Hepatology Commons^™

Rising Incidence Of Acute Hepatitis A Among Adults And Clinical Characteristics In A Tertiary Care Center Of Pakistan, Yumna Shahid, Amna Subhan Butt, Iqra Jamali, Faisal Wasim Ismail

Section of Gastroenterology

Background: For decades, hepatitis A virus (HAV) has been a leading cause of acute hepatitis among children and was less prevalent among adults. However, recently a paradigm shift has been observed in the epidemiology of HAV, as evident by cases of acute hepatitis due to HAV among adults.
Aim: To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus (HEV) infection.
Methods: This was a trend analysis conducted at Aga Khan University Hospital Karachi (Sindh, Pakistan) from February 2024 to May 2024. Individuals aged 18 years and older diagnosed with acute viral …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Silvia S Chiang, Megan B Murray, Alexander W Kay, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …

Global Burden Of Major Chronic Liver Diseases In 2021, Gong Feng, Yusuf Yilmaz, Luca Valenti, Wai Kay Seto, Calvin Q. Pan, Nahum Méndez Sánchez, Feng Ye, Silvia Sookoian, Giovanni Targher, Christopher Opio

Internal Medicine, East Africa

Background: This study utilised the Global Burden of Disease data (2010–2021) to analyse the rates and trends in point preva-lence, annual incidence and years lived with disability (YLDs) for major chronic liver diseases, such as hepatitis B, hepatitis C,metabolic dysfunction-associated liver disease, cirrhosis and other chronic liver diseases.

Methods: Age-standardised rates per 100,000 population for prevalence, annual incidence and YLDs were compared acrossregions and countries, as well as the socio-demographic index (SDI). Trends were expressed as percentage changes (PC) andestimates were reported with uncertainty intervals (UI).

Results: Globally, in 2021, the age-standardised rates per 100,000 population for the …

Phase 3 Validation Of Paam For Hepatocellular Carcinoma Risk Stratification In Cirrhosis, Naoto Fujiwara, Camden Lopez, Tracey L Marsh, Indu Raman, Cesia A Marquez, Subhojit Paul, Sumit K Mishra, Naoto Kubota, Courtney Katz, Hiroaki Kanzaki, Michael Gonzalez, Lisa Quirk, Sneha Deodhar, Pratibha Selvakumar, Prithvi Raj, Neehar D Parikh, Lewis R Roberts, Myron E Schwartz, Mindie H Nguyen, Alex S Befeler, Stephanie Page-Lester, Sudhir Srivastava, Ziding Feng, K Rajender Reddy, Saira Khaderi, Sumeet K Asrani, Fasiha Kanwal, Hashem B El-Serag, Jorge A Marrero, Amit G Singal, Yujin Hoshida

Faculty, Staff and Students Publications

Background & aims: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.

Methods: Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The …

Tuberculosis In Adult Migrants In Europe: A Tbnet Consensus Statement, Heinke Kunst, Berit Lange, Olga Hovardovska, Annabelle Bockey, Dominik Zenner, Aase B Andersen, Sally Hargreaves, Manish Pareek, Jon S Friedland, Christian Wejse, Graham Bothamley, Lorenzo Guglielmetti, Dumitru Chesov, Simon Tiberi, Alberto Matteelli, Anna M Mandalakas, Jan Heyckendorf, Johannes Eimer, Akanksha Malhotra, Javier Zamora, Anca Vasiliu, Christoph Lange, Tbnet

Faculty, Staff and Students Publications

INTRODUCTION: Global migration has increased in recent decades owing to war, conflict, persecution and natural disasters, but also secondary to increased opportunities related to work or study. Migrants' risk of tuberculosis (TB) differs depending on migration, socioeconomic status, mode of travel and TB risk in transit, TB incidence and healthcare provision in country of origin. Despite advances in TB care for migrants and new treatment strategies, decisions for managing migrants at risk of TB often rely on expert opinions, rather than clinical evidence.

METHODS: A systematic literature search was conducted, studies were mapped to different recommendation groups and included studies …

Loss Of Mucin 2 And Mhc Ii Molecules Causes Rare Resistance To Murine Rv Infection, Carolyn Bomidi, Faith M Sawyer, Noah Shroyer, Margaret Conner, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, …

2′-Fucosyllactose Inhibits Human Norovirus Replication In Human Intestinal Enteroids, Ketki Patil, B Vijayalakshmi Ayyar, Nicole M Hayes, Frederick H Neill, Lars Bode, Mary K Estes, Robert L Atmar, Sasirekha Ramani

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2′-fucosyllactose …

Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is strongly associated with the development of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. PTLD is one of the most common malignancies following liver transplantation and is associated with significant morbidity and mortality. Factors such as EBV-serostatus mismatch and prolonged or high levels of immunosuppression impact a patient's risk of developing PTLD. While pre-transplant EBV serological screening and post-transplant monitoring of EBV-DNA levels are strongly recommended, universal guidelines for its prevention and management are lacking. Due to a lack of robust prospective studies, current clinical practices vary widely. The treatment of PTLD typically involves reducing …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Acute-On-Chronic Liver Failure (Aclf): The ‘Kyoto Consensus’-Steps From Asia, Ashok Choudhury, Anand V Kulkarni, Vinod Arora, A S Soin, Abdul Kadir Dokmeci, Abhijeet Chowdhury, Abraham Koshy, Ajay Duseja, Ajay Kumar, Ajay Kumar Mishra, Ajay Kumar Patwa, Ajit Sood, Akash Roy, Akash Shukla, Albert Chan, Aleksander Krag, Amar Mukund, Ameet Mandot, Amit Goel, Amna Subhan Butt, Amrish Sahney, Ananta Shrestha, Andrés Cárdenas, Angelo Di Giorgio, Anil Arora, Anil Chandra Anand, Anil Dhawan, Ankur Jindal, Anoop Saraya, Anshu Srivastava, Anupam Kumar, Apichat Kaewdech, Apurva Pande, Archana Rastogi, Arun Valsan, Ashish Goel, Ashish Kumar, Ashwani K Singal, Atsushi Tanaka, Audrey Coilly, Ayaskanta Singh, Babu Lal Meena, Barath Jagadisan, Barjesh Chander Sharma, Bikrant Bihari Lal, C E Eapen, Cesar Yaghi, Chandan Kumar Kedarisetty, Chang Wook Kim, Charles Panackel, Chen Yu, Chetan R Kalal, Chhagan Bihari, Chien Hao Huang, Chitranshu Vasishtha, Christian Jansen, Christian Strassburg, Chun Yen Lin, Constantine J Karvellas, Cosmas Rinaldi Adithya Lesmana, Cyriac Abby Philips, Debbie Shawcross, Dharmesh Kapoor, Dhiraj Agrawal, Diana Alcantara Payawal, Dibya Lochan Praharaj, Dinesh Jothimani, Do Seon Song, Dong Joon Kim, Dong-Sik Kim, Duan Zhongping, Fazal Karim, Francois Durand, Gamal E Shiha, Gennaro D'Amico, George K Lau, Girish Kumar Pati, Graciela Elia Castro Narro, Guan-Huei Lee, Gupse Adali, Guru Prasad Dhakal, Gyongyi Szabo, H C Lin, Hai Li, Hari Kumar Nair, Harshad Devarbhavi, Harshvardhan Tevethia, Hasmik Ghazinian, Hemamala Ilango, Hong Ling Yu, Irsan Hasan, J Fernandez, Jacob George, Jaideep Behari, James Fung, Jasmohan Bajaj, Jaya Benjamin, Jennifer C Lai, Jidong Jia, Jin Hua Hu, Jin Jun Chen, Jin Lin Hou, Jin Mo Yang, Johannes Chang, Jonel Trebicka, Jörg C Kalf, Jose D Sollano, Joy Varghese, Juan Pablo Arab, Jun Li, K Rajender Reddy, Kaiser Raja, Kalpana Panda, Kamal Kajal, Karan Kumar, Kaushal Madan, Kemal Fariz Kalista, Kessarin Thanapirom, Khin Maung Win, Ki Tae Suk, Krishnadas Devadas, Laurentius A Lesmana, Lubna Kamani, Madhumita Premkumar, Madunil A Niriella, Mamun Al Mahtab, Man Fung Yuen, Manal Hel Sayed, Manasa Alla, Manav Wadhawan, Manoj Kumar Sharma, Manoj Sahu, Manya Prasad, Mark Dhinesh Muthiah, Martin Schulz, Meenu Bajpai, Mettu Srinivas Reddy, Michael Praktiknjo, Ming Lung Yu, Mithra Prasad, Mithun Sharma, Mohamed Elbasiony, Mohammed Eslam, Mohd Golam Azam, Mohd Rela, Moreshwar S Desai, Mukul Vij, Nadim Mahmud, Narendra Singh Choudhary, Navin Kumar Marannan, Necati Ormeci, Neeraj Saraf, Nipun Verma, Nobuaki Nakayama, Norifumi Kawada, Oidov Baatarkhuu, Omesh Goyal, Osamu Yokosuka, P N Rao, Paolo Angeli, Pathik Parikh, Patrick S Kamath, Paul J Thuluvath, Philipp Lingohr, Piyush Ranjan, Prashant Bhangui, Pravin Rathi, Puja Sakhuja, Puneet Puri, Qin Ning, R K Dhiman, Rahul Kumar, Rajan Vijayaraghavan, Rajeev Khanna, Rakhi Maiwall, Ravi Mohanka, Richard Moreau, Rino Alvani Gani, Rohit Loomba, Rohit Mehtani, Ruveena Bhavani Rajaram, S S Hamid, Sachin Palnitkar, Sadhna Lal, Sagnik Biswas, Sakkarin Chirapongsathorn, Samagra Agarwal, Sanjeev Sachdeva, Sanjiv Saigal, Santhosh E Kumar, Sargsyan Violeta, Satender Pal Singh, Satoshi Mochida, Saurabh Mukewar, Seema Alam, Seng Gee Lim, Shahinul Alam, Shalimar, Shantan Venishetty, Shikha S Sundaram, Shiran Shetty, Shobna Bhatia, Shweta A Singh, Shyam Kottilil, Simone Strasser, S M Shasthry, Soe Thiha Maung, Soek Siam Tan, Sombat Treeprasertsuk, Sonal Asthana, Steffen Manekeller, Subhash Gupta, Subrat Kumar Acharya, Sudhamshu K C, Sudhir Maharshi, Sumeet Asrani, Sunil Dadhich, Sunil Taneja, Suprabhat Giri, Surender Singh, Tao Chen, Tarana Gupta, Tatsuo Kanda, Tawesak Tanwandee, Teerha Piratvishuth, Ulrich Spengler, V G Mohan Prasad, Vandana Midha, Venera Rakhmetova, Vicente Arroyo, Vikrant Sood, Vinay Kumar Br, Vincent Wai-Sun Wong, Viniyendra Pamecha, Virendra Singh, Vishwa Mohan Dayal, Vivek A Saraswat, Wray Kim, Wasim Jafri, Wenyi Gu, Wong Yu Jun, Xiaolong Qi, Yogesh K Chawla, Yoon Jun Kim, Yu Shi, Zaigham Abbas, Guresh Kumar, Shuichiro Shiina, Lai Wei, Masao Omata, Shiv Kumar Sarin, Apasl-Aclf Research Consortium (Aarc) For Apasl-Aclf Working Party

Faculty, Staff and Students Publications

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the …

Sudden Cardiac Death Associated With Fatty Liver Disease, Jonathan Vo, Thien T T T Truyen, Audrey Uy-Evanado, Arayik Sargsyan, Harpriya Chugh, Christopher Young, Sean Hurst, Christina Y Miyake, Kyndaron Reinier, Sumeet S Chugh

Faculty, Staff and Students Publications

BACKGROUND: Fatty liver disease or steatotic liver disease (SLD) affects 25% of the global population and has been associated with heart disease. However, there is a lack of postmortem studies in the context of sudden cardiac death (SCD).

OBJECTIVES: To investigate the relationship between SLD and SCD.

METHODS: A post-mortem case-case study was conducted in victims of SCD from an ongoing community-based study in Southern California (Ventura, CA, 2015-2023). Diagnosis of SLD was determined from post-mortem liver histopathology reports. For each patient, demographic variables, laboratory values, and presence of co-morbidities were ascertained from medical records and were compared between patients …

Hes V20 Outperforms Galad For Detection Of Hcc: A Phase 3 Biomarker Study In The United States, Hashem B El-Serag, Qingchun Jin, Nabihah Tayob, Emad Salem, Michelle Luster, Abeer Alsarraj, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.

APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and …

Dna Methylation Profile In Buffy Coat Identifies Methylation Differences Between Cirrhosis With And Without Hepatocellular Carcinoma, Hyeyeun Lim, Hashem B El-Serag, Michelle Luster, Megan L Grove, Jinyoung Byun, Yuri Jung, Younghun Han, Eric Boerwinkle, Christopher I Amos, Aaron P Thrift

Faculty, Staff and Students Publications

Background/Objectives: Cirrhosis is the precursor to most cases of hepatocellular carcinoma (HCC). Understanding the mechanisms leading to the transition from cirrhosis to HCC and identifying key biomarkers is crucial to developing effective screening strategies and reducing HCC-related mortality. DNA methylation is associated with gene inactivation and plays an important role in physiological and pathological processes; however, its role in cirrhosis progression to HCC is unknown.

Methods: We performed genome-wide DNA methylation profiling using Illumina Infinium MethylationEPI BeadChip in pre-diagnostic samples from 22 cirrhosis patients who subsequently developed HCC and 22 cirrhosis patients who remained HCC-free during an average 4-year follow-up. …

Acute Hepatitis B Infection In A Patient With Confirmed Immunity On Long-Acting Cabotegravir/Rilpivirine, William K B Boateng, Neil Carlin, Etan Spira, Maria E Szabela, Kosisochukwu J Ezeh

Faculty and Staff Publications

Long-acting injectable formulation of cabotegravir/rilpivirine (CAB/RPV) is a promising novel maintenance therapy for HIV infection. However, coinfection with active hepatitis B virus (HBV) infection is a contraindication to initiating this therapy. Despite guidelines, patients with HBV immunity can still contract acute HBV infection. We report a case of a 30-year-old man with HIV who transitioned from antiretroviral therapy to CAB/RPV and had confirmed HBV immunity. The patient, though asymptomatic, showed significantly elevated liver function tests (LFTs) before his monthly CAB/RPV injection. He was hospitalized and diagnosed with acute HBV infection. His LFTs improved, and he was taken off CAB/RPV and …

Semaglutide And The Evolving Landscape Of Metabolic Dysfunction–Associated Steatotic Liver Disease, Rohan Karkra

Digital Journal of Clinical Medicine

The FDA approved Semaglutide (Wegovy™) on August 15, 2025, for adults with MASLD and moderate to advanced fibrosis (F2–F3), making it the second approved therapy after Resmetirom. MASLD affects up to 38% of adults and is now the leading cause of liver disease. In the phase 3 ESSENCE trial, Semaglutide achieved resolution of steatohepatitis without worsening fibrosis in 62.9% versus 34.3% with placebo, with additional benefits in weight loss and glycemic control. While long-term data remain pending and access barriers exist, this approval marks a significant advance in MASLD therapy with meaningful histologic and metabolic improvements.

Correspondence To Letter To The Editor On “Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial”, Sung Hwan Lee, Sun Young Yim, Ji Hoon Kim, Sunyoung S Lee, Ahmed O Kaseb, Peng Wei, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

The Impact Of Post-Remission Granulocyte Colony-Stimulating Factor Use In The Phase 3 Studies Of Venetoclax Combination Treatments In Patients With Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Keith W Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher

Faculty, Staff and Student Publications

No abstract provided.

Bcg-Induced Dna Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing The Risk For Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Santiago Carrero Longlax, Kent J Koster, Ashish M Kamat, Marisa Lozano, Seth P Lerner, Rebecca Hannigan, Tomoki Nishiguchi, Abhimanyu, Daanish Sheikh, Malik Ladki, Alexandra Portillo, Amrit Koirala, Tajhal D Patel, Zoe Spieler, Aaron B Benjamin, Maxim Lebedev, Theresa U Ofili, Robert W Hutchison, George Udeani, Lynne A Opperman, Gabriel Neal, Anna M Mandalakas, Mihai G Netea, Moshe Arditi, Pablo Avalos, Sandra L Grimm, Cristian Coarfa, Jeffrey D Cirillo, Andrew R Dinardo

Faculty, Staff and Students Publications

BACKGROUND: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

METHODS: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19-specific vaccines.

RESULTS: Study enrollment was halted early, prior to reaching …