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Scholarly Works (4 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2015)

Background

The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis, and cirrhosis, varies significantly by ethnicity.

Methods

With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg- and HIV-positive subjects, we reviewed the charts of 791 patients with ALD including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis.

Results

When controlling for all variables in the model, Hispanic patients presented at significantly 4 to 10 years younger ages than White/Caucasian patients, in each of the 3 disease severity categories, and the results were confirmed after excluding HCV Ab-/RNA-positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African American subjects with alcoholic hepatitis, and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African American subjects.

Conclusions

Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD.
    Cover page: Ethnic Differences in Presentation and Severity of Alcoholic Liver Disease
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2008)

    Noninvasive serial monitoring of the fate of transplanted cells would be invaluable to evaluate the potential therapeutic use of human hepatocyte transplantation. Therefore, we assessed the feasibility of bioluminescent imaging using double or triple fusion lentiviral vectors in a NOD-SCID mouse model transplanted with immortalized human fetal hepatocytes. Lentiviral vectors driven by the CMV promoter were constructed carrying reporter genes: firefly luciferase and green fluorescence protein with or without herpes simplex virus type 1 thymidine kinase. Human fetal hepatocytes immortalized by telomerase reconstitution (FH-hTERT) were successfully transduced with either of these fusion vectors. Two million stably transduced cells selected by fluorescence-activated cell sorting were injected into the spleens of NOD-SCID mice pretreated with methylcholanthrene and monocrotaline. The transplanted mice were serially imaged with a bioluminescence charged-coupled device camera after D-luciferin injection. Bioluminescence signal intensity was highest on day 3 (6.10 +/- 2.02 x 10(5) p/s/cm2/sr, mean +/- SEM), but decreased to 2.26 +/- 1.54 x 10(5) and 7.47 +/- 3.09 x 10(4) p/s/cm2/sr on day 7 and 10, respectively (p = 0.001). ELISA for human albumin in mice sera showed that levels were similar to those of control mice on day 2 (3.25 +/- 0.92 vs. 2.84 +/- 0.59 ng/ml, mean +/- SEM), peaked at 18.04 +/- 3.11 ng/ml on day 7, and decreased to 8.93 +/- 1.40 and 3.54 +/- 0.87 ng/ml on day 14 and 21, respectively (p = 0.02). Real-time quantitative RT-PCR showed gene expression levels of human albumin, alpha1-antitrypsin, and transferrin in mouse liver were 60.7 +/- 6.5%, 26.0 +/- 1.4%, and 156.8 +/- 62.4% of those of primary human adult hepatocytes, respectively, and immunohistochemistry revealed cells with human albumin and alpha1-antitrypsin expression in the mouse liver. In conclusion, our study demonstrated that bioluminescent imaging appears to be a sensitive, noninvasive modality for serial monitoring of transplanted hepatic stem cells.

      Cover page: Use of bioluminescent imaging to assay the transplantation of immortalized human fetal hepatocytes into mice.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2020)

      Background and aims

      Coronavirus disease 2019 (COVID-19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID-19 are open for study.

      Approach and results

      We conducted a multicenter study in the United States of 112 adult LT recipients with COVID-19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID-19 showed moderate liver injury (ALT 2-5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT > 5× ULN) in 12.3% (n = 10). Compared to age- and sex-matched nontransplant patients with chronic liver disease and COVID-19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age (P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), Hispanic ethnicity (P = 0.011; OR, 6.01; 95% CI, 1.51-23.9), metabolic syndrome (P = 0.016; OR, 5.87; 95% CI, 1.38-24.99), vasopressor use (P = 0.018; OR, 7.34; 95% CI, 1.39-38.52), and antibiotic use (P = 0.046; OR, 6.93; 95% CI, 1.04-46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury (P = 0.156) or mortality (P = 0.084). Liver injury during COVID-19 was significantly associated with mortality (P = 0.007; OR, 6.91; 95% CI, 1.68-28.48) and ICU admission (P = 0.007; OR, 7.93; 95% CI, 1.75-35.69) in LT recipients.

      Conclusions

      Liver injury is associated with higher mortality and ICU admission in LT recipients with COVID-19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID-19 did not increase risk for mortality or graft failure.
        Cover page: Liver Injury in Liver Transplant Recipients With Coronavirus Disease 2019 (COVID‐19): U.S. Multicenter ExperienceCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2021)

        Background & aims

        Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19).

        Methods

        We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD.

        Results

        Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19.

        Conclusions

        The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.
          Cover page: Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center StudyCreative Commons 'BY' version 4.0 license
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