Bio

Clinical Focus


  • Hepatology
  • Transplant Hepatology
  • Gastroenterology

Academic Appointments


Professional Education


  • Fellowship:California Pacific Medical Center (2005) CA
  • Residency:California Pacific Medical Center (2002) CA
  • Internship:California Pacific Medical Center (2000) CA
  • Medical Education:Columbia University College of Physicians and Surgeons (1999) NY
  • Board Certification: Transplant Hepatology, American Board of Internal Medicine (2010)
  • Board Certification: Gastroenterology, American Board of Internal Medicine (2005)

Research & Scholarship

Current Research and Scholarly Interests


Dr. Daugherty is a transplant Hepatologist with full-time clinical responsibilities. She is particularly interested in the natural course and management of recurrent Hepatitis C after liver transplant, and the effect of immunosuppression on HCV recurrence.

Teaching

2014-15 Courses


Publications

All Publications


  • The liver in heart failure: a biopsy and explant series of the histopathologic and laboratory findings with a particular focus on pre-cardiac transplant evaluation. Modern pathology Louie, C. Y., Pham, M. X., Daugherty, T. J., Kambham, N., Higgins, J. P. 2015; 28 (7): 932-943

    Abstract

    The pathologic liver changes in chronic heart failure have been characterized mostly based on autopsy series and include sinusoidal dilation and congestion progressing to pericellular fibrosis, bridging fibrosis, and ultimately to cardiac cirrhosis or sclerosis. Liver biopsies are commonly obtained as part of the work up before heart transplantation in patients with longstanding right heart failure, particularly if ascites, abnormal liver function tests or abnormal abdominal imaging are noted as part of the pre-transplant evaluation. In these cases, the liver biopsy findings may be used to further risk stratify patients for isolated heart or combined heart and liver transplantation. Thus, it is important to be able to correlate the histologic changes with post-transplant outcomes. We report the pathologic and clinical findings in liver explants from six patients who underwent combined heart-liver transplantation. We also report preoperative liver biopsy findings from 21 patients who underwent heart transplantation without simultaneous liver transplantation. We staged the changes related to chronic passive congestion as follows: stage 0-no fibrosis; stage I-pericellular fibrosis; stage II-bridging fibrosis; and stage III-regenerative nodules. Nineteen biopsies showed fibrosis with bridging fibrosis in 13 and regenerative nodules in 6. Fifteen patients were alive at 1 year post transplant. Only three patients had a post-operative course that was characterized by signs and symptoms of chronic liver disease. Pre-transplant liver biopsies from these patients all showed at least stage II fibrosis. These patients survived for 3, 6, and 10 months after cardiac transplant. The presence of bridging fibrosis was not significantly associated with post-operative survival (P=0.336) or post-operative liver failure (P=0.257). We conclude that patients with bridging fibrosis may still be considered viable candidates for isolated heart transplantation. Because the pattern of fibrosis due to passive congestion is highly variable throughout the liver, a diagnosis of cirrhosis, which implies fibrosis and regenerative nodules throughout the liver, should be made with great caution on biopsy.

    View details for DOI 10.1038/modpathol.2015.40

    View details for PubMedID 25793895

  • Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis TRANSPLANT INFECTIOUS DISEASE Perumpail, R. B., Wong, R. J., Ha, L. D., Pham, E. A., Wang, U., Luong, H., Kumari, R., Daugherty, T. J., Higgins, J. P., Younossi, Z. M., Kim, W. R., Glenn, J. S., Ahmed, A. 2015; 17 (2): 275-278

    Abstract

    We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

    View details for DOI 10.1111/tid.12348

    View details for Web of Science ID 000352219400013

    View details for PubMedID 25641426

  • Recurrent Hepatocellular Carcinoma and Poorer Overall Survival in Patients Undergoing Left-sided Compared With Right-sided Partial Hepatectomy. Journal of clinical gastroenterology Valenzuela, A., Ha, N. B., Gallo, A., Bonham, C., Ahmed, A., Melcher, M., Kim, L. H., Esquivel, C., Concepcion, W., Ayoub, W. S., Lutchman, G. A., Daugherty, T., Nguyen, M. H. 2015; 49 (2): 158-164

    Abstract

    We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy.Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed.This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC.The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection.HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

    View details for DOI 10.1097/MCG.0000000000000144

    View details for PubMedID 24804988

  • Mutations in HBV DNA polymerase associated with nucleos(t)ide resistance are rare in treatment-naive patients. Clinical gastroenterology and hepatology Vutien, P., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Nguyen, K., da Silveira, E., Daugherty, T., Ahmed, A., Garcia, G., Lutchman, G. A., Nguyen, M. H. 2014; 12 (8): 1363-1370

    Abstract

    Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment naïve patients. However, most of these studies used either direct PCR sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well characterized. We investigated the prevalence of HBV mutations in DNA polymerase using a line probe assay.In a prospective, cross-sectional study, we enrolled 198 treatment-naïve patients with chronic hepatitis B (52.5% male, mean age 41 y), from February 2009 through May 2011, from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or HIV. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected using the INNO-LiPA HBV DR v.3 assay.Most patients were Vietnamese (48.5%) or Chinese (36.4%), and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%): rtI233V (n = 1) and rtM250M/L (n = 1).In a multicenter prospective study of treatment-naïve patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Given the low prevalence of these mutations and the uncertain clinical significance of such quasi-species, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naïve patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.

    View details for DOI 10.1016/j.cgh.2013.11.036

    View details for PubMedID 24342744

  • Primary Surgical Resection Versus Liver Transplantation for Transplant-Eligible Hepatocellular Carcinoma Patients DIGESTIVE DISEASES AND SCIENCES Wong, R. J., Wantuck, J., Valenzuela, A., Ahmed, A., Bonham, C., Gallo, A., Melcher, M. L., Lutchman, G., Concepcion, W., Esquivel, C., Garcia, G., Daugherty, T., Nguyen, M. H. 2014; 59 (1): 183-191

    Abstract

    Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08-6.86).Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.

    View details for DOI 10.1007/s10620-013-2947-8

    View details for Web of Science ID 000330585500029

  • Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians JOURNAL OF IMMIGRANT AND MINORITY HEALTH Lin, H., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T. J., Lutchman, G. A., Garcia, G., Nguyen, M. H. 2013; 15 (6): 1023-1029

    Abstract

    The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.

    View details for DOI 10.1007/s10903-013-9871-z

    View details for Web of Science ID 000326888100003

  • Precore and basal core promoter mutations in Asian American patients with hepatitis B e antigen-positive chronic hepatitis B ALIMENTARY PHARMACOLOGY & THERAPEUTICS VuTien, P., Trinh, H. N., Nguyen, K., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Nguyen, L., Ha, N. B., Ahmed, A., Daugherty, T., Garcia, G., Nguyen, M. H. 2013; 37 (4): 464-472

    Abstract

    Prior studies have shown that precore mutations abolish and basal core promoter (BCP) mutations down-regulate hepatitis B e antigen (HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus (HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B.To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B.We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009.A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations.The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation.

    View details for DOI 10.1111/apt.12193

    View details for Web of Science ID 000313891900011

    View details for PubMedID 23278246

  • Incidence of Hepatocellular Carcinoma Among US Patients With Cirrhosis of Viral or Nonviral Etiologies CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Mair, R. D., Valenzuela, A., Ha, N. B., Ayoub, W. S., Daugherty, T., Lutchman, G. A., Garcia, G., Ahmed, A., Nguyen, M. H. 2012; 10 (12): 1412-1417

    Abstract

    We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of ?-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo).The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not.In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.

    View details for DOI 10.1016/j.cgh.2012.08.011

    View details for Web of Science ID 000312265900021

    View details for PubMedID 22902757

  • Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case-control study CANCER CAUSES & CONTROL Ha, N. B., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T. J., Chang, E. T., Lutchman, G. A., Garcia, G., Cooper, A. D., Keeffe, E. B., Nguyen, M. H. 2012; 23 (3): 455-462

    Abstract

    The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case-control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one's lifetime. Diabetes mellitus (DM) was defined by random glucose level of ?200 mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR = 8.5 [2.6-28.3]), male gender (OR = 3.5 [2.2-5.8]), presence of cirrhosis (OR = 2.8 [1.6-4.9]), Asian ethnicity (OR = 2.8 [1.8-4.6]), AFP > 50 (OR = 4.2 [2.6-6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR = 1.7 [1.0-2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.

    View details for DOI 10.1007/s10552-012-9895-z

    View details for Web of Science ID 000300891100006

    View details for PubMedID 22258434

  • Prospective study of risk factors for hepatitis C virus acquisition by Caucasian, Hispanic, and Asian American patients JOURNAL OF VIRAL HEPATITIS Ho, E. Y., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T., Garcia, G., Cooper, A., Keeffe, E. B., Nguyen, M. H. 2012; 19 (2): E105-E111

    Abstract

    Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74-75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P < 0.0001). The most common risk factors in Asians were blood transfusions (50%) and acupuncture (50%). Furthermore, 74% of Caucasians and 66% of Hispanics identified more than one major risk factor, while only 20% of Asians reported having more than one risk factor (P < 0.0001). Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans. These findings may guide the development of HCV screening in our increasingly diverse population.

    View details for DOI 10.1111/j.1365-2893.2011.01513.x

    View details for Web of Science ID 000299097400014

    View details for PubMedID 22239506

  • Hepatic Arteriovenous Malformations from Hereditary Hemorrhagic Telangiectasia: Treatment with Liver Transplantation DIGESTIVE DISEASES AND SCIENCES Lee, M., Sze, D. Y., Bonham, C. A., Daugherty, T. J. 2010; 55 (11): 3059-3062

    View details for DOI 10.1007/s10620-010-1353-8

    View details for Web of Science ID 000283300400008

    View details for PubMedID 20844961

  • Fulminant Clostridium difficile Colitis in a Post-Liver Transplant Patient DIGESTIVE DISEASES AND SCIENCES Lee, M., Shelton, A. A., Concepcion, W. L., Bonham, C. A., Daugherty, T. J. 2010; 55 (9): 2459-2462

    View details for DOI 10.1007/s10620-010-1318-y

    View details for Web of Science ID 000280595500006

    View details for PubMedID 20635145

  • Recurrent Pyogenic Cholangitis DIGESTIVE DISEASES AND SCIENCES Nguyen, T., Powell, A., Daugherty, T. 2010; 55 (1): 8-10

    View details for DOI 10.1007/s10620-009-0912-3

    View details for Web of Science ID 000273520500002

    View details for PubMedID 19669879

  • Acute Liver Failure at 26 Weeks' Gestation in a Patient with Sickle Cell Disease LIVER TRANSPLANTATION Greenberg, M., Daugherty, T. J., Elihu, A., Sharaf, R., Concepcion, W., Druzin, M., Esquivel, C. O. 2009; 15 (10): 1236-1241

    Abstract

    Orthotopic liver transplantation (OLT) for acute liver failure (ALF) during pregnancy is an uncommon occurrence with variable outcomes. In pregnancy-related liver failure, prompt diagnosis and immediate delivery are essential for a reversal of the underlying process and for maternal and fetal survival. In rare cases, the reason for ALF during pregnancy is either unknown or irreversible, and thus OLT may be necessary. This case demonstrates the development of cryptogenic ALF during the 26th week of pregnancy in a woman with sickle cell disease. She underwent successful cesarean delivery of a healthy male fetus at 27 weeks with concurrent OLT. This report provides a literature review of OLT in pregnancy and examines the common causes of ALF in the pregnant patient. On the basis of the management and outcome of our case and the literature review, we present an algorithm for the suggested management of ALF in pregnancy.

    View details for DOI 10.1002/It.21820

    View details for Web of Science ID 000270931500014

    View details for PubMedID 19790148

  • Therapy of hepatitis C in patients with HIV infection. Expert review of anti-infective therapy Daugherty, T., Bonacini, M. 2005; 3 (3): 375-384

    Abstract

    Hepatitis C is found in approximately a third of patients infected with HIV. Therapy of hepatitis C in HIV patients is very important from several view points. First, hepatitis C in the setting of immunosuppression may progress faster, although recent data show that mortality from liver disease was decreased in highly active antiretroviral therapy. HIV/hepatitis C coinfection is associated with more frequent elevation in liver tests (drug-induced liver injury) during highly active antiretroviral therapy, and in some studies, hepatitis C has been associated with lower CD4+ recoveries. The therapeutic standard of care is a combination of peginterferon and ribavirin at a fixed dose, 800 mg/day, although higher ribavirin doses may further improve virologic outcomes. In patients that do not respond virologically, maintenance therapy with peginterferon monotherapy is a potential avenue to stem the advance of liver fibrosis, although controlled data in coinfected patients are needed to issue formal recommendations.

    View details for PubMedID 15954854

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