Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

Kanwal, Fasiha; Kramer, Jennifer R.; Mapakshi, Srikar; Natarajan, Yamini; Chayanupatkul, Maneerat; Richardson, Peter; Li, Liang; Desiderio, Roxanne; Thrift, Aaron P.; Asch, Steven M.; Chu, Jinna; El–Serag, Hashem B.

doi:10.1053/j.gastro.2018.08.024

Cited by 562 publications

(607 citation statements)

References 25 publications

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“…Furthermore, NAFLD was classified as an underlying etiology of HCC purely based on risk factors (diabetes and obesity in the absence of other evidence of CLD), which raises concern for misclassification. Another recent VA study showed that diabetes is associated with a 3‐fold increased risk of HCC in NAFLD patients after adjusting for covariates . In the cirrhosis subgroup, a higher incidence rate of HCC was observed in patients with diabetes (12.4 in diabetics vs. 8.5 in nondiabetics per 1,000 person‐years) .…”

Section: Discussionmentioning

confidence: 97%

“…Another recent VA study showed that diabetes is associated with a 3‐fold increased risk of HCC in NAFLD patients after adjusting for covariates . In the cirrhosis subgroup, a higher incidence rate of HCC was observed in patients with diabetes (12.4 in diabetics vs. 8.5 in nondiabetics per 1,000 person‐years) . Multivariate analysis was not performed in the cirrhosis subgroup; thus, an adjusted HR was not reported .…”

Section: Discussionmentioning

confidence: 99%

“…In the cirrhosis subgroup, a higher incidence rate of HCC was observed in patients with diabetes (12.4 in diabetics vs. 8.5 in nondiabetics per 1,000 person‐years) . Multivariate analysis was not performed in the cirrhosis subgroup; thus, an adjusted HR was not reported . A recent single‐center, retrospective, cross‐sectional study showed an independent association between diabetes and HCC in patients with NASH cirrhosis who underwent LT. BMI, hypertension, or smoking was not associated with the risk of HCC .…”

Section: Discussionmentioning

confidence: 99%

“…HCC is one of most common life‐threatening complications of NAFLD. Among NAFLD patients, incidence rates of HCC have been estimated to be 0.44 per 1,000 person‐years (range, 0.29‐0.66) and 9‐26 per 1,000 person‐years among patients with NASH cirrhosis . NASH has been reported to be the third‐leading cause of HCC in the United States .…”

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confidence: 99%

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Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease

et al. 2019

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Diabetes increases the risk of liver disease progression and cirrhosis development in patients with nonalcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow‐up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.1‐11.9; P = 0.04) and multivariable analysis (HR = 4.2; 95% CI = 1.2‐14.2; P = 0.02). In addition, age (per decade, HR = 1.8; 95% CI = 1.2‐2.6; P < 0.01) and low serum albumin (HR = 2.1; 95% CI = 1.5‐2.9; P < 0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors, including body mass index, hyperlipidemia, and hypertension, were not associated with HCC risk. Among UNOS NASH registrants (N = 6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4; 95% CI = 1.1‐1.8; P < 0.01) and multivariable (HR = 1.3; 95% CI = 1.0‐1.7; P = 0.03) analysis. Conclusion: Diabetes is associated with an increased risk of HCC in patients with NASH cirrhosis.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease

et al. 2019

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“…Increasing secular trends in incidence and mortality have been observed across many countries including the United Kingdom, Poland, Brazil, Germany and Norway . Major risk factors for liver cancer include hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, heavy alcohol drinking and nonalcoholic fatty liver disease (NAFLD) . With further increases in liver cancer incidence predicted, there is growing interest in identifying modifiable risk factors for liver cancer, especially those that can be targeted with medications, such as aspirin and nonsteroidal antiinflammatory drugs (NSAIDs).…”

Section: Introductionmentioning

confidence: 99%

Statin use and risk of liver cancer: Evidence from two population‐based studies

Tran

McMenamin

Coleman

et al. 2019

Intl Journal of Cancer

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Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self‐reported statin use and cancer‐registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case–control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43–0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24–0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45–2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.

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Treatment of Fatty Liver Disease—Time to Implement Common Sense Measures

Adler

Brandman

2019

JAMA Intern Med

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Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases in which excess fat deposits in the liver (steatosis, NAFL) are separate from but can progress to inflammation and fibrosis (nonalcoholic steatohepatitis, NASH), fibrosis, and cirrhosis. Nonalcoholic fatty liver disease has become a major public health issue, affecting about 25% of adults worldwide and two-thirds of adults with obesity. 1 Hepatocellular carcinoma associated with NAFLD increased 10-fold between 2000 and 2010, and trends suggest that NAFLD will emerge as the leading cause of end-stage liver disease in the coming decades. 2 Beyond liver disease, patients with NAFLD are at significant risk of cardiovascular morbidity and mortality. 3 Approximately 20% of patients with NAFLD progress to NASH, which is associated with more rapid rates of fibrosis and liver-related mortality. Liver biopsy is the gold standard for classification of NAFLD. However, owing to cost and risk for morbidity, biopsy is often reserved for cases of clinical suspicion for NASH or advanced fibrosis. Noninvasive assessment of fibrosis stage such as clinical prediction rules (eg, NAFLD Fibrosis score, FIB-4) and/or imaging (ultrasonography or magnetic resonance-based elastography) are also helpful for diagnosing and staging of NAFLD. Obesity is the most common and well-documented risk factor for NAFLD.The link between obesity and NAFLD has prompted investigation of weight loss interventions as a potential treatment for NAFLD. However, there has been considerable variability in intervention types and outcome measures. The metaanalysis by Koutoukidis et al 4 in this issue of JAMA Internal Medicine better characterizes the impact of weight loss interventions and builds a compelling case for implementing formal weight loss programs as a mainstay in the treatment of NAFLD. In their systematic review of 22 randomized clinical trials that included 2588 participants with NAFLD, Koutoukidis et al 4 found that weight loss interventions were associated with improvements in blood biomarkers of liver disease, as well as radiologic and histologic markers. 4 This study confirms the importance of weight loss interventions in the treatment of NAFLD. Koutoukidis et al 4 specifically observed the association between weight loss by various intervention types and improvement in liver blood biomarkers, such as alanine transaminase (ALT) and aspartate transaminase (AST), and improvement in steatosis based on a collection of outcome measures from various studiesincluding histologic analysis, magnetic resonance imaging, ultrasonography, and NAFLD activity score. Whereas AST and ALT are surrogate markers for steatosis and NASH, they are

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Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

Abstract: Risk of HCC was higher in NAFLD patients than that observed in general clinical population. Most HCC cases in NAFLD developed in patients with cirrhosis. The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis.

Cited by 562 publications

References 25 publications

Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease

Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease

Statin use and risk of liver cancer: Evidence from two population‐based studies

Treatment of Fatty Liver Disease—Time to Implement Common Sense Measures

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