Quantitative Assessment of Hypovascular Component in Arterial Phase to Help the Discrimination of Combined Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma.

Purpose: To explore the imaging performance for discrimination of combined hepatocellular- cholangiocarcinoma (cHCC-CCA) and hepatocellular carcinoma (HCC). Methods: In total, 35 patients with cHCC-CCA and a matched control group of HCC patients (n = 35) were included retrospectively. We quantitatively evaluated the hypovascular component in tumor and qualitatively assessed LI-RADS features and other aggressive features to develop model for cHCC-CCA diagnose. Subgroup analyses were performed by tumor size and LI-RADS category. Results: cHCC-CCA frequently showed a larger proportion (≥50%) of hypovascular areas followed by HCC (P = 0.000). Among those patients with ≥50% hypovascular areas, 8 patients did not present rim enhancement in atrial phase. The LI-RADS major features were more commonly observed in HCC (82.9-45.7%,), than cHCC-CCA (P = 0.003-0.022). The targetoid appearances and non-smooth margin frequently appeared in cHCC-CCA (34.3-63.9%), compared with HCC (P = 0.000-0.023). We developed a radiologic model based on ≥50% hypovascular component and delayed enhancement, which presented AUC of 0.821, accuracy of 80%. We also obtained good performance by radiologic model in LR-M group and tumor size <50mm group (AUC: 0.841 and 0.866, respectively). Combined group which included CA 19-9 and ≥50% hypovascular component and delayed enhancement did not improve the distinction performance between cHCC-CCA and HCC, which presented good performance of identifying cHCC-CCA in the LR-4/5 subgroup and tumor size ≥50 mm subgroup (AUC: 0.717, 0.730, respectively). cHCC-CCA group presented heterogeneous dominant pathology involving 15 of HCC, 7 of intrahepatic cholangiocarcinoma (iCCA) or cholangiolocellular carcinoma (CLC), 13 of intermediate cells component. Macrotrabecular appearances were higher in cHCC-CCA than that in HCC. The proportion of Hepa-1 was significantly higher in true negative (TN) patients (29 [93.5%]) and false negative (FN) patients (10 [100%]) than in true positive (TP) patients (16 [64%]; P = 0.036). Conclusion: Quantitative assessment of hypovascular component could help the discrimination of cHCC-CCA. Macrotrabecular appearances were more exhibited in cHCC-CCA than that in HCC.

Body mass index trajectories, weight gain and risks of liver and biliary tract cancers.

BACKGROUND: Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). METHODS: We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). BMI was self-reported at ages 20, 50, and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 15.9 years among 138,922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI does not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 had increased risks of liver cancer (HR = 2.03, 95% CI: 1.26-3.28) and BTC (HR = 1.99, 95% CI: 1.16-3.39). Compared to participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI: 1.55-4.04) and BTC (HR = 1.83, 95% CI: 1.03-3.22). Compared to adults with stable weight (+/-5kg) between age 20 to 50 years, weight gain ≥20 kg between ages 20 to 50 years had higher HRs of 2.24 (95%CI: 1.40-3.58) for liver cancer and 1.86 (95% CI: 1.12-3.09) for BTC. CONCLUSIONS: Being overweight/obese at age 20, and BMI trajectories that result in being overweight and/or obese, may increase risk for both liver cancer and BTC.

A prospective study of carbohydrate intake and risk of all-cause and specific-cause mortality.

PURPOSE: To investigate the associations between carbohydrate intake and the risk of overall and specific-cause mortality in a prospective cohort study. METHODS: Diet was measured using 24 h dietary recalls. Underlying cause of death was identified through linkage to the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: During a median follow-up of 7.1 years among 35,692 participants who aged 20-85 years, a total of 3854 deaths [783 cardiovascular disease (CVD)-specific and 884 cancer-specific death] were identified. Carbohydrate intake was not associated with risk of overall mortality (multivariable-adjusted HR comparing extreme quartiles 1.03, 95% CI 0.94, 1.13, ptrend = 0.799), while higher fiber intake was associated with lower mortality risk (HR 0.86, 95% CI 0.77, 0.95, ptrend = 0.004). Replacing 5% of energy from carbohydrate with both plant fat and plant protein was associated with 13% (95% CI 8%, 17%) and 13% (95% CI 3%, 22%) lower risk of total and CVD mortality, respectively. Whereas a positive or null association was found when replacing carbohydrate with both animal fat and animal protein. Higher carbohydrate-to-fiber ratio was associated with increased risk of overall (HR 1.20, 95% CI 1.09, 1.33, ptrend < 0.001) and cancer-specific (HR 1.17, 95% CI 0.95, 1.44, ptrend = 0.031) mortality. CONCLUSIONS: Our findings suggested that high fiber diet or diet with low carbohydrate-to-fiber ratio was associated with lower long-term death risk, and provided evidence for the health benefit from dietary substitution of both plant fat and plant protein for carbohydrate.

Higher dietary insulinaemic potential is associated with increased risk of liver steatosis and fibrosis.

BACKGROUND AND AIMS: Hyperinsulinaemia and insulin resistance play a central role in the progression of hepatic steatosis and fibrosis, and diet can modulate insulin response. We thus hypothesised that diet with higher insulinaemic potential is associated with an increased risk of these conditions. METHODS: Two empirically dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were derived to identify food groups most predictive of fasting concentrations of C-peptide and insulin and homeostatic model assessment for insulin resistance respectively. Hepatic steatosis and fibrosis were defined by controlled attenuation parameter and liver stiffness measurement using transient elastography (TE). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. RESULTS: Of the 4171 participants with TE examination, 1436 (age-standardised prevalence, 33.8%) were diagnosed with steatosis, 255 (5.6%) with advanced fibrosis and 101 (2.2%) with cirrhosis. The multivariable-adjusted ORs for participants comparing the highest to the lowest EDIH tertile were 1.17 (95% CI: 0.99-1.39, Ptrend  = .005) for steatosis, 1.74 (95% CI: 1.24-2.44, Ptrend  = .001) for advanced fibrosis and 2.05 (95% CI: 1.21-3.46, Ptrend  = .004) for cirrhosis. Similar associations were observed for EDIR with ORs of 1.32 (95% CI: 1.11-1.55, Ptrend  < .001) for steatosis and 1.43 (95% CI: 1.03-1.99, Ptrend  = .006) for advance fibrosis. These positive associations remained among never drinkers and individuals who were free of hepatitis B and/or C. CONCLUSIONS: Our findings suggest that hyperinsulinaemia and insulin resistance may partially underlie the influence of diet on hepatic steatosis and fibrosis, and highlight the importance of reducing or avoiding insulinaemic dietary pattern.

Association of dietary inflammatory potential with risk of overall and cause-specific mortality.

Inflammation is a central mechanism in metabolic disorders associated with morbidity and mortality and dietary factors can modulate inflammation. We aimed to prospectively investigate the association between an empirically developed, food-based dietary inflammatory pattern (EDIP) score and the risk of overall and cause-specific mortality, using data from the US National Health and Nutrition Examination Survey from 1999 to 2014. EDIP score was derived by entering thirty-nine predefined commonly consumed food groups into the reduced rank regression models followed by stepwise linear regression, which was most predictive of two plasma inflammation biomarkers including C-reactive protein and leucocyte count among 25 500 US adults. This score was further validated in a testing set of 9466 adults. Deaths from baseline until 31 December 2015 were identified through record linkage to the National Death Index. During a median follow-up of 7·8 years among 40 074 participants, we documented 4904 deaths. Compared with participants in the lowest quintile of EDIP score, those in the highest quintile had a higher risk of overall death (hazard ratio (HR) = 1·19, 95 % CI 1·08, 1·32, Ptrend = 0·002), and deaths from cancer (HR = 1·41, 95 % CI 1·14, 1·74, Ptrend = 0·017) and CVD (HR = 1·22, 95 % CI 0·98, 1·53, Ptrend = 0·211). When stratified by age, the association of EDIP with overall mortality was stronger among individuals under 65 years of age (Pinteraction = 0·001). Diets with a higher inflammatory potential were associated with increased risk of overall and cancer-specific mortality. Interventions to reduce the adverse effect of pro-inflammatory diets may potentially promote health and longevity.

A prospective study of healthful and unhealthful plant-based diet and risk of overall and cause-specific mortality.

PURPOSE: Although emphasis has recently been placed on the importance of diet high in plant-based foods, the association between plant-based diet and long-term risk of overall and cause-specific mortality has been less studied. We aimed to investigate whether plant-based diet was associated with lower death risk. METHODS: This prospective cohort study used data from the US National Health and Nutrition Examination Survey. Diet was assessed using 24 h dietary recalls. We created three plant-based diet indices including an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). Deaths from baseline until December 31, 2015, were identified. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: We documented 4904 deaths among 40,074 participants after a median follow-up of 7.8 years. Greater adherence to PDI was associated with lower risk of overall (HR comparing extreme quintiles 0.80, 95% CI 0.73, 0.89, ptrend < 0.001) and cancer-specific (HR = 0.68, 95% CI 0.55, 0.85, ptrend < 0.001) mortality. These inverse associations remained for hPDI and overall mortality with a HR of 0.86 (95% CI 0.77, 0.95, ptrend = 0.001), but not for cancer or CVD mortality. Conversely, uPDI was associated with higher risk of total (HR = 1.33, 95% CI 1.19, 1.48, ptrend < 0.001) and CVD-specific (HR = 1.42, 95% CI 1.12, 1.79, ptrend = 0.015) mortality. CONCLUSIONS: Increased intake of a plant-based diet rich in healthier plant foods is associated with lower mortality risk, whereas a plant-based diet that emphasizes less-healthy plant foods is associated with high mortality risk among US adults.

Diets with higher insulinaemic potential are associated with increased risk of overall and cardiovascular disease-specific mortality.

Hyperinsulinaemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinaemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinaemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-h recalls. Two empirical dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinaemia (C-peptide and insulin) and insulin resistance (homoeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until 31 December 2015 were identified by the National Death Index. Multivariable hazard ratios (HR) and 95 % CI were calculated using Cox regression models. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants. For EDIH, the multivariable-adjusted HR (comparing extreme quintiles) were 1·20 (95 % CI 1·09, 1·32, P-trend<0·001) for overall mortality and 1·41 (95 % CI 1·15, 1·74, P-trend = 0·002) for CVD mortality. Similar associations were observed for EDIR with HR of 1·18 (95 % CI 1·07, 1·29, P-trend < 0·001) for total and 1·35 (95 % CI 1·09, 1·67, P-trend = 0·005) for CVD mortality. After further adjustments for BMI and diabetes, these positive associations were somewhat attenuated. Our findings suggested that diets with higher insulinaemic potential are associated with increased risk of overall and CVD-specific mortality.

Association of Inflammatory and Insulinemic Potential of Diet and Lifestyle with Risk of Hepatocellular Carcinoma.

BACKGROUND: We prospectively examined the extent to which greater inflammatory and insulinemic potential of diet and lifestyle are associated with the risk of developing hepatocellular carcinoma (HCC) in two nationwide cohorts. METHODS: Five kinds of pattern scores, including the empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH) and insulin resistance (EDIR), empirical lifestyle pattern score for hyperinsulinemia (ELIH) and insulin resistance (ELIR) were calculated. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. RESULTS: After an average follow-up of 25.6 years among 119,316 participants, 142 incident HCC cases were documented. Higher adherence to EDIP (HR by comparing extreme tertiles: 2.03; 95% CI, 1.31-3.16; P trend = 0.001), EDIH (HR, 1.61; 95% CI, 1.06-2.43; P trend = 0.02), and EDIR (HR, 1.62; 95% CI: 1.08-2.42; P trend = 0.02) was associated with increased risk of HCC. Likewise, participants with higher scores of ELIH (HR, 1.89; 95% CI, 1.25-2.87; P trend = 0.001) and ELIR (HR, 2.05; 95% CI, 1.34-3.14, P trend = 0.0004) had higher risk of developing HCC. Additional adjustment for diabetes mellitus and/or body mass index attenuated the magnitude of the associations, indicating that diabetes and/or adiposity may partly mediate the association of these patterns with HCC risk. CONCLUSIONS: Our findings suggest that inflammation and insulin resistance/hyperinsulinemia are potential mechanisms linking dietary or lifestyle factors and HCC development. IMPACT: Inflammation and insulin resistance/hyperinsulinemia may partly mediate the association of diet and other lifestyles with HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyperinsulinemic diet and lifestyle may reduce HCC risk.

Diet and liver cancer risk: a narrative review of epidemiological evidence.

Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.