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1
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Ryu T, Chang Y, Jeong SW, Yoo JJ, Lee SH, Kim SG, Kim YS, Kim HS, Kim SU, Jang JY. Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C. Clin Mol Hepatol 2025; 31:548-562. [PMID: 39788108 PMCID: PMC12016602 DOI: 10.3350/cmh.2024.0904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/20/2024] [Accepted: 01/05/2025] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND/AIMS Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus. This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC). METHODS This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) was defined as >200 mg/dL. RESULTS The median age of the study population was 59.6 years, with a predominance of male patients (n=4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30-12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE. Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4. CONCLUSION Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.
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Affiliation(s)
- Tom Ryu
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Seung Up Kim
- Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
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Gundling F. Der hepatogene Diabetes – aktueller Stand der Diagnostik und Therapie. JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2022; 15:42-52. [DOI: 10.1007/s41969-022-00158-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 01/04/2025]
Abstract
Zusammenfassung
Hintergrund
Patienten mit Leberzirrhose entwickeln häufig Störungen des Glukosemetabolismus wie Glukoseintoleranz oder einen hepatogenen Diabetes, welche neben der hepatozellulären Funktionseinschränkung durch die ausgeprägte Insulinresistenz als Folge der chronischen Lebererkrankung verursacht sind.
Diskussion
Empfehlungen mit Leitliniencharakter zur Diagnostik und Therapie des hepatogenen Diabetes fehlen bislang. Im Hinblick auf basistherapeutische Maßnahmen sollte eine ausreichende Deckung des Energie- und Proteinstoffwechsels gewährleistet sein, da ein Großteil der Zirrhosepatienten mangelernährt ist. Bei der medikamentösen Behandlung des hepatogenen Diabetes muss auf die erhöhte Hypoglykämiegefährdung geachtet werden. Aufgrund der Nebenwirkungen sind Biguanide sowie PPAR-gamma-Liganden bei Leberzirrhose kontraindiziert. Geeignete orale Antidiabetika sind insbesondere Sulfonylharnstoffanaloga und kurz wirksame Sulfonylharnstoffe. Wenn eine suffiziente Diabeteseinstellung mit oralen Antidiabetika nicht gelingt, sollte eine prandiale Insulintherapie mit Insulinen von kurzer Wirkdauer oder kurz wirksamen Insulinanaloga eingesetzt werden.
Schlussfolgerung
Die Optimierung einer diabetischen Stoffwechsellage hat neben der Vermeidung typischer diabetischer Spätkomplikationen eine wichtige Bedeutung für die Vermeidung und Reduzierung von Zirrhose-assoziierten Komplikationen wie z. B. gastrointestinalen Blutungsereignissen, hepatischer Enzephalopathie oder dem Auftreten eines hepatozellulären Karzinoms.
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Chen VL, Burkholder DA, Moran IJ, DiBattista JV, Miller MJ, Chen Y, Du X, Oliveri A, Cushing KC, Lok AS, Speliotes EK. Hepatic decompensation is accelerated in patients with cirrhosis and alpha-1 antitrypsin Pi∗MZ genotype. JHEP Rep 2022; 4:100483. [PMID: 35571533 PMCID: PMC9097455 DOI: 10.1016/j.jhepr.2022.100483] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 03/01/2022] [Accepted: 03/22/2022] [Indexed: 02/03/2023] Open
Abstract
Background & Aims Alpha-1 antitrypsin deficiency is caused by mutations in SERPINA1, most commonly homozygosity for the Pi∗Z variant, and can present as liver disease. While heterozygosity for Pi∗Z (Pi∗MZ) is linked to increased risk of cirrhosis, whether the Pi∗MZ genotype is associated with an increased rate of decompensation among patients who already have compensated cirrhosis is not known. Methods This was a retrospective study of Michigan Genomics Initiative participants with baseline compensated cirrhosis. The primary predictors were Pi∗MZ or Pi∗MS genotype (vs. Pi∗MM). The primary outcomes were hepatic decompensation with ascites, hepatic encephalopathy, or variceal bleeding, or the combined endpoint of liver-related death or liver transplant, both modeled with Fine-Gray competing risk models. Results We included 576 patients with baseline compensated cirrhosis who had undergone genotyping, of whom 474 had Pi∗MM, 49 had Pi∗MZ, and 52 had Pi∗MS genotypes. Compared to Pi∗MM genotype, Pi∗MZ was associated with increased rates of hepatic decompensation (hazard ratio 1.81; 95% CI 1.22-2.69; p = 0.003) and liver transplant or liver-related death (hazard ratio 2.07; 95% CI 1.21-3.52; p = 0.078). These associations remained significant after adjustment for severity of underlying liver disease, and were robust across subgroup analyses based on etiology, sex, obesity, and diabetes status. Pi∗MS was not associated with decompensation or death/transplantation. Conclusions The SERPINA1 Pi∗MZ genotype is associated with an increased rate of hepatic decompensation and decreased transplant-free survival among patients with baseline compensated cirrhosis. Lay summary There is a mutation in the gene SERPINA1 called Pi∗MZ which increases risk of liver scarring (cirrhosis); however, it is not known what effect Pi∗MZ has if someone already has cirrhosis. In this study, we found that people who had cirrhosis and Pi∗MZ developed complications from cirrhosis faster than those who did not have the mutation.
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Affiliation(s)
- Vincent L. Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
| | | | - Isabel J. Moran
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
| | | | - Matthew J. Miller
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Yanhua Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
| | - Xiaomeng Du
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
| | - Antonino Oliveri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
| | - Kelly C. Cushing
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
| | - Anna S. Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
| | - Elizabeth K. Speliotes
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Ann Arbor, MI, USA
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García-Compeán D, Orsi E, Kumar R, Gundling F, Nishida T, Villarreal-Pérez JZ, Del Cueto-Aguilera ÁN, González-González JA, Pugliese G. Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives. World J Gastroenterol 2022; 28:775-793. [PMID: 35317103 PMCID: PMC8900578 DOI: 10.3748/wjg.v28.i8.775] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/19/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, Fdn IRCCS Ca Granda, Endocrine Unit, Padigl Granelli, Milan 20121, Italy
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Felix Gundling
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Diabetics, Metabolism and Infectious Diseases, Sozialstiftung Bamberg, Bamberg 96049, Germany
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka 560-8565, Japan
| | | | - Ángel N Del Cueto-Aguilera
- Department of Gastroenterology and Internal Medicine, Faculty of Medicine, University Hospital, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service and Department of Internal Medicine, University Hospital Dr. José E González and Medical School, Monterrey 64460, Nuevo León, Mexico
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, La Sapienza University, Roma 00161, Italy
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Teymourzadeh E, Bahadori M, Fattahi H, Rahdar HA, Mirzaei Moghadam S, Shokri A. Prevalence and Predictive Factors for Nosocomial Infection in the Military Hospitals: A Systematic Review and Meta-Analysis. IRANIAN JOURNAL OF PUBLIC HEALTH 2021; 50:58-68. [PMID: 34178764 PMCID: PMC8213630 DOI: 10.18502/ijph.v50i1.5072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Background: To assess prevalence and predictive factors for Nosocomial Infection (NI) in the military hospitals. Methods: PubMed, Scopus, Cochrane and PreQuest databases were systematically searched for studies published between Jan 1991 and Oct 2017 that reported the prevalence of NI and predictive factors among military hospitals. We performed the meta-analysis using a random effects model. Subgroup analysis was done for heterogeneity and the Egger test to funnel plots was used to assess publication bias. Results: Twenty-eight studies with 250,374 patients were evaluated in meta-analysis. The overall pooled estimate of the prevalence of NI was 8% (95% 6.0–9.0). The pooled prevalence was 2% (95% CI: 2.0–3.0) when we did sensitivity analysis and excluding a study. The prevalence was highest in burn unit (32%) and ICU (15%). Reported risk factors for NI included gender (male vs female, OR: 1.45), age (Age≥65, OR: 2.4), diabetes mellitus (OR: 2.32), inappropriate use of antibiotics (OR: 2.35), received mechanical support (OR: 2.81), co-morbidities (OR: 2.97), admitted into the ICU (OR: 2.26), smoking (OR: 1.36) and BMI (OR: 1.09). Conclusion: The review revealed a difference of prevalence in military hospitals with other hospitals and shows a high prevalence of NI in burn units. Therefore careful disinfection and strict procedures of infection control are necessary in places that serve immunosuppressed individuals such as burn patient. Moreover, a vision for the improvement of reports and studies in military hospitals to report the rate of these infections are necessary.
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Affiliation(s)
- Ehsan Teymourzadeh
- Health Management Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohamadkarim Bahadori
- Health Management Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hamed Fattahi
- Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran.,Center for Health Human Resources Research & Studies, Ministry of Health and Medical Education, Tehran, Iran
| | - Hossein Ali Rahdar
- Department of Microbiology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Sima Mirzaei Moghadam
- Department of Midwifery, School of Nursing and Midwifery, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Azad Shokri
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
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6
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Uno S, Asakura T, Morimoto K, Yoshimura K, Uwamino Y, Nishimura T, Hoshino Y, Hasegawa N. Comorbidities associated with nontuberculous mycobacterial disease in Japanese adults: a claims-data analysis. BMC Pulm Med 2020; 20:262. [PMID: 33036598 PMCID: PMC7547454 DOI: 10.1186/s12890-020-01304-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 09/29/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Nontuberculous mycobacterial (NTM) lung disease is one of a growing number of chronic health problems that is difficult to cure in aging societies. While it is important to be vigilant about associated comorbidities in order to provide better patient care, data on the prevalence of comorbidities stratified by country or region are scarce. We aimed to elucidate the comorbidities associated with NTM disease based on Japanese health insurance claims data. METHODS Cross-sectional analyses were performed using the claims data for 2014 provided by the Japan Medical Data Center Co., Ltd. Patients aged 20-75 years with ≥3 claims associated with NTM disease were identified and matched to 10 sex-and-age-matched controls that had never made a claim for NTM disease. Thirty-one comorbidities previously suspected to be associated with NTM disease were selected, and the prevalence of these comorbidities compared between cases and controls. RESULT Overall, 419 NTM patients (134 males and 285 females) and 4190 non-NTM controls were identified from the JMDC database. Aspergillosis, asthma, chronic heart failure, diffuse panbronchiolitis, gastroesophageal reflux, interstitial pneumonia, lung cancer, cancer other than breast, lung, ovary, or prostate cancer, and rheumatoid arthritis were associated with NTM disease in both males and females. Chronic obstructive pulmonary disease was associated with NTM in males while chronic kidney disease, osteoporosis, and Sjögren syndrome were associated with NTM in females. CONCLUSION NTM disease was associated with multiple comorbidities that should be considered when providing medical care to individuals with NTM disease.
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Affiliation(s)
- Shunsuke Uno
- Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Takanori Asakura
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.,Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan
| | - Kozo Morimoto
- The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.,Division of Clinical Research, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
| | - Kimio Yoshimura
- Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan
| | - Yoshifumi Uwamino
- Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.,Department of Laboratory medicine, Keio University School of Medicine, Tokyo, Japan
| | | | - Yoshihiko Hoshino
- Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan
| | - Naoki Hasegawa
- Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.
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Chen Y, Ji H, Shao J, Jia Y, Bao Q, Zhu J, Zhang L, Shen Y. Different Hepatitis C Virus Infection Statuses Show a Significant Risk of Developing Type 2 Diabetes Mellitus: A Network Meta-Analysis. Dig Dis Sci 2020; 65:1940-1950. [PMID: 31758432 DOI: 10.1007/s10620-019-05918-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 10/22/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of hepatitis C virus (HCV) infection statuses in the development of type 2 diabetes mellitus (T2DM) has not been completely understood. AIM To evaluate the prevalence of T2DM in patients with different HCV infection statuses. METHODS We conducted a systematic study on T2DM risk in five types of individuals with different HCV infection statuses: non-HCV controls, HCV-cleared patients, chronic HCV patients without cirrhosis, patients with HCV cirrhosis and patients with decompensated HCV cirrhosis. Studies published from 2010 to 2019 were selected. Both pairwise and network meta-analyses were employed to compare the T2DM risk among patients with different HCV infection statuses. RESULTS The pairwise meta-analysis showed that non-HCV (OR = 0.60, 95% CI [0.47-0.78]) had a lower risk of T2DM compared with CHC, while cirrhosis had a significant higher risk (OR = 1.90, 95% CI [1.60-2.26]). Network meta-analysis further demonstrated patients with HCV infection were at a significantly higher risk of T2DM than those without HCV infection or with HCV clearance, while decompensated cirrhosis had a significant higher T2DM risk than non-HCV (OR = 3.84, 95% CI [2.01-7.34]), patients with HCV clearance (OR = 3.17, 95% CI [1.49-6.73]), and CHC patients (OR = 2.21, 95% CI [1.24-3.94]). CONCLUSIONS HCV infection is a significant risk factor for developing T2DM. CHC, cirrhosis, and decompensated cirrhosis contribute to an increasingly greater risk of T2DM, but HCV clearance spontaneously or through clinical treatment may immediately reduce the risk of the onset and development of T2DM.
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Affiliation(s)
- Ying Chen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Hanzhen Ji
- Centre for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Jianguo Shao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
- Centre for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Yulong Jia
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Qi Bao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Jianan Zhu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China
| | - Lei Zhang
- Research Centre for Public Health, School of Medicine, Tsinghua University, Beijing, China
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia
- Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, Australia
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Yi Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, 226019, Jiangsu, China.
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8
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Chang CH, Sakaguchi M. Incidence and causes of mildly to moderately elevated aminotransferase in Japanese patients with type 2 diabetes. Diabetol Int 2020; 11:57-66. [PMID: 31938683 DOI: 10.1007/s13340-019-00405-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 08/04/2019] [Indexed: 11/24/2022]
Abstract
Objectives To identify the association of type 2 diabetes (T2DM) and liver disease with elevated ALT and factors associated with increased ALT in patients with and without T2DM. Design and setting We performed a retrospective study in adults with ≥ 2 claims for blood tests recorded in the Medical Data Vision claims database between 2010 and 2016. Participants Patients were entered into T2DM and non-DM groups based on diagnosis and medication claim codes. Primary outcome measure The primary endpoint was the first follow-up ALT elevation over three times the normal value, and etiologies were categorized by subsequent diagnoses. We estimated the ALT elevation incidence and association with T2DM using Poisson regression and Cox proportional hazard models. Results We identified 3161 cases of elevated ALT in 104,903 patients (follow-up, 280,659 patient-years). The age- and sex-adjusted incidence of elevated ALT in the T2DM group (13.47 per 1000 patient-years; 95% confidence interval (CI) 12.53-14.48) was significantly higher than that in the non-DM group (8.43 per 1000 patient-years; 95% CI 7.72-9.20, p < 0.0001). Compared to the non-DM group, the T2DM group had an approximately 3.5 times higher risk of fatty liver-related ALT elevation (adjusted hazard ratio (HR), 3.54; 95% CI 1.90-6.58). T2DM was not associated with an increased incidence of jointly elevated ALT and total bilirubin (adjusted HR, 0.94; 95% CI 0.77-1.15). Conclusion T2DM is strongly associated with increased liver enzymes secondary to fatty liver. The causes of liver enzyme abnormalities were not fully characterized due to a high proportion of unexplained ALT elevation.
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Affiliation(s)
- Chia-Hsien Chang
- Global Patient Safety Evaluation Japan, Takeda Pharmaceutical Company Limited, 1-1, Doshomachi-4-Chome, Chuo-ku, Osaka, 540-8645 Japan
| | - Motonobu Sakaguchi
- Global Patient Safety Evaluation Japan, Takeda Pharmaceutical Company Limited, 1-1, Doshomachi-4-Chome, Chuo-ku, Osaka, 540-8645 Japan
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9
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Semmler G, Scheiner B, Schwabl P, Bucsics T, Paternostro R, Chromy D, Stättermayer AF, Trauner M, Mandorfer M, Ferlitsch A, Reiberger T. The impact of hepatic steatosis on portal hypertension. PLoS One 2019; 14:e0224506. [PMID: 31693695 PMCID: PMC6834246 DOI: 10.1371/journal.pone.0224506] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/15/2019] [Indexed: 12/20/2022] Open
Abstract
Background and aims Studies in animal models have suggested that hepatic steatosis impacts on portal pressure, potentially by inducing liver sinusoidal endothelial dysfunction and thereby increasing intrahepatic resistance. Thus, we aimed to evaluate the impact of hepatic steatosis on hepatic venous pressure gradient (HVPG) in patients with chronic liver disease. Method 261 patients undergoing simultaneous HVPG measurements and controlled attenuation parameter (CAP)-based steatosis assessment were included in this retrospective study. Results The majority of patients had cirrhosis (n = 205; 78.5%) and n = 191 (73.2%) had clinically significant portal hypertension (CSPH; HVPG≥10mmHg). Hepatic steatosis (S1/2/3; CAP ≥248dB/m) was present in n = 102 (39.1%). Overall, HVPG was comparable between patients with vs. without hepatic steatosis (15.5±7.5 vs. 14.8±7.7mmHg; p = 0.465). Neither in patients with HVPG (<6mmHg; p = 0.371) nor in patients with mild portal hypertension (HVPG 6–9mmHg; p = 0.716) or CSPH (HVPG≥10mmHg; p = 0.311) any correlation between CAP and HVPG was found. Interestingly, in patients with liver fibrosis F2/3, there was a negative correlation between CAP and HVPG (Pearson’s ρ:-0.522; p≤0.001). In multivariate analysis, higher CAP was an independent ‘protective’ factor for the presence of CSPH (odds ratio [OR] per 10dB/m: 0.92, 95% confidence interval [CI]:0.85–1.00; p = 0.045), while liver stiffness was associated with the presence of CSPH (OR per kPa: 1.26, 95%CI: 1.17–1.36; p≤0.001). In 78 patients, in whom liver biopsy was performed, HVPG was neither correlated with percentage of histological steatosis (p = 0.714) nor with histological steatosis grade (p = 0.957). Conclusion Hepatic steatosis, as assessed by CAP and liver histology, did not impact on HVPG in our cohort comprising a high proportion of patients with advanced chronic liver disease. However, high CAP values (i.e. pronounced hepatic steatosis) might lead to overestimation of liver fibrosis by ‘artificially’ increasing transient elastography-based liver stiffness measurements.
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Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Department of Internal Medicine I, Hospital of St. John of God, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
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Wu J, Zhou Y, Fu X, Deng M, Zheng Y, Tian G, Li Y, Wang C, Ding C, Ruan B, Yang S, Li L. The Burden of Chronic Hepatitis C in China From 2004 to 2050: An Individual-Based Modeling Study. Hepatology 2019; 69:1442-1452. [PMID: 30561833 DOI: 10.1002/hep.30476] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 11/15/2018] [Indexed: 12/12/2022]
Abstract
The launch of new direct-acting antivirals (DAAs) is expected to substantially reduce the burden of hepatitis C virus (HCV) in China. However, the effect of these changes has not yet been modeled in China. Therefore, we aim to predict the burden of HCV-related diseases in China by simulating different scenarios that incorporate recent therapeutic advances of HCV and China's current screening strategy. We developed an individual-based microsimulation Markov model that simulated disease progression of HCV-infected patients in China from 2004 to 2050. We simulated four scenarios with different assumptions about treatment, including a natural history scenario, a pre-DAAs scenario, a DAA treatment for all patients with a METAVIR fibrosis score ≥F3 (DAAs [≥F3]) scenario, and a DAAs (≥F0) scenario. The introduction of DAAs is predicted to have great impacts on the burden of HCV in China, particularly under the DAAs (≥F0) scenario in which we rapidly expand DAAs to all HCV-infected patients (≥F0) in 2021. Under this scenario, prevalence of chronic HCV is expected to peak at 10.75 million (95% confidence interval [CI], 8.30-12.85) around 2020 and then decrease to 7.92 million (95% CI, 5.41-10.08) in 2050. Conclusion: If the future increasing burden of HCV-related diseases is to be averted, China needs to start launching the new DAA treatment and rapidly increase the number of patients treated. However, to maximize the benefits of new DAAs, expanded screening is necessary to identify more cases that require treatment in the short term. Without these changes, the HCV burden in China will remain high in the future.
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Affiliation(s)
- Jie Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yuqing Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaofang Fu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Min Deng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yang Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Guo Tian
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yiping Li
- Zhejiang Institute of Medical-care Information Technology, Hangzhou, China
| | - Chencheng Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Cheng Ding
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Bing Ruan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Shigui Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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11
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Clinical and Economic Burden of Patients with Chronic Hepatitis C with Versus Without Antiviral Treatment in Japan: An Observational Cohort Study Using Hospital Claims Data. Infect Dis Ther 2019; 8:285-299. [PMID: 30771220 PMCID: PMC6522600 DOI: 10.1007/s40121-019-0234-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Indexed: 12/28/2022] Open
Abstract
Introduction Japan has one of the highest prevalence rate of chronic hepatitis C (CHC) in the industrialized world. However, the burden of CHC treatment is poorly understood. Thus, the healthcare resource utilization and costs of treated versus untreated patients, and patients with early versus delayed treatment initiation, were assessed in Japan. Methods Adult patients with ≥ 2 CHC diagnoses were identified from the Medical Data Vision hospital claims database (1 April 2008–31 May 2016). The presence or absence of antiviral treatment claims was used to form the treated and untreated cohorts, respectively. Among treated patients, the presence of a cirrhosis-related diagnosis was used as an indicator of delayed treatment. The index date was defined as the date of the first antiviral claim for treated patients and randomized to any date with a medical visit for untreated patients. Annualized total healthcare costs and costs associated with hepatic manifestations (HMs) or extrahepatic manifestations (EHMs) were evaluated from the index date to the last observed medical visit. Results Of 100,125 patients with CHC, 12,984 were treated (early: 8104, delayed: 4880) and 87,141 were untreated. After adjusting for covariates, untreated patients had ¥613,034 ($5456 USD; ¥1 = $0.0089) higher annual medical costs compared with treated patients (P < 0.001), a difference driven by higher inpatient costs. Between 65% (treated patients) and 70% (untreated patients) of medical costs were EHM-related and between 14% (untreated patients) and 15% (treated patients) were HM-related. Patients in the delayed treatment cohort had ¥114,347 ($1018) higher annual medical costs (P < 0.001) versus those in the early treatment cohort. About 95% of these costs were EHM-related, and 64% were HM-related. Conclusion Withholding or delaying antiviral treatment initiation for Japanese patients with CHC increases the clinical and economic burden associated with HMs and EHMs. Funding AbbVie.
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Zhao Y, Xing H, Wang X, Ou W, Zhao H, Li B, Li Y, Duan Y, Zhuang L, Li W, Cheng D, Quan M, Zhang Y, Ji S. Management of Diabetes Mellitus in Patients with Chronic Liver Diseases. J Diabetes Res 2019; 2019:6430486. [PMID: 31915709 PMCID: PMC6931017 DOI: 10.1155/2019/6430486] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 11/09/2019] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is a common chronic disease affecting humans globally. During the last few years, the incidence of diabetes has increased and has received more attention. In addition to growing DM populations, DM complications are involving injuries to more organs, such as the heart and cerebral vessel damage. DM complications can reduce quality of life and shorten life spans and eventually also impede social and economic development. Therefore, effective measures to curb the occurrence and development of diabetes assist in improving patients' quality of life, delay the progression of DM in the population, and ease a social burden. The liver is regarded as an important link in the management and control of DM, including the alleviation of glucose metabolism and lipid metabolism and others via glucose storage and endogenous glucose generation from glycogen stored in the liver. Liver cirrhosis is a very common chronic disease, which often lowers the quality of life and decreases life expectancy. According to a growing body of research, diabetes shows a close correlation with hepatitis, liver cirrhosis, and liver cancer. Moreover, coexistence of liver complications would accelerate the deterioration of patients with diabetes. Liver cirrhosis and diabetes influence each other. Thus, in addition to pharmacological treatments and lifestyle interventions, effective control of cirrhosis might assist in a better management of diabetes. When it comes to different etiologies of liver cirrhosis, different therapeutic methods, such as antiviral treatment, may be more effective. Effective control of cirrhosis might be a strategy for better management of diabetes.
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Affiliation(s)
- Yingying Zhao
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Huichun Xing
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Xiaomei Wang
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Weini Ou
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Hong Zhao
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Ben Li
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Yue Li
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Ying Duan
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Liwei Zhuang
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Wei Li
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Danying Cheng
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Min Quan
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Yu Zhang
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Shibo Ji
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
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13
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Pfeiffer AFH. Hepatogener Diabetes. DER DIABETOLOGE 2016; 12:468-472. [DOI: 10.1007/s11428-016-0141-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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