Effect of Statin Use on Cancer-related Mortality in Nonalcoholic Fatty Liver Disease

Hajifathalian, Kaveh; Tafesh, Zaid H.; Rosenblatt, Russell; Kumar, Sonal; Homan, Edwin A.; Sharaiha, Reem Z.; Cohen, David E.; Brown, Robert S.; Fortune, Brett E.

doi:10.1097/mcg.0000000000001503

Cited by 11 publications

(9 citation statements)

References 48 publications

(86 reference statements)

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“…5 Forest plot for HCC recurrence 5 years after liver surgery [39,41]. Furthermore, statins can inhibit progression of liver fibrosis and cirrhosis in HCC patients [42] and can reduce the risk of HCC in patients with Hepatitis C Virus (HCV) infection and also with nonalcoholic fatty liver disease (NAFLD) [43,44]. Lipophilic statins seem to be more effective at preventing HCC than hydrophilic statins are [39].…”

Section: Discussionmentioning

confidence: 99%

Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery

et al. 2022

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Background Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. Methods PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. Results The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44–0.63; p < 0.001). Moreover, Statins decreased the recurrence 1 year after surgery (OR: 0.27; 95% CI: 0.16–0.47; P < 0.001), 3 years after surgery (OR: 0.22; 95% CI: 0.15–0.33; P < 0.001), and 5 years after surgery (OR: 0.28; 95% CI: 0.19–0.42; P < 0.001). The certainty of evidence for the outcomes was moderate. Conclusion Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

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Section: Discussionmentioning

confidence: 99%

Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery

et al. 2022

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“…Also, long-term statin use was associated with reduced risk of cancer in NAFLD. This protection was greater with increasing the time of statin exposure, becoming significant after 1 year of treatment[ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Is there a role of lipid-lowering therapies in the management of fatty liver disease?

Tzanaki¹,

Agouridis²,

Kostapanos³

2022

WJH

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Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol concentrations. It is highly prevalent in non-alcoholic fatty liver disease (NAFLD) and contributes to the increased cardiovascular risk associated with this condition. Alongside insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis (NASH) development and progression. It has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD vs non-NAFLD high-risk individuals. This evidence highlights the importance of effective lipid modulation in NAFLD. In this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically discussed. Preclinical and clinical evidence suggests that statins reduce hepatic steatosis, inflammation and fibrosis in patients with NAFLD/NASH. Most data are derived from observational and small prospective clinical studies using changes in liver enzyme activities, steatosis/fibrosis scores, and imaging evidence of steatosis as surrogates. Also, relevant histologic benefits were noted in small biopsy studies. Atorvastatin and rosuvastatin showed greater benefits, whereas data for other statins are scarce and sometimes conflicting. Similar studies to those of statins showed efficacy of ezetimibe against hepatic steatosis. However, no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been shown. Preclinical studies showed that fibrates through peroxisome proliferator-activated receptor (PPAR)α activation may have a role in NAFLD prevention and management. Nevertheless, no relevant benefits have been noted in human studies. Species-related differences in PPARα expression and its activation responsiveness may help explain this discrepancy. Omega-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies, but their benefits on hepatic inflammation and fibrosis have not been established. Promising preliminary data for the highly purified eicosapentaenoic acid require further confirmation. Observational studies suggest that proprotein convertase subtilisin/kexin9 inhibitors may also have a role in the management of NAFLD, though this needs to be established by future prospective studies.

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“…Furthermore, statins can inhibit progression of liver brosis and cirrhosis in HCC patients (41) and can reduce the risk of HCC in patients with Hepatitis C Virus (HCV) infection and also with nonalcoholic fatty liver disease (NAFLD) (42,43). Lipophilic statins seem to be more effective at preventing HCC than hydrophilic statins are (38).…”

Section: Discussionmentioning

confidence: 99%

Statin Use is Associated With The Reduction in Hepatocellular Carcinoma Recurrence After Liver Surgery

Khajeh

Moghadam

Eslami

et al. 2021

Preprint

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Background Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. Methods PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. Results The literature search retrieved 1,362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2,243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.41; 95% CI: 0.31– 0.54; p <0.001). Moreover, Statins decreased the recurrence one year after surgery (OR: 0.27; 95% CI: 0.16–0.47; P < 0.001), three years after surgery (OR: 0.22; 95% CI: 0.15–0.33; P < 0.001), and five years after surgery (OR: 0.28; 95% CI: 0.19–0.42; P < 0.001). The certainty of evidence for the outcomes was moderate. Conclusion Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

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Effect of Statin Use on Cancer-related Mortality in Nonalcoholic Fatty Liver Disease

Cited by 11 publications

References 48 publications

Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery

Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery

Is there a role of lipid-lowering therapies in the management of fatty liver disease?

Statin Use is Associated With The Reduction in Hepatocellular Carcinoma Recurrence After Liver Surgery

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