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Ilagan-Ying YC, Gordon KS, Tate JP, Lim JK, Torgersen J, Lo Re V, Justice AC, Taddei TH. Risk Score for Hepatocellular Cancer in Adults Without Viral Hepatitis or Cirrhosis. JAMA Netw Open 2024; 7:e2443608. [PMID: 39504020 PMCID: PMC11541635 DOI: 10.1001/jamanetworkopen.2024.43608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 09/16/2024] [Indexed: 11/08/2024] Open
Abstract
IMPORTANCE Hepatocellular carcinoma (HCC) is typically detected only at advanced stages when treatment options are limited. Most of the current HCC risk models focus on patients with viral hepatitis or diagnosed cirrhosis or require variables not routinely available in clinical care. OBJECTIVE To identify modifiable HCC risk factors in the general population and to develop a risk score to inform HCC screening and risk-factor modification interventions for high-risk individuals without viral hepatitis or decompensated cirrhosis. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed demographic, clinical, laboratory, and diagnostic data from the US Department of Veterans Affairs (VA) electronic health records. Data were divided into development and validation samples. Veterans aged 30 to 95 years were included, and those with hepatitis B or C virus infection, hepatic decompensation, or prevalent HCC were excluded. Patients were followed up until the occurrence of HCC diagnosis, death, or December 31, 2021. A Cox proportional hazards regression model for 10-year risk of HCC was developed and used to create an HCC risk score, and performance in development and validation samples and in patient subgroups was evaluated. One outpatient visit date per person at least 18 months after VA entry, between October 1, 2007, and March 31, 2020, was randomly selected and used as the index date for the start of follow-up. Analyses were performed from March 2023 to May 2024. EXPOSURES Age, sex, race and ethnicity, body mass index, liver fibrosis (detected with Fibrosis-4 Index [FIB-4]), diabetes status, smoking status, and alcohol use. MAIN OUTCOMES AND MEASURES First HCC diagnosis during follow-up. This information was ascertained from VA national cancer registry topography and histology codes and from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for the inpatient or outpatient visits. RESULTS This study of 6 509 288 veterans included 6 048 917 males (92.9%), with a median (IQR) age of 65 (54-74) years, who identified as being of Hispanic (5.3%), non-Hispanic Black (15.0%), non-Hispanic White (68.9%), or other (4.6%) race and ethnicity. Overall, 15 142 patients (0.2%) developed HCC, 69.5% of whom had FIB-4 of 3.25 or lower at baseline. While FIB-4 was the most important variable, age, sex, race and ethnicity, body mass index, diabetes, smoking, and alcohol use were also informative. Discrimination in the development sample was better than FIB-4 alone (C statistic, 0.83 [95% CI, 0.82-0.85] vs 0.79 [95% CI, 0.77-0.80]). The HCC risk score performed consistently well in the validation sample and in all subgroups. A FIB-4 threshold of 3.25 would screen 5.0% of the cohort at a cost of 28 false-positives for every true-positive; a model risk score of 58 would screen 4.7% of the cohort at a cost of 23 false-positives for every true-positive. CONCLUSIONS AND RELEVANCE Results of this study suggest that a multivariable risk score that uses routinely available clinical data outperforms FIB-4 alone in identifying patients at risk of HCC who do not have viral hepatitis or hepatic decompensation at baseline.
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Affiliation(s)
- Ysabel C. Ilagan-Ying
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Medicine, Veterans Affairs Connecticut Healthcare, West Haven, Connecticut
| | - Kirsha S. Gordon
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Medicine, Veterans Affairs Connecticut Healthcare, West Haven, Connecticut
| | - Janet P. Tate
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Medicine, Veterans Affairs Connecticut Healthcare, West Haven, Connecticut
| | - Joseph K. Lim
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Medicine, Veterans Affairs Connecticut Healthcare, West Haven, Connecticut
| | - Jessie Torgersen
- Division of Infectious Diseases, Department of Medicine and Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine and Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Amy C. Justice
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Medicine, Veterans Affairs Connecticut Healthcare, West Haven, Connecticut
- Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
| | - Tamar H. Taddei
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Medicine, Veterans Affairs Connecticut Healthcare, West Haven, Connecticut
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Zijlstra MK, Gampa A, Joseph N, Sonnenberg A, Fimmel CJ. Progressive changes in platelet counts and Fib-4 scores precede the diagnosis of advanced fibrosis in NASH patients. World J Hepatol 2023; 15:225-236. [PMID: 36926233 PMCID: PMC10011908 DOI: 10.4254/wjh.v15.i2.225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 08/02/2022] [Accepted: 01/13/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Cirrhosis and its complications develop in a subgroup of patients with non-alcoholic fatty liver disease (NASH). Early detection of liver fibrosis represents an important goal of clinical care.
AIM To test the hypothesis that the development of cirrhosis in nonalcoholic fatty liver disease patients is preceded by the long-term trends of platelet counts and Fib-4 scores.
METHODS We identified all patients in our healthcare system who had undergone fibrosis staging by liver biopsy or magnetic resonance elastography (MRE) for non-alcoholic fatty liver disease during the past decade (n = 310). Platelet counts, serum glutamic-pyruvic transaminase and serum glutamic oxalacetic transaminase values preceding the staging tests were extracted from the electronic medical record system, and Fib-4 scores were calculated. Potential predictors of advanced fibrosis were evaluated using multivariate regression analysis.
RESULTS Significant decreases in platelet counts and increases in Fib-4 scores were observed in all fibrosis stages, particularly in patients with cirrhosis. In the liver biopsy group, the presence of cirrhosis was best predicted by the combination of the Fib-4 score at the time closest to staging (P < 0.0001), the presence of diabetes (P = 0.0001), and the correlation coefficient of the preceding time-dependent drop in platelet count (P = 0.044). In the MRE group, Fib4 score (P = 0.0025) and platelet drop (P = 0.0373) were significant predictors. In comparison, the time-dependent rise of the Fib-4 score did not contribute in a statistically significant way.
CONCLUSION Time-dependent changes in platelet counts and Fib-4 scores contribute to the prediction of cirrhosis in NASH patients with biopsy- or MRE-staged fibrosis. Their incorporation into predictive algorithms may assist in the earlier identification of high-risk patients.
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Affiliation(s)
- Michael K Zijlstra
- Department of Internal Medicine, NorthShore University Health System, Evanston, IL 60201, United States
| | - Anuhya Gampa
- Division of Gastroenterology and Hepatology, University of Chicago Pritzker School of Medicine, Chicago, IL 60637, United States
| | - Nora Joseph
- Department of Pathology, NorthShore University Health System, Evanston, IL 60201, United States
| | - Amnon Sonnenberg
- Portland VA Medical Center, Portland, OR 97239, United States
- Department of Gastroenterology, Oregon Health Sciences University, Portland, OR 97201, United States
| | - Claus J Fimmel
- Division of Gastroenterology, Department of Internal Medicine, NorthShore University Health System, Evanston, IL 60201, United States
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Abstract
BACKGROUND AND OBJECTIVES Little is known regarding the diagnostic performance of fibrosis scoring systems in the diagnosis of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the risk factors of NAFLD and evaluate the diagnostic performance of noninvasive fibrosis scoring systems. MATERIALS AND METHODS The study included consecutive patients presented with dyspepsia from January 2017 to January 2019. Clinicodemographic and laboratory parameters including HOMA-IR were recorded. Anthropometric measurements were performed. NAFLD was diagnosed with ultrasonography. The FIB4, NAFLD, BARD, and Nippon scores were calculated. RESULTS Totally, 1008 patients were enrolled. The mean age was 52.3 ± 15 years in the NAFLD group (25.8%) and 36.7 ± 15.7 years in the non-NAFLD group (74.2%). The frequency of NAFLD was 25.8%. Age, body mass index (BMI), diabetes mellitus (DM), platelet count, HbA1c, HDL, ALT, and AST/ALT ratio were independent risk factors for NAFLD. The most sensitive and specific tests in diagnosing NAFLD were HOMA-IR and Nippon score, respectively. CONCLUSIONS Age, BMI, DM, HbA1c, platelet count, HDL, ALT, and AST/ALT ratio were independent predictors of NAFLD. The most specific and sensitive predictors of the presence of NAFLD were Nippon score and HOMA-IR value, respectively. The place of fibrosis scores in the diagnosis of NAFLD patients requires further scrutinization.
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Affiliation(s)
- Muharrem Bayrak
- Department of Internal Medicine, University of Health Sciences, Erzurum Regional Training and Research Hospital, Erzurum, Turkey
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Han E, Lee YH, Kim YD, Kim BK, Park JY, Kim DY, Ahn SH, Lee BW, Kang ES, Cha BS, Han KH, Nam HS, Heo JH, Kim SU. Nonalcoholic Fatty Liver Disease and Sarcopenia Are Independently Associated With Cardiovascular Risk. Am J Gastroenterol 2020; 115:584-595. [PMID: 32141917 DOI: 10.14309/ajg.0000000000000572] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 01/16/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) and sarcopenia have a close association with an increased risk of atherosclerotic cardiovascular disease (ASCVD). This study investigated the influence of NAFLD and sarcopenia on ASCVD risk. METHODS Data from the 2008-2011 Korean National Health and Nutrition Examination Surveys database were analyzed (n = 7,191). The sarcopenia index was calculated using dual-energy x-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cutoffs = 0.882 for men and 0.582 for women). NAFLD was defined as a comprehensive NAFLD score ≥40. Liver fibrosis was assessed using the fibrosis-4 (FIB-4) index. ASCVD risk was evaluated using American College of Cardiology/American Heart Association guidelines. High probability of ASCVD was defined as ASCVD risk >10%. RESULTS The prevalence rates of NAFLD and sarcopenia were 31.2% (n = 2,241) and 19.5% (n = 1,400), respectively. The quartile-stratified ASCVD risk scores were positively associated with NAFLD and sarcopenia (all P for trend < 0.001). Subjects with both NAFLD and sarcopenia had a higher risk for high probability of ASCVD (odds ratio = 1.83, P = 0.014) compared with controls without NAFLD and sarcopenia. Among subjects with NAFLD, FIB-4-defined significant liver fibrosis and sarcopenia additively raised the risk for high probability of ASCVD (odds ratio = 3.56, P < 0.001) compared with controls without FIB-4-defined significant liver fibrosis or sarcopenia. DISCUSSION NAFLD and sarcopenia were significantly associated with an increased risk of ASCVD in the general population. In addition, NAFLD with significant liver fibrosis and sarcopenia were significantly associated with an increased risk of ASCVD in subjects with NAFLD.
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Affiliation(s)
- Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Yong-Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Young Dae Kim
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Byung-Wan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Bong-Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hyo Suk Nam
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Hoe Heo
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Telbivudine Treatment during Late Pregnancy Prevents Mother-to-Child Transmission of Hepatitis B Virus: A Retrospective Study. Can J Gastroenterol Hepatol 2019; 2019:9046260. [PMID: 31380321 PMCID: PMC6652084 DOI: 10.1155/2019/9046260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 04/01/2019] [Accepted: 06/24/2019] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To investigate the efficacy of telbivudine (LdT) in blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) during late pregnancy. METHODS A total of 651 pregnant women aged 18-40 in Nantong Third People's Hospital and Hospital affiliated to Nantong University with positive hepatitis B surface antigen (HBsAg) and HBV DNA were enrolled between January 2011 and December 2015. Patients with HBV DNA≥106 copies/mL (n=251) received LdT during late pregnancy according to the patients' will, while 136 high viral patients with HBV DNA≥106 copies/mL who did not take LdT therapy and 268 low viral patients with HBV DNA<106 copies/mL served as the controls. RESULTS At 7 months and 1 year postpartum, the basal HBV DNA serum level of treated patients declined significantly (P<0.001), while no obvious decline was observed in the untreated high viraemic controls (P<0.05) and untreated low viraemic controls (P<0.05). Only 1 infant (0.4%) in LdT group was HBsAg positive at 7 months, while 14 (5.2%) were in the untreated low viraemic controls (P<0.001) and 15 (11.0%) were in untreated high viraemic controls (P<0.001). CONCLUSION For pregnant women with HBV DNA≥106 copies/mL, the use of LdT during late pregnancy could effectively reduce the MTCT rate of HBV.
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Nie J, Li CP, Li JH, Chen X, Zhong X. Analysis of non‑alcoholic fatty liver disease microRNA expression spectra in rat liver tissues. Mol Med Rep 2018; 18:2669-2680. [PMID: 30015905 PMCID: PMC6102666 DOI: 10.3892/mmr.2018.9268] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 06/14/2018] [Indexed: 12/14/2022] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing in recent years. Previous studies have suggested that micro (mi)RNAs may be involved in the pathogenesis of NAFLD. To investigate the role of miRNAs in rat NAFLD, a total of 16 male Sprague Dawley rats were randomly divided into a control group and a model group. Rats in the control group were fed a normal diet for 12 weeks, whereas the rats in the model group were fed a high‑fat and high‑sugar diet for 12 weeks. Following this, the animals were sacrificed and liver tissues were rapidly removed to investigate the severity of NAFLD. Blood samples were collected to investigate liver function, in addition to total cholesterol, total triglyceride and fasting plasma glucose levels. Total RNA from three fresh liver samples per experimental group was extracted for subsequent miRNA gene chip analysis using GeneChip miRNA 4.0 to investigate differentially expressed miRNAs, and miRNA expression was further verified via reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Compared with the control group, the results revealed that there were 10 differentially expressed miRNAs in the model group, five of which were overexpressed and five of which were underexpressed compared with the control group. The results of the RT‑qPCR analysis revealed that miR‑182, miR‑29b‑3p and miR‑741‑3p were significantly overexpressed in the model group compared with the control group, which was largely consistent with the results of the microarray analysis. The results suggested that the differentially expressed microRNAs demonstrated in the present study may be involved in the pathogenesis of NAFLD; however, the mechanism underlying the differential expression of miRNAs in NAFLD requires further investigation.
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Affiliation(s)
- Jiao Nie
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Chang-Ping Li
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Jue-Hong Li
- Graduate School, College of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
| | - Xia Chen
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Xiaoling Zhong
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
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