Statin use and the risk of hepatocellular carcinoma in patients at high risk: A nationwide nested case-control study

Kim, Gyuri; Jang, Suk‐Yong; Nam, Chung Mo; Kang, Eun Seok

doi:10.1016/j.jhep.2017.10.018

Cited by 106 publications

(78 citation statements)

References 33 publications

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“…In this study, adjustment for important confounders of HCC included host factors (age and sex), severity of liver disease (cirrhosis and elevated ALT levels), viral factors (serum HBV DNA levels and antiviral therapy as a time‐dependent variable), and metabolic factors (DM, hypertension, cholesterol, and antiplatelet therapy as a time‐dependent variable). Although several observational studies, including meta‐analysis, have suggested reduced HCC risk by statin use, inhomogeneous population, variable degree of adjustment of potential confounder, and cross‐sectional designs were limitations of previous findings. Using a homogeneous cohort, rigorous adjustment of important confounders for HCC, and a cohort study design with a long‐term follow‐up period, these data provide further support for the causal relationship between statin use and HCC risk.…”

Section: Discussionmentioning

confidence: 77%

“…Several observational studies have shown that statin use was associated with a reduction in the risk of HCC, and a meta‐analysis showed that statin use was associated with a 37% lower risk of HCC . However, the studies included a heterogeneous spectrum of clinical conditions, including viral hepatitis, alcoholic liver disease, and nonalcoholic fatty liver disease, and the degrees of adjustment for strong HCC risk factors, including liver cirrhosis, HBV DNA levels, and antiviral therapy, varied . Hence, the association between statin use and HCC remains elusive, especially for CHB‐infected patients, in whom these important confounders for HCC development have not been rigorously adjusted.…”

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confidence: 99%

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Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

et al. 2020

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BaCKgRoUND aND aIMS:Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. appRoaCH aND ReSUltS: A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow-up period were defined as statin users (n = 713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time-dependent covariates. During a median follow-up of 7.2 years (min-max: 0.5-9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio = 0.36, 95% confidence interval: 0.19-0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose-dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31-1.29]; 0.51 [0.21-1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28-365, 366-730, 731-1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. CoNClUSIoN:Statin use was associated with a reduced risk of HCC development in chronic HBV-infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation. (Hepatology 2020;71:2023-2032.

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Section: Discussionmentioning

confidence: 77%

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confidence: 99%

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

et al. 2020

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“…A nested case‐control study from Korea in patients with newly diagnosed diabetes reported an adjusted OR of 0.36 (95% CI 0.22‐0.60) in statin users vs non‐users. Risk reduction was accentuated with an increase of cumulative defined daily doses …”

Section: Progression To Hccmentioning

confidence: 99%

Natural history of NASH and HCC

Negro

2020

Liver International

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Widespread unhealthy dietary habits associated with a sedentary lifestyle have made NAFLD the most frequent chronic liver disease worldwide, with a global prevalence of ~25%. Although NAFLD is mainly considered to be a benign disease, it can progress to severe liver fibrosis and hepatocellular carcinoma (HCC), with the latter found in non‐cirrhotic livers in about 40% of cases. Factors favouring the progression of liver disease in NAFLD are only partially understood. Male sex, older age and Caucasian ethnicity have frequently been identified as factors accelerating the progression of fibrosis in NAFLD, although data are not consistent. Host genetic variants appear to be very important, especially in the gene coding for the patatin‐like phospholipase domain‐containing 3 (PNPLA3), and they may also play a role in the development of HCC, independent of activity and the extent of liver damage. However, the most important factors affecting disease progression are found in the metabolic syndrome, that is, obesity, type 2 diabetes and arterial hypertension. This mini‐review will discuss the contribution of these factors to NAFLD‐associated morbidity, emphasizing the importance of preventive measures such as physical activity and weight control in view of the current pandemic of the metabolic syndrome.

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“…Thus, close monitoring and education of prescribers can help to distinguish liver injury from underlying NAFLD and idiosyncratic drug‐induced liver injury. Beyond the CVD risk, statins have been attributed to a favorable effect on hepatocellular carcinoma incidence in a case‐control study, and thus their use can be beneficial from both a liver and CVD perspective. Additional measures to improve the CV risk could be the addition of omega n‐3 fatty acid supplements that were recently shown to decrease CV risk …”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Risk Categories in Patients With Nonalcoholic Fatty Liver Disease and the Role of Low‐Density Lipoprotein Cholesterol

et al. 2019

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Cardiovascular disease (CVD) is the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The current analysis expands the knowledge on atherogenic lipid profiles in NAFLD by modeling changes in low‐density lipoprotein cholesterol (LDL‐C) and total cholesterol (TC) in a prospectively enrolling real‐life study cohort to inform physicians on the cardiovascular (CV) event risk based on these changes. A total of 304 patients with histologically confirmed NAFLD were included (mean age, 52 years; equal sex distribution). Of these, 129 (42.4%) patients exhibited a NAFLD activity score ≥4 and 186 (61.2%) had at least intermediate fibrosis ≥F2. The median TC levels were 209 mg/dL (interquartile range [IQR], 183, 239), LDL‐C 131 mg/dL (IQR, 103, 152), and high‐density lipoprotein cholesterol (HDL‐C) 45 mg/dL (IQR, 38, 52). Only 16.9% of patients received lipid‐lowering therapy. According to the LDL/HDL ratio, 69 (23.7%) patients exhibited a high CV risk. The 10‐year CV event risk according to the Framingham risk score (FRS) was low in 91 (41.2%), intermediate in 59 (26.7%), and high in 71 (32.1%) patients and higher in the ≥F2 NAFLD population. A moderate increase in LDL‐C levels by 20 mg/dL led to a transition of 20% of patients into the high‐risk group when assessing the LDL/HDL ratio. According to the FRS, 6 (2.7%) patients moved from low to intermediate and 11 (4.9%) from intermediate to high CV risk. Conclusion: Patients with NAFLD exhibit a substantial CV event risk and are frequently undertreated with lipid‐lowering medication. Moderate increases in LDL‐C would result in worsening of the CV event risk in approximately 7.8% of all patients without a history of CVD.

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Statin use and the risk of hepatocellular carcinoma in patients at high risk: A nationwide nested case-control study

Cited by 106 publications

References 33 publications

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

Natural history of NASH and HCC

Cardiovascular Risk Categories in Patients With Nonalcoholic Fatty Liver Disease and the Role of Low‐Density Lipoprotein Cholesterol

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