Lower Risk Of Liver Cancer Research Articles

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

A Comparative Study of Healthy Dietary Patterns for Incident and Fatal Digestive System Cancer.

We examined multiple dietary patterns in relation to total digestive system cancer (DSC) incidence and death. A total of 213,038 health professionals from the Health Professionals Follow-up Study (1986-2016), the Nurses' Health Study (1986-2018), and the Nurses' Health Study II (1991-2017) with no cancer diagnosis at baseline were analyzed. DSC incidence and death were estimated using time-varying Cox proportional hazards regression models. During up to 32 years of follow-up, 5,724 DSC cases accrued. Adherence to 8 healthy diet patterns was associated with a 7%-13% lower risk of DSC, particularly for digestive tract cancers. An inverse association with gastrointestinal tract cancer was also shown for all pattern scores except Alternate Mediterranean Diet and the healthful Plant-based Diet Index, with hazard ratios between 0.84 and 0.89. Inverse associations were shown for the reversed empirical dietary index for hyperinsulinemia (hazard ratio for 90th vs 10th percentile 0.64, 95% confidence interval [CI] 0.47-0.87) and the empirical dietary index associated with lower inflammation (rEDIP) (0.53, 95% CI 0.39-0.72) for stomach cancer, and for the rEDIP (0.58, 95% CI 0.37-0.92) for small intestine cancer. Among accessory cancers, the Alternate Healthy Eating Index-2010, alternate Mediterranean diet, and diabetes risk reduction diet were associated with a 43%-51% lower risk of liver cancer. The reversed empirical dietary index for hyperinsulinemia, rEDIP, and the Alternate Healthy Eating Index-2010 were inversely associated with the risk of fatal DSC. Adherence to healthy diets was associated with a lower risk of incident and fatal DSC, although the magnitude of the association varied slightly among the patterns.

LipoCol Forte capsules reduce the risk of liver cancer: A propensity score-matched, nationwide, population-based cohort study.

Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules (LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies. To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study. We used data from Taiwan's National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan's population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had follow-up data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios (aHRs) after adjusting for potential confounders. We enrolled 33231 LFC users and 33231 non-LFC users (controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference (SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91; 95% confidence interval (CI): 0.86-0.95; P < 0.001]. The risk of liver cancer was significantly reduced in both females (aHR 0.87; 95%CI: 0.8-0.94; P < 0.001) and males (aHR 0.93; 95%CI: 0.87-0.98; P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities (including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls (P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time; the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years (27.44 vs 31.49 per 1,000 person-years; aHR 0.75; 95%CI: 0.68-0.82; P < 0.001). This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

Abstract 6457: Blood magnesium level is associated with liver cancer risk in a prospective cohort of liver cirrhosis patients

Abstract Background: Previous studies showed that higher magnesium intake was linked to a lower risk of liver cancer. However, the relationship between blood magnesium level and the risk of liver cancer has not been fully established, especially among cirrhosis patients where magnesium deficiency commonly occurred. To address this knowledge gap, we have established a prospective cohort of patients with liver cirrhosis based on real-world, electronic health record data. Methods: In the Mass General Brigham Biobank, a biorepository of consented patients, we established a prospective cohort by identifying liver cirrhosis patients using the International Classification of Diseases 9th and 10th version codes (ICD-9: 571.2, 571.5, and 571.6; ICD-10: K70.3, K74.3-6). We excluded patients with liver cancer history or without blood magnesium assessment at the time of cirrhosis diagnosis (baseline). We identified subsequent incident liver cancer (ICD-9: 155; ICD-10: C22) and levels of liver function biomarkers assessed at each hospital visit, including alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). We used Cox regression models to generate ratios (HRs) with 95% confidence intervals (CIs) for developing liver cancer according to quartiles (Qs) of baseline blood magnesium levels, adjusting for age, sex, race, smoking status, alcohol intake, physical activity, body mass index, diabetes, ALT, and hepatitis B/C infection. We used generalized estimating equation (GEE) models to estimate the associations between baseline blood magnesium levels and repeated measurements of liver function biomarkers after cirrhosis diagnosis. Results: We included 1257 liver cirrhosis patients (median age at diagnosis 59.5 years; 36% female; 87% white) with magnesium levels measured at baseline. During a median follow-up period of 3.55 (range: 0.1-12) years from liver cirrhosis diagnosis, 106 developed liver cancer. In multivariable-adjusted Cox models, higher baseline blood magnesium (Q4: ≥2.10 mg/dL vs. Q1: &amp;lt;1.80 mg/dL) was associated with a lower risk of liver cancer (HRQ4 vs. Q1 = 0.57; 95% CI: 0.33, 0.99; p-trend =0.03). Results remained similar in 1-year lagged analysis. In multivariable-adjusted GEE models, higher magnesium was associated with a slower change of ALT (coefficientQ4 vs. Q1 = -7.09; 95% CI: -12.6, -1.62) and AST (coefficientQ4 vs. Q1 = -8.06; 95% CI: -13.9, -2.25). Conclusions: In a prospective cohort of high-risk population with liver cirrhosis, higher blood magnesium was associated with a lower risk of developing liver cancer and a slower change of biomarkers suggestive of liver function. Magnesium is implicated in liver carcinogenesis and progression, therefore monitoring and maintaining blood magnesium could be important to delay the progression from cirrhosis to cancer. Citation Format: Xinyuan Zhang, Longgang Zhao, Tao Hou, Michelle Lai, Qi Dai, Xuehong Zhang. Blood magnesium level is associated with liver cancer risk in a prospective cohort of liver cirrhosis patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6457.

Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project

Background & AimsIncidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. MethodsConcentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. ResultsHigher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). ConclusionsHigher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implicationsThis study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.

Specific botanical groups of fruit and vegetable consumption and liver cancer and chronic liver disease mortality: a prospective cohort study

BackgroundBeyond alcohol and coffee, the relationship between other dietary factors, including specific vegetables and fruits, and liver outcomes remains poorly understood. ObjectiveTo evaluate the associations between fruit and vegetable intake with the risk of liver cancer and chronic liver disease (CLD) mortality. MethodsThis study was based on the National Institutes of Health-American Association of Retired Persons Diet and Health Study, including 485,403 participants aged 50–71 y from 1995 to 1996. Fruit and vegetable intake was estimated using a validated food frequency questionnaire. Cox proportional hazards regression was used to estimate the multivariable hazard ratios (HR) and 95% confidence intervals (CI) for liver cancer incidence and CLD mortality. ResultsDuring a median follow-up of 15.5 y, 947 incident liver cancers and 986 CLD deaths (other than liver cancer) were confirmed. A higher intake of total vegetables was associated with a lower risk of liver cancer (HRQuintile 5 vs. Quintile 1 = 0.72, 95% CI: 0.59, 0.89; Ptrend < 0.001). When further subclassified into botanical groups, the observed inverse association was mainly driven by lettuce and the cruciferous family (broccoli, cauliflower, cabbage, etc.) (Ptrend < 0.005). Additionally, higher total vegetable intake was associated with a lower risk of CLD mortality (HRQuintile5 vs. Quintile1 = 0.61, 95% CI: 0.50, 0.76; Ptrend < 0.001). Inverse associations were observed for lettuce, sweet potatoes, cruciferous vegetables, legumes, and carrots with CLD mortality (all Ptrend < 0.005). In contrast, total fruit intake was not associated with liver cancer or CLD mortality. ConclusionsHigher intakes of total vegetables, especially lettuce and cruciferous vegetables, were associated with lower liver cancer risk. Higher intakes of lettuce, sweet potatoes, cruciferous vegetables, legumes, and carrots were associated with a lower risk of CLD mortality.

Cumulative consumption of tea is associated with lower risk of liver cancer: Updated results from the Shanghai Women's Health Study.

Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range=1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer.

Circulating vitamin C and digestive system cancers: Mendelian randomization study

SummaryBackground & aimsVitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers.MethodsTen genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables. Effect size estimates for the genetic associations of the vitamin C-associated genetic variants with six major malignancies of digestive system were obtained from the FinnGen (N=309 154) and UK Biobank (N=367 542) studies. Results from the two studies were combined using meta-analysis.ResultsGenetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32-0.94; P=0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73-0.96; P=0.013) for colorectal cancer. There was a suggestive association between genetically predicted higher circulating vitamin C with lower risk of liver cancer in FinnGen but no association in the meta-analysis (odds ratio 0.69; 95% CI 0.36-1.32; P=0.265). Genetically predicted circulating vitamin C was not associated with cancers of the esophagus, stomach, or pancreas.ConclusionThis Mendelian randomization study indicates that vitamin C might play a role in the prevention of small intestine and colorectal cancer.

Dietary Manganese Intake and Risk of Liver Cancer in Japanese Men and Women: The JACC Study

We explored the association between dietary manganese intake and the risk of liver cancer in 14,517 men and 21,583 women who participated in the Japan Collaborative Cohort Study for Cancer Risk Assessment. We assessed dietary manganese intake using a food frequency questionnaire and incident liver cancer by reviewing cancer registries. According to manganese intake, we estimated the liver cancer risk by Cox regression analyses. During the 513,657 person-year follow-ups within a median of 17.9 years of 36,100 participants, there were 239 incident cases of liver cancer. The multivariable hazard ratio (HR) (95% confidence interval [CI]; P-trend) for liver cancer risk in the highest vs. the lowest quintiles of dietary manganese intake was 0.56 (0.32–0.99; 0.04) in men and 1.16 (0.56–2.40; 0.79) in women; P-interaction = 0.06. The history of liver disease modified the observed association in men (P-interaction = 0.02), in which the multivariable HR (95%CI) of liver cancer risk comparing the highest vs. lowest quintiles of dietary manganese intake was 0.32 (0.14–0.74) in Japanese men without a history of liver disease, while it was 1.54 (0.62–3.79) in men with a history of liver disease. In conclusion, a higher dietary manganese intake was associated with a lower risk of liver cancer in men without a history of liver disease.

Abstract 730: Fruit and vegetable consumption and risk of liver cancer and liver disease mortality: A prospective cohort study

Abstract Background: In the US, liver cancer incidence has been tripled since the 1980s. Beyond alcohol and coffee, the relationship between other dietary factors and liver cancer remains poorly understood. One objective of this study is to comprehensively evaluate the relationship between overall and specific botanical groups of fruit and vegetable intake with liver cancer risk. Although liver disease mortality is the 11th leading cause of death in the US, its relationship with diet remains unclear. We also aimed to evaluate the association between fruit and vegetable intake and liver disease mortality. Methods: The study was conducted in the US NIH-AARP Diet and Health Study with 470,653 participants aged 50-71 years in 1995-1996. Fruits (14 items plus fruit juice) and vegetables (23 items without white potatoes included) were estimated using a validated Food Frequency Questionnaire. Cox proportional hazards regression modeling was used to estimate the multivariable hazard ratios (HR) and 95% confidence intervals (95% CI) for liver cancer incidence and liver disease mortality. We adjusted a priori for potential confounders including age, sex, education, race, alcohol intake, body mass index, smoking, total energy intake, physical activity, diabetes, and aspirin use. Results: During a median follow-up of 15.5 years, 899 incident liver cancers and 934 chronic liver disease deaths occurred. Higher intake of total vegetables was associated with a lower risk of liver cancer (HRQuintile 5 vs Quintile 1=0.66, 95%CI=0.53-0.82, Ptrend&amp;lt;0.01). When further subclassified into botanical groups, the observed inverse association was mainly driven by Cruciferae (broccoli, cauliflower, cabbage, et. al., HRQ5 vs Q1=0.64, 95%CI=0.52-0.79, Ptrend&amp;lt;0.01), Compositae (lettuce, HRQ5 vs Q1=0.67, 95%CI=0.54-0.83, Ptrend&amp;lt;0.01), Leguminosae (dried beans, string beans and peas, HRQ5 vs Q1=0.77, 95%CI=0.62-0.94, Ptrend=0.01), and Umbelliferae (carrots, HRQ5 vs Q1=0.77, 95%CI=0.62-0.95, Ptrend=0.01). Additionally, higher total vegetable intake was associated with a lower risk of liver disease mortality (HRQ5 vs Q1=0.60, 95%CI=0.49-0.74, Ptrend&amp;lt;0.01). Inverse associations were observed for lettuce, cruciferous vegetables, legumes, and carrots and liver disease mortality (all Ptrend&amp;lt;0.01). In contrast, total fruit intake was not associated with liver cancer (HRQ5 vs Q1=0.96, 95%CI=0.77-1.19, Ptrend=0.29) or liver disease mortality (HRQ5 vs Q1=1.07, 95%CI=0.87-1.32, Ptrend=0.71). Conclusions: Based on a large prospective US cohort study, higher intakes of total vegetables, and especially lettuce, cruciferous vegetables, legumes, and carrots, were associated with lower liver cancer incidence and liver disease mortality. Citation Format: Longgang Zhao, Lina Jin, Jessica L. Petrick, Fenglei Wang, Tang Li, Hongmei Zeng, Stephanie A. Smith-Warner, A. Heather Eliassen, Fang Fang Zhang, Peter T. Campbell, Edward Giovannucci, Linda M. Liao, Susan E. Steck, Katherine A. McGlynn, Xuehong Zhang. Fruit and vegetable consumption and risk of liver cancer and liver disease mortality: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 730.

Association of the presence of allergic disease with subsequent risk of liver cancer in a nationwide retrospective cohort among Koreans

A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68–0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62–0.85) but not ICC (aHR, 0.95; 95% CI 0.73–1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62–0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52–0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71–1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71–1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44–0.81) and 0.77 (95% CI 0.64–0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63–0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.

Aspirin Use and the Risk of Hepatocellular Carcinoma: A Meta-analysis.

The use of aspirin is a potential protective factor against the development of hepatocellular carcinoma (HCC). Therefore, we conducted a meta-analysis to evaluate the contribution of aspirin to the risk of HCC. We searched for PubMed and EMBASE through September 2021. Eighteen studies (16 cohort, 2 case-control) were included. Aspirin users were less likely to develop HCC than nonusers [adjusted odds ratio (OR), 0.54; 95% confidence interval (CI): 0.44-0.66]. Stratified analysis showed that aspirin reduced the risk of HCC in Asian and Western populations (OR, 0.59 vs. 0.67). Besides, aspirin has protective effects against HCC after hepatitis B virus (OR, 0.70; 95% CI: 0.52-0.93) and hepatitis C virus infections (OR, 0.41; 95% CI: 0.23-0.73). Aspirin has protective effects on people with chronic liver disease (OR, 0.46; 95% CI: 0.31-0.67) and on the general population (OR, 0.65; 95% CI: 0.54-0.79). In addition, confounding factors have an important impact on the results of aspirin prevention of liver cancer before (OR, 0.28; 95% CI: 0.06-1.27) and after (OR, 0.58; 95% CI: 0.47-0.71) adjustment. Further studies have shown that those in the long duration group do not experience better effects in preventing HCC (OR, 0.62 vs. 0.63). A further meta-analysis of 3 articles showed that the use of aspirin did not increase the risk of bleeding in patients with HCC (OR, 1.19; 95% CI: 0.87-1.64). Our meta-analysis shows that the use of aspirin is associated with a lower risk of liver cancer.

A Meta-Analysis of Statin Use and Risk of Hepatocellular Carcinoma.

Background The use of statins is a potential protective factor against the development of hepatocellular carcinoma. Therefore, we conducted a meta-analysis to evaluate the contribution of statins to the risk of hepatocellular carcinoma. Methods We searched for PubMed and EMBASE through January 2021. Results Thirty-two studies (eighteen cohort, eleven case-control, and three randomized controlled trials) reporting 56,838 cases of hepatocellular carcinoma in 4,963,518 persons were included. Statin users were less likely to develop hepatocellular carcinoma than nonusers (adjusted odds ratio, 0.58; 95% CI: 0.51–0.67). Stratified analysis showed that statins reduced the risk of hepatocellular carcinoma in Asian and Western populations (odds ratio, 0.54 vs. 0.60). Besides, statins have protective effects against hepatocellular carcinoma after hepatitis B virus (odds ratio, 0.44; 95% CI: 0.22–0.85) and hepatitis C virus infections (odds ratio, 0.53; 95% CI: 0.49–0.57). Statins have protective effects on people with chronic liver disease (odds ratio, 0.52; 95% CI: 0.40–0.68) and on the general population (odds ratio, 0.60; 95% CI: 0.50–0.72). Lipophilic statins can prevent hepatocellular carcinoma (odds ratio, 0.51, 95% CI: 0.46–0.57), while hydrophilic statins cannot (odds ratio, 0.77, 95% CI: 0.58–1.02). The single-drug analyses showed that simvastatin (odds ratio, 0.53, 95% CI: 0.48–0.59), atorvastatin (odds ratio, 0.54, 95% CI: 0.45–0.64), rosuvastatin (odds ratio, 0.55, 95% CI: 0.37–0.83), lovastatin (odds ratio, 0.30, 95% CI: 0.15–0.62), and pitavastatin (odds ratio, 0.36, 95% CI: 0.17–0.75) had significant benefits. Further studies have shown that those in the high-dose group experienced better effects in preventing hepatocellular carcinoma (adjusted hazard ratio, 0.38 vs. 0.55). Further research found that the combined use of aspirin did not increase the chemoprevention effect of liver cancer (odds ratio, 0.57; 95% CI: 0.40–0.81). In addition, the preventive effect of statins improved with the extension of follow-up time (odds ratio, 0.54 vs. 0.65). Conclusion Our meta-analysis shows that the use of statins is associated with a lower risk of liver cancer.

Higher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality

The relationship between dietary factors and liver disease remains poorly understood. This study evaluated the associations of whole grain and dietary fiber intake with liver cancer risk and chronic liver disease mortality. The National Institutes of Health–American Association of Retired Persons Diet and Health Study cohort recruited 485, 717 retired U.S. participants in 1995–1996. Follow-up through 2011 identified 940 incident liver cancer cases and 993 deaths from chronic liver disease. Compared with the lowest, the highest quintile of whole grain intake was associated with lower liver cancer risk (Hazard ratio [HR]Q5 vs. Q1 = 0.78, 95% confidence interval [CI]: 0.63–0.96) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.44, 95% CI: 0.35–0.55) in multivariable Cox models. Dietary fiber was also associated with lower liver cancer risk (HRQ5 vs. Q1 = 0.69, 95% CI: 0.53–0.90) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.37, 95% CI: 0.29–0.48). Fiber from vegetables, beans and grains showed potential protective effect. Here, we show that higher intake of whole grain and dietary fiber are associated with lower risk of liver cancer and liver disease mortality.

Dietary Fats, Serum Cholesterol and Liver Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Studies.

Simple SummaryDue to the rapid increase of primary liver cancer incidence and the poor prognosis, it is imperative to identify new modifiable factors such as diet and nutrition for the prevention of liver cancer. Diet high in saturated fatty acids (SFA) has been hypothesized to be associated with increased risk of cancers. However, the associations between dietary fatty acids and liver cancer are not consistent. We aimed to examine the association between dietary total fat, its major components, serum cholesterol, and risk of liver cancer combining current evidence from prospective studies. Our meta-analyses provided new evidence on associations between dietary fats, serum cholesterol, and liver cancer risk. Higher intake of dietary SFA was associated with higher risk of liver cancer while higher serum levels of cholesterol and high-density lipoprotein (HDL) were associated with a lower risk of liver cancer with high between-studies variability. Based on our findings, reducing dietary SFA may help to prevent the development of liver cancer.To quantify the associations between dietary fats and their major components, as well as serum levels of cholesterol, and liver cancer risk, we performed a systematic review and meta-analysis of prospective studies. We searched PubMed, Embase, and Web of Science up to October 2020 for prospective studies that reported the risk estimates of dietary fats and serum cholesterol for liver cancer risk. We carried out highest versus lowest intake or level and dose-response analyses. Higher intake of dietary saturated fatty acids (SFA) was associated with a higher liver cancer risk in both category analysis (relative risk [RR]highest vs. lowest intake = 1.34, 95% confidence interval [CI]: 1.06, 1.69) and dose-response analysis (RR1% energy = 1.04, 95%CI: 1.01, 1.07). Higher serum total cholesterol was inversely associated with liver cancer but with large between-studies variability (RR1 mmol/L = 0.72, 95%CI: 0.69, 0.75, I2 = 75.3%). The inverse association was more pronounced for serum high-density lipoprotein (HDL) cholesterol (RR1 mmol/L = 0.42, 95%CI: 0.27, 0.64). Higher intake of dietary SFA was associated with higher risk of liver cancer while higher serum levels of cholesterol and HDL were associated with a lower risk of liver cancer with high between-studies variability.

Magnesium intake is associated with a reduced risk of incident liver cancer, based on an analysis of the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort

Liver cancer incidence and mortality are escalating globally. Magnesium intake has been studied extensively in nonmalignant liver pathology, but the association between dietary intake of magnesium and primary liver malignancy has not been previously evaluated. We aimed to determine the association between total magnesium intake and primary liver cancer risk. Using the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort, we estimated the association between magnesium intake and the risk of incident primary liver cancer using Cox proportional hazard modeling adjusted for relevant confounders. Comprehensive stratified and sensitivity analyses were performed. During 6.4 million person-years of follow-up time, 1067 primary liver cancers occurred in 536,359 participants. Higher magnesium intake was independently associated with a lower risk of liver cancer (P-trend=0.005), with intakes in the highest compared with lowest quartile associated with 35% lower risk (HR: 0.65; 95% CI: 0.48, 0.87). The dose-related inverse association was more pronounced in moderate and heavy alcohol users (HR: 0.54; 95% CI: 0.35, 0.82; P-trend=0.006), and this interaction was statistically significant (P-interaction=0.04). Based on a prospective cohort analysis, we demonstrated that magnesium intake is associated with a lower risk of primary liver cancer, which was more pronounced among moderate and heavy alcohol users. Robust experimental and mechanistic data provide a biological basis to support these findings.

HIV co-infection is associated with lower risk of liver cancer after HCV-cure

HIV co-infection is associated with lower risk of liver cancer after HCV-cure

Aspirin associated with lower risk of liver cancer.

Aspirin associated with lower risk of liver cancer.

Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study

BackgroundHigher choline and betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival.Methods866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsSerum choline levels were associated with better LCSS (T3 vs. T1: HR = 0.69, 95% CI: 0.51–0.94; P-trend < 0.05) and OS (T3 vs. T1: HR = 0.73, 95% CI: 0.54–0.99; P-trend < 0.05). The associations were significantly modified by C-reactive protein (CRP) levels but not by other selected prognostic factors including sex, age, etc. The favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS.ConclusionsThis study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our findings suggest the benefits of choline on HCC survival.Trial registrationThe Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT03297255.

Vitamin D and liver cancer risk: A meta-analysis of prospective studies.

The association between circulating vitamin D and liver cancer risk has been controversial on the basis of epidemiological studies. The aim of this study was to quantitatively evaluate this association with prospective studies. A systematic literature search was implemented in PubMed and Scopus databases up to June 2019. Using a random-effects model, the multivariate-adjusted relative risks (RRs) with corresponding 95% confidence interval (CI) were pooled for the highest versus lowest category. Trend estimation was conducted with a two-stage dose-response meta-analysis. Six independent prospective studies (992 liver cancer events and 60,811 participants) were included for data synthesis. The summary estimate showed that a higher circulating vitamin D was associated with lower risk of liver cancer (Summary RR=0.78; 95% CI: 0.63, 0.95; I2=53.6%, p=0.035). Dose-response analysis indicated that liver cancer was associated with 8% (95% CI: 0.89, 0.95) lower risk with a 10 nmol/L increment of circulating vitamin D concentration. The present study provides substantial evidence that a higher concentration of circulating vitamin D would have conferred protection against liver cancer.