Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population

Simon, Tracey G.; Duberg, Ann‐Sofi; Aleman, Soo; Hagström, Hannes; Nguyen, Long H.; Khalili, Hamed; Chung, Raymond T.; Ludvigsson, Jonas F.

doi:10.7326/m18-2753

Cited by 110 publications

(115 citation statements)

References 40 publications

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“…Third, as already observed in previous individual studies [24,27], lipophilic statins (atorvastatin, lovastatin, and simvastatin) were associated with significantly reduced HCC (51% compared to 27% in hydrophilic statin users). Among several agents tested, the more pronounced chemopreventive effect was observed with atorvastatin (57% reduction in HCC occurrence), although further studies are warranted to provide definitive results in this regard.…”

Section: Discussionsupporting

confidence: 68%

“…The recruitment period ranged from 1988 to 2018. Nine studies [8,10,[12][13][14]18,20,22] were retrospective case-control, twelve were cohort studies [9,11,[15][16][17]19,23,24,26,27,29,30], one study was a randomized controlled trial (RCT) [28], and two studies that were included as RCTs represented individual patient data analysis of patients enrolled in prospective controlled trials of cholesterol in heart disease [31,32]. The study by Tran et al [25] included two different stages, a nested case-control and a prospective cohort drawn from two different populations, hence they were analyzed separately.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

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Statin Use Decreases the Incidence of Hepatocellular Carcinoma: An Updated Meta-Analysis

Facciorusso

Aziz

Singh

et al. 2020

Cancers

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Statins can decrease hepatocellular carcinoma (HCC) occurrence, but the magnitude and the predictors of these effects remain unclear. This meta-analysis provides a pooled estimate of the impact of statin use on HCC occurrence. Pooled effects were calculated using a random-effects model by means of the DerSimonian and Laird test. Primary endpoint was the time-dependent correlation between statin use and HCC incidence expressed as hazard ratio (HR), both crude and adjusted. The crude and adjusted odds ratios (OR) for HCC occurrence between statin users and non-users were analyzed. Twenty-five studies with 1,925,964 patients were included. Crude OR for HCC incidence was 0.59 (95% CI: 0.47–0.74), confirmed in adjusted analysis (OR: 0.74, 95% CI: 0.70–0.78). Adjusted HR was 0.73 (95% CI: 0.69–0.76). This effect was more pronounced in HBV patients (HR: 0.46, 95% CI: 0.36–0.60) and with a cumulative daily dose beyond 365 (HR: 0.27, 95% CI: 0.11–0.67). Lipophilic statins were associated with reduced HCC incidence (HR: 0.49, 95% CI: 0.39–0.62). Atorvastatin determined the greater magnitude of effect (HR: 0.43, 95% CI: 0.28–0.65). This meta-analysis demonstrates the beneficial chemopreventive effect of statins against HCC occurrence. This effect is dose-dependent and more pronounced with lipophilic statins.

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Section: Discussionsupporting

confidence: 68%

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Statin Use Decreases the Incidence of Hepatocellular Carcinoma: An Updated Meta-Analysis

Facciorusso

Aziz

Singh

et al. 2020

Cancers

View full text Add to dashboard Cite

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“…Of these, 12 were further excluded because four of them did not evaluate statin use as exposure, five did not report outcome of HCC risk, one did not provide available data for the multivariate adjusted association between statin use and HCC risk, and the remaining three were abstracts of already included studies. Finally, we included 13 studies in this meta-analysis [13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Resultsmentioning

confidence: 99%

“…All of them were observational studies, among which one was a prospective cohort study, another one was a nested case-control study, and the remaining 11 were retrospective cohort studies. Since two studies reported the association between statin use and HCC risk in patients with HBV and HCV infection separately, these datasets were included independently [22,24]. Overall, 15 datasets from 13 studies, with 519,707 adult patients with HBV or HCV infection were included [13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Study Characteristics and Quality Evaluationmentioning

confidence: 99%

“…Besides, previous studies evaluating the association between statin use and HCC risk in patients with HBV or HCV infection retrieved inconsistent results. Although most studies indicated that statin use was associated with a reduced risk of HCC in patients with HBV or HCV infection [13][14][15][16][17][18][19][20][21][22], some studies showed a nonsignificant association between statin use and HCC risk in these patients [23][24][25]. Therefore, we aimed to perform a meta-analysis of longitudinal follow-up studies to systematically evaluate the association between statin use and HCC risk in high-risk patients with HBV and HCV infection.…”

Section: Introductionmentioning

confidence: 99%

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Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis

Li¹,

Sheng²,

Liu³

et al. 2020

BMC Gastroenterol

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Background: Statin may confer anticancer effect. However, the association between statin and risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C (HCV) virus infection remains inconsistent according to results of previous studies. A meta-analysis was performed to summarize current evidence. Methods: Related follow-up studies were obtained by systematic search of PubMed, Cochrane's Library, and Embase databases. A random-effect model was used to for the meta-analysis. Stratified analyses were performed to evaluate the influences of study characteristics on the outcome. Results: Thirteen studies with 519,707 patients were included. Statin use was associated with reduced risk of HCC in these patients (risk ratio [RR]: 0.54, 95% CI: 0.44 to 0.66, p < 0.001; I 2 = 86%). Stratified analyses showed that the association between statin use and reduced HCC risk was consistent in patients with HBV or HCV infection, in elder (≥ 50 years) or younger (< 50 years) patients, in males or females, in diabetic or non-diabetic, and in those with or without cirrhosis (all p < 0.05). Moreover, lipophilic statins was associated with a reduced HCC risk (RR: 0.52, p < 0.001), but not for hydrophilic statins (RR: 0.89, p = 0.21). The association was more remarkable in patients with highest statin accumulative dose compared to those with lowest accumulative dose (p = 0.002). Conclusions: Satin use was independently associated with a reduced risk of HCC in patients with HBV or HCV infection.

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Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel

Benhammou,

Leng,

Shah

et al. 2023

JAMA Netw Open

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ImportanceHepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers.ObjectiveTo assess the association of AO exposure and HCC in a national cohort of Vietnam veterans.Design, Setting, and ParticipantsThis retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO exposure were identified in the disability data via validated clinical surveys. Relevant clinical risk factors for cirrhosis and HCC were collected. Patients were stratified based on cirrhosis status, as defined by consecutive diagnosis found by documented International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision scores or calculated Fibrosis-4 scores. Data were collected from January 1, 2019, to December 31, 2020, and analyzed from December 2020 to October 2023.Main Outcome and MeasuresIncident HCC was the primary outcome. AO and HCC association was estimated using a multivariable Cox regression analysis, with death and liver transplant as competing events.ResultsOf the 296 505 eligible veterans (222 545 [75.1%] White individuals and 44 342 [15.0%] Black individuals), 170 090 (57%) had AO exposure (mean [SD] age, 21.62 [3.49] years; 131 552 White individuals [83.2%] and 22 767 Black individuals [14.4%]) and 35 877 (12.1%) had cirrhosis. Veterans who were not exposed to AO were more likely to smoke (109 689 of 126 413 [86.8%] vs 146 061 of 170 090 [85.9%]); use alcohol (54 147 of 126 413 [42.8%] vs 71 951 of 170 090 [42.3%]) and have viral hepatitis (47 722 of 126 413 [37.8%] vs 58 942 of 170 090 [34.7%]). In a multivariable competing risk model, AO exposure was not associated with HCC. Among veterans with cirrhosis, self-identification as Hispanic individuals (aHR, 1.51; 95% CI, 1.30-1.75; P &lt;.001) or Black individuals (aHR, 1.18; 95% CI, 1.05-1.32; P = .004), and having a diagnosis of viral hepatitis (aHR, 3.71; 95% CI, 3.26-4.24; P &lt;.001), alcohol-associated liver disease (aHR, 1.32; 95% CI, 1.19-1.46; P &lt;.001), and nonalcoholic fatty liver disease (NAFLD) (aHR, 1.92; 95% CI, 1.72-2.15; P &lt;.001) were associated with HCC. Among veterans without cirrhosis, hypertension (aHR, 1.63; 95% CI, 1.23-2.15; P &lt;.001) and diabetes (aHR, 1.52; 95% CI, 1.13-2.05; P = .005) were also associated with HCC. Early smoking and alcohol use were significant risk factors for HCC.Conclusions and RelevanceIn this large nationwide cohort study of Vietnam veterans, AO exposure was not associated with HCC. Smoking, alcohol, viral hepatitis, and NAFLD were the most important clinical risk factors for HCC.

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Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population

Cited by 110 publications

References 40 publications

Statin Use Decreases the Incidence of Hepatocellular Carcinoma: An Updated Meta-Analysis

Statin Use Decreases the Incidence of Hepatocellular Carcinoma: An Updated Meta-Analysis

Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis

Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel

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