Asian Pacific Liver Center

Los Angeles, CA, United States

Asian Pacific Liver Center

Los Angeles, CA, United States
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Chang M.,Asian Pacific Liver Center | Readhead H.,The Wellness Center at the Historic General Hospital | Kuo T.,University of California at Los Angeles
Preventing Chronic Disease | Year: 2015

The Los Angeles County Department of Public Health teamed with a culturally tailored, community-based organization to augment their hepatitis B screening program with blood pressure assessments. During 6 months, 2,298 people were served by the program; descriptive statistics and models were generated to describe demographics and screening and assessment results. Despite the program having good reach, sustainability was challenging. This experience draws attention to the need for invested desire to change at both the organizational and patient levels to sustain interdisciplinary provision of clinical preventive services.


PubMed | Thomas Jefferson University, Asian Pacific Liver Center, Vanderbilt University and PLA Fourth Military Medical University
Type: | Journal: Oncotarget | Year: 2016

The predictive value of circulating microRNAs (miRNAs) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has been demonstrated in retrospective studies, but it has rarely been tested in prospective studies. In a cohort of 373 cancer-free HBV patients with a median follow-up of 4.5 years, we measured the expression of 24 retrospectively identified HCC-related miRNAs in baseline serum samples. When we analyzed the prospective associations of miRNA expression with HCC risk using the Cox proportional hazards model, we found that 15 of the 24 miRNAs exhibited a significant association with HCC risk. In particular, 7 miRNAs (miR-122, miR-99a, miR-331, miR-125b, miR-23b, miR-92a, and miR-26a) were associated with an increased risk, and 8 miRNAs (miR-652, miR-23a, miR-27a, miR-34a, miR-145, miR-10a, miR-150, and let-7f) were associated with a decreased risk. Compared to HBV patients with a low miRNA-based risk score, those with a high miRNA-based risk score exhibited a significantly elevated HCC risk in both univariate (hazard ratio [HR] 6.56, 95% confidence interval [CI] 2.74-15.70) and multivariate (HR 3.57, 95% CI 1.34-9.48) analyses. The risk score significantly increased the HCC prediction performance of alpha-fetoprotein (concordance index increased from 0.68 to 0.82, P < 0.0001). In silico analyses indicated that the genes targeted by the 15 miRNAs are mainly enriched in the transforming growth factor-beta signaling pathway. Collectively, these results provide prospective evidence that circulating miRNAs serve as non-invasive markers for risk prediction of HCC in HBV patients.


Fong T.-L.,Asian Pacific Liver Center | Fong T.-L.,University of Southern California | Tien A.,Asian Pacific Liver Center | Jo K.J.,California Pacific Medical Center | And 12 more authors.
Digestive Diseases and Sciences | Year: 2015

Introduction: Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos(t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. Methods: We retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. Results: Only 4 (7 %) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24 %) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69 %) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62 %) remained HBeAg negative/anti-HBe positive, 12 (32 %) became HBeAg positive, and 2 (5 %) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. Conclusions: Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy. © 2015, Springer Science+Business Media New York.


Pan C.Q.,New York University | Trinh H.,San Jose Gastroenterology | Yao A.,AE and LY Medical Associates | Bae H.,Asian Pacific Liver Center | And 3 more authors.
PLoS ONE | Year: 2014

Background and aims: Chronic hepatitis B (CHB) disproportionately affects the Asian-American population in the USA. Tenofovir disoproxil fumarate (TDF) has demonstrated potent antiviral activity in clinical trials, but data in Asian-Americans from community studies are lacking. Methods: Adult Asian-American patients with CHB from private medical and community-based practices were prospectively enrolled and treated with open-label TDF 300 mg once daily in a single-arm study for 48 weeks. After Week 48, patients had the option to transition to commercially available CHB therapy. The primary efficacy endpoint was hepatitis B virus (HBV) DNA <400 copies/mL at Week 48. Secondary endpoints were safety and tolerability, serologic and biochemical responses, liver fibrosis by FibroTest, and the development of drug-resistant mutations. Results: Of the 90 patients enrolled, 53 (58%) were hepatitis B e antigen (HBeAg)-positive at baseline. At Week 48, 74 patients (82% overall; 70% HBeAg-positive and 100% HBeAg-negative) had HBV DNA <400 copies/mL. Six (12%) HBeAg-positive patients achieved HBeAg loss/seroconversion. The percentage of patients with alanine aminotransferase in the normal range increased from 26% at baseline to 66% at Week 48. The percentage of patients with F0 (no or minimal) fibrosis by FibroTest increased from 48% to 51%, and those with F4 (severe) fibrosis decreased from 4% to 1%. No resistance to TDF developed. Treatment was well tolerated. Most adverse events were mild in severity and considered unrelated to study drug. Conclusions: TDF is effective and well tolerated in Asian-American CHB patients in community clinic-based settings, consistent with larger registration trials. Improvement in liver fibrosis was seen in a proportion of patients. No resistance to TDF developed through 48 weeks of treatment. Trial Registraton: Clinicaltrial.gov identifier NCT00736190 © 2014 Pan et al.


PubMed | Mount Sinai Beth Israel, New York University, Thomas Jefferson University, Stanford University and 19 more.
Type: Journal Article | Journal: The American journal of gastroenterology | Year: 2016

Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence.The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases.Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was significantly lower than predicted by the fourth year (SIR, 0.37; 95% confidence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a significantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confidence interval: 0.35-0.905).Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.


Pan C.Q.,City University of New York | Chan S.,Sing Chan Endoscopy | Trinh H.,San Jose Gastroenterology | Yao A.,AE and LY Medical Asociates | And 2 more authors.
World Journal of Gastroenterology | Year: 2015

AIM: To compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) in Asian and non-Asian chronic hepatitis B (CHB) patients. METHODS: The efficacy and safety of the initial 48 wk of treatment with TDF was compared in a posthoc analysis of combined data from 217 Asians and 299 non-Asians included in Studies 102 and 103 and a post-approval, open-label trial (Study 123). Patient groups were compared according to baseline hepatitis B e antigen (HBeAg) status and viral load. The main outcome measures included the proportion of patients who achieved a hepatitis B virus (HBV) DNA level < 400 copies/mL at Week 48 of treatment. Secondary measures included: HBV DNA and alanine aminotransaminase (ALT) levels over time; proportion of patients with normal ALT levels; proportion of patients with HBeAg loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion; changes in liver histology. Safety and tolerability were evaluated by the occurrence of adverse events (AEs), serious AEs, laboratory abnormalities, discontinuation of the study drug due to AEs, or death. The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug. RESULTS: At week 48, similar proportions of Asians and non-Asians reached HBV DNA < 400 copies/mL (96% of Asian and 97% of non-Asian patients with HBeAg-negative CHB and 83% of Asian and 79% of non-Asian patients with HBeAg-positive CHB had HBV DNA) and normal ALT (78% of Asian and 81% of non-Asian patients with HBeAg-negative CHB and 71% of Asian and 74% of non-Asian patients with HBeAgpositive CHB had normal ALT). On-treatment HBV DNA decline rates were similar between Asians and non-Asians regardless of baseline HBeAg status and viral load. HBV DNA decline during the first four weeks was 2.9 log10 copies/mL in HBeAg-negative Asians and non-Asians, and in HBeAg-positive non-Asians, and 3.1 log10 copies/mL in HBeAg-positive Asians. HBeAg loss and seroconversion was achieved in 14% of Asians vs 26% and 24%, respectively, in non-Asians. Liver histology improved in 77.2% of Asians and 71.5% of non-Asians. No resistance to TDF developed. No renal safety signals were observed. CONCLUSION: TDF demonstrated similar viral suppression, normalization of ALT, improvements in liver fibrosis, and no detectable resistance in Asian and non-Asian patients regardless of baseline HBeAg status. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.


PubMed | New York University, Sing Chan Endoscopy, Asian Pacific Liver Center, Nexus Development and 2 more.
Type: Clinical Trial, Phase IV | Journal: PloS one | Year: 2014

Chronic hepatitis B (CHB) disproportionately affects the Asian-American population in the USA. Tenofovir disoproxil fumarate (TDF) has demonstrated potent antiviral activity in clinical trials, but data in Asian-Americans from community studies are lacking.Adult Asian-American patients with CHB from private medical and community-based practices were prospectively enrolled and treated with open-label TDF 300 mg once daily in a single-arm study for 48 weeks. After Week 48, patients had the option to transition to commercially available CHB therapy. The primary efficacy endpoint was hepatitis B virus (HBV) DNA <400 copies/mL at Week 48. Secondary endpoints were safety and tolerability, serologic and biochemical responses, liver fibrosis by FibroTest, and the development of drug-resistant mutations.Of the 90 patients enrolled, 53 (58%) were hepatitis B e antigen (HBeAg)-positive at baseline. At Week 48, 74 patients (82% overall; 70% HBeAg-positive and 100% HBeAg-negative) had HBV DNA <400 copies/mL. Six (12%) HBeAg-positive patients achieved HBeAg loss/seroconversion. The percentage of patients with alanine aminotransferase in the normal range increased from 26% at baseline to 66% at Week 48. The percentage of patients with F0 (no or minimal) fibrosis by FibroTest increased from 48% to 51%, and those with F4 (severe) fibrosis decreased from 4% to 1%. No resistance to TDF developed. Treatment was well tolerated. Most adverse events were mild in severity and considered unrelated to study drug.TDF is effective and well tolerated in Asian-American CHB patients in community clinic-based settings, consistent with larger registration trials. Improvement in liver fibrosis was seen in a proportion of patients. No resistance to TDF developed through 48 weeks of treatment.Clinicaltrial.gov identifier NCT00736190.


PubMed | Asian Pacific Liver Center
Type: Journal Article | Journal: Digestive diseases and sciences | Year: 2015

Increased risk of defective urinary phosphate reabsorption and osteoporosis has been reported in HIV and chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF).Goals of this study were to evaluate the prevalence of renal phosphate wasting and abnormal bone mineral density in CHB patients taking TDF compared to CHB patients treated with entecavir (ETV) and untreated CHB patients.This is a cross-sectional study of 146 consecutive Asian-American CHB patients who were treatment nave (n = 60) or treated with either TDF (n = 42) or ETV (n = 44). Proximal tubular handling of phosphate was assessed by the maximal rate of tubular reabsorption of phosphate (TmPO4) divided by glomerular filtration rate (GFR) (TmPO4/GFR). Bone mineral density (BMD) was measured using dual X-ray absorptiometry.TmPO4/GFR was similar among CHB patients treated with TDF compared to untreated patients and patients taking ETV. However, among patients treated with 18 months of TDF or ETV, prevalence of abnormal TmPO4/GFR was higher among patients treated with TDF compared to ETV (48.5 % (16/33) vs. 12.5 % (3/24), p = 0.005). Overall prevalence of osteoporosis in this cohort of CHB patients was 14 %, with no significant difference between the three groups. Renal phosphate handling did not correlate with osteoporosis.Chronic hepatitis B patients treated with 18 months of TDF experienced an increased risk of proximal tubular dysfunction. TDF did not increase the risk of osteoporosis. Longitudinal studies are needed to confirm these findings.


Tien C.,Asian Pacific Liver Center | Xu J.J.,Asian Pacific Liver Center | Chan L.S.,University of Southern California | Chang M.,Asian Pacific Liver Center | And 6 more authors.
Digestive Diseases and Sciences | Year: 2015

Background: Increased risk of defective urinary phosphate reabsorption and osteoporosis has been reported in HIV and chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF).Aims: Goals of this study were to evaluate the prevalence of renal phosphate wasting and abnormal bone mineral density in CHB patients taking TDF compared to CHB patients treated with entecavir (ETV) and untreated CHB patients.Methods: This is a cross-sectional study of 146 consecutive Asian-American CHB patients who were treatment naïve (n = 60) or treated with either TDF (n = 42) or ETV (n = 44). Proximal tubular handling of phosphate was assessed by the maximal rate of tubular reabsorption of phosphate (TmPO4) divided by glomerular filtration rate (GFR) (TmPO4/GFR). Bone mineral density (BMD) was measured using dual X-ray absorptiometry.Results: TmPO4/GFR was similar among CHB patients treated with TDF compared to untreated patients and patients taking ETV. However, among patients treated with ≥18 months of TDF or ETV, prevalence of abnormal TmPO4/GFR was higher among patients treated with TDF compared to ETV (48.5 % (16/33) vs. 12.5 % (3/24), p = 0.005). Overall prevalence of osteoporosis in this cohort of CHB patients was 14 %, with no significant difference between the three groups. Renal phosphate handling did not correlate with osteoporosis.Conclusions: Chronic hepatitis B patients treated with ≥18 months of TDF experienced an increased risk of proximal tubular dysfunction. TDF did not increase the risk of osteoporosis. Longitudinal studies are needed to confirm these findings. © 2014, Springer Science+Business Media New York.


Xu J.J.,Asian Pacific Liver Center | Tien C.,Asian Pacific Liver Center | Chang M.,Asian Pacific Liver Center | Rhee J.,Asian Pacific Liver Center | And 5 more authors.
Journal of Viral Hepatitis | Year: 2013

There is limited information regarding follow-up and hepatitis B serological status of Asian Americans diagnosed with chronic hepatitis B (CHB) through community screening. The aims of this study were to evaluate the prevalence and characterize CHB among Asians living in Los Angeles, assess follow-up of individuals with CHB diagnosed at screening and compare with patients with CHB followed by community gastroenterologists. Between October 2007 and May 2010, 7387 Asians were tested for HBV. HBsAg positive individuals (CHB) underwent additional testing for ALT, HBeAg/anti-HBe and HBV DNA. Patients with CHB were contacted 6 months later to determine whether they received follow-up care. We compared serological patterns of these individuals with CHB to patients with CHB who were seen for the first time (treatment naïve) by community gastroenterologists during the study period. Prevalence of CHB was 5.2%. About 99% patients with CHB were foreign-born, and only 27% could read/write English. 297 (77%) patients with CHB could be reached 6 months after diagnosis; 43% did not receive follow-up care, mostly because of lack of medical insurance. Patients with CHB followed by gastroenterologists were more likely to have insurance (69% vs 26%, P < 0.0001). 90% patients with CHB at screening were HBeAg negative/anti-HBe positive with 62% having inactive disease compared to only 30% of patients seen by gastroenterologists (P < 0.0001). Among CHB participants, 13% met criteria for treatment compared to 51% of patients with CHB (P < 0.0001). Only a small number of CHB screening participants require antiviral therapy. Lack of medical insurance is the main reason for most patients with CHB not seeking follow-up care after screening. © 2013 John Wiley & Sons Ltd.

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