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.
- Transplant Hepatology
Clinical Associate Professor, Medicine - Gastroenterology & Hepatology
Board Certification: American Board of Internal Medicine, Internal Medicine (2015)
Fellowship: California Pacific Medical Center Gastroenterology Fellowship (2005) CA
Residency: California Pacific Medical Center Internal Medicine Residency (2002) CA
Internship: California Pacific Medical Center Internal Medicine Residency (2000) CA
Board Certification: American Board of Internal Medicine, Transplant Hepatology (2010)
Board Certification: American Board of Internal Medicine, Gastroenterology (2005)
Medical Education: Columbia University College of Physicians and Surgeons (1999) NY
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.
THE INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B VIRUS INFECTION SUBJECTS WITH CIRRHOSIS NOT MEETING CURRENT TREATMENT GUIDANCE
WILEY. 2021: 500A-501A
View details for Web of Science ID 000707188002225
Selection Criteria for Liver Transplantation for Acute Alcohol-Associated Hepatitis.
Clinics in liver disease
2021; 25 (3): 635-644
Severe acute alcohol-associated hepatitis that is nonresponsive to medical therapy has an extremely high mortality. Liver transplantation is a feasible treatment option and available at certain transplant centers globally. Selection criteria for liver transplantation are not, uniform but there are important key criteria shared across protocols. Of equal importance to the management of liver disease is the treatment of alcohol use disorder. A thorough assessment of candidates involves input from an addiction specialist and psychiatrist. With careful selection practices, graft and patient survival among transplant recipients with severe alcohol-associated hepatitis is similar to other etiologies of chronic liver disease.
View details for DOI 10.1016/j.cld.2021.03.007
View details for PubMedID 34229845
Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation.
2021; 5 (3): 516-525
Liver transplantation (LT) is definitive treatment for end-stage liver disease. This study evaluated factors predicting successful evaluation in patients transferred for urgent inpatient LT evaluation. Eighty-two patients with cirrhosis were transferred for urgent LT evaluation from January 2016 to December 2018. Alcohol-associated liver disease was the common etiology of liver disease (42/82). Of these 82 patients, 35 (43%) were declined for LT, 27 (33%) were wait-listed for LT, 5 (6%) improved, and 15 (18%) died. Psychosocial factors were the most common reasons for being declined for LT (49%). Predictors for listing and receiving LT on multivariate analysis included Hispanic race (odds ratio [OR], 1.89; P = 0.003), Asian race (OR, 1.52; P = 0.02), non-Hispanic ethnicity (OR, 1.49; P = 0.04), hyponatremia (OR, 1.38; P = 0.04), serum albumin (OR, 1.13; P = 0.01), and Model for End-Stage Liver Disease (MELD)-Na (OR, 1.02; P = 0.003). Public insurance (i.e., Medicaid) was a predictor of not being listed for LT on multivariate analysis (OR, 0.77; P = 0.02). Excluding patients declined for psychosocial reasons, predictors of being declined for LT on multivariate analysis included Chronic Liver Failure Consortium (CLIF-C) score >51.5 (OR, 1.26; P = 0.03), acute-on-chronic liver failure (ACLF) grade 3 (OR, 1.41; P = 0.01), hepatorenal syndrome (HRS) (OR, 1.38; P = 0.01), and respiratory failure (OR, 1.51; P = 0.01). Predictors of 3-month mortality included CLIF-C score >51.5 (hazard ratio [HR], 2.52; P = 0.04) and intensive care unit (HR, 8.25; P < 0.001). Conclusion: MELD-Na, albumin, hyponatremia, ACLF grade 3, HRS, respiratory failure, public insurance, Hispanic race, Asian race, and non-Hispanic ethnicity predicted liver transplant outcome. Lack of psychosocial support was a major reason for being declined for LT. The CLIF-C score predicted being declined for LT and mortality.
View details for DOI 10.1002/hep4.1644
View details for PubMedID 33681683
View details for PubMedCentralID PMC7917272
- Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation HEPATOLOGY COMMUNICATIONS 2020
THE INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B VIRUS INFECTION SUBJECTS NOT MEETING CRITERIA FOR ANTIVIRAL THERAPY
WILEY. 2020: 472A–473A
View details for Web of Science ID 000574027001230
OUTCOMES AFTER HOSPITALIZATION WITH ACUTE DECOMPENSATION DUE TO ALCOHOL-RELATED LIVER DISEASE
WILEY. 2020: 181A–182A
View details for Web of Science ID 000574027000272
Does liver biopsy accurately measure fibrosis in Fontan associated liver disease? A comparison of liver biopsy pre-combined heart and liver transplant and liver explant post-transplant.
The accuracy of liver biopsy to stage fibrosis due to Fontan associated liver disease (FALD) remains unclear. We compared results of biopsy pre-combined heart and liver transplantation (CHLT) to results of whole liver explant. Liver biopsy and explants from 15 Fontan patients (ages 16 - 49, median 28 years) were retrospectively reviewed. Staging was as follows: stage 0: no fibrosis, stage 1: pericellular fibrosis, stage 2: bridging fibrosis, stage 3: regenerative nodules. There is no stage 4. Clinical characteristics including Model of End-stage Liver Disease eXcluding INR and Varices, Ascites, Splenomegaly, and Thrombocytopenia (VAST) scores were collected, and descriptive statistics and Mann-Whitney U tests used to analyze data. All patients had biopsies with at least bridging fibrosis, and all had nodularity on explant; transjugular biopsy never overestimated fibrosis. Explant showed higher grade fibrosis (Stage 3) than pre-CHLT biopsy (Stage 2) in 6 of 15 patients and equal grade of fibrosis (Stage 3) in 9 of 15 patients. Though clinical characteristics varied significantly, VAST score was ≥ 2 in all but two patients. Transjugular liver biopsy does not overestimate and can underestimate fibrosis in Fontan patients undergoing CHLT, likely due to the patchy nature of fibrosis in FALD.
View details for DOI 10.1111/ctr.14120
View details for PubMedID 33053213
Clinical Response to Treatment for Acute Kidney Injury (AKI) in Patients With Cirrhosis
LIPPINCOTT WILLIAMS & WILKINS. 2020: S587–S588
View details for Web of Science ID 000607196703094
Characterizing Ascites in Subjects With Nonhepatic Solid Tumors
LIPPINCOTT WILLIAMS & WILKINS. 2020: S507
View details for Web of Science ID 000607196702295
- Tenofovir Alafenamide Attenuates Effects of Diabetes and Body Mass on Serum Alanine Aminotransferase Activities in Patients with Chronic Hepatitis B. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2020
THE ROLE OF LOCOREGIONAL THERAPY (LRT), POST LRT IMAGING, AND EXPLANT PATHOLOGY AS PREDICTORS OF HEPATOCELLULAR CARCINOMA (HCC) RECURRENCE POST ORTHOTOPIC LIVER TRANSPLANT (OLT)
WILEY. 2019: 691A–692A
View details for Web of Science ID 000488653502295
- Sustained Decline of Noninvasive Fibrosis Index Values in Patients With Chronic Hepatitis C (CHC) With Sustained Virologic Response (SVR) After Receiving Direct-Acting Antiviral Agents (DAAs) LIPPINCOTT WILLIAMS & WILKINS. 2019: S553–S554
- Short-term outcomes of en bloc combined heart and liver transplantation in the failing Fontan CLINICAL TRANSPLANTATION 2019; 33 (6)
Short-Term Outcomes of en bloc Combined Heart and Liver Transplantation in the Failing Fontan.
Patients with failing Fontan physiology and liver cirrhosis are being considered for combined heart and liver transplantation. We performed a retrospective review of our experience with en bloc combined heart and liver transplantation in Fontan patients > 10 years old from 2006-18 per Institutional Review Board approval. Six females and 3 males (median age 20.7, range 14.2-41.3 years) underwent en bloc combined heart and liver transplantation. Indications for heart transplant included ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia and/or lymphatic abnormalities. Indication for liver transplant included portal hypertension and cirrhosis. Median Fontan/single ventricular end diastolic pressure was 18/12 mm Hg, respectively. Median Model for End-Stage Liver Disease excluding International Normalized Ratio score was 10 (7-26), eight patients had a Varices, Ascites, Splenomegaly, Thrombocytopenia score of>2, and all patients had cirrhosis. Median cardiopulmonary bypass and donor ischemic times were 262 (178-307) and 287 (227-396) minutes, respectively. Median intensive care and hospital stay were 19 (5-96) and 29 (13-197) days, respectively. Survival was 100% and rejection was 0% at 30 days and 1 year post-transplant. En bloc combined heart and liver transplantation is an acceptable treatment in the failing Fontan patient with liver cirrhosis. This article is protected by copyright. All rights reserved.
View details for PubMedID 30891780
- OUTCOME OF EN-BLOC COMBINED HEART AND LIVER TRANSPLANTATION IN THE ADULT FAILING FONTAN ELSEVIER SCIENCE INC. 2018: 539
Sofosbuvir Use in the Setting of End-stage Renal Disease: A Single Center Experience.
Journal of clinical and translational hepatology
2017; 5 (1): 23-26
Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysis-dependent form a unique group, in which safety, tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation. Methods: We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy. We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience. Results: Sustained virological response (defined as undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15 (86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15 treatment courses, patients completed the designated treatment duration. One patient was treated twice and developed SVR-12 with the retreatment. One patient was lost to follow-up and counted as a non-responder. Premature discontinuations were not due to DAA-related adverse effects. There were no reports of severe adverse effects or drug interactions. Conclusion: We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.
View details for DOI 10.14218/JCTH.2016.00060
View details for PubMedID 28507922
Real-world experience with interferon-free, direct acting antiviral therapies in Asian Americans with chronic hepatitis C and advanced liver disease.
2017; 96 (6)
Real-life data on interferon (IFN)-free direct acting antiviral (DAA) therapies for chronic hepatitis C (CHC) is limited for Asian Americans.To evaluate sustained virologic response (SVR) and adverse events (AE) in Asian Americans treated with sofosbuvir (SOF)-based, IFN-free DAA therapies.This is a retrospective study of 110 consecutive Asian Americans with HCV genotypes 1 to 3 or 6 treated with IFN-free SOF-based regimens for 8 to 24 weeks between February 2014 and March 2016 at a university center in Northern California.Mean age was 63 ± 12 years, mean BMI was 25 ± 6 (kg/m), and about half (52%) were male. Most patients were infected with HCV genotype 1 (HCV-1, 64%), followed by HCV-2 (14%), HCV-6 (13%), and HCV-3 (8%). Half had cirrhosis, and the majority of these (67%) had decompensation. Overall SVR12 was 93% (102/110), and highest among patients without cirrhosis, liver transplant, or HCC (100%, 37/37). SVR12 was lower among patients with HCC (82%, 14/17), decompensated cirrhosis (84%, 31/37), or liver transplant (89%, 17/19), regardless of treatment and genotype. Most common AEs were anemia (25%), fatigue (20%), and headache (12%). Anemia was highest in patients receiving SOF/RBV (67%). There was 1 treatment-unrelated serious adverse effect (SAE). There were 7 dose reductions due to anemia or fatigue from RBV and 2 treatment discontinuations due to fatigue or loss of insurance authorization.This real-life cohort of Asian American CHC patients treated with IFN-free SOF-based therapies showed high overall treatment response and good tolerability, despite very high rates of advanced disease and prior treatment failure.
View details for DOI 10.1097/MD.0000000000006128
View details for PubMedID 28178174
Effectiveness and tolerability of simeprevir and sofosbuvir in nontransplant and post-liver transplant patients with hepatitis C genotype 1.
Alimentary pharmacology & therapeutics
2016; 44 (7): 738-746
Hepatitis C virus genotype 1a (HCV-1a), prior treatment, cirrhosis and post-transplant status are historically associated with poor treatment responses. The new oral direct-acting agents appear to be effective and safe in these patients.To evaluate the effectiveness and tolerability of simeprevir and sofosbuvir in a diverse real-life cohort of patients, including difficult-to-treat patients.We conducted a retrospective cohort study in 198 consecutive patients with hepatitis C genotype 1 (148 nontransplant, 50 post transplant), who were treated with simeprevir and sofosbuvir for 12 weeks between December 2013 and December 2014. Primary outcome was sustained virological response with undetectable HCV RNA 12 weeks after completion of therapy (SVR12). Risk factors evaluated for lack of SVR12 included HCV 1a (vs. 1b), prior treatment (vs. none), and cirrhosis (vs. no cirrhosis).SVR12 rates were similar in non- and post-transplant settings, 82% and 88%, respectively. There were no significant differences in adverse events in patients regardless of cirrhosis or transplant status. On multivariate analysis also inclusive of gender and liver transplant status, negative predictors of SVR12 were having at least 2 or 3 risk factors (OR 0.30, 95% CI 0.10-0.87, P = 0.027 or 0.29, 95% CI 0.09-0.85, P = 0.025, respectively).Simeprevir and sofosbuvir combination is a safe and effective regimen for the treatment of non- and post-transplant patients with traditional risk factors for poor treatment response, unless more than 2 difficult-to-treat risk factors are present.
View details for DOI 10.1111/apt.13761
View details for PubMedID 27506182
- A New Standard of Care? Standard Dose Sofosbuvir in an HCV-Infected Liver Transplant Recipient Undergoing Hemodialysis DIGESTIVE DISEASES AND SCIENCES 2016; 61 (1): 39-41
- A New Standard of Care? Standard Dose Sofosbuvir in an HCV-Infected Liver Transplant Recipient Undergoing Hemodialysis. Digestive diseases and sciences 2016; 61 (1): 39-41
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.
2015; 28 (7): 932-943
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
2015; 17 (2): 275-278
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
2015; 49 (2): 158-164
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
2014; 12 (8): 1363-1370
Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction 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 by using a line probe assay.In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. 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 by 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-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive 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
- Mutations in HBV DNA Polymerase Associated With Nucleos(t)ide Resistance Are Rare in Treatment-naive Patients. Clinical gastroenterology and hepatology 2014; 12 (8): 1363-1370
Primary surgical resection versus liver transplantation for transplant-eligible hepatocellular carcinoma patients.
Digestive diseases and sciences
2014; 59 (1): 183-191
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 PubMedID 24282054
Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians.
Journal of immigrant and minority health
2013; 15 (6): 1023-1029
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 PubMedID 23864445
Precore and basal core promoter mutations in Asian American patients with hepatitis B e antigen-positive chronic hepatitis B
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
2013; 37 (4): 464-472
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
2012; 10 (12): 1412-1417
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 α-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
View details for PubMedCentralID PMC3511850
Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case-control study
CANCER CAUSES & CONTROL
2012; 23 (3): 455-462
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
2012; 19 (2): E105-E111
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 2010; 55 (11): 3059-3062
LOW PREVALENCE OF HEPATITIS B VIRUS REVERSE TRANSCRIPTASE MUTATIONS IN TREATMENT-NAiVE PATIENTS WITH CHRONIC HEPATITIS B USING INNO-LIPA HBV DR3 IN A MULTICENTER STUDY
61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases
WILEY-BLACKWELL. 2010: 1001A–1001A
View details for Web of Science ID 000288775602036
- Fulminant Clostridium difficile Colitis in a Post-Liver Transplant Patient DIGESTIVE DISEASES AND SCIENCES 2010; 55 (9): 2459-2462
- Recurrent Pyogenic Cholangitis DIGESTIVE DISEASES AND SCIENCES 2010; 55 (1): 8-10
Acute Liver Failure at 26 Weeks' Gestation in a Patient with Sickle Cell Disease
2009; 15 (10): 1236-1241
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
2005; 3 (3): 375-384
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