Influence of Metabolic Risk Factors on Risk of Hepatocellular Carcinoma and Liver-Related Death in Men With Chronic Hepatitis B: A Large Cohort Study

Yu, Ming‐Whei; Lin, Chih–Lin; Liu, Chun‐Jen; Yang, Sheau-Fang; Tseng, Yu-Lin; Wu, Chin-Chin

doi:10.1053/j.gastro.2017.07.001

Cited by 144 publications

(171 citation statements)

References 39 publications

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“…Prior studies, predominantly from Asia, have demonstrated associations between metabolic risk factors and higher risk of HCC in CHB patients. A significantly higher risk for HCC has been noted with ≥3 metabolic risk factors, and concurrent fatty liver on biopsy was found to be an independent predictor of HCC development . Other risk factors for HCC in the prior study included age, cirrhosis, and apolipoprotein C3, but not patatin‐like phospholipase domain containing 3 ( PNPLA3 ), polymorphism .…”

Section: Discussionmentioning

confidence: 95%

Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

et al. 2019

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Background and Aims Chronic hepatitis B (CHB) and nonalcoholic fatty liver disease are increasingly observed together in clinical practice, and development of nonalcoholic steatohepatitis (NASH) represents another leading cause of liver‐related morbidity and mortality. Our aims were to determine whether biopsy‐proven NASH impacts clinical outcomes in CHB patients and assess prognostic risk factors. Approach and Results CHB patients attending two tertiary centers in North America and Europe over 13 years with available clinical and biopsy data were included. Patients were categorized as no‐NASH or probable/definite NASH based on standardized histological assessment. Clinical events (death, decompensation, transplant, and hepatoma) were evaluated, and Kaplan‐Meier survival estimates and Cox proportional hazards regression were used to analyze the incidence of events. There were 1,089 CHB patients, classified as no‐NASH (n = 904, 83%) or NASH (n = 185, 17%), with 52 (6%) versus 27 (15%) experiencing outcome events during follow‐up, respectively. In the multivariable analysis adjusting for age, sex, hepatitis B e antigen serostatus, and diabetes, the presence of NASH and concomitant advanced fibrosis (AF) was significantly associated with clinical outcomes (hazard ratio [95% confidence interval], 4.8 [2.6‐9.0], P < 0.01) when compared to absence of NASH and AF (reference). NASH and AF were associated with a greater risk of outcomes compared to AF (P = 0.01) or NASH alone (P < 0.01). Of the three histological determinants of NASH, ballooning and inflammation, but not steatosis, were independently associated with clinical outcomes (P < 0.05) in place of NASH. NASH was significantly associated with increased risk of hepatocellular carcinoma and death (P < 0.01) but not decompensation (P = 0.33). Conclusions In our large combined tertiary center cohort, patients with concomitant NASH and CHB had more AF and shorter time to development of liver‐related outcomes or death compared to patients with CHB alone. Among patients with AF, superimposed NASH predicted poorer clinical outcomes.

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Section: Discussionmentioning

confidence: 95%

Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

et al. 2019

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“…However, these results were likely impacted by the small number of patients in the type 2 diabetes mellitus subgroup. A recent study revealed that diabetes mellitus had a large effect on HCC risk in patients with low viral loads . The mechanism of how HBV DNA levels affect NAFLD incidence in patients with concurrent type 2 diabetes mellitus and low viral loads warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus infection and risk of non‐alcoholic fatty liver disease: A population‐based cohort study

Zhu

Jiang

Zhai

et al. 2018

Liver International

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“…First, this study confirmed the performance of these tests in patients without cirrhosis, who represented 86% of the cohort. Thus far, most patients without cirrhosis have been investigated in CHB cohorts . Only one study has used elastography, which was found to have predictive value, however, no multi‐analyte test was constructed .…”

Section: Discussionmentioning

confidence: 99%

“…GGT was the third component of interest, as several studies have demonstrated its strong independent predictive value for PLC. Although the underlying mechanisms are unclear, GGT is significantly associated with cytotoxicity induced by cholestatic and metabolic disorders, as well as with excessive alcohol consumption …”

Section: Introductionmentioning

confidence: 99%

LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

Poynard

Peta

Deckmyn

et al. 2018

Aliment Pharmacol Ther

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Summary Background No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis. Aim To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis. Methods We performed a retrospective analysis in prospectively collected specimens from an ongoing cohort. We designed an early sensitive high‐risk test (LCR1) that combined (using Cox model) hepatoprotective proteins (apolipoproteinA1, haptoglobin) with known risk factors (gender, age, gammaglutamyltranspeptidase), and a marker of fibrosis (alpha2‐macroglobulin). To increase the specificity, we then combined (LCR2) these components with alpha‐fetoprotein. Results A total of 9892 patients, 85.9% without cirrhosis, were followed up for 5.9 years [IQR: 4.3‐9.4]. LCR1 and LCR2 time‐dependent AUROCs were not different in construction and validation randomised subsets. Among 2027 patients with high‐LCR1 then high‐LCR2, 167 cancers (113 with cirrhosis, 54 without cirrhosis) were detected, that is 12 patients needed to screen one cancer. The negative predictive value was 99.5% (95% CI 99.0‐99.7) in the 2026 not screened patients (11 cancers without cirrhosis) higher than the standard surveillance, which detected 113 cancers in 755 patients screened, that is seven patients needed to screen one cancer, but with a lower negative predictive value 98.0% (97.5‐98.5; Z = 4.3; P < 0.001) in 3298 not screened patients (42 cancers without cirrhosis). Conclusions In patients with chronic liver disease the LCR1 and LCR2 tests identify those with a high risk of liver cancer, including in those without cirrhosis. NCT01927133.

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Influence of Metabolic Risk Factors on Risk of Hepatocellular Carcinoma and Liver-Related Death in Men With Chronic Hepatitis B: A Large Cohort Study

Cited by 144 publications

References 39 publications

Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

Hepatitis B virus infection and risk of non‐alcoholic fatty liver disease: A population‐based cohort study

LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

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