Rising Prevalence of Osteoporosis and Bone Fracture in Chronic Hepatitis B Patients: A United States Population-Based Study

( Mindie H. Nguyen ),( Joseph Lim ),( A. Burak Ozbay ),( Jeremy Fraysse ),( Iris Liou ),( Laura Moore-schiltz ),( Geoffrey Dusheiko ),( Stuart Gordon ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Older patients and those of Asian descent are at higher risk for osteoporosis. In the U.S., most patients with chronic hepatitis B (CHB) are Asians. The aim of this study was to characterize the longitudinal trends in osteoporosis and bone fractures and to describe comorbidities and concomitant medications use in a large diverse population of U.S. CHB patients between 2006 and 2015. Methods: Adult patients diagnosed with CHB (without HDV) with continuous enrollment in the 6 months before and after CHB diagnosis were identified from the MarketScan® Commercial, Medicare, and Medicaid Databases during 7/1/2004- 6/30/2015. These CHB patients were matched to non-CHB controls by payer type, year, age, gender. The prevalence (per 1000 persons) and incidence (per 1000 person- years) of osteoporosis and bone fracture were calculated for each year during 2006-2015. Comorbidities and medication use which may influence bone mineralization were also evaluated. Results: Among the 44,026 CHB patients identified for the study, the prevalence of fracture and osteoporosis increased significantly between 2006 and 2015 by nearly 2-fold (91 to 177 per 1000) overall (Figure). This trend was observed for both males (76 to 133 per 1000) and females (109 to 228 per 1000). When compared to matched non-CHB controls, the prevalence and incidence were significantly higher in CHB patients during each study year period. In CHB patients, the prevalence of osteoporosis, osteoarthritis, or vitamin D deficiency also increased nearly 3-folds from 7% to 20%, (p<0.001). During the same period, the concomitant use of corticosteroids increased from 17% to 24%. Conclusions: : Between 2006-2015, the prevalence of bone fracture and osteoporosis increased significantly in U.S. patients with CHB, and was much higher in CHB patients than non-CHB controls. During the same period, comorbidities related to bone mineral loss also increased and should be considered in the management of CHB patients.

Chronic Hepatitis B (CHB) Patients Have Increasing Prevalence and Incidence of Chronic Kidney Disease: Real-World Analysis of 165,594 U.S. Patients

( Mindie H. Nguyen ),( Joseph Lim ),( A. Burak Ozbay ),( Jeremy Fraysse ),( Iris Liou ),( Laura Moore-schiltz ),( Geoffrey Dusheiko ),( Stuart Gordon ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Chronic kidney disease (CKD) is a significant comorbidity that may be more common among patients with chronic hepatitis B (CHB). Our goal was to characterize the prevalence and incidence of CKD over time during the period from 2006 to 2015 in a diverse population of CHB patients across the U.S. Methods: Using the Truven Health MarketScan^® Commercial (general population), Medicare (mostly older than 65), and Medicaid (low income population) insurance databases, we identified a cohort of CHB cases (without HDV). We matched these to non-CHB controls by calendar year of diagnosis date, age, gender, and geographic region. Primary outcomes were CKD prevalence (per 1000 persons) and incidence (per 1000 person-years). We analyzed CKD outcomes by age group and by presence of diabetes and hypertension for CHB patients in 2015. Results: This study included 44,026 CHB patient cases and 121,568 non-CHB controls CKD prevalence increased significantly over time and was higher in CHB than non-CHB controls (Figure 1). CKD prevalence increased by nearly 3-fold from 44 to 114, p<0.001. CKD incidence increased by 56% (13 to 20, p=0.003). Between 2006 to 2015, the proportion of patients with comorbidities that may predispose patients to CKD increased: 12.2%-17.7% for diabetes, 22.0% -37.3% for hypertension. For CHB patients in 2015, CKD prevalence in patients with diabetes and hypertension was 10-fold higher than those without, and 6-fold higher in patients older than 60 compared to younger than 45. Conclusions: CKD prevalence in CHB patients has increased by almost 3-fold from 2006 to 2015 and is significantly higher than matched non-CHB controls and with similar trends observed for CKD incidence. CKD is particularly prevalent in older CHB patients and those with the comorbidities of diabetes and hypertension. Whether CHB has contributed to the prevalence of CKD in the cohort requires further analysis.

Real-World Sustained Virologic Response Rates (SVR12) with Interferon (IFN)-Free Direct Acting Antiviral (DAA) Therapy in East Asia- Results from REAL-C (Real-World Effectiveness from the Asia Liver Consortium for Chronic Hepatitis C)

( Mindie H. Nguyen ),( Norihiro Furusyo ),( Dae Won Jun ),( Ming-Lung Yu ),( Jia-Horng Kao ),( Masaru Enomoto ),( Eiichi Ogawa ),( Etsuko Ilio ),( Chen-Hua Liu ),( Akihiro Tamori ),( Chia-Yen Dai ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Since their recent introduction in Asia, IFN-free DAAs have revolutionized treatment of chronic hepatitis C across all HCV genotypes. However, experience from large and diverse routine clinical practice is still limited. The aim of this study was to report real-world outcomes from a large multinational co hort of East Asian HCV patients treated with IFN-free DAAs. Methods: Data were obtained using a required case report form from the REAL-C registry of patients who were initiated on IFN-free DAA therapy in routine practice and represented 10 study centers inclusive of 30 clinical sites in Hong Kong, Japan, Korea, and Taiwan. Cirrhosis was determined by liver biopsy, noninvasive tests (elastography/fibroscan, fibrotest), or the presence of clinical, radiologic, endoscopic, laboratory evidence of cirrhosis and/or portal hypertension. Results: A total of 3702 patients have been registered. Table 1 displays the patient characteristics. The average age was 63.6±12.8; 17.7% had diabetes, 8.7% had chronic renal impairment, 26% had cirrhosis (5.1% decompensated cirrhosis), and 5.4% had HCC at baseline or prior to DAA treatment initiation. The majority of patients were HCV GT1 (68.7%), followed by HCV GT2 (30.4%). Ten different DAA regimens were used, with the majority receiving LDV/SOF (43.7%), followed by SOF+RBV (27.8%). One-third were treatment experienced (24.8% with prior PEG-IFN+RBV, 4.5% with prior DAA). SVR12 overall rate was 96.6%. Significant decreases noted in all major liver enzymes at week 12 and 24 post treatment. No increase in creatinine noted across treatments; 3.2% stopped treatment and 13.4% had an adverse event with fatigue (5.6% in patients treated with RBV vs. 6.4% in those treated without RBV, P=0.61) and anemia (5.6%) the most reported. Table 2 displays SVR12 rates by cirrhosis and prior treatment status for the most commonly used DAA treatments for GT1 and GT2 patients. SVR12 rates were excellent ranging from 97.1% (95%CI: 94.1-98.8%) to 99.7% (95%CI: 99.0-99.9%) for GT1 patients treated with LDV/SOF who did not have cirrhosis regardless of prior treatment history and who were treatment-naive with cirrhosis but lower in the cirrhotic treatment-experienced group (92.2%; 95%CI: 86.7-95.9%) (P<0.0001). Sub-analysis results for GT1b were similar, with SVR12 99.7% for non-cirrhotic treatment-naive, 99.5% for non-cirrhotic treatment-experienced, 97.4% for cirrhotic treatment-naive, and 93.0% for cirrhotic treatment-experienced, (P<0.0001). For GT2 patients, SVR12 was excellent for all groups (96.8-98.0%) except for cirrhotic treatment-experienced patients (n=66) who experienced an SVR12 of 87.9% (95%CI: 77.5-94.6%) (P=0.002). Conclusions: HCV cure rates were high overall in the REALC cohort-LDV/SOF GT1 98%; SOF+RBV GT2 96% except for cirrhotic, treatment-experienced patients especially in GT2, suggesting alternative therapy is needed.

Response to DAA in HCV Patients with HCC from East Asia: A REAL-C Study with Propensity Score Matching (PSM)

( Mindie H. Nguyen ),( Norihiro Furusyo ),( Dae Won Jun ),( Ming-Lung Yu ),( Jia-Horng Kao ),( Masaru Enomoto ),( Eiichi Ogawa ),( Etsuko Ilio ),( Chen-Hua Liu ),( Akihiro Tamori ),( Chia-Yen Dai ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Reports suggest HCV-HCC patients do not respond as well to the IFN-free DAAs, but background risks and confounders for treatment failures may not have been adequately controlled. Our goal was to compare SVR12 of DAAs in East Asian patients with HCV-HCC to those without HCC using PSM to balance the HCC and non-HCC groups. Methods: Data were from 10 study centers comprising of 30 clinical sites in Hong Kong, Japan, Korea, and Taiwan representing the Real-World Evidence from the Asia Liver Consortium for Chronic Hepatitis C (REAL-C) - a registry of patients treated with IFN-free DAAs in routine practice (n=3702). 1:1 PSM matching on cirrhosis, prior treatment, baseline platelet, age, sex, baseline HCV RNA, treatment regimen, baseline ALT, HCV genotype, and BMI was used to balance the groups at baseline. Results: In our cohort, there were 195 patients with HCC at baseline or prior to DAA initiation and 3507 patients who did not have HCC at baseline. Prior to PSM, HCC patients were significantly older, more likely male, more likely to have renal insufficiency, cirrhosis, and decompensation (all P< 0.004). After PSM, there were 171 HCC and N=171 non-HCC patients for analysis. As shown in Table 1, there were no significant differences in the baseline characteristics between the matched HCC and non-HCC cohorts. The majority (51-55%) of both groups received LDV/SOF; eight (three HCC, five non-HCC) stopped treatment before completion while ~10-12% had an adverse reaction (most common: anemia [ >~5-6%] and fatigue [~3-5%]). There were seven deaths: five in the HCC group (four were liver-related) and two in the non-HCC group (both were non-liver-related). Overall, SVR12 rate was >96% for both groups with no significant differences. (Table 2) Conclusions: This PSM study compared treatment for HCV patients with/without HCC, finding no difference in treatment tolerability, completion, and cure rates.

Increasing Age and Comorbidities of U.S. Chronic Hepatitis B Patients : A Longitudinal Analysis of 44,026 Patients over 10 Years

( Mindie H. Nguyen ),( Joseph Lim ),( A. Burak Ozbay ),( Jeremy Fraysse ),( Iris Liou ),( Laura Moore-schiltz ),( Geoffrey Dusheiko ),( Stuart Gordon ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Little is known about the age, prevalence of comorbidities, and co-medications among U.S. patients with chronic hepatitis B (CHB). Our aim was to characterize these longitudinal trends in a large diverse population of U.S. CHB patients, between 2006 and 2015. Methods: We conducted a study of CHB patients ≥ 18 years of age (without HDV) who were continuously enrolled for 6 months before and after CHB diagnosis, using de-identified and U.S. administrative healthcare claims extracted from the Truven Health MarketScan® Commercial (general population), Medicare (older than 65), and Multi-State Medicaid (low income population) databases between 7/1/2004 and 6/30/2015. Results: We identified a total of 44,026 U.S. CHB patients. The median age of CHB patients increased from 47 in 2006 to 52 in 2015 (p<0.001). Deyo-Charlson Comorbidity Index scores increased over time from a mean of 1.1 in 2006 to 1.4 in 2015 (p<0.001). The proportion of CHB patients with diabetes, hypertension, and hyperlipidemia also increased significantly between 2006 and 2015 (p<0.001) (Figure). Specifically, from 2006 to 2015, diabetes increased from 12.2% to 17.7%, renal impairment increased from 9.8% to 16.7%, hypertension increased by almost two-fold from 22.0% to 37.3%, hyperlipidemia increased by almost 3-fold from 8.1% to 24.0%, and non-alcoholic fatty liver disease (NAFLD) increased over 2-folds from 1.7% to 5.2% (p<0.001). From 2006 to 2015, use of cardiovascular medications increased from 27.0% to 37.1% and use of antidiabetic medications increased from 10.3% to 13.2% (p<0.001). Conclusions: Between 2006 and 2015, the median age of patients with CHB significantly increased with increasing prevalence of associated comorbidities and concomitant medication use, up to 3-fold increase in some major comorbidities. The contribution of hepatitis B to these comorbidities in an aging population merits further analysis but advancing age and comorbidities in this group require appropriate management.

Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study

Vy H. Nguyen,Isaac Le,Audrey Ha,Richard Hieu Le,Nicholas Ajit Rouillard,Ashley Fong,Surya Gudapati,Jung Eun Park,Mayumi Maeda,Scott Barnett,Ramsey Cheung,Mindie H. Nguyen 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.4

Background/Aims: Understanding of nonalcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients. Methods: Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995–2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related). Results: The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5–3.5% and 4.3–7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022). Conclusions: Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liverrelated mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.

Global incidence of adverse clinical events in nonalcoholic fatty liver disease: A systematic review and meta-analysis

Michael H. Le,David M. Le,Thomas C. Baez,Hansen Dang,Vy H. Nguyen,KeeSeok Lee,Christopher D. Stave,Takanori Ito,Yuankai Wu,Yee Hui Yeo,Fanpu Ji,Ramsey Cheung,Mindie H. Nguyen 대한간학회 2024 Clinical and Molecular Hepatology(대한간학회지) Vol.30 No.2

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. Results: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). Conclusions: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach

Michael H. Le,Yee Hui Yeo,Biyao Zou,Scott Barnet,Linda Henry,Ramsey Cheung,Mindie H. Nguyen 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.4

Background/Aims: Due to increases in obesity and type 2 diabetes, the prevalence of nonalcoholic fatty liver disease (NAFLD) has also been increasing. Current forecast models may not include non-obese NAFLD. Here, we used the Bayesian approach to forecast the prevalence of NAFLD through the year 2040. Methods: Prevalence data from 245 articles involving 2,699,627 persons were used with a hierarchical Bayesian approach to forecast the prevalence of NAFLD through 2040. Subgroup analyses were performed for age, gender, presence of metabolic syndrome, region, and smoking status. Sensitivity analysis was conducted for clinical setting and study quality. Results: The forecasted 2040 prevalence was 55.7%, a three-fold increase since 1990 and a 43.2% increase from the 2020 prevalence of 38.9%. The estimated average yearly increase since 2020 was 2.16%. For those aged <50 years and ≥50 years, the 2040 prevalence were not significantly different (56.7% vs. 61.5%, P=0.52). There was a significant difference in 2040 prevalence by sex (males: 60% vs. 50%) but the trend was steeper for females (annual percentage change: 2.5% vs. 1.5%, P=0.025). There was no difference in trends overtime by region (P=0.48). The increase rate was significantly higher in those without metabolic syndrome (3.8% vs. 0.84%, P=0.003) and smokers (1.4% vs. 1.1%, P=0.011). There was no difference by clinical/community setting (P=0.491) or study quality (P=0.85). Conclusions: By 2040, over half the adult population is forecasted to have NAFLD. The largest increases are expected to occur in women, smokers, and those without metabolic syndrome. Intensified efforts are needed to raise awareness of NAFLD and to determine long-term solutions addressing the driving factors of the disease.

In response to: Steatotic liver disease-know your enemies

Michael H. Le,Linda Henry,Mindie H. Nguyen 대한간학회 2024 Clinical and Molecular Hepatology(대한간학회지) Vol.30 No.2

Nonalcoholic fatty liver disease and non-liver comorbidities

Richie Manikat,Mindie H. Nguyen 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.-

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.