Research Article Details
| Article ID: | A52319 |
| PMID: | 28711626 |
| Source: | Gastroenterology |
| Title: | Influence of Metabolic Risk Factors on Risk of Hepatocellular Carcinoma and Liver-Related Death in Men With Chronic Hepatitis B: A Large Cohort Study. |
| Abstract: | BACKGROUND & AIMS: Little is known about the absolute risk of hepatocellular carcinoma (HCC) and liver-disease related death, in association with metabolic risk factors, for patients with hepatitis B virus (HBV) infection. METHODS: We collected data from 5373 male Taiwanese civil servants who visited Taiwan's Government Employees' Central Clinics and received routine free physical examinations from 1989 through 1992. We obtained information on liver-related morbidity and mortality in HBV carriers, 40-65 years of age (n=1690), with different metabolic risk factors. We compared their medical histories with those of study participants without HBV or HCV infection in the same age range (n=1289). We used patients' baseline data on obesity, diabetes, hypertriglyceridemia, and high blood pressure to assign them to metabolic risk categories. We then performed a case-cohort analysis of the effects of hepatitis B viral factors on risk for HCC, based on metabolic factors and insulin resistance. RESULTS: Over a median follow-up period of 19 years, 158 of the 1690 HBV carriers developed HCC and 126 died from liver-related diseases. Among participants without HBV or HCV infection, only 6 developed HCC or died from liver-related disease. HBV carriers with different metabolic risk factors had significant differences in cumulative incidence of HCC and liver-related death. Patients with 3 or more metabolic risk factors had a substantially higher risk for HCC (10-year cumulative incidence, 13.60%) than patients with a low metabolic risk profile (10-year cumulative incidence, 4.83%; adjusted-hazard ratio, 2.32; 95% CI, 1.18-4.54). Smoking had a significant effect on this association (Pinteraction = .0044). Having 3 or more metabolic risk factors, compared with no factors, significantly increased the risk of HCC (adjusted-hazard ratio, 5.06; 95% CI, 2.23-11.47) and 10-year cumulative incidence of HCC (25.0% in smokers with 3 or more metabolic risk factors vs 3.87% in smokers with none; P < .0001) in smokers, but did not increase risk of HCC in nonsmokers. Metabolic risk factors and insulin resistance had the largest effect on HCC risk in patients with levels of HBV-DNA <10,000 copies/mL. CONCLUSIONS: In a study of men with chronic HBV infection ages 40-65 years in Taiwan, we associated a high burden of metabolic risk factors with increased risk of HCC; smoking has a significant effect on this association. |
| DOI: | 10.1053/j.gastro.2017.07.001 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |