Novel Implementation of Hepatitis B to Hepatitis Delta Reflex Testing in a US Healthcare System.

Introduction: Hepatitis delta virus (HDV) is the most aggressive form of viral hepatitis, yet screening rates in the United States are low, and few institutions have attempted interventions to improve the screening cascade. We assessed barriers to reflex test implementation, including lack of a Food and Drug Administration-approved reflex test, and implemented hepatitis B surface antigen (HBsAg) to HDV antibody (HDV Ab) reflex testing in our large, urban, academic healthcare system.

Methods: We evaluated outcomes 1 year after implementation using summary statistics.

The relationships between MASLD, extrahepatic multimorbidity and all-cause mortality in UK Biobank cohort.

Background & Aims: This study aimed to estimate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), with and without multimorbidity, on all-cause mortality.

Methods: We analysed data from the UK Biobank. MASLD was identified as a fatty liver index (FLI) ≥ 60 and presence of cardiometabolic risk factors.

Heavy metals are liver fibrosis risk factors in people without traditional liver disease etiologies.

Liver fibrosis is an important predictor of mortality. Liver disease case definitions changed in 2023. These definitions include an easily over-looked group with no traditional etiology (NTE) of liver disease and no steatosis.

Mixture analysis of associations between environmental and workplace toxins and liver damage and telomere length, stratified by race/ethnicity.

This study aimed to identify the worst "bad actors" in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S. population, using weighted quantile sum (WQS) modeling with stratification by race/ethnicity.

AI-enabled opportunistic measurement of liver steatosis in coronary artery calcium scans predicts cardiovascular events and all-cause mortality: an AI-CVD study within the Multi-Ethnic Study of Atherosclerosis (MESA).

Introduction: About one-third of adults in the USA have some grade of hepatic steatosis. Coronary artery calcium (CAC) scans contain more information than currently reported. We previously reported new artificial intelligence (AI) algorithms applied to CAC scans for opportunistic measurement of bone mineral density, cardiac chamber volumes, left ventricular mass, and other imaging biomarkers collectively referred to as AI-cardiovascular disease (CVD).

Fibrosis and steatotic liver disease in US adolescents according to the new nomenclature.

Objective: To apply the new nomenclature for steatotic liver diseases (SLD), replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD), in adolescents using National Health and Nutrition Examination Survey (NHANES) data.

Methods: Among 1410 adolescents (12-19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa).

Imprinted immune abnormalities in liver transplant patients cured of hepatitis C with antiviral drugs.

Chronic HCV infection induces interferon and dysregulates immune responses through inflammation and chronic antigenic stimulation. Antiviral drugs can cure HCV, providing a unique opportunity to examine the immunological restoration that does and does not occur when a chronic viral infection is eradicated. We quantified blood cytokines levels and used mass cytometry to immunophenotype peripheral blood mononuclear cells before and after HCV cure in 2 groups of patients and controls.

The adverse characteristics of hepatocellular carcinoma in the non-cirrhotic liver disproportionately disadvantage Black patients.

Background: Black patients have higher hepatocellular carcinoma (HCC)-related mortality than White patients and more often develop HCC in non-cirrhotic liver. HCC surveillance is primarily directed toward cirrhotic patients. We aimed to characterize HCC in non-cirrhotic patients and to identify factors associated with HCC beyond Milan criteria.

A Prospective Open-Label Dose-Response Study to Correct Vitamin D Deficiency in Cirrhosis.

Background: Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown.

Objective: We aimed to establish the dose-response relationship between vitamin D and 25(OH)D in patients with liver cirrhosis.

Design: An open-label study of orally-administered vitamin D (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717).

Modification of the diabetes prevention program for the treatment of nonalcoholic fatty liver disease: A pilot study.

Objective: The Diabetes Prevention Program (DPP) is the gold standard lifestyle modification program that reduces incident type 2 diabetes mellitus. Patients with prediabetes and patients with non-alcoholic fatty liver disease (NAFLD) often share metabolic features; we hypothesized that the DPP could be adapted and used to improve outcomes in patients with NAFLD.

Methods: NAFLD patients were recruited into a 1 year modified DPP.

Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis.

Background: Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC).

Aims: To identify risk factors for new-onset HCC in patients cured of hepatitis C.

Methods: Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post-SVR were analyzed.

Environmental exposures are important risk factors for advanced liver fibrosis in African American adults.

Background & Aims: The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States.

Methods: Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018).

Association of HSD17B13 and PNPLA3 With Liver Enzymes and Fibrosis in Hispanic/Latino Individuals of Diverse Genetic Ancestries.

Background & Aims: Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease-associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry.

IL-6/STAT3 axis dictates the PNPLA3-mediated susceptibility to non-alcoholic fatty liver disease.

Background & Aims: A number of genetic polymorphisms have been associated with susceptibility to or protection against non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain unknown. Here, we focused on the rs738409 C>G single nucleotide polymorphism (SNP), which produces the I148M variant of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and is strongly associated with NAFLD.

Methods: To enable mechanistic dissection, we developed a human pluripotent stem cell (hPSC)-derived multicellular liver culture by incorporating hPSC-derived hepatocytes, hepatic stellate cells, and macrophages.

Hepatocellular carcinoma surveillance, incidence, and tumor doubling times in patients cured of hepatitis C.

Background: Hepatocellular carcinoma (HCC) incidence and mortality vary by race/ethnicity and both are higher in Black patients than in Whites. For HCC surveillance, all cirrhotic patients are advised to undergo lifelong twice-annual abdominal imaging. We investigated factors associated with surveillance and HCC incidence in a diverse HCC risk group, cirrhotic patients recently cured of hepatitis C virus (HCV) infection.

Liver Cancer Has a Distinctive Profile in Black Patients: Current Screening Guidelines May Be Inadequate.

There is mounting evidence that Black patients develop more advanced liver cancers with less advanced liver disease. These findings have important implications for the future of liver cancer screening.

A comparative study of cirrhosis sub-staging using the Laennec system, Beijing classification, and morphometry.

There is constant remodeling in a cirrhotic liver resulting in cirrhosis being spatially heterogeneous. The Laennec system, and, more recently the Beijing classification, have been used to sub-classify various degrees of cirrhosis. It is unknown how these two schemes compare with each other, how they are impacted by geographic variation, and how they correlate with clinical outcomes.

A Digital Case-Finding Algorithm for Diagnosed but Untreated Hepatitis C: A Tool for Increasing Linkage to Treatment and Cure.

Background And Aims: Although chronic HCV infection increases mortality, thousands of patients remain diagnosed-but-untreated (DBU). We aimed to (1) develop a DBU phenotyping algorithm, (2) use it to facilitate case finding and linkage to care, and (3) identify barriers to successful treatment.

Approach And Results: We developed a phenotyping algorithm using Java and SQL and applied it to ~2.

Dose-response relationship between World Trade Center dust exposure and hepatic steatosis.

Background: The World Trade Center (WTC) attack exposed thousands of workers to toxic chemicals that have been linked to liver diseases and cancers. This study examined the relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis in the WTC General Responders Cohort (GRC).

Methods: All low-dose computed tomography (CT) scans of the chest performed on the WTC GRC between September 11, 2001 and December 31, 2018, collected as part of the World Trade Center Health Program, were reviewed.

Kidney injury biomarkers during exposure to tenofovir-based preexposure prophylaxis.

We previously reported a higher incidence of non-albumin proteinuria and a small but significant decline in estimated glomerular filtration rate (eGFR) among HIV-negative adults randomized to emtricitabine/tenofovir disoproxil fumarate preexposure prophylaxis (FTC/TDF PrEP) versus placebo. In a nested case--control study among participants randomized to FTC/TDF PrEP, established kidney injury biomarkers measured at 12 months were not significantly different between participants who subsequently experienced one of these kidney endpoints and randomly selected controls who did not.

Innovations in Hepatitis C Screening and Treatment.

New therapies offer hope for a cure to millions of persons living with hepatitis C virus (HCV) infection. HCV elimination is a global goal that will be difficult to achieve using the traditional paradigms of diagnosis and care. The current standard has evolved toward universal HCV screening and treatment, to achieve elimination goals.

Hepatitis C-positive Black patients develop hepatocellular carcinoma at earlier stages of liver disease and present with a more aggressive phenotype.

Background: In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection.

Methods: Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed.

A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function.

Viral hepatitis leads to immune-mediated liver injury. The rate of disease progression varies between individuals. We aimed to phenotype immune cells associated with preservation of normal liver function during hepatitis C virus (HCV) infection.

How to Survive COVID-19 Even If the Vaccine Fails.

Coronavirus disease 2019 (COVID-19) has created an emergency of epic proportions. While a vaccine may be forthcoming, this is not guaranteed, as discussed herein. The potential problems and ominous signs include (1) lung injury that developed in animals given an experimental vaccine for the severe acute respiratory syndrome coronavirus (SARS-CoV)-1; (2) a perversion of adaptive immune responses called antibody-dependent enhancement of infection that occurs in SARS-CoV-1 and that may occur in people vaccinated for COVID-19; (3) the frequent and recurrent infections that are caused by respiratory coronaviruses; and (4) the appearance of mutations in SARS-CoV-2 proteins, which raise the specter of vaccine escape mutants.