Chronic Liver Disease Mortality Research Articles

Palliative care and end stage liver disease: A survey study comparing perspectives of hepatology and palliative care physicians and clinical scenarios that could require palliative care intervention

Background and aimsThe prevalence and mortality of chronic liver disease has risen significantly. In end stage liver disease (ESLD) the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is reduced. We aim to analyze the agreement between palliative care and hepatology physicians of clinical scenarios that could require palliative care intervention. MethodsA cross-sectional study was conducted. Palliative care and hepatology physicians were surveyed. Using a five-point Likert scale, their perceptions of palliative care in ESLD were rated. Their agreement in clinical scenarios that could require palliative care intervention were evaluated. Analyses were conducted to assess any differences by primary role (hepatology vs. palliative care) and length of practice (<10 years vs. 10 years). ResultsA total of 123 responses were obtained: 52% from palliative care and 48% from hepatology. The majority (66.7%) work in the field for up to ten years. There was a great consensus in 4 of the 8 clinical scenarios. In scenarios with less consensus, the area of activity and length of practice influence the reliance of physicians on palliative care. Involvement of palliative care in ESLD was considered “rare” by 30% and 61% consider difficult to predict the prognosis. More than 90% support medical training in both areas of activity. ConclusionThe current involvement of palliative care is considered low, but there are clinical conditions that reveal a clear consensus and there's a unanimous view of the relevance of training.

Diabetes Risk Reduction Diet and Risk of Liver Cancer and Chronic Liver Disease Mortality: A Prospective Cohort Study

Diabetes Risk Reduction Diet and Risk of Liver Cancer and Chronic Liver Disease Mortality: A Prospective Cohort Study

Preservation of fat mass at the expense of lean mass in children with end-stage chronic liver disease.

Sarcopenia predicts morbidity and mortality in end-stage chronic liver disease (ESCLD). Here, we describe changes in body composition in children with ESCLD before and after liver transplantation (LT). Retrospective analysis of whole body DXA scans performed before and after LT over 4 years. Appendicular and whole-body fat mass and lean mass were expressed as fat mass (FMI) and lean mass (LMI) index z-scores. Sarcopenia was defined as leg LMI z-score <-1.96. Eighty-three DXA scans of children before or after LT were studied. Sarcopenia had a positive correlation with weight (0.8, p < .01), height (0.48, p < .05), and BMI z-score (0.77, p < .01), as well as arm, trunk, and total mean mass indices. It correlated negatively with indices of hypersplenism: PLTs (-0.57, p < .01), Neu (-0.50, p < .05), WCC (-0.44, p < .05), and days to discharge (-0.46, p < .05). At baseline: 13/25 (52%) children were sarcopenic and stayed in the hospital after LT for longer. Eight were stunted with a higher WCC and Ne/Ly ratio. All had normal FM indices. One year after LT, 12/26 children remained sarcopenic. Seven were stunted. Two years after LT, 5/15 were sarcopenic, and 5 were stunted. Three years after LT, 1/10 was sarcopenic, and 2 were stunted. By 4 years after LT, 1/7 was sarcopenic, and the same one was stunted. FM indices remained normal. Sarcopenic patients stayed longer in the hospital after LT. Lean mass indices were mostly within the normal range by 4 years after LT. 32% of children were stunted, and markers of inflammation were correlated with stunting. Fat mass was preserved at the cost of lean mass.

Clinical and laboratory parameters as predictors of mortality in patients with chronic liver disease presenting to emergency department- a cross sectional study

BackgroundThe World Health Organization (WHO) reports that Asia and Africa have the highest Chronic Liver Disease (CLD) mortality rate. Cirrhosis, responsible for 22.2 fatalities per 100,000 people, is India’s 10th most common cause of mortality. The increasing prevalence of chronic liver disease necessitates a study to identify predictive factors for patients who visit the emergency department. Identifying elements that enhance the predictive value of mortality in unstable patients with CLD complications is important in emergency departments. This study aims to determine Clinical and Laboratory Parameters as mortality predictors in adult chronic liver disease patients.MethodologyThe study was conducted at the emergency department of a tertiary healthcare center in Northern India. Patients with chronic liver disease above 18 years of age who satisfied the inclusion criteria were clinically evaluated. Clinical and demographic details were collected, and data was analyzed.ResultsTwo hundred thirty-six patients were enrolled. The mean age was 50.77 ± 14.26 years. 78.4% of the participants were men. Abdominal distension, affecting 59.7% of patients, was the most common presenting ailment, followed by melena and hematemesis, affecting 41.9% and 32.6%, respectively. The mean stay in the emergency department was 10.29 ± 8.10 h. Refractory septic shock, the leading cause of mortality, accounts for 69.2% of all deaths, alongside grade 4 hepatic encephalopathy and massive Upper Gastrointestinal (UGI) bleeding, as identified in our study. Factors such as altered mental sensorium, high respiratory rate, low SpO2, increased heart rate, low systolic blood pressure, low diastolic blood pressure, and low Glasgow Coma Scale (GCS) on Emergency Department (ED) arrival are significantly associated with mortality.ConclusionsChronic liver disease, a prevalent condition in India, most commonly seen in middle aged men and lower socioeconomic groups. The parameters independently associated with mortality in our study were presence of altered mental sensorium, Glasgow coma scale, Child Pugh class and need for ICU admission. Understanding the presentation pattern, and mortality predictors can help ED physicians in managing acute events and follow-ups.

Global mortality of chronic liver diseases attributable to Hepatitis B virus and Hepatitis C virus infections from 1990 to 2019 and projections to 2030.

BackgroundThe burden of chronic liver disease (CLD) deaths attributable to the hepatitis B virus (HBV) and hepatitis C virus (HCV) remains unknown. Further research is required to elucidate the extent of this burden in the eventual elimination of these diseases. MethodsData on liver cancer, cirrhosis, and other CLD among 204 countries and territories between 1990 and 2019 was extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) published in 2019. The Bayesian age-period-cohort model was used to analyze the temporal trend and predict the disease burden by 2030. ResultsThe number of HCV-related CLD deaths surpassed that of CLD deaths caused by HBV in 2019 (536833 deaths versus 523003 deaths) and is expected to be maintained until 2030 (689124 deaths versus 628824 deaths). East Asia had the highest burden of chronic HBV and HCV infections during the study period. In 2019, the largest age-standardized death rates (ASDR) of CLD deaths caused by HBV and HCV were mainly observed in Western Sub-Saharan Africa (18.75%) and Eastern Sub-Saharan Africa (16.42%), respectively. South Asia and East Asia are predicted to have the highest number of CLD deaths related to HCV and HBV by 2030. Eastern Europe and South Asia show the largest expected increase in disease burden caused by HCV or HBV between 2019 and 2030. No GBD region is projected to achieve the WHO target of a 65% reduction in mortality from chronic HBV and HCV infections by 2030. ConclusionsAlthough the mortality of CLD caused by HBV and HCV decreased in the last three decades (from 1990 to 2019), the number of deaths will continue to increase until 2030. Therefore, governments and international organizations need to strengthen the effectiveness of vaccines, screening, and treatment, especially in potential emerging hotspot regions.

Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank

Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants. Here we show plasma levels of n-3 poly-unsaturated fatty acids (PUFA) and n-6 PUFA are negatively associated with the risk of incident HCC [HRQ4vsQ1: 0.48 (95% CI: 0.33–0.69) and 0.48 (95% CI: 0.28–0.81), respectively] and CLD mortality [HRQ4vsQ1: 0.21 (95% CI: 0.13–0.33) and 0.15 (95% CI: 0.08–0.30), respectively], whereas plasma levels of saturated fatty acids are positively associated with these outcomes [HRQ4vsQ1: 3.55 (95% CI: 2.25–5.61) for HCC and 6.34 (95% CI: 3.68–10.92) for CLD mortality]. Furthermore, fibrosis stage significantly modifies the associations between PUFA and CLD mortality. This study contributes to the limited prospective evidence on the associations between plasma-specific fatty acids and end-stage liver outcomes.

Non-invasive Assessment of Liver Damage Degree in Patients with Viral Hepatitis: Is It Feasible and Acceptable?

Background: Hepatitis C and B virus infections significantly contribute to global chronic liver disease mortality. Objectives: This study explores the role of serum markers (AST/ALT ratio, APRI Score, FIB-4 Score, and Forns index) in non-invasively assessing liver damage in patients with chronic hepatitis C and B. Methods: In this single-center, retrospective, observational study, we analyzed data from 327 patients to establish correlations between serological markers and fibrosis grade using Spearman's correlation. Receiver operator characteristic (ROC) analysis evaluated the ability of these markers to predict advanced fibrosis. Results: In hepatitis B and C cohorts, all markers show significant positive correlations with liver fibrosis (P &lt; 0.001). FIB-4 and the Forns index exhibit moderate correlation (Spearman’s rho 0.48), while AST/ALT and APRI score show mild correlation (Spearman’s rho 0.21 and 0.31). In hepatitis C, the Forns index (0.814) and FIB-4 (0.80) outperform other markers. In hepatitis B, Forns (AUC = 0.73), APRI (AUC = 0.68), and FIB-4 (AUC = 0.68) demonstrate significant predictive ability. Conclusions: FIB-4 and the Forns index hold clinical significance as fibrosis biomarkers in the management of chronic viral hepatitis. FIB-4 is a universal marker, while the interpretation of the Forns index requires consideration of the etiology of chronic viral hepatitis.

The mortality of hospitalized patients with COVID-19 and non-cirrhotic chronic liver disease: a retrospective multi-center study

Background Patients with chronic liver disease (CLD) have a higher risk of mortality when infected with severe acute respiratory syndrome coronavirus 2. Although the fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and albumin-bilirubin grade (ALBI) score can predict mortality in CLD, their correlation with the clinical outcomes of CLD patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to investigate the association between the liver severity and the mortality in hospitalized patients with non-cirrhotic CLD and COVID-19. Methods This retrospective study analyzed 231 patients with non-cirrhotic CLD and COVID-19. Clinical characteristics, laboratory data, including liver status indices, and clinical outcomes were assessed to determine the correlation between liver status indices and the mortality among patients with non-cirrhotic CLD and COVID-19. Results Non-survivors had higher levels of prothrombin time-international normalized ratio (PT-INR), alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein (hs-CRP) and lower albumin levels. Multivariable analysis showed that ALBI grade 3 (odds ratio (OR): 22.80, 95% confidence interval (CI) [1.70–305.38], p = 0.018), FIB-4 index ≥ 3.25 (OR: 10.62, 95% CI [1.12–100.31], p = 0.039), PT-INR (OR: 19.81, 95% CI [1.31–299.49], p = 0.031), hs-CRP (OR: 1.02, 95% CI [1.01–1.02], p = 0.001), albumin level (OR: 0.08, 95% CI [0.02–0.39], p = 0.002), and use of vasopressors (OR: 4.98, 95% CI [1.27–19.46], p = 0.021) were associated with the mortality. Conclusion The ALBI grade 3 and FIB-4 index ≥ 3.25, higher PT-INR, hsCRP levels and lower albumin levels could be associated with mortality in non-cirrhotic CLD patients with COVID-19. Clinicians could assess the ALBI grade, FIB-4 index, PT-INR, hs-CRP, and albumin levels of patients with non-cirrhotic CLD upon admission.

Potential role of Natural Herbal Tea as a healthy beverage in reducing the risk of liver cancer and chronic liver disease mortality

Potential role of Natural Herbal Tea as a healthy beverage in reducing the risk of liver cancer and chronic liver disease mortality

Chronic Liver Disease and Cirrhosis Mortality Rates Are Disproportionately Increasing in Younger Women in the United States Between 2000-2020

Background and aimsPrevious studies show that mortality from chronic liver disease (CLD) and cirrhosis is increasing in the U.S. However, there are limited data on sex-specific mortality trends by age, race, and geographical location. The aim of this study was to conduct a comprehensive time-trend analysis of liver disease related mortality rates in the National-Center-of-Health-Statistics(NCHS) database. MethodsCLD and cirrhosis mortality rates between 2000-2020(age-adjusted to the 2000-standard-U.S.-population) were collected from the NCHS database and categorized by sex and age into older adults(≥55 years) and younger adults(<55 years), race (Non-Hispanic-White, Non-Hispanic-Black, Hispanic, Non-Hispanic-America- Indian/Alaska-Native, and Non-Hispanic-Asian/Pacific-Islander), U.S. state, and cirrhosis etiology. Time-trends, annual percentage change (APC) and average APC (AAPC), were estimated using Joinpoint Regression utilizing Monte Carlo permutation analysis. We used tests for parallelism and identicalness for sex-specific pairwise comparisons of mortality trends(two-sided P-value cut-off=0.05). ResultsBetween 2000-2020, there were 716,651 deaths attributed to CLD and cirrhosis in the U.S. (35.68% women). In the overall population and in older adults, CLD and cirrhosis-related mortality rates were increasing similarly in men and women. However, in younger adults (246,149 deaths, %32.72 women), the rate of increase was greater in women compared to men(AAPC=3.04 vs 1.08, AAPC-Difference=1.96,P<0.001), with non-identical non-parallel data(P-values<0.001). The disparity was driven by Non-Hispanic-White(AAPC=4.51 vs 1.79, AAPC-difference=2.71,P<0.001) and Hispanic(AAPC=1.89 vs -0.65,AAPC-difference=2.54,P=0.001) individuals. The disparity varied between U.S. states and was seen in 16 states, mostly in West Virginia(AAPC=4.96 vs 0.88, AAPC-difference=4.08,P<0.001) and Pennsylvania(AAPC=2.81 vs -1.02, AAPC-difference=3.84,P<0.001). Etiology-specific analysis did not show significant sex disparity in younger adults. ConclusionMortality rates due to CLD and cirrhosis in the U.S. are increasing disproportionately in younger women. This finding was driven by higher rates in Non-Hispanic White and Hispanic individuals, with variation between U.S. states. Future studies are warranted to identify the reasons for these trends with the ultimate goal of improving outcomes.

Risk of chronic liver disease and cirrhosis mortality among patients with digestive system cancers: a registry-based analysis.

Non-cancer deaths are now becoming a great threat to the health of cancer survivors. There are no comprehensive and systematic reports on chronic liver disease and cirrhosis mortality (CLDCM) among patients with digestive system cancers (DSCs). This research aimed to quantitatively assess the risks and patterns of CLDCM among patients with DSCs. From the surveillance, epidemiology and end results (SEER) program, we extracted the data of patients diagnosed with DSCs between 2000 and 2017. Trends in incidence-based mortality rate (IBMR) were calculated using Joinpoint software. The standardized mortality ratio (SMR) was obtained based on the reference of the general United States population. The cumulative incidence function curves were constructed by all causes of death. Independent indicators were identified using the multivariate Fine and Gray competing risk model. We included 906,292 eligible patients from the SEER program, of which 3068 (0.34%) died from chronic liver disease and cirrhosis (CLDC). The IBMR of CLDC continued to increase during the study period [average annual percent change (APC): 6.7%; 95% confidence interval (CI) 5.1-8.2] and the SMR was significantly increased (SMR: 3.19; 95% CI 3.08-3.30). The cumulative mortality of CLDC was the lowest in all causes of death. Furthermore, the age at diagnosis, race, gender, marital status, year of diagnosis, SEER stage, surgery, chemotherapy and radiotherapy were identified as independent indicators. Better screening, diagnostic and management approaches need to be implemented as a preferred method to protect the liver among patients with DSCs.

S1476 Social and Demographic Parameters Affecting Chronic Liver Disease and Cirrhosis Mortality: 5-Year Trend in the United States

S1476 Social and Demographic Parameters Affecting Chronic Liver Disease and Cirrhosis Mortality: 5-Year Trend in the United States

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality

Approximately 65% of adults in the US consume sugar-sweetened beverages daily. To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Poor Access to Liver Transplantation and Survival of Children With Acute Liver Failure, Acute-on-chronic Liver Failure or Chronic Liver Disease.

We describe the survival of children with acute liver failure (ALF), chronic liver disease (CLD), or acute-on-chronic liver failure (ACLF) with poor access to liver transplantation (LT). A retrospective cohort study of 42 patients <18 years of age was conducted in the Hospital Civil de Guadalajara "Dr. Juan I. Menchaca". The median age was 76 months; 57.1% were female, 40.5% presented with ALF, 35.7% with CLD, and 23.8% with ACLF. Also, 38.1% (16/42) presented liver disease of unknown etiology. Death occurred in 45.2%; 14.3% were transferred to another hospital, and none received LT. Mortality in ALF, CLD, and ACLF was 76%, 0%, and 60%, respectively. In the survival analysis, within the first 20 months after diagnosis, the mortality rate was greater than 50% with ALF. The importance of having referral programs that perform liver transplantation is highlighted by the poor prognosis of the patients, despite conservative treatment.

Association of dietary insulinemic and inflammatory potential with risk of liver cancer and chronic liver disease mortality in postmenopausal women: a prospective cohort study

BackgroundLow diet quality, diabetes, and chronic inflammation are risk factors of liver cancer and chronic liver disease (CLD), but the extent to which insulinemic and inflammatory diets are independently associated with risk of liver cancer and CLD mortality is unknown. MethodsWe conducted a prospective cohort analysis among 78,356 postmenopausal women in the Women’s Health Initiative Observational Study. Two validated dietary indices, the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammation pattern (EDIP), were estimated from a food-frequency questionnaire. Incident cases of liver cancer and CLD mortality were adjudicated via review of medical records and linkage to National Death Index. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models, adjusted for age, diabetes, body mass index, and other covariates. ResultsDuring a median 22.1 y of follow-up, we documented 176 primary liver cancer cases and 156 CLD mortality cases. EDIH was positively associated with incident liver cancer (HRQuartile 4 vs. Quartile 1 = 1.68; 95% CI: 1.00, 2.83; P-trend = 0.05) and CLD mortality (HRQ4 vs. Q1 = 2.28; 95% CI: 1.25, 4.15; P-trend = 0.02) in the multivariable model. EDIP was also positively associated with liver cancer (HRQ4 vs. Q1 = 1.88; 95% CI: 1.17, 3.03; P-trend = 0.009) and CLD mortality (HRQ4 vs. Q1 = 1.85; 95% CI: 1.09, 3.15; P-trend = 0.007). Estimates remained significant and robust in sensitivity analyses. Further analyses indicated positive associations for refined grains, processed meat, sugary beverages, and eggs, and inverse associations for coffee/tea and poultry. ConclusionsDietary insulinemic and inflammatory potentials were independently associated with higher risk of liver cancer and CLD mortality in U.S. postmenopausal women. These findings suggest a potential role for diet modification to reduce risk of liver cancer and CLD.

Daytime napping, nighttime sleeping duration, and risk of hepatocellular carcinoma and liver disease-related mortality

Background & AimsSleep duration has been linked to metabolic dysfunction and chronic inflammation, which may contribute to the development of liver cancer and chronic liver disease (CLD). However, little is known about the relationship between sleep or napping duration and hepatocellular carcinoma (HCC) risk and CLD mortality. MethodsWe followed 295,837 individuals in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. We examined the associations of nighttime sleep duration and daytime napping duration with risk of HCC incidence and CLD mortality. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs). ResultsA total of 357 incident HCC cases and 578 CLD deaths were identified after a median follow-up time of 15.5 years. After adjusting for confounder factors, we found U-shaped associations of nighttime sleep duration with the incidence of HCC (HR<5 vs. 7–8 h = 2.00, 95% CI: 1.22–3.26 and HR≥9 vs. 7–8 h = 1.63, 95% CI: 1.04–2.65) and CLD mortality (HR<5 vs. 7–8 h = 1.78, 95% CI: 1.18–2.69 and HR≥9 vs. 7–8 h = 1.91, 95% CI: 1.35–2.70). Daytime napping was associated with higher risk of HCC (HR≥1 vs. non-nappers = 1.46, 95% CI: 1.04–2.06) and higher CLD mortality (HR≥1 h vs. non-nappers = 1.54, 95% CI: 1.18–2.01) compared with no napping. ConclusionsWe observed U-shaped associations for nighttime sleeping and risk of HCC and CLD mortality. Additionally, longer daytime napping duration was associated with higher risk of HCC and CLD death. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep. Impact and implicationsSleep or napping duration may play a role in the development of liver cancer and chronic liver disease, but little is known about the relationship between them. In addition, abnormal sleep patterns in patients with chronic liver disease may further promote the development of liver disease, creating a vicious cycle. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep, as they can be potentially important factors in the development and progression of liver disease.

Low vitamin A levels are associated with liver-related mortality: a nationally representative cohort study.

Vitamin A, a fat-soluble vitamin that includes retinol and carotenoids, is implicated in liver fibrosis, whereas its deficiency has been associated with various liver diseases and higher overall mortality. This study aims to determine the relationship between levels of vitamin A species and liver fibrosis, as well as liver-related mortality in the population of the US. A total of 12,299 participants from the National Health and Nutrition Examination Survey III (NHANES III) were analyzed to provide nationally representative estimates of the relationship between the levels of vitamin A species and liver fibrosis measured by Fibrosis-4 (FIB-4) index and liver-related mortality. A low blood level of retinol, but not other retinoid derivatives, was associated with significant liver fibrosis after adjustment for demographics, anthropometric measurements, medical history, retinol, and carotene intakes. Compared with vitamin D and E, retinol deficiency demonstrated much stronger associations with a high FIB-4 score. Individuals with known risks of chronic liver disease (CLD) and the lowest pentile of retinol levels had ORs of 3.12 (95% CI, 1.64-5.91) for possible fibrosis and 19.7 (95% CI, 5.71-67.7) for likely fibrosis, and an HR of 7.76 (95% CI, 1.19-50.5) for liver-related mortality compared with those in the highest retinol-level pentile. These relationships were more pronounced among individuals with known risks of chronic liver disease than without. A low circulating retinol level is associated with liver fibrosis and liver-related mortality in chronic liver disease. This relationship is potentially driven by a mechanistic link rather than the malabsorption of fat-soluble vitamins and may be leveraged for disease prognostication and have therapeutic implications.

Abstract 6456: Association of dietary inflammatory and insulinemic potential with risk of liver cancer and chronic liver disease mortality

Abstract Background: Increasing burdens of liver cancer and chronic liver disease (CLD) urge investigation of modifiable risk factors for primary prevention. Despite strong experimental evidence showing the role of chronic insulin resistance/hyperinsulinemia and inflammation in liver cancer and CLD, whether the insulinemic and inflammatory potential of diet are independently associated with higher risk of these outcomes requires further investigation. Methods: We conducted a prospective cohort study among 78,356 postmenopausal women in the Women’s Health Initiative Observational Study. Two validated dietary indices that predict circulating C-peptide or biomarkers of inflammation, namely, the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammation pattern (EDIP), were estimated from a food frequency questionnaire. Incident cases of liver cancer and CLD mortality were ascertained via review of medical records and linkage to national registries. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazard models, adjusted for age, diabetes, body mass index (BMI), and other covariates. Results: During a median 22.1 years of follow-up, we documented 176 primary liver cancer cases and 156 CLD mortality cases. The EDIH was positively associated with incident liver cancer risk (HRQuartile4 vs. Quartile1 = 1.70; 95% CI: 1.03, 2.81; p-trend = 0.03) and CLD mortality risk (HRQ4 vs. Q1 = 2.75; 95% CI: 1.54, 4.93; p-trend = 0.01) in the multivariable adjusted model, including diabetes and BMI as covariates. The EDIP was also positively associated with liver cancer (HRQ4 vs. Q1 = 1.93; 95% CI: 1.21, 3.09; p-trend &amp;lt;0.001) and CLD mortality risk (HRQ4 vs. Q1 = 2.09; 95% CI: 1.24, 3.52; p-trend &amp;lt;0.001) in the multivariable adjusted model. The estimates remained significant and robust in sensitivity analyses, after exclusion of cases in the first 2 years of follow-up or with liver disease history. There was no additive effect between the two dietary indices. Further analyses of individual food groups and liver outcomes indicated positive associations with refined grains, processed meat, butter, and eggs, and inverse associations with coffee, poultry, green leafy vegetables, and dark yellow vegetables. Conclusions: Dietary insulinemic and inflammatory potential were independently associated with higher risk of liver cancer and CLD mortality in US postmenopausal women. Monitoring dietary patterns to reduce chronic hyperinsulinemia and inflammation may contribute to the primary prevention of liver cancer and CLD mortality. Citation Format: Xinyuan Zhang, Longgang Zhao, Cami Christopher, Fred K. Tabung, Wei Bao, David O. Garcia, Marian L. Neuhouser, Aladdin H. Shadyab, Nazmus Saquib, Lesley Tinker, Xuehong Zhang. Association of dietary inflammatory and insulinemic potential with risk of liver cancer and chronic liver disease mortality. [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 6456.

Dietary inflammatory and insulinemic potential, risk of hepatocellular carcinoma, and chronic liver disease mortality.

Diet modulates inflammation and insulin response and may be an important modifiable factor in the primary prevention of hepatocellular carcinoma (HCC) and chronic liver disease (CLD). We developed the empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores to assess the inflammatory and insulinemic potentials of diet. We prospectively examined the associations of EDIP and EDIH at baseline with the following HCC risk and CLD mortality. We followed 485 931 individuals in the National Institutes of Health-American Association of Retired Persons Diet and Health Study since 1995. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). We confirmed 635 incident HCC cases and 993 CLD deaths. Participants in the highest compared with those in the lowest EDIP quartile had a 1.35 times higher risk of developing HCC (95% CI = 1.08 to 1.70, Ptrend = .0005) and a 1.70 times higher CLD mortality (95% CI = 1.41 to 2.04, Ptrend < .0001). For the same comparison, participants with the highest EDIH were at increased risk of HCC (HR = 1.53, 95% CI = 1.20 to 1.95, Ptrend = .0004) and CLD mortality (HR = 1.72, 95% CI = 1.42 to 2.01, Ptrend < .0001). Similar positive associations of scores with HCC risk and CLD mortality were observed for both women and men. Moreover, individuals in both the highest EDIP and EDIH tertiles had a 92% increased HCC risk (95% CI = 1.43 to 2.58) and 98% increased CLD mortality (95% CI = 1.27 to 3.08) compared with those in both lowest tertiles. Our findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking diet to HCC development and CLD mortality.

Statin can reduce the risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Currently, nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and liver-related mortality worldwide. Hepatocellular carcinoma (HCC) is a fatal complication in patients with NAFLD. However, whether statins can reduce the risk of HCC in patients with NAFLD remains controversial. We aimed to determine the relationship between statin use and HCC occurrence among patients with NAFLD. We independently retrieved related studies from PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrial.gov (from 1 January 2000 to 27 February 2022). The main outcome was the development of HCC. A fixed-effects model was used to merge odds ratio (OR) in the meta-analysis. Five studies involving 684 363 patients were included. The results of the meta-analysis suggested a significantly lower risk of HCC among statin users with NAFLD [OR = 0.59; 95% confidence interval (CI), 0.39-0.89; I2 = 87.90%]. Additionally, a lower risk of HCC was observed among patients with NAFLD aged less than 65 years (OR = 0.59; 95% CI, 0.46-0.77; I2 = 20.50%). Statins can reduce the risk of HCC in patients aged less than 65 years with NAFLD.