Distinctive Features and Outcomes of Hepatocellular Carcinoma in Patients With Alcohol-Related Liver Disease: A US Multicenter Study

Introduction: The burden of hepatocellular carcinoma (HCC) occurring in patients with alcoholic liver disease (ALD) is increasing at an alarming rate. The aims of this study were to compare the patient and tumor characteristics of HCC occurring in ALD-alone relative to and in addition to other chronic liver diseases. Methods: Patients diagnosed with HCC between 2000 and 2014 were identified at 5 US clinical centers. The patients were categorized as ALD-alone, ALD plus viral hepatitis, or a non-ALD etiology. Clinical and tumor characteristics among the 3 groups were compared, and survival probability was estimated by the Kaplan-Meier method. The frequency of noncirrhotic HCC was compared across the 3 groups. Results: A total of 5,327 patients with HCC were analyzed. Six hundred seventy (12.6%) developed HCC due to underlying ALD. Ninety-one percent of ALD-related HCC arose in men, in contrast to non-ALD etiologies where men accounted for 70% of HCCs cases (P < 0.001). Patients with ALD-alone-related HCC were older at diagnosis and had tumors less likely to be detected as part of routine surveillance. The ALD-alone cohort was least likely to be within the Milan criteria and to undergo liver transplantation. Overall survival in the ALD-alone HCC cohort was lower than the other 2 groups (1.07 vs 1.31 vs 1.41 years, P < 0.001). HCC in the noncirrhotic ALD cohorts occurred in only 3.5% of the patients compared with 15.7% in patients with non-ALD etiologies (P < 0.001). Discussion: HCC occurring in patients with ALD occurred mostly in older men and almost exclusively in a cirrhotic background. They present with advanced tumors, and their survival is lower than HCCs occurring in non-ALD

Decreased Quality of Life is Significantly Associated with Body Composition in Patients with Nonalcoholic Fatty Liver Disease

Background & Aims We studied impaired quality of life (QOL) and its determinants among individuals with nonalcoholic fatty liver disease (NAFLD). Methods We collected data from 341 patients with NAFLD who completed the short form 36 (SF-36) questionnaire. Body composition and liver fibrosis were assessed in patients with NAFLD using bioelectrical impedance and transient elastography, respectively. Advanced fibrosis was defined as liver stiffness measurements (LSMs) of 12.1 kPa or greater. SF-36 scores of patients with NAFLD were compared with SF36 scores of individuals with chronic medical illnesses and the general population obtained from the published literature. Results Among patients with NAFLD, percent body fat was negatively associated with scores from all 8 SF-36 scales, whereas lean body mass was positively associated with scores from 5 of 8 SF-36 scales. On multivariable analysis, SF-36 PF scores were negatively associated with type 2 diabetes, body mass index, and LSM and positively associated with lean body mass and level of alanine aminotransferase. Patients with NAFLD, and even those without advanced fibrosis, had significantly lower mean QOL scores than the control group or the general population. Conclusions Individuals with NAFLD, even those without advanced fibrosis, have lower QOL than controls. Body composition associates with QOL in patients with NAFLD; both of the modifiable factors independently associated with QOL are related to body composition. Further studies are needed to investigate if interventions to improve body composition can increase QOL for patients with NAFLD

A Randomized Trial to Compare a Tailored Web-Based Intervention and Tailored Phone Counseling to Usual Care for Increasing Colorectal Cancer Screening

Background: Colorectal cancer mortality could be decreased with risk-appropriate cancer screening. We examined the efficacy of three tailored interventions compared with usual care for increasing screening adherence. Methods: Women (n = 1,196) ages 51 to 74, from primary care networks and nonadherent to colorectal cancer guidelines, were randomized to (1) usual care, (2) tailored Web intervention, (3) tailored phone intervention, or (4) tailored Web + phone intervention. Average-risk women could select either stool test or colonoscopy, whereas women considered at higher than average risk received an intervention that supported colonoscopy. Outcome data were collected at 6 months by self-report, followed by medical record confirmation (attrition of 23%). Stage of change for colorectal cancer screening (precontemplation or contemplation) was assessed at baseline and 6 months. Results: The phone (41.7%, P < 0.0001) and combined Web + phone (35.8%, P < 0.001) interventions significantly increased colorectal cancer screening by stool test compared with usual care (11.1%), with ORs ranging from 5.4 to 6.8 in models adjusted for covariates. Colonoscopy completion did not differ between groups except that phone significantly increased colonoscopy completion compared with usual care for participants in the highest tertile of self-reported fear of cancer. Conclusions: A tailored phone with or without a Web component significantly increased colorectal cancer screening compared with usual care, primarily through stool testing, and phone significantly increased colonoscopy compared with usual care but only among those with the highest levels of baseline fear. Impact: This study supports tailored phone counseling with or without a Web program for increasing colorectal cancer screening in average-risk women

An RCT to Increase Breast and Colorectal Cancer Screening

Introduction Adherence to breast and colorectal cancer screenings reduce mortality from these cancers, yet screening rates remain suboptimal. This 2 × 2 RCT compared 3 theory-based interventions to usual care to simultaneously increase breast and colon cancer screening in women who were nonadherent to both screenings at study entry. Design RCT. Setting/participants Women (n=692) who were nonadherent to both breast and colon cancer screenings and aged 51–75 years were recruited. Enrollment, intervention delivery, and data collection were completed between 2013 and 2017, and data analyzed in 2018. Intervention The randomized intervention included the following 4 groups: 3 intervention arms (personally tailored messages using a web-based intervention, phone delivery by a trained navigator, or both) compared with usual care. Women at an average risk for colon cancer were allowed to select either colonoscopy or stool test as their preferred colon cancer screening. Mammography was promoted for breast cancer screening. Main outcome measures Outcome data at 6 months included self-report and medical records for screening activity. Results All intervention arms significantly increased receipt of either a mammogram or stool test compared with control (web: p<0.0249, phone: p<0.0001, web + phone: p<0.0001). When considering receipt of both mammogram and stool test, all intervention arms were significantly different from usual care (web: p<0.0249, phone: p<0.0003, web + phone: p<0.0001). In addition, women who were adherent to mammography had a 4.5 times greater odds of becoming adherent to colonoscopy. Conclusions The tailored intervention simultaneously supporting both breast and colon cancer screenings significantly improved rates of obtaining one of the screenings and increased receipt of both tests

The relationship between cholesterol and cognitive function is homocysteine-dependent

Introduction Previous studies have identified hyperlipidemia as a potential risk factor for dementia and Alzheimer’s disease. However, studies on cholesterol measured in late-life and cognitive function have been inconsistent. Few studies have explored nonlinear relationships or considered interactions with other biomarker measures. Methods A cross-sectional sample of 1,889 participants from four rural counties in the People’s Republic of China was included in this analysis. Serum total cholesterol, high-density lipoprotein, triglycerides, and homocysteine levels were measured in fasting blood samples. A composite cognitive score was derived based on nine standardized cognitive test scores. Analysis of covariance models were used to investigate the association between biomarker measures and the composite cognitive scores. Results There was a significant interaction between the homocysteine quartile group and the cholesterol quartile group on cognitive scores (P=0.0478). In participants with normal homocysteine levels, an inverse U-shaped relationship between total cholesterol level and cognitive score was found, indicating that both low and high cholesterol levels were associated with lower cognitive scores. In participants with high homocysteine levels, no significant association between cholesterol and cognition was found. Conclusion The relationship between cholesterol levels and cognitive function depends upon homocysteine levels, suggesting an interactive role between cholesterol and homocysteine on cognitive function in the elderly population. Additional research is required to confirm our findings in other populations, and to explore potential mechanisms underlying the lipid–homocysteine interaction

ARDaC Common Data Model Facilitates Data Dissemination and Enables Data Commons for Modern Clinical Studies

Modern clinical studies collect longitudinal and multimodal data about participants, treatments and responses, biospecimens, and molecular and multiomics data. Such rich and complex data requires new common data models (CDM) to support data dissemination and research collaboration. We have developed the ARDaC CDM for the Alcoholic Hepatitis Network (AlcHepNet) Research Data Commons (ARDaC) to support clinical studies and translational research in the national AlcHepNet consortium. The ARDaC CDM bridges the gap between the data models used by the AlcHepNet electronic data capture platform (REDCap) and the Genomic Data Commons (GDC) data model used by the Gen3 data commons framework. It extends the GDC data model for clinical studies; facilitates the harmonization of research data across consortia and programs; and supports the development of the ARDaC. ARDaC CDM is designed as a general and extensible CDM for addressing the needs of modern clinical studies. The ARDaC CDM is available at https://dev.ardac.org/DD

A composite score using quantitative magnetic resonance cholangiopancreatography predicts clinical outcomes in primary sclerosing cholangitis

Background & aims: Magnetic resonance cholangiopancreatography (MRCP) for evaluation of biliary disease currently relies on subjective assessment with limited prognostic value because of the lack of quantitative metrics. Artificial intelligence-enabled quantitative MRCP (MRCP+) is a novel technique that segments biliary anatomy and provides quantitative biliary tree metrics. This study investigated the utility of MRCP+ as a prognostic tool for the prediction of clinical outcomes in primary sclerosing cholangitis (PSC). Methods: MRCP images of patients with PSC were post-processed using MRCP+ software. The duration between the MRCP and clinical event (liver transplantation or death) was calculated. Survival analysis and stepwise Cox regression were performed to investigate the optimal combination of MRCP+ metrics for the prediction of clinical outcomes. The resulting risk score was validated in a separate validation cohort and compared with an existing prognostic score (Mayo risk score). Results: In this retrospective study, 102 patients were included in a training cohort and a separate 50 patients formed a validation cohort. Between the two cohorts, 34 patients developed clinical outcomes over a median duration of 3 years (23 liver transplantations and 11 deaths). The proportion of bile ducts with diameter 3-5 mm, total bilirubin, and aspartate aminotransferase were independently associated with transplant-free survival. Combined as a risk score, the overall discriminative performance of the MRCP+ risk score (M+BA) was excellent; area under the receiver operator curve 0.86 (95% CI: 0.77, 0.95) at predicting clinical outcomes in the validation cohort with a hazard ratio 5.8 (95% CI: 1.5, 22.1). This was superior to the Mayo risk score. Conclusions: A composite score combining MRCP+ with total bilirubin and aspartate aminotransferase (M+BA) identified PSC patients at high risk of liver transplantation or death. Prospective studies are warranted to evaluate the clinical utility of this novel prognostic tool. Impact and implications: Primary sclerosis cholangitis (PSC) is a disease of the biliary tree where inflammation and fibrosis cause areas of narrowing (strictures) and expansion (dilatations) within the biliary ducts leading to liver failure and/or cancer (cholangiocarcinoma). In this study, we demonstrate that quantitative assessment of the biliary tree can better identify patients with PSC who are at high risk of either death or liver transplantation than a current blood-based risk score (Mayo risk score)

Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma

Background: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss. Aim: To explore the relationship between BMI and survival in patients with cirrhosis and HCC. Methods: This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC. Results: A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36). Conclusion: Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications

The prognostic impact of acute kidney injury recovery patterns in critically ill patients with cirrhosis

Background: The prognostic impact of acute kidney injury (AKI) recovery patterns in critically ill patients with cirrhosis is unknown. We aimed to compare mortality stratified by AKI recovery patterns and identify predictors of mortality in patients with cirrhosis and AKI admitted to the intensive care unit. Materials and methods: Patients with cirrhosis and AKI from 2016 to 2018 at 2 tertiary care intensive care units were analyzed (N=322). AKI recovery was defined by Acute Disease Quality Initiative consensus: return of serum creatinine 7 d). Landmark competing risk univariable and multivariable models (liver transplant as competing risk) was used to compare 90-day mortality between AKI recovery groups and to determine independent predictors of mortality. Results: Sixteen percent (N=50) and 27% (N=88) achieved AKI recovery within 0-2 and 3-7 days, respectively; 57% (N=184) had no-recovery. Acute on chronic liver failure was prevalent (83%) and patients with no-recovery were more likely to have grade 3 acute on chronic liver failure (N=95, 52%) compared to patients with AKI recovery [0-2: 16% (N=8); 3-7: 26% (N=23); p<0.001]. Patients with no-recovery had significantly higher probability of mortality [unadjusted-sub-HR (sHR): 3.55; 95% CI: 1.94-6.49; p<0.001] compared to patients with recovery within 0-2 days, while the probability was similar between 3-7 and 0-2 days (unadjusted-sub-HR: 1.71; 95% CI: 0.91-3.20; p=0.09). On multivariable analysis, AKI no-recovery (sub-HR: 2.07; 95% CI: 1.33-3.24; p=0.001), severe alcohol-associated hepatitis (sub-HR: 2.41; 95% CI: 1.20-4.83; p=0.01), and ascites (sub-HR: 1.60; 95% CI: 1.05-2.44; p=0.03) were independently associated with mortality. Conclusion: AKI no-recovery occurs in over half of critically ill patients with cirrhosis and AKI and is associated with worse survival. Interventions that facilitate AKI recovery may improve outcomes in this patient population

Increasing breast, cervical, and colorectal cancer screening among rural women: Baseline characteristics of a randomized control trial

Background Rural women suffer disproportionately from breast, cervical, and colorectal cancer mortality compared to those in urban areas. Screening behaviors for these three cancers share many similar beliefs and barriers. Unfortunately, published interventions have not attempted to simultaneously bring women up to date with screening for three cancers (breast, cervical, and colorectal) even though multiple behavior change interventions are effective. The aim of this randomized controlled study was to compare the effectiveness of a mailed interactive and tailored DVD vs. DVD plus telephonic patient navigation (DVD + PN) vs. Usual Care (UC) to increase the percentage of rural women (aged 50–74) up to date for breast, cervical, and colorectal cancer screening. Methods Nine hundred eighty-three participants needing one, two, or three cancer screening tests were consented and randomized to one of three groups. Prior to randomization, women were assessed for baseline characteristics including sociodemographics, health status, and cancer screening test beliefs. Screening status was assessed by medical record review. Results At baseline, the average age of participants was 58.6 years. Nineteen percent of the sample was not up to date with screenings for all three cancers. Colorectal cancer had the highest percentage of women (69%) who were not up to date with screening followed by cervical (57%) and then breast cancer (41%). Sixty percent of women reported receiving a reminder for mammography; 30%, for cervical cancer screening; 15% for colonoscopy; and 6% for FOBT/FIT. Discussion Increasing adherence to colorectal cancer screening may be the most urgent need among all screening tests