About

David Edward Kaplan, MD, MSc, is a Professor of Medicine in the Division of Gastroenterology at the Hospital of the University of Pennsylvania and the Veteran's Administration Medical Center. He serves as the Attending Gastroenterologist and Hepatologist at the Corporal Michael J. Crescenz VA Medical Center and is the Section Chief of Hepatology within the Division of Gastroenterology and Hepatology. His research expertise encompasses clinical epidemiology related to cirrhosis, hepatocellular carcinoma, MASLD/MASH, and viral hepatitis, with a focus on clinical trials in chronic liver disease. Dr. Kaplan's work involves the development of algorithms for estimating liver disease severity from healthcare data and investigating the genetic and clinical factors associated with liver diseases. His contributions include numerous publications on risk stratification, management of portal hypertension, and the impact of various treatments on liver disease outcomes.

Research topics

• Medicine
• Internal medicine
• Genetics
• Biology
• Surgery
• Radiology
• Oncology

Selected publications

• Outcomes of Simultaneous Liver-Kidney Transplant and Kidney After Liver Transplant Using the Safety Net Criteria—A Single-center Experience

  Transplantation Direct · 2026-04-22

  articleOpen access

  Background. The impact of revised Organ Procurement and Transplantation Network policy defining eligibility for simultaneous liver-kidney (SLK) and the safety net criteria for kidney after liver (KAL) transplantation remains insufficiently characterized. Methods. We conducted a retrospective study of adults (>18 y) evaluated for liver transplant alone (LTA), SLK, or KAL at the University of Pennsylvania from August 10, 2017, to February 28, 2023. The primary outcome was mortality among SLK and KAL recipients and those patients waitlisted for KAL. Secondary outcomes included native kidney recovery in LTA recipients, estimated glomerular filtration rate (eGFR) at 1 y post-kidney transplant, and time between liver and kidney transplants. Results. Of 1655 patients evaluated, 57 (3.4%) met SLK criteria; 49 (86%) underwent SLK and 8 (14%) received LTA. Among 1598 LTA candidates, 1010 (63%) were waitlisted and 717 (71%) received LTA. After excluding 9 early deaths (1.3%) that were unrelated to KAL delay, 67 survivors (9.5%) met KAL safety net criteria. Thirty-four (50.8%) were waitlisted (15 transplanted over a median of 220 d), 30 (44.8%) declined, and 3 (4.8%) remained under evaluation. Mortality was 4.1% after SLK and no deaths occurred after KAL >3.7 and 3.1 y of follow-up, with 3 deaths (8.8%) among KAL waitlisted patients. Of the 16 KAL waitlisted patients alive without kidney transplant at last follow-up, 2 (12.5%) were delisted after documented renal recovery and an additional 9 (56.3%) had eGFR >20 ml/min/1.73 m 2 and were being considered for delisting; together, 11 (68.8%) met predefined criteria for substantial native kidney recovery. One-year median eGFR was similar (SLK 51 versus KAL 54 mL/min/1.73 m 2 ; P = 0.6). Conclusions. Early post-LTA mortality was unrelated to delayed KAL transplantation. Recovery of native kidney function while waiting for KAL was frequent. KAL transplants occurred within a year of LTA with favorable survival and graft outcomes.

  PublisherDOI

• Clinical outcomes and care for spontaneous bacterial peritonitis: A national cohort study

  Hepatology · 2025-01-29 · 8 citations

  articleOpen access

  BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) leads to high rates of acute kidney injury (AKI), hepatorenal syndrome, and mortality. Population-based studies on contemporary SBP epidemiology are needed to inform care. In a large, national cohort of patients diagnosed with SBP and confirmed by ascitic fluid criteria, we characterized ascitic fluid characteristics, in-hospital and 12-month mortality, AKI, and recurrent SBP. APPROACH AND RESULTS: We investigated how individual and bundled quality measures for SBP associated with outcomes after multi-level adjustment for health-system, patient clinical factors, and quality measures. Individual and bundled quality metrics were inpatient antibiotics within 48 hours, i.v. albumin, repeat paracentesis within 48 hours, recognition of SBP, and prophylactic antibiotics upon discharge. Among 4330 patients with newly diagnosed SBP, in-hospital mortality was 15.5%, and 12-month mortality was 56.6%. The incidence of stage 1 AKI was 26.6%, 15.7% for stage 2, and 22.8% for stage 3. The cumulative incidence of recurrent SBP was 10.3%. Guideline-recommended albumin was the only individual metric associated with reduced in-hospital mortality (HR: 0.73, 95% CI: 0.59-0.91). Receipt of a higher number of metrics from the SBP bundle was associated with progressively lower 12-month post-discharge mortality: patients who received 3, 4, and 5 SBP bundle components had 20%, 38%, and 56% lower hazard of mortality, respectively, relative to those receiving 2 or fewer (all p <0.001). The SBP bundle was associated with a lower incidence of stage 3 versus stage 0-2 AKI (OR: 0.66, 95% CI: 0.51-0.86). CONCLUSIONS: Prospective implementation of evidence-based SBP bundles may improve care outcomes and mortality in SBP.

  PublisherOA PDFDOI

• Impact of changing liver transplant exception policies to address blood type disparities in access to transplantation

  Liver Transplantation · 2025-08-05

  articleSenior author
  PublisherDOI

• Detection of Circulating mRNA Variants in Hepatocellular Carcinoma Patients Using Targeted RNAseq

  Liver Cancer · 2025-04-04

  articleOpen access

  Introduction: Mutations in circulating nucleic acids can be used as biomarkers for the early detection and management of hepatocellular carcinoma (HCC). However, while circulating tumor DNA and microRNA have been extensively explored, circulating tumor mRNA and circulating mRNA mutants (ctmutRNA), which may provide advantages over other analytes, remain less well described. We previously reported the identification of 288 HCC selective ctmutRNA variants, called "candidates," from a small cohort of HCC patients using total RNAseq. The objective of the current study was to use targeted RNAseq to validate the specificity and sensitivity of these HCC selective variants in an independent cohort of patients with liver cirrhosis (LC). Methods: = 11), a normal liver tissue and 3 cell lines were also studied. cDNA synthesis was followed by library construction using QIAseq RNA Fusion XP panel. QC analysis was carried out with an Agilent Bioanalyzer before sequencing on a NextSeq 550 instrument. A GATK HaplotypeCaller was used for variant calling and annotation carried out using snpEff. Results: Among the test panel of 288 ctmutRNA candidates in the original cohort, 75 were detected in the new cohort of plasma samples. Moreover, 388 other variants in proximity to the original lesions were also found in multiple HCC but not LC plasma samples. A subset of 36 HCC selective variants was able to identify all HCC patients. The most common tumor specific variants were Indels and SNPs. Novel mRNA fusion variants, corresponding to SENP7, HYI, SAR1A, RASA2, TUBA transcripts, etc., were identified in HCC and LC patients. Conclusion: Circulating RNA could be a robust analyte for noninvasive early detection of HCC and circulating RNA panels could be powerful tools in the entire spectrum of clinical management.

  PublisherOA PDFDOI

• Diet composition impacts the natural history of steatotic liver disease

  Hepatology Communications · 2025-06-19 · 7 citations

  articleOpen accessCorresponding

  BACKGROUND: Metabolic-associated steatotic liver disease (MASLD), caused by insulin resistance and the metabolic syndrome, may result in progressive liver fibrosis. Animal studies suggest that dietary content modulates liver fibrosis progression. Our aim was to identify dietary components and food-related behaviors that may be associated with fibrosis progression and liver-related outcomes in a well-characterized human MASLD cohort. METHODS: Patients with MASLD who had completed a detailed Lifestyle Survey, including a semiquantitative Food Frequency Questionnaire in the Veterans Health Administration Million Veteran Program, were included. The primary outcome was liver fibrosis progression using the Fibrosis-4 slope; the secondary outcome was time to cirrhosis by ICD9/10 codes. Key baseline covariates included: race/ethnicity, body mass index, diabetes mellitus, AUDIT-C score, and baseline Fibrosis-4 score. Using bootstrapped Elastic Net regression in R, self-reported food intake and scaled nutrient variables of interest associated with the outcomes were identified and then validated using multivariable Generalized Linear Model and Cox models. RESULTS: A total of 84,024 individuals with MASLD with nutritional data were included in this study. Median age at MASLD diagnosis was 56 years (IQR 49-63). Frequency of consumption of coffee, tea, vegetables (broccoli, spinach/collard greens), legumes, nuts, modest alcohol, white meat, rice/pasta, dairy, and intakes of specific nutrients including nitrate/vitamin K, caffeine, betaine, amino acids, and beta carotene were associated with reduced fibrosis progression. Consumption of white bread, cookies, breakfast cereals, and specific nutrients such as iron (non-heme), B vitamins, and flavanones were all significantly associated with increased fibrosis progression in MASLD (p<0.05). CONCLUSIONS: Dietary choices such as intake of processed foods, high-fructose foods, and refined carbohydrates may be associated with MASLD progression, while intake of vegetables, nuts, whole grains, and caffeine may be protective.

  PublisherDOI

• Trans-ancestry genome-wide association meta-analysis of gallstone disease

  medRxiv · 2025-03-17

  preprintOpen access

  Gallstone disease is a highly prevalent and costly gastrointestinal disease. Yet, genetic variation in susceptibility to gallstone disease and its implication in metabolic regulatory pathways remain to be explored. We report a trans-ancestry genome-wide association meta-analysis of gallstone disease including 88,063 cases and 1,490,087 controls in the UK Biobank, FinnGen, Biobank Japan, and Million Veteran Program. We identified 91 (37 novel) risk loci across the meta-analysis and found replication in statistically compelling signals in the All of Us Research Program. A polygenic risk score constructed from trans-ancestry lead variants was positively associated with liver chemistry and alpha-1-antitrypsin deficiency and negatively associated with total cholesterol and low-density lipoprotein levels among trans-ancestry and European ancestry groups in the Penn Medicine BioBank. Cross-trait colocalization analysis between risk loci and 44 liver, metabolic, renal, and inflammatory traits yielded 350 significant colocalizations as well as 97 significant colocalizations and 65 prioritized genes from expression quantitative trait loci from eight tissues. These findings broaden our understanding of the genetic architecture of gallstone disease.

  PublisherOA PDFDOI

• Changes in Liver Disease Etiology Support a Lower Alpha-Fetoprotein Threshold for Hepatocellular Carcinoma Screening

  Gastroenterology · 2025-11-14 · 4 citations

  article
  PublisherDOI

• Trends in surgical volume and mortality by surgery type among patients with cirrhosis: A Veterans Affairs study

  Liver Transplantation · 2025-01-27 · 2 citations

  article
  PublisherDOI

• Su1630: PREDICTORS AND OUTCOMES OF PALLIATIVE CARE CONSULTATION IN HOSPITALIZED VETERANS WITH ALCOHOL-ASSOCIATED HEPATITIS

  Gastroenterology · 2025-05-01

  article
  PublisherDOI

• Simulating the impact of survival benefit-based liver transplant organ allocation

  Hepatology · 2025-04-04

  articleOpen access

  BACKGROUND AND AIMS: In the United States and much of the world, prioritization for a deceased donor liver transplant focuses on sickest-first, based on allocating organs using the MELD score. There have been calls to instead allocate organs based on transplant survival benefit, but the impact of such a system on the broader waitlist population is unknown. APPROACH AND RESULTS: We performed a simulation study using the Liver Simulated Allocation Model to compare the current US system of liver allocation to the one using different time horizons, focused on pretransplant survival only, posttransplant survival only, and survival benefit (difference of posttransplant survival and pretransplant survival). Changing liver allocation to a survival benefit-based system was simulated to lead to a small improvement in average patient-level posttransplant survival (mean survival over a 5-year time horizon of 4.24 y vs. 4.19 y in the current system). However, this small improvement was associated with a simulated decrease in transplants and an increase in waitlist mortality of 400 deaths per year. The resulting net benefit overall (pretransplant deaths and posttransplant survival) was negligible under a survival benefit-based allocation approach. CONCLUSIONS: Our simulations predicted that survival benefit-based allocation would only increase posttransplant survival by an average of 18 days per recipient at the expense of a simulated increase in waitlist mortality of 400 deaths per year. In the current practice of liver transplantation, with the sickest-first allocation operating in a system where transplant physicians ration organs to maximize outcomes, the overall survival benefit is maintained and not compromised.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21CA149908

  NIH · $296k · 2012

• Tumor antigen-specific T-cells and hepatocellular carcinoma

  NIH · $1.3M · 2013–2018

• B-Cell Dysregulation in Cirrhosis due to Chronic Hepatitis C Infection

  NIH · 2014–2018

Frequent coauthors

• Marina Serper

  University of Pennsylvania

  442 shared

• Kimberly A. Forde

  Temple University

  310 shared

• Gina Choi

  University of California, Los Angeles

  291 shared

• Gregory J. Gores

  WinnMed

  290 shared

• Jay Hoof- Nagle

  Inovio Pharmaceuticals (United States)

  289 shared

• Jay H. Hoofnagle

  National Institute of Diabetes and Digestive and Kidney Diseases

  289 shared

• Conatus Lewis

  AbbVie (United States)

  289 shared

• Richard B. Roberts

  General Atomics (United States)

  289 shared