{
  "abstract": "Background Gamma-glutamyl transferase (GGT) is a well-established marker of hepatic injury and alcohol consumption. While elevated GGT has been linked to overall mortality and certain malignancies, its specific association with the risk of incident pancreatic and hepatobiliary pathologies in a diverse U.S. population remains less defined. Methods We conducted a multi-institutional retrospective cohort study using the TriNetX global analytics platform. We identified adult patients (age ≥40 years) with persistently elevated GGT (≥65 U/L on two occasions, 6 months to 1 year apart) and a comparison cohort with consistently normal GGT (≤65 U/L). To minimize confounding, we performed 1:1 propensity score matching (PSM) adjusting for age, sex, race, ethnicity, baseline comorbidities (including diabetes, obesity, and alcohol-related disorders), and other liver enzymes (ALT, AST, ALP). Patients with pre-existing pancreatic or hepatobiliary disease at baseline were excluded. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression.Results Before matching, the study identified 26,136 patients with elevated GGT and 97,649 with normal GGT. After 1:1 PSM, the final analysis included 23,961 matched pairs with balanced baseline characteristics (mean age 57.2 years). Persistently elevated GGT was associated with a markedly increased risk of hepatobiliary malignancies, including cholangiocarcinoma (HR 3.92; 95% CI: 2.75-5.59; p<0.001) and HCC (HR 4.01; 95% CI: 3.44-4.69; p<0.001). Regarding pancreatic pathology, elevated GGT was significantly associated with incident acute pancreatitis (HR 2.57; 95% CI: 2.14-3.08; p<0.001), chronic pancreatitis (HR 1.89; 95% CI: 1.52-2.34; p<0.001), and pancreatic cysts (HR 2.00; 95% CI: 1.66-2.42; p<0.001). However, no statistically significant association was observed for pancreatic cancer (HR 1.26; 95% CI: 0.87-1.82; p=0.224). Additionally, the elevated GGT cohort demonstrated a two-fold increase in all-cause mortality (HR 2.07; 95% CI: 1.99-2.16; p<0.001) and a 35% increased risk of hospitalization (HR 1.35; 95% CI: 1.29-1.41; p<0.001). ( IDDF2026-ABS-0328 Figure 1. Risk association of elevated GGT with key clinical outcomes)Conclusions In this large matched cohort study, persistently elevated GGT was identified as an independent risk factor for cholangiocarcinoma, hepatocellular carcinoma, and benign pancreatic diseases, including pancreatitis and pancreatic cysts. While GGT elevation predicted a two-fold increase in all-cause mortality, it was not significantly associated with incident pancreatic cancer.Abstract IDDF2026-ABS-0328 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom"
      ],
      "name": "Arkadeep Dhali"
    },
    {
      "affiliations": [
        "CMH Multan Institute of Medical Sciences, Pakistan"
      ],
      "name": "Asad Zaman"
    },
    {
      "affiliations": [
        "CMH Multan Institute of Medical Sciences, Pakistan"
      ],
      "name": "Abdul Rafae Faisal"
    },
    {
      "affiliations": [
        "Roswell Park Comprehensive Cancer Center, United States"
      ],
      "name": "Fayaz Khan"
    }
  ],
  "title": "IDDF2026-ABS-0328 Persistent elevation of gamma-glutamyl transferase and risk of hepatobiliary and pancreatic pathology: a multi-institutional cohort analysis",
  "uid": "048d961d-a410-598a-8f81-7654531978ce"
}