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  • Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-term Mortality in Patients With Chronic Hepatitis C. JAMA internal medicine Ogawa, E., Chien, N., Kam, L., Yeo, Y. H., Ji, F., Huang, D. Q., Cheung, R., Nguyen, M. H. 2022


    Chronic hepatitis C (CHC) and its complications are associated with high rates of morbidity and mortality. However, large-scale data analysis of the long-term liver and nonliver effects of direct-acting antiviral (DAA) treatment has been limited.To assess the association of hepatitis C virus elimination through DAA treatment with the risk of liver and nonliver morbidity and mortality during long-term follow-up among a large nationwide cohort of insured patients with CHC in the US.This was a retrospective cohort study of 245 596 adult patients with CHC using data from the Optum Clinformatics Data Mart database, 2010 to 2021. Of the total cohort, 40 654 patients had received 1 or more prescriptions for DAA medication (without interferon), and 204 942 patients were untreated.Treatment with a DAA.Incidence of hepatocellular carcinoma (HCC), liver decompensation, relevant nonliver events (nonliver cancer, diabetes, chronic kidney disease, cardiovascular disease), and overall mortality.The DAA-treated cohort (vs untreated) were older (mean [SD] age, 59.9 [10.8] vs 58.5 [13.0] years; P < .001); more likely to be male (25 060 [62%] vs 119 727 [58%] men; P < .001) and White (23 937 [59%] vs 115 973 [57%]; P < .001) individuals; and more likely to have diabetes (10 680 [26%] vs 52 091 [25%]; P < .001) or cirrhosis (17 971 [44%] vs 60 094 [29%]; P < .001). Comparing DAA-treated with untreated patients, the incidence (per 1000 person-years) of liver outcomes (eg, decompensation, 28.2 [95% CI, 27.0-29.4] vs 40.8 [95% CI, 40.1-41.5]; P < .001, and HCC in compensated cirrhosis, 20.1 [95% CI, 18.4-21.9] vs 41.8 [95% CI, 40.3-43.3]; P < .001) and nonliver outcomes (eg, diabetes, 30.2 [95% CI, 35.4-37.7] vs 37.2 [95% CI, 36.6-37.9]; P < .001; and chronic kidney disease, 31.1 [95% CI, 29.9-32.2] vs 34.1 [95% CI, 33.5-34.7]; P < .001) were significantly lower in treated patients. The all-cause mortality rates per 1000 person-years were also significantly lower in DAA-treated compared with untreated patients (mortality, 36.5 [95% CI, 35.4-37.7] vs 64.7 [95% CI, 63.9-65.4]; P < .001). In multivariable regression analysis, DAA treatment was independently associated with a significant decrease in the risk of liver (adjusted hazard ratio [aHR] for HCC, 0.73; decompensation, 0.36), nonliver (aHR for diabetes, 0.74; chronic kidney disease, 0.81; cardiovascular disease, 0.90; nonliver cancer, 0.89), and mortality outcomes (aHR, 0.43).The findings of this retrospective cohort study indicate that DAA treatment for insured patients with CHC was associated with improved liver- and nonliver outcomes, and ultimately, with long-term overall survival.

    View details for DOI 10.1001/jamainternmed.2022.5699

    View details for PubMedID 36508196

  • Characteristics and Treatment Rate of Patients With Hepatitis C Virus Infection in the Direct-Acting Antiviral Era and During the COVID-19 Pandemic in the United States. JAMA network open Nguyen, V. H., Kam, L., Yeo, Y. H., Huang, D. Q., Henry, L., Cheung, R., Nguyen, M. H. 2022; 5 (12): e2245424


    Clinical data on hepatitis C virus (HCV) treatment rates in the United States are sparse.To evaluate HCV treatment rates in the era of direct-acting antivirals (DAAs).This retrospective cohort study used data from the deidentified Optum Cliniformatics Data Mart Database (2014-2021) on patients with HCV in the DAA and COVID-19 eras. The database includes patients with private health insurance in the US.The treatment rate and changes over time were assessed with adjusted log-binomial regression, and factors associated with treatment were examined using multivariable logistic regression.A total of 133 348 patients with HCV (79 567 [59.7%] men; mean [SD] age, 59.7 [12.3] years; 4448 [3.3%] Asian, 24 662 [18.5%] Black, and 74 750 [56.1%] White individuals) were included; 38 180 (26.8%) had HCV RNA data, and of those, 20 277 (53.1%) had positive HCV RNA. Overall, 13 214 patients with positive HCV RNA tests (65.2%) received DAA treatment; 6456 of 6634 patients treated with DAAs (97.3%) achieved sustained virologic response. After adjusting for age, sex, and race and ethnicity, the treatment rate in 2018 was 0.5 times greater than the rate in 2014 (adjusted prevalence ratio, 1.50; 95% CI, 1.42-1.59) but declined after 2018, decreasing from 64.8% to 61.2%, and especially after 2019, when it decreased to less than 60% (P < .001). The number of patients with viremic HCV identified in between April 2020 and March 2021 also decreased to 496 from 2761 and 3258 in the preceding 2 years. Receiving care from a gastroenterologist or infectious disease specialist with advanced care practitioner (ie, nurse practitioner, physician assistant, or clinical nurse specialist) was independently associated with greater odds of DAA treatment (adjusted odds ratio [aOR], 1.64; 95% CI, 1.07-1.50). Patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) were 31% less likely to receive treatment compared with those without (aOR, 0.69; 95% CI, 0.54-0.90).In this cohort study, less than two-thirds of insured patients with viremic HCV received DAA treatment, with declines in both the treatment rate and the number of viremic HCV diagnoses since 2019 and especially during the COVID-19 pandemic. Further efforts are needed to increase HCV diagnosis and treatment, especially for those with cirrhosis and HCC. An urgent call for nationwide actions to improve access to DAA treatment, community outreach programs, and specialists through referral pipelines is needed in the United States to stay on track to meet the World Health Organization goal of reducing the burden of viral hepatitis with the eventual goal to eliminate viral hepatitis.

    View details for DOI 10.1001/jamanetworkopen.2022.45424

    View details for PubMedID 36477481

  • Impact of advanced practice providers on characteristics and quality of care of patients with chronic hepatitis B. Alimentary pharmacology & therapeutics Kam, L. Y., Huang, D. Q., Tobias, A. F., Poon, K., Henry, L., Kwo, P., Cheung, R., Nguyen, M. H. 2022


    Advanced practice providers (APP) may be able to play a role in improving the linkage to care in chronic hepatitis B (CHB), but data are limited.To compare management of CHB patients under APP-assisted versus physician-only care.This retrospective analysis identified patients with CHB infection from Optum's de-identified Clinformatics® Data Mart Database (2003-2021) using ICD-9/ICD-10 codes. We compared the proportion of patients with CHB who had adequate evaluation for treatment (defined as ALT, HBV DNA, ± HBeAg), and the proportion of treatment-eligible patients with CHB who received treatment between APP versus physician-only care.We included 42,140 eligible patients (mean age: 51.9 ± 15.1, 56.1% male). Overall, 34.3% received APP care with increasing utilisation over time. Compared to physician-only care, patients who also received APP care were more likely to have viral co-infection, and more likely to have been seen by a specialist (72.1%). Overall, 62.8% and 56.2% of treatment-eligible patients based on AASLD and EASL guidelines, respectively, received treatment; APP care patients were more likely to be treated (AASLD adjusted HR: 1.18, 95%CI: 1.03-1.34; EASL adjusted HR:1.24, 95%CI: 1.09-1.41) after adjustment for age, sex, race/ethnicity, viral dual infection, baseline cirrhosis/liver cancer, number of HBV DNA and alanine aminotransferase measurements, and physician provider type.Treatment-eligible patients with CHB receiving APP care were more likely to receive antiviral therapy. APP care may help to expand the pool of providers for patients with CHB, and to improve current suboptimal treatment rates.

    View details for DOI 10.1111/apt.17254

    View details for PubMedID 36266768

  • Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis. Digestive diseases (Basel, Switzerland) Kam, L., Huang, D. Q., Teng, M. L., Takahashi, H., Tanaka, K., Yasuda, S., Fung, J., Lee, T. Y., Hyogo, H., Ono, M., Saruwatari, J., Oniki, K., Yeo, Y. H., Barnett, S., Henry, L., Li, J., Zou, B., Cheung, R. C., Kumada, T., Yuen, M. F., Eguchi, Y., Toyoda, H., Nguyen, M. H. 2021


    NAFLD is increasingly prevalent in Asia, where people suffer more metabolic comorbidities at a lower body mass index (BMI), suggesting potential differences in their clinical profile. Therefore, we attempted to characterize the clinical profile of Asians with NAFLD via a meta-analytic approach.We searched Pubmed, EMBASE, and Cochrane databases from January 1, 2000 to January 17, 2019. Two authors independently reviewed and selected 104 articles (2,247,754 persons) that identified NAFLD in Asians and reported relevant data, especially BMI and ALT, and excluded individuals with other liver disease and excessive alcohol consumption. Individual patient-level data were obtained from seven cohorts in Asia to complement meta-analyzed data.Overall, the mean age was 52.07 (95%CI:51.28-52.85) years with those from Southeast Asia (42.66, 95%CI: 32.23-53.11) being significantly younger. The mean BMI was 26.2 kg/m2, higher in moderate-severe vs. mild hepatic steatosis (28.3 vs. 25.7) patients and NFS ≥-1.455 vs. <-1.455 (27.09 vs. 26.02), with 34% having non-obese NAFLD. The mean ALT was 31.74 U/L, higher in NFS <-1.455 vs. ≥-1.455 (33.74 vs. 27.83), though no differences were found by obesity or steatosis severity. The majority of males (85.7%) and females (60.7%) had normal to minimally elevated ALT (1-1.5x 95% ULN). Individual patient-level data analysis (N=7,668) demonstrated similar results.About one-third of Asians with NAFLD were non-obese and the majority did not have markedly elevated ALT. Therefore, abnormal ALT or BMI are not recommended as a criterion for NAFLD screening in this population. Additionally, there were significant differences in the clinical profiles of NAFLD among the different regions of Asia.

    View details for DOI 10.1159/000521662

    View details for PubMedID 34942625

  • A population-based US study of hepatitis C diagnosis rate. European journal of gastroenterology & hepatology Yeo, Y. H., Kam, L. Y., Le, M. H., Jeong, D., Dang, N., Henry, L., Cheung, R., Nguyen, M. H. 2021


    BACKGROUND: Underdiagnosis of HCV infection may hinder the obtainment of 2030 elimination goal.OBJECTIVE: To estimate the pre-DAA HCV diagnosis rate to inform future public health effort.METHODS: Data were obtained from three nationwide databases (Truven Health MarketScan Research Database 2007-2014, US Census Bureau 2012-2016 and NHANES 2007-2014). HCV diagnosis was defined with either one inpatient or two outpatient HCV International Classification of Disease 9 codes, providing the number of patients with diagnosed HCV (Truven). US Census Bureau data were used for age- and sex-standardization. We derived the total (diagnosed and undiagnosed) HCV infection using the NHANES database. To determine the rate and number of undiagnosed HCV, we subtracted diagnosed HCV burden (Truven) from the total HCV burden (NHANES).RESULTS: Of the 198 073 302 privately insured Americans, 1.49% (2 951 490 persons) had HCV infection. However, only 362 672 (12.29%) persons were diagnosed with HCV, leaving 2 588 818 (87.71%) undiagnosed. About two-third (68.04%) and one-third (33.04%) of diagnosed HCV patients had HCV RNA or genotype tests overall, with even lower rates for the ≥65 age group, respectively.CONCLUSION: In the pre-DAA era, only 12% of insured Americans with HCV were diagnosed. While this grim statistic is expected to rise, much more effort is needed to enhance the HCV care cascade.

    View details for DOI 10.1097/MEG.0000000000002149

    View details for PubMedID 33867444

  • Surveillance of patients with cirrhosis remains suboptimal in the United States. Journal of hepatology Yeo, Y. H., Hwang, J. n., Jeong, D. n., Dang, N. n., Kam, L. Y., Henry, L. n., Park, H. n., Cheung, R. n., Nguyen, M. H. 2021


    Regular monitoring/surveillance for liver complications is crucial in the management of patients with cirrhosis to reduce morbidity and mortality. Recommendations from professional societies are available but adherence is not well studied, especially outside of academic centers. We aimed to determine the frequencies and factors associated with laboratory monitoring, hepatocellular carcinoma (HCC) and esophageal varices (EV) surveillance in patients with cirrhosis.We identified 82,427 patients with cirrhosis (43,280 compensated and 39,147 decompensated) from the Truven Health MarketScan Research Database®, 2007-2016. We calculated the proportion of patients with cirrhosis with various frequencies of procedures/testing for laboratory (complete blood count, comprehensive metabolic panel, and prothrombin time), HCC and EV surveillance. We also used multivariable logistic regression to determine factors associated with having procedures.The proportions of patients undergoing HCC surveillance (8.78%), laboratory testing (29.72%) at least every 6-12 months, or EV surveillance (10.6%) at least every 1-2 years were suboptimal. The majority did not have HCC (45.4%) or EV (80.3%) surveillance during the entire study period. On multivariable regression, age 41-55 (vs. <41) years, PPO (vs. HMO) insurance plan, specialist care (vs. primary care and other specialties), diagnosis between 2013-2016 (vs. 2007-2009), decompensated (vs. compensated) cirrhosis, NAFLD (vs. viral hepatitis), and higher Charlson's comorbidity index were associated with significantly higher odds of undergoing procedures/testing every 6-12 months and EV surveillance every 1-2 years.Despite having modest improvement in the more recent years, routine monitoring and surveillance for patients with cirrhosis is suboptimal. Further efforts including provider awareness, patient education, and system/incentive-based quality improvement measures are urgently needed.Patients with cirrhosis should undergo health monitoring for liver complications to achieve early detection and treatment. In a large nationwide cohort of 82,427 patients with cirrhosis in the United States, we found a low rate of adherence (well less than half) to routine blood test monitoring and surveillance for liver cancer and esophageal varices (swollen blood vessels in the abdomen that could lead to fatal bleeding). Adherence has increased in the recent years, but much more improvement is needed.

    View details for DOI 10.1016/j.jhep.2021.04.042

    View details for PubMedID 33965477

  • ALT levels in Treatment-Naïve, Chronic Hepatitis B Patients with Concurrent Fatty Liver Disease: A U.S. Nationwide Study. Digestive diseases (Basel, Switzerland) Chang, C. Y., Kam, L., Dang, N., Cheung, R., Nguyen, M. H. 2021

    View details for DOI 10.1159/000518645

    View details for PubMedID 34348281

  • Substantial gaps in evaluation and treatment of patients with hepatitis B in the US. Journal of hepatology Ye, Q., Kam, L. Y., Yeo, Y. H., Dang, N., Huang, D. Q., Cheung, R., Nguyen, M. H. 2021


    HBV associated liver complication is reduced by antiviral therapy. Prior studies using local institutional cohorts have suggested suboptimal evaluation and treatment. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort.This retrospective analysis utlized claims data of approximately 73 million enrollees across the US from Optum's de-identified Clinformatics® Data Mart Database, 2003-2019. Adults with chronic HBV infection observed for ≥ 6 months before and after index chronic HBV infection diagnosis were identified via ICD-9/ICD-10 codes and confirmed by positive HBsAg, HBeAg or HBV DNA PCR.We included 12,608 eligible patients in the study analysis (mean age 45.7 years, 52.1% male, 54.6% Asian, 18.1% Caucasian, 10.5% African American). About half of the cohort (n=6,559, 52.3%) did not have a complete laboratory evaluation (defined as having HBeAg, HBV DNA, and ALT tests) and only 72.4% (n=9,129) had an "adequate" evaluation (at least HBV DNA and ALT) during the entire study period. Of those with an adequate evaluation, 11.2% were treatment eligible by AASLD criteria and 13.9% by EASL criteria; and of these, 60.4% of AASLD eligible patients and 54.3% of EASL eligible patients received treatment within 12 months from becoming eligible.Half of chronic HBV infection patients in the US with private insurance did not have a complete laboratory assessment. Over one third of treatment-eligible patients did not receive antiviral therapy. Patients who visited a GI/ID specialist had a higher chance of receiving adequate evaluation and treatment. Urgent intervention is needed to identify and address the barriers for these care gaps.In this study, we used a national database that includes laboratory data in addition to medical and pharmacy claims data to assess the current real-world situation of chronic HBV infection care in the US. Among the 12,608 patients with chronic HBV infection included in our study, 52.3% never had a complete laboratory and only 73% had adequate evaluation. Among those who were treatment eligible by AASLD or EASL guidelines, only 60.4% and 54.3% received treatment within 12 months, respectively.

    View details for DOI 10.1016/j.jhep.2021.08.019

    View details for PubMedID 34474097

  • ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation. Hepatology communications Huang, D. Q., Yeo, Y. H., Tan, E., Takahashi, H., Yasuda, S., Saruwatari, J., Tanaka, K., Oniki, K., Kam, L. Y., Muthiah, M. D., Hyogo, H., Ono, M., Barnett, S. D., Li, J., Zou, B., Fung, J., Lee, T. Y., Wong, V. W., Yuen, M. F., Dan, Y. Y., Lim, S. G., Cheung, R., Toyoda, H., Eguchi, Y., Nguyen, M. H. 2020; 4 (11): 1624-1636


    The current alanine aminotransferase (ALT) upper limit of normal was defined using selected healthy Caucasian blood donors. Given the global rise in obesity and different body habitus in Asians, we aimed to perform a systematic review and meta-analysis combined with bootstrap modeling and individual patient data validation to estimate the ALT upper threshold for Asians, including the overweight and diabetics. We included studies from PubMed, Embase, and Cochrane database searches that identified individuals without known liver diseases (i.e., viral hepatitis, alcohol, and ultrasound-detected nonalcoholic fatty liver disease). The mean ALT (U/L) was estimated using a random-effects mixed model and upper threshold (95th-percentile value, U/L) via a bootstrap model with 10,000 resamples. We screened 4,995 studies and identified 86 studies that reported ALT values for 526,641 individuals without excessive alcohol intake or known liver diseases, yielding a mean ALT of 19 and ALT upper threshold of 32. The ALT upper threshold was 37 in males versus 31 in females, 39 in overweight versus 28 in normal-weight individuals, and 36 for diabetics versus 33 for nondiabetics. We validated our study level data with individual patient level data in 6,058 individuals from five study centers in Japan. Consistent with our study-level data, we found that the ALT upper threshold in our individual patient data analysis was indeed higher in overweight versus normal-weight individuals (39 vs. 32) and in diabetics versus nondiabetics (42 vs. 33). Conclusion: We provide validated reference ranges for ALT upper threshold derived from Asians without known liver disease, including individuals with ultrasound-detected nonalcoholic fatty liver disease who are normal weight, overweight, nondiabetic, and diabetic, to inform practice.

    View details for DOI 10.1002/hep4.1593

    View details for PubMedID 33163833

    View details for PubMedCentralID PMC7603525

  • SEQUENTIAL THERAPY WITH TENOFOVIR ALAFENAMIDE (TAF) IN PATIENTS WITH CHRONIC HEPATITIS B (CHB): AN INTERIM ANALYSIS OF AN ONGOING MULTINATIONAL PROSPECTIVE STUDY Ogawa, E., Toyoda, H., Jun, D., Hsu, Y., Yoon, E., Ahn, S., Yeh, M., Yasuda, S., Kawashima, K., Do, S. T., Trinh, H. N., Takahashi, H., Enomoto, M., Tseng, C., Inoue, K., Haga, H., Maeda, M., Kam, L., Cheung, R., Ueno, Y., Eguchi, Y., Furusyo, N., Yu, M., Tanaka, Y., Nguyen, M. H. WILEY. 2020: 495A–496A
  • HIGH HCV CURE RATES WITH APPROVED INTERFERON-FREE DIRECT ACTING ANTIVIRALS AMONG DIVERSE MAINLAND CHINESE PATIENTS INCLUDING GENOTYPES 3a AND 3b Ji, F., Li, J., Liu, L., Jing, L., Wang, X., Liu, J., Cai, D., Huang, R., Zhang, J., Wang, Q., Nan, Y., Li, J., Ye, Q., Zhang, M., Xu, Q., Guo, F., Zhao, C., Liu, L., He, C., Yu, L., Wang, W., Kam, L., Tran, S., Maeda, M., Mizuta, A., Li, Z., Dang, S., Zhu, Q., Ren, W., Cheung, R., Niu, J., Xie, W., Pan, H., Ren, H., Wu, C., Shang, J., Wang, F., Nguyen, M. H. WILEY. 2020: 532A–533A
  • ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation HEPATOLOGY COMMUNICATIONS Huang, D. Q., Yeo, Y., Tan, E., Takahashi, H., Yasuda, S., Saruwatari, J., Tanaka, K., Oniki, K., Kam, L. Y., Muthiah, M. D., Hyogo, H., Ono, M., Barnett, S. D., Li, J., Zou, B., Fung, J., Lee, T., Wong, V., Yuen, M., Dan, Y., Lim, S., Cheung, R., Toyoda, H., Eguchi, Y., Nguyen, M. H. 2020

    View details for DOI 10.1002/hep4.1593

    View details for Web of Science ID 000570299500001

  • High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Ji, F., Li, J., Liu, L., Liang, J., Wang, X., Liu, J., Cai, D., Huang, R., Zhang, J., Wang, Q., Nan, Y., Li, J., Ye, Q., Zhang, M., Xu, Q., Guo, F., Zhao, C., Liu, L., He, C., Li, Y., Wang, W., Kam, L. Y., Tran, S., Maeda, M., Mizuta, A., Li, Z., Dang, S., Ren, W., Zhu, Q., Cheung, R., Niu, J., Xie, W., Pan, H., Ren, H., Wu, C., Shang, J., Wang, F., Nguyen, M. H. 2020

    View details for DOI 10.1111/jgh.15192

    View details for Web of Science ID 000555678900001

  • High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b. Journal of gastroenterology and hepatology Ji, F., Li, J., Liu, L., Liang, J., Wang, X., Liu, J., Cai, D., Huang, R., Zhang, J., Wang, Q., Nan, Y., Li, J., Ye, Q., Zhang, M., Xu, Q., Guo, F., Zhao, C., Liu, L., He, C., Li, Y., Wang, W., Kam, L. Y., Tran, S., Maeda, M., Mizuta, A., Li, Z., Dang, S., Ren, W., Zhu, Q., Cheung, R., Niu, J., Xie, W., Pan, H., Ren, H., Wu, C., Shang, J., Wang, F., Nguyen, M. H. 2020


    Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3.The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index).We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+. The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin).In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.

    View details for DOI 10.1111/jgh.15192

    View details for PubMedID 32840326

  • Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. The lancet. Gastroenterology & hepatology Ye, Q. n., Zou, B. n., Yeo, Y. H., Li, J. n., Huang, D. Q., Wu, Y. n., Yang, H. n., Liu, C. n., Kam, L. Y., Tan, X. X., Chien, N. n., Trinh, S. n., Henry, L. n., Stave, C. D., Hosaka, T. n., Cheung, R. C., Nguyen, M. H. 2020


    Although non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, it is increasingly being identified in non-obese individuals. We aimed to characterise the prevalence, incidence, and long-term outcomes of non-obese or lean NAFLD at a global level.For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library from inception to May 1, 2019, for relevant original research articles without any language restrictions. The literature search and data extraction were done independently by two investigators. Primary outcomes were the prevalence of non-obese or lean people within the NAFLD group and the prevalence of non-obese or lean NAFLD in the general, non-obese, and lean populations; the incidence of NAFLD among non-obese and lean populations; and long-term outcomes of non-obese people with NAFLD. We also aimed to characterise the demographic, clinical, and histological characteristics of individuals with non-obese NAFLD.We identified 93 studies (n=10 576 383) from 24 countries or areas: 84 studies (n=10 530 308) were used for the prevalence analysis, five (n=9121) were used for the incidence analysis, and eight (n=36 954) were used for the outcomes analysis. Within the NAFLD population, 19·2% (95% CI 15·9-23·0) of people were lean and 40·8% (36·6-45·1) were non-obese. The prevalence of non-obese NAFLD in the general population varied from 25% or lower in some countries (eg, Malaysia and Pakistan) to higher than 50% in others (eg, Austria, Mexico, and Sweden). In the general population (comprising individuals with and without NAFLD), 12·1% (95% CI 9·3-15·6) of people had non-obese NAFLD and 5·1% (3·7-7·0) had lean NAFLD. The incidence of NAFLD in the non-obese population (without NAFLD at baseline) was 24·6 (95% CI 13·4-39·2) per 1000 person-years. Among people with non-obese or lean NALFD, 39·0% (95% CI 24·1-56·3) had non-alcoholic steatohepatitis, 29·2% (21·9-37·9) had significant fibrosis (stage ≥2), and 3·2% (1·5-5·7) had cirrhosis. Among the non-obese or lean NAFLD population, the incidence of all-cause mortality was 12·1 (95% CI 0·5-38·8) per 1000 person-years, that for liver-related mortality was 4·1 (1·9-7·1) per 1000 person-years, cardiovascular-related mortality was 4·0 (0·1-14·9) per 1000 person-years, new-onset diabetes was 12·6 (8·0-18·3) per 1000 person-years, new-onset cardiovascular disease was 18·7 (9·2-31·2) per 1000 person-years, and new-onset hypertension was 56·1 (38·5-77·0) per 1000 person-years. Most analyses were characterised by high heterogeneity.Overall, around 40% of the global NAFLD population was classified as non-obese and almost a fifth was lean. Both non-obese and lean groups had substantial long-term liver and non-liver comorbidities. These findings suggest that obesity should not be the sole criterion for NAFLD screening. Moreover, clinical trials of treatments for NAFLD should include participants across all body-mass index ranges.None.

    View details for DOI 10.1016/S2468-1253(20)30077-7

    View details for PubMedID 32413340

  • DISTRIBUTION OF BMI, SERUM ALT, HEPATIC STEATOSIS AND LIVER FIBROSIS IN ASIANS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD): A SYSTEMATIC REVIEW AND META-ANALYSIS OF 108 STUDIES WITH 2,260,207 INDIVIDUALS Kam, L., Yeo, Y., Huang, D., Fung, J., Lee, T., Yasuda, S., Wong, V., Saruwatari, J., Barnett, S., Oniki, K., Li, J., Zou, B., Cheung, R., Kumada, T., Yuen, M., Toyoda, H., Nguyen, M. H. WILEY. 2019: 741A–742A
  • IMPACT OF SVR ON LONG-TERM LIVER-RELATED OUTCOMES: RESULTS OF THE REAL-C REGISTRY AT 23 CENTERS FROM HONG KONG, KOREA, JAPAN AND TAIWAN Tanaka, Y., Toyoda, H., Jun, D., Enomoto, M., Huang, C., Ogawa, E., Yasuda, S., Iio, E., Iwane, S., Haga, H., Dai, C., Jeong, J., Park, S., Wong, G. L., Lee, D., Takahashi, H., Huang, J., Tran, S., Maeda, M., Cheung, R., Ueno, Y., Eguchi, Y., Hayashi, J., Furusyo, N., Tamori, A., Kumada, T., Yu, M., Nguyen, M. H., Ahn, S., Henry, L., Hsu, Y., Huang, C., Jun, M., Jung, J., Kam, L., Lee, M., Liang, P., Mizuta, A., Song, D., Tsai, P., Tseng, C., Yang, H., Yeh, M., Yoon, E., Real-C Investigators WILEY. 2019: 908A–909A
  • REDEFINING THE UPPER LIMIT OR NORMAL (ULN) OF ALANINE TRANSAMINASE (ALT) LEVELS FOR ASIANS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 60 STUDIES AND 335,163 INDIVIDUALS Huang, D., Yeo, Y., Tan, X., Kam, L., Fung, J., Lee, T., Wong, V., Saruwatari, J., Muthiah, M., Barnett, S., Oniki, K., Li, J., Zou, B., Dan, Y., Lim, S., Cheung, R., Yuen, M., Nguyen, M. H. WILEY. 2019: 1055A–1056A
  • Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis LANCET GASTROENTEROLOGY & HEPATOLOGY Li, J., Zou, B., Yeo, Y., Feng, Y., Xie, X., Lee, D., Fujii, H., Wu, Y., Kam, L. Y., Ji, F., Li, X., Chien, N., Wei, M., Ogawa, E., Zhao, C., Wu, X., Stave, C. D., Henry, L., Barnett, S., Takahashi, H., Furusyo, N., Eguchi, Y., Hsu, Y., Lee, T., Ren, W., Qin, C., Jun, D., Toyoda, H., Wong, V., Cheung, R., Zhu, Q., Nguyen, M. H. 2019; 4 (5): 389–98
  • Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis. The lancet. Gastroenterology & hepatology Li, J., Zou, B., Yeo, Y. H., Feng, Y., Xie, X., Lee, D. H., Fujii, H., Wu, Y., Kam, L. Y., Ji, F., Li, X., Chien, N., Wei, M., Ogawa, E., Zhao, C., Wu, X., Stave, C. D., Henry, L., Barnett, S., Takahashi, H., Furusyo, N., Eguchi, Y., Hsu, Y., Lee, T., Ren, W., Qin, C., Jun, D. W., Toyoda, H., Wong, V. W., Cheung, R., Zhu, Q., Nguyen, M. H. 2019


    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Asia is a large, heterogeneous area with substantial variation in socioeconomic status and prevalence of obesity. We estimated the prevalence, incidence, and outcomes of NAFLD in the Asian population to assist stakeholders in understanding NAFLD disease burden.METHODS: We searched PubMed, EMBASE, and the Cochrane Library from database inception to Jan 17, 2019, for studies reporting NAFLD prevalence, incidence, or outcome in Asia. We included only cross-sectional and longitudinal observational studies of patients with NAFLD diagnosed by imaging, serum-based indices, or liver biopsy. Studies that included patients with overlapping liver disease or that did not screen for excess alcohol consumption were excluded. Two investigators independently screened and extracted data. The main outcomes were pooled NAFLD prevalence, incidence, and hepatocellular carcinoma incidence and overall mortality in patients with NAFLD. Summary estimates were calculated using a random-effects model. This study is registered with PROSPERO, number CRD42018088468.FINDINGS: Of 4995 records identified, 237 studies (13 044 518 participants) were included for analysis. The overall prevalence of NAFLD regardless of diagnostic method was 29·62% (95% CI 28·13-31·15). NAFLD prevalence increased significantly over time (25·28% [22·42-28·37] between 1999 and 2005, 28·46% [26·70-30·29] between 2006 and 2011, and 33·90% [31·74-36·12] between 2012 and 2017; p<0·0001). The pooled annual NAFLD incidence rate was 50·9 cases per 1000 person-years (95% CI 44·8-57·4). In patients with NAFLD, the annual incidence of hepatocellular carcinoma was 1·8 cases per 1000 person-years (0·8-3·1) and overall mortality rate was 5·3 deaths per 1000 person-years (1·5-11·4).INTERPRETATION: NAFLD prevalence in Asia is increasing and is associated with poor outcomes including hepatocellular carcinoma and death. Targeted public health strategies must be developed in Asia to target the drivers of this rising epidemic and its associated complications, especially in high-risk groups, such as older obese men.FUNDING: None.

    View details for PubMedID 30902670

  • Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis GASTROENTEROLOGY Yeo, Y., Ho, H. J., Yang, H., Tseng, T., Hosaka, T., Trinh, H. N., Kwak, M., Park, Y., Fung, J., Buti, M., Rodriguez, M., Treeprasertsuk, S., Preda, C., Ungtrakul, T., Charatcharoenwitthaya, P., Li, X., Li, J., Zhang, J., Le, M., Wei, B., Zou, B., Le, A., Jeong, D., Chien, N., Kam, L., Lee, C., Riveiro-Barciela, M., Istratescu, D., Sriprayoon, T., Chong, Y., Tanwandee, T., Kobayashi, M., Suzuki, F., Yuen, M., Lee, H., Kao, J., Lok, A. S., Wu, C., Nguyen, M. H. 2019; 156 (3): 635-+
  • Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium. Hepatology international Huang, C. F., Iio, E. n., Jun, D. W., Ogawa, E. n., Toyoda, H. n., Hsu, Y. C., Haga, H. n., Iwane, S. n., Enomoto, M. n., Lee, D. H., Wong, G. n., Liu, C. H., Tada, T. n., Chuang, W. L., Cheung, R. n., Hayashi, J. n., Tseng, C. H., Yasuda, S. n., Tran, S. n., Kam, L. n., Henry, L. n., Jeong, J. Y., Nomura, H. n., Park, S. H., Nakamuta, M. n., Huang, J. F., Tai, C. M., Lo, G. H., Lee, M. H., Yang, H. I., Kao, J. H., Tamori, A. n., Eguchi, Y. n., Ueno, Y. n., Furusyo, N. n., Tanaka, Y. n., Yu, M. L., Nguyen, M. H. 2019


    One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia.Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25 IU/mL 12 week post-therapy).A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5 years, p < 0.0001), had lower body mass indices (22.9 kg/m2 vs. 24.6 kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes.In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

    View details for DOI 10.1007/s12072-019-09974-z

    View details for PubMedID 31463665

  • Factors Associated with Rates of HBsAg Seroclearance in Adults with Chronic HBV Infection: A systematic review and meta-analysis. Gastroenterology Yeo, Y. H., Ho, H. J., Yang, H. I., Tseng, T. C., Hosaka, T. n., Trinh, H. N., Kwak, M. S., Park, Y. M., Fung, J. Y., Buti, M. n., Rodriguez, M. n., Treeprasertsuk, S. n., Preda, C. M., Ungtrakul, T. n., Charatcharoenwitthaya, P. n., Li, X. n., Li, J. n., Zhang, J. n., Le, M. H., Wei, B. n., Zou, B. n., Le, A. n., Jeong, D. n., Chien, N. n., Kam, L. n., Lee, C. C., Riveiro-Barciela, M. n., Istratescu, D. n., Sriprayoon, T. n., Chong, Y. n., Tanwandee, T. n., Kobayashi, M. n., Suzuki, F. n., Yuen, M. F., Lee, H. S., Kao, J. H., Lok, A. S., Wu, C. Y., Nguyen, M. H. 2018


    Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations.We searched PubMed, Embase, and Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model.We analyzed 34 published studies (with 42,588 patients; 303,754 person-years of follow-up; and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between sexes. A higher proportion of patients negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than patients positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P<.01). HBsAg seroclearance was also associated with a lower baseline HBV DNA (6.61 log10IU/mL; 95% CI, 5.94-7.27) than in patients without HBsAg seroclearance (7.71 log10IU/mL; 95% CI, 7.41-8.02) (P<.01) and lower level of HBsAg at baseline (2.74 log10IU/mL; 95% CI, 1.88-3.60) than in patients without HBsAg seroclearance (3.90 log10IU/mL, 95% CI, 3.73-4.06) (P<.01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I2=97.49%).In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.

    View details for PubMedID 30342034