Impact of metabolic risk factors on HCC 소화기내과 목요세미나 Impact of metabolic risk factors on HCC in patients with chronic HBV infection 이 윤 빈

Improvement of Survival and Quality of Life Goals of chronic hepatitis B treatment Early and sustained suppression of HBV replication Potent antiviral drugs with high barriers to resistance Treatment-naïve patients vs. patients with drug-resistance Patients with comorbidities Possible side effects of antiviral drugs during long-term antiviral treatment Prevention of disease progression to cirrhosis Long-term antiviral treatment for indicated patients Alcohol abstinence Prevention of HCC development Management of other modifiable risk factors Improvement of Survival and Quality of Life

Risk factors of HCC in CHB patients Demographic factors Age Male gender Ethnicity: African origin Family history of HCC Virologic factors High viral loads HBV genotype: C > B Hepatic fibrosis, cirrhosis Excessive alcohol consumption Active smoking Diabetes or metabolic syndrome EASL 2017 Clinical Practice Guidelines

Risk factors of HCC in CHB patients Demographic factors Age Male gender Ethnicity: African origin Family history of HCC Virologic factors High viral loads HBV genotype: C > B Hepatic fibrosis, cirrhosis Excessive alcohol consumption Active smoking Diabetes or metabolic syndrome Long-term antiviral treatment EASL 2017 Clinical Practice Guidelines

Yu MW et al. Gastroenterology 2017;153:1006-1017 Chan AW et al. J Gastroenterol Hepatol 2017;32: 667-76

HCV-infected patients vs. Non-infected controls Metabolic risk factors and chronic hepatitis C The relationship between chronic hepatitis C and type 2 diabetes Increased risk of type 2 diabetes in patients with HCV infection HCV-infected patients vs. Non-infected controls White DL et al. J Hepatol. 2008;49:831-44

HCV-infected patients vs. HBV-infected patients Metabolic risk factors and chronic hepatitis C The relationship between chronic hepatitis C and type 2 diabetes Excessive risk of diabetes in comparison to HBV-infected patients HCV-infected patients vs. HBV-infected patients White DL et al. J Hepatol. 2008;49:831-44

Metabolic risk factors and chronic hepatitis C Extrahepatic manifestation of chronic hepatitis C Improvement of cardiovascular outcomes after antiviral treatment Hsu YC et al. Gut 2015;64:495-503

Metabolic risk factors and chronic hepatitis B Yu MW et al. Gastroenterology 2017;153:1006-1017

Annual prevalence of steatosis in HBV-infected patients Nonalcoholic fatty liver and chronic hepatitis B NAFLD as hepatic manifestation of metabolic syndrome Concurrent fatty liver was histologically diagnosed in 39.6% of the HBV-infected patients The prevalence of histologically proven fatty liver in HBV-infected patients had gradually increased from 8.2% to 31.8% over 10 years Annual prevalence of steatosis in HBV-infected patients Prevalence Chan AW et al. J Gastroenterol Hepatol 2017;32: 667-76 Wang MM et al. Dig Dis Sci 2014; 59:2571-9

Nonalcoholic fatty liver and chronic hepatitis B HBV infection is a potential trigger of hepatic steatosis HBV infection Liver steatosis Shi YX et al. World J Gastroenterol 2016;22:8161-7

※ HOMA-IR = fasting insulin (μU/mL) × plasma glucose (mmol/L)/22.5 Metabolic risk factors and HCC risk Insulin resistance and the risk of hepatic fibrosis and HCC in CHC Insulin resistance and diabetes increase hepatic fibrosis in patients with genotype 1 HCV infection Insulin resistance is associated with HCC in patients with HCV infection P < 0.0001 ※ HOMA-IR = fasting insulin (μU/mL) × plasma glucose (mmol/L)/22.5 Petta S et al. Am J Gastroenterol 2008;103:1136-1144 Hung CH et al. World J Gastroenterol 10;16:2265-2271

(95% confidence interval) Nonalcoholic fatty liver and HCC risk Concurrent histologically proven fatty liver is an independent risk factor potentiating HBV-associated HCC development Adjusted hazard ratio (95% confidence interval) 7.272 (1.521–34.76) P = 0.013 Chan AW et al. J Gastroenterol Hepatol 2017;32: 667-76

Nonalcoholic fatty liver and HCC risk Lee YB et al. Under Review

Nonalcoholic fatty liver and HCC risk Before IPW After IPW aHR (95% CI) Steatosis ≥5% vs. <5% 3.01 (1.12–8.05) aHR (95% CI) Steatosis ≥5% vs. <5% 1.71 (0.40–7.23) Lee YB et al. Under Review

Nonalcoholic fatty liver and HCC risk Cho H et al. Under Review

Nonalcoholic fatty liver and HCC risk Before IPW After IPW aHR (95% CI) Fatty liver (yes vs. no) 1.67 (1.05–2.63) aHR (95% CI) Fatty liver (yes vs. no) 1.61 (1.06–2.47) Cho H et al. Under Review

Metabolic risk factors and liver-related mortality Adjusted hazard ratio (95% confidence interval) No. of metabolic risk factors ≥3 vs. 0 2.72 (1.32–5.59) ≥3 metabolic risk factors vs. non-obese, non-diabetic 2.96 (1.45–6.04) Yu MW et al. Gastroenterology 2017;153:1006-1017

Metabolic risk factors and mortality in CHB patients Lee YB et al. In Preparation

Metabolic risk factors and mortality in CHB patients Lee YB et al. In Preparation

Criteria for Diagnosis of Metabolic risk factors and mortality in CHB patients Death, n (%) 2,951 (9.73) Death from unknown cause 28 (0.96) Death from known cause 2,923 (99.05) Liver-related mortality 1,304 (44.19) Non-liver-related mortality 1,619 (54.86) Extrahepatic cancer-related mortality 689 (23.35) Cardiovascular mortality 247 (8.37) Criteria for Diagnosis of Metabolic Syndrome Lee YB et al. In Preparation

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