Liver Injury., Rebecca L Mccullough, Megan R Mcmullen, Megan M Sheehan, Kyle L Poulsen, Sanjoy Roychowdhury, Dian J Chiang, Michele T Pritchard, Juan Caballeria, Laura E Nagy

Articles, Abstracts, and Reports

Complement plays a crucial role in microbial defense and clearance of apoptotic cells. Emerging evidence suggests complement is an important contributor to alcoholic liver disease. While complement component 1, Q subcomponent (C1q)-dependent complement activation contributes to ethanol-induced liver injury, the role of the alternative pathway in ethanol-induced injury is unknown. Activation of complement via the classical and alternative pathways was detected in alcoholic hepatitis patients. Female C57BL/6J [wild type (WT)], C1q-deficient ( C1qa

Extracorporeal Cellular Therapy (Elad) In Severe Alcoholic Hepatitis: A Multinational, Prospective, Controlled, Randomized Trial., Julie Thompson, Natasha Jones, Ali Al-Khafaji, Shahid Malik, David Reich, Santiago Munoz, Ross Macnicholas, Tarek Hassanein, Lewis Teperman, Lance Stein, Andrés Duarte-Rojo, Raza Malik, Talal Adhami, Sumeet Asrani, Nikunj Shah, Paul Gaglio, Anupama Duddempudi, Brian Borg, Rajiv Jalan, Robert Brown, Heather Patton, Rohit Satoskar, Simona Rossi, Amay Parikh, Ahmed Elsharkawy, Parvez Mantry, Linda Sher, David Wolf, Marquis Hart, Charles Landis, Alan Wigg, Shahid Habib, Geoffrey Mccaughan, Steven Colquhoun, Alyssa Henry, Patricia Bedard, Lee Landeen, Michael Millis, Robert Ashley, William Frank, Andrew Henry, Jan Stange, Ram Subramanian

Articles, Abstracts, and Reports

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of …

A Research Agenda For Curing Chronic Hepatitis B Virus Infection., Harvey Alter, Timothy Block, Nathaniel Brown, Alan Brownstein, Carol Brosgart, Kyong-Mi Chang, Pei-Jer Chen, Francis V Chisari, Chari Cohen, Hashem El-Serag, Jordan Feld, Robert Gish, Jeffrey Glenn, Tim Greten, Haitao Guo, Ju-Tao Guo, Yujin Hoshida, Jianming Hu, Kris V Kowdley, Wenhui Li, Jake Liang, Stephan Locarnini, Anna S Lok, William Mason, Brian Mcmahon, Anand Mehta, Robert Perrillo, Peter Revill, Charles M Rice, Joann Rinaudo, Raymond Schinazi, Christoph Seeger, Kirty Shetty, John Tavis, Fabien Zoulim

Articles, Abstracts, and Reports

No abstract provided.

The Natural History Of Severe Acute Liver Injury., David G Koch, J L Speiser, V Durkalski, R J Fontana, T Davern, B Mcguire, R T Stravitz, A M Larson, I Liou, Oren K Fix, M L Schilsky, T Mccashland, J E Hay, N Murray, O S Shaikh, D Ganger, A Zaman, S B Han, R T Chung, R S Brown, S Munoz, K R Reddy, L Rossaro, R Satyanarayana, A J Hanje, J Olson, R M Subramanian, C Karvellas, B Hameed, A H Sherker, W M Lee, A Reuben

Articles, Abstracts, and Reports

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death.

METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × …

Nutritional Approaches To Achieve Weight Loss In Nonalcoholic Fatty Liver Disease., Christine C Hsu, Erik Ness, Kris V Kowdley

Articles, Abstracts, and Reports

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches …

New Developments In The Treatment Of Primary Biliary Cholangitis - Role Of Obeticholic Acid., Manan A Jhaveri, Kris V Kowdley

Articles, Abstracts, and Reports

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease that predominantly affects women in early to middle age. It is typically associated with autoantibodies to mitochondrial antigens and results in immune-mediated destruction of small and medium-sized intrahepatic bile ducts leading to cholestasis, hepatic fibrosis and may progress to cirrhosis or hepatic failure and, in some cases, hepatocellular carcinoma. The clinical presentation and the natural history of PBC have improved over the years due to recognition of earlier widespread use of ursodeoxycholic acid (UDCA); about one-third of patients show suboptimal biochemical response to UDCA with poor prognosis. Until recently, …