Noninvasive Tests to Assess Fibrosis and Disease Severity in Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic-Dysfunction-Associated Steatohepatitis.

Risk of disease progression and clinical outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with fibrosis stage and presence of "at-risk metabolic dysfunction-associated steatohepatitis (MASH)." Although liver biopsy is considered the gold standard to diagnose MASH and stage of fibrosis, biopsy is infrequently performed in clinical practice and has associated sampling error, lack of interrater reliability, and risk for procedural complications. Noninvasive tests (NITs) are routinely used in clinical practice for risk stratification of patients with MASLD. Several NITs are being developed for detecting "at-risk MASH" and cirrhosis. Clinical care guidelines apply NITs to identify patients needing subspecialty referral. With recently approved Food and Drug Administration treatment for MASH and additional emerging pharmacotherapy, NITs will identify patients who will most benefit from treatment, monitor treatment response, and assess risk for long-term clinical outcomes. In this review, we examine the performance of NITs to detect "at-risk MASH," fibrosis stage, response to treatment, and risk of clinical outcomes in MASLD and MASH.

Positron emission tomography myocardial perfusion imaging (PET MPI) findings predictive of post-liver transplant major adverse cardiac events.

Positron emission tomography myocardial perfusion imaging (PET MPI) is a noninvasive diagnostic test capable of detecting coronary artery disease, structural heart disease, and myocardial flow reserve (MFR). We aimed to determine the prognostic utility of PET MPI to predict post-liver transplant (LT) major adverse cardiac events (MACE). Among the 215 LT candidates that completed PET MPI between 2015 and 2020, 84 underwent LT and had 4 biomarker variables of clinical interest on pre-LT PET MPI (summed stress and difference scores, resting left ventricular ejection fraction, global MFR). Post-LT MACE were defined as acute coronary syndrome, heart failure, sustained arrhythmia, or cardiac arrest within the first 12 months post-LT. Cox regression models were constructed to determine associations between PET MPI variable/s and post-LT MACE. The median LT recipient age was 58 years, 71% were male, 49% had NAFLD, 63% reported prior smoking, 51% had hypertension, and 38% had diabetes mellitus. A total of 20 MACE occurred in 16 patients (19%) at a median of 61.5 days post-LT. One-year survival of MACE patients was significantly lower than those without MACE (54% vs. 98%, p =0.001). On multivariate analysis, reduced global MFR ≤1.38 was associated with a higher risk of MACE [HR=3.42 (1.23-9.47), p =0.019], and every % reduction in left ventricular ejection fraction was associated with an 8.6% higher risk of MACE [HR=0.92 (0.86-0.98), p =0.012]. Nearly 20% of LT recipients experienced MACE within the first 12 months of LT. Reduced global MFR and reduced resting left ventricular ejection fraction on PET MPI among LT candidates were associated with increased risk of post-LT MACE. Awareness of these PET-MPI parameters may help improve cardiac risk stratification of LT candidates if confirmed in future studies.

Weight Loss and Weight Regain in Usual Clinical Practice: Results From the TARGET-NASH Observational Cohort.

First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.

Antiviral therapy use and related outcomes in patients with cancer and viral infections: results from SWOG S1204.

PURPOSE: Information is limited about adherence to practice guidelines in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection receiving anticancer treatment. METHODS: Newly diagnosed adult cancer patients were enrolled in a multicenter, prospective cohort study (SWOG S1204) during 2013-2017 to evaluate the prevalence of HBV, HCV, or HIV in patients initiating anticancer treatment. At 6 months, records of virus-positive patients were reviewed for antiviral therapy use; anticancer treatment dose reduction; and HBV reactivation (elevated viral load). Categorical variables were compared using chi-square or Fisher's exact test. RESULTS: Of 3055 enrolled patients with viral testing, 230 had chronic or past HBV, HCV, or HIV with 6-month follow-up data (chronic HBV, 15 patients; past HBV, 158; HCV, 49; HIV, 30). Twenty percent (3/15) of chronic HBV and 11% (17/158) of past HBV patients were co-infected with HCV and/or HIV. Rates of antiviral therapy use by 6 months were as follows: chronic HBV, 85% (11/13); past HBV receiving anti-B cell therapy, 60% (3/5); past HBV receiving systemic anticancer therapy without anti-B cell therapy, 8% (8/105); HCV, 6% (2/35); and HIV, 90% (19/21). Among patients with available data, anticancer treatment dose was reduced in 1 of 145 patients with past HBV and 1 of 42 with HCV. HBV reactivation occurred in 1 of 15 patients with chronic HBV; this patient was not receiving antiviral therapy. CONCLUSION: Many patients with cancer and viral infections either do not receive guideline-recommended antiviral treatment or receive antiviral treatment that is not recommended in guidelines. Further education is needed to improve adherence to guidelines.

Disease Knowledge, Health-Related Quality of Life, and Lifestyle Behavior Change in Patients with Nonalcoholic Fatty Liver Disease: Impact of an Educational Intervention.

BACKGROUND: Lifestyle modification is currently the only treatment for nonalcoholic fatty liver disease (NAFLD). The most effective way to motivate behavior change in this population is not well understood. AIMS: The aims of this study were to characterize the association between patient disease knowledge, attitudes, and behaviors and to determine the impact of an educational intervention. METHODS: Adults with NAFLD had the following assessed before and after an educational intervention: (1) disease knowledge; (2) health-related quality of life (HRQOL); (3) physical activity; (4) diet; (5) stages of change; and (6) clinical variables. RESULTS: Median age of the cohort (N = 248) was 53.5, 46% were male, 85% were white, and median body mass index was 33.9. Forty-eight percentage had nonalcoholic steatohepatitis, and 28% had cirrhosis. The median correct knowledge score was 73.6%, median Chronic Liver Disease Questionnaire-NAFLD was 5.2/7, and diet score was 7/16 (higher indicating unhealthy diets). The cohort was sedentary at baseline, with 46% and 60% in active phases of change for nutrition and physical activity, respectively. Fifty-six (22%) had all three high-risk behaviors (sedentary, poor diet scores, low stage of change), which was independently associated with depression. The educational intervention improved diet scores, HRQOL, stages of change, and weight. CONCLUSIONS: Despite good disease knowledge, NAFLD participants were sedentary and 1/4 had high-risk lifestyle behaviors. An educational intervention had positive impacts on clinical outcomes, though effect size was small. Pairing educational interventions with targeted interventions to motivate behavior change can improve care for patients with NAFLD.

Impact of a Pilot Structured Mobile Technology Based Lifestyle Intervention for Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Lifestyle modification is the main treatment for nonalcoholic fatty liver disease (NAFLD), but remains challenging to implement. The aim of this pilot was to assess the acceptability and feasibility of a mobile-technology based lifestyle program for NAFLD patients. METHODS: We enrolled adult patients with NAFLD in a 6-month mobile-technology based program where participants received a FitBit with weekly tailored step count goals and nutritional assessments. Anthropometrics, hepatic and metabolic parameters, Fibroscan, physical function and activity, and health-related quality of life measures were obtained at enrollment and month 6. Semi-structured exit interviews were conducted to assess patient's experience with the program. RESULTS: 40 (63%) eligible patients were enrolled. Median age was 52.5 with 53% males, 93% whites, 43% with diabetes and median BMI 33.9. On baseline Fibroscan, 59% had F0-2 fibrosis and 70% had moderate-severe steatosis. 33 patients completed the study. Median percentage of days with valid FitBit data collection was 91. 4 patients increased and maintained, 19 maintained, and 8 increased but subsequently returned to baseline weekly step count. 59% of patients reported Fitbit was easy to use and 66% felt step count feedback motivated them to increase their activity. Roughly 50% of patients had reduction in weight, triglycerides and Fibroscan liver stiffness, and 75% had improvement in controlled attenuation parameter and physical function. CONCLUSIONS: A 6-month mobile-technology based pilot lifestyle intervention was feasible and acceptable to NAFLD patients. The program promoted physical activity and was associated with improvement in clinical parameters in some patients.

Eliciting patient views on the allocation of limited healthcare resources: a deliberation on hepatitis C treatment in the Veterans Health Administration.

BACKGROUND: In response to the development of highly effective but expensive new medications, policymakers, payors, and health systems are considering novel and pragmatic ways to provide these medications to patients. One approach is to target these treatments to those most likely to benefit. However, to maximize the fairness of these policies, and the acceptance of their implementation, the values and beliefs of patients should be considered. The provision of treatments for chronic hepatitis C (CHC) in the resource-constrained context of the Veterans Health Administration (VHA) offered a real-world example of this situation, providing the opportunity to test the value of using Democratic Deliberation (DD) methods to solicit the informed opinions of laypeople on this complex issue. METHODS: We recruited Veterans (n = 30) from the VHA to attend a DD session. Following educational presentations from content experts, participants engaged in facilitated small group discussions to: 1) identify strategies to overcome CHC treatment barriers and 2) evaluate, vote on, and modify/improve two CHC treatment policies - "first come, first served" (FCFS) and "sickest first" (SF). We used transcripts and facilitators' notes to identify key themes from the small group discussions. Additionally, participants completed pre- and post-DD surveys. RESULTS: Most participants endorsed the SF policy over the FCFS policy, emphasizing the ethical and medical appropriateness of treating the sickest first. Concerns about SF centered on the difficulty of implementation (e.g., how is "sickest" determined?) and unfairness to other Veterans. Proposed modifications focused on: 1) the need to consider additional health factors, 2) taking behavior and lifestyle into account, 3) offering education and support, 4) improving access, and 5) facilitating better decision-making. CONCLUSIONS: DD offered a robust and useful method for addressing the allocation of the scarce resource of CHC treatment. Participants were able to develop a modified version of the SF policy and offered diverse recommendations to promote fairness and improve quality of care for Veterans. DD is an effective approach for incorporating patient preferences and gaining valuable insights for critical healthcare policy decisions in resource-limited environments.

New and emerging treatments for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the cornerstone of therapy. Real-world efficacy and sustainability of lifestyle interventions are low, however. Pharmacotherapy development for MASH is emerging with promising data from several agents with different mechanisms of action (MOAs) in phase 3 clinical trials. In this review, we highlight ongoing challenges and potential solutions in drug development for MASH and provide an overview of available data from emerging therapies across multiple MOAs.

Implementation of a randomized mobile-technology lifestyle program in individuals with nonalcoholic fatty liver disease.

Identifying effective, feasible, low-cost interventions that promote sustainable lifestyle changes in nonalcoholic fatty liver disease (NAFLD) is a key unmet need. The aim of this study was to assess predictors of lifestyle practice patterns of NAFLD patients and evaluate the implementation of a mobile technology-based intervention. We prospectively enrolled adults with NAFLD (diagnosed by imaging or biopsy). Individuals with additional liver diseases or decompensated cirrhosis were excluded. Patient were randomized to usual care or a FitBit based program for 6-months. We obtained anthropometrics, labs, vibration controlled transient elastography (VCTE), health-related quality of life (HRQOL), physical activity, diet and motivation to change data. 70 patients were enrolled, 33% with cirrhosis. Median age was 52.1 years, 47% males, 83% white, body mass index 32.3, liver stiffness 7.6 kPa, controlled attenuation parameter 319 db/m, and 50% had diabetes. Baseline HRQOL was 5.4/7 and independently negatively correlated with level of concern about their disease and positively with physical function. Younger age was independently associated with unhealthy diets whereas diabetes was independently associated with unhealthy diets and higher VCTE kPa. 6-month follow-up data available on 31 patients showed trends in improvement in weight. In a cohort of NAFLD patients, we identified independent correlates of lifestyle behaviors and HRQOL. Implementation of interventions that improve physical function may improve HRQOL in NAFLD. Younger patients and those with diabetes appeared to have the greatest need for dietary interventions. Structured mobile technology lifestyle interventions using Fitbit and personalized coaching showed promise but require further validation with a focus on sustainability of intervention and improvement in outcomes.

Non-invasive diagnosis and monitoring of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent form of chronic liver disease that poses challenges in diagnosis and risk stratification. Non-alcoholic steatohepatitis (NASH), the more progressive form of NAFLD, is particularly challenging to diagnose in the absence of histology. Liver biopsy is infrequently performed due to its invasive nature, potential for sampling error, and lack of inter-rater reliability. Non-invasive tests that can accurately identify patients with at-risk NASH (ie, individuals with biopsy-proven NASH with NAFLD activity score [NAS] ≥4 and fibrosis stage ≥2) are key tools to identify candidates for pharmacologic therapy in registrational trials for the treatment of NASH-related fibrosis. With emerging pharmacotherapy, non-invasive tests are required to track treatment response. Lastly, there is an unmet need for non-invasive tests to assess risk for clinical outcomes including progression to cirrhosis, hepatic decompensation, liver-related mortality, and overall mortality. In this Review we examine advances in non-invasive tests to diagnose and monitor NAFLD and NASH.

Universal Viral Screening of Patients with Newly Diagnosed Cancer in the United States: A Cost-efficiency Evaluation.

Recommendations for universal screening of patients with cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are inconsistent. A recent multisite screening study (S1204) from the SWOG Cancer Research Network found that a substantial number of patients with newly diagnosed cancer had previously unknown viral infections. The objective of this study was to determine the cost-efficiency of universal screening of patients with newly diagnosed cancer. We estimated the cost-efficiency of universal screening of new cancer cases for HBV, HCV, or HIV, expressed as cost per virus detected, from the health care payer perspective. The prevalence of each virus among this cohort was derived from S1204. Direct medical expenditures included costs associated with laboratory screening tests. Costs per case detected were estimated for each screening strategy. Secondary analysis examined the cost-efficiency of screening patients whose viral status at cancer diagnosis was unknown. Among the possible options for universal screening, screening for HBV alone ($581), HCV alone ($782), HBV and HCV ($631) and HBV, HCV, and HIV ($841) were most efficient in terms of cost per case detected. When screening was restricted to patients with unknown viral status, screening for HBV alone ($684), HBV and HCV ($872), HBV and HIV ($1,157), and all three viruses ($1,291) were most efficient in terms of cost per newly detected case. Efficient viral testing strategies represent a relatively modest addition to the overall cost of managing a patient with cancer. Screening for HBV, HCV, and HIV infections may be reasonable from both a budget and clinical standpoint. SIGNIFICANCE: Screening patients with cancer for HBV, HCV, and HIV is inconsistent in clinical practice despite national recommendations and known risks of complications from viral infection. Our study shows that while costs of viral screening strategies vary by choice of tests, they present a modest addition to the cost of managing a patient with cancer.

The Utility of Noninvasive PET/CT Myocardial Perfusion Imaging in Adult Liver Transplant Candidates.

Background: The optimal cardiovascular (CV) risk stratification in liver transplant (LT) candidates remains unclear. The aim of this study was to evaluate concordance of findings between dobutamine stress echocardiography (DSE), positron emission tomography/computed tomography myocardial perfusion imaging (PET/CT MPI), and left heart catheterization in adult LT candidates. Methods: Data on 234 consecutive adult LT candidates from February 2015 to June 2018 with PET/CT MPI were reviewed. Adverse CV outcomes were adjudicated via chart review by a board-certified cardiologist. Results: Median age was 60.8, body mass index 30.2 kg/m2, and model of end-stage liver disease-sodium 14; 61% were male, and 54% had diabetes. Thirty-seven percent had nonalcoholic steatohepatitis and 29% alcohol-related liver disease. Sixty-five percent of patients had a DSE, of which 41% were nondiagnostic. No factors were independently associated with having a nondiagnostic DSE. The median global myocardial flow reserve correlated positively with hemoglobin and negatively with model of end-stage liver disease-sodium, age, ejection fraction, and body mass index. Moderate/high-risk MPIs were associated with older age and known CV disease. In patients with 2 cardiac testing modalities, findings were concordant in 87%. Eleven of 53 LT recipients experienced an adverse CV outcome, but no independent predictors were identified for this outcome. Conclusions: Results of different cardiac risk-stratification modalities were concordant across modalities the majority of the time in LT candidates, although these findings were not independently correlated with risk of post-LT CV outcomes. Given the high rates of nondiagnostic DSEs in this population, PET/CT MPI may be the preferred CV risk-stratification modality in older patients and those with known CV disease.

Cognitive Impairment and Physical Frailty in Patients With Cirrhosis.

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

Patient disease knowledge, attitudes and behaviours related to non-alcoholic fatty liver disease: a qualitative study.

OBJECTIVE: Despite clear evidence that weight loss via nutritional and physical activity changes improves histological outcomes in non-alcoholic fatty liver disease (NAFLD), many patients struggle to implement and maintain these health behaviour changes. The aim of this study was to characterise disease knowledge, attitudes and behaviours among persons with NAFLD and to identify the factors driving these health behaviours and perceptions. DESIGN: We conducted semistructured interviews among patients with NAFLD. We used purposeful sampling to enroll equivalent percentages based on age and sex, and enrolled approximately one-third of patients with cirrhosis to capture those perspectives. Interviews were conducted until thematic saturation was achieved. Transcripts were coded using NVivo software to identify themes and subthemes. RESULTS: A total of 29 patient interviews were completed. Ambiguity about the diagnosis and aetiology of their liver disease was a key theme, though the vast majority of patients were aware that weight loss via nutrition and exercise was the primary therapy. Most patients were asymptomatic, diagnosed incidentally, and reported low level of concern regarding their diagnosis. The primary barriers and facilitators to health behaviour change were the presence of social support, competing medical comorbidities and low motivation to change behaviours. CONCLUSIONS: Although patients are aware that lifestyle interventions are the primary therapy for NAFLD, there is a gap in knowledge about the condition. The presence of social support and competing medical comorbidities were the most consistent facilitators and barriers to lifestyle change. Tailoring treatment recommendations to provide relevant disease education, specific nutrition and exercise regimens, and personalised approaches based on specific individual barriers and facilitators will likely aid in uptake and maintenance of first-line therapy for NAFLD.

Primary care and referring physician perspectives on non-alcoholic fatty liver disease management: a nationwide survey.

INTRODUCTION: The optimal approach to screening and risk stratification for non-alcoholic fatty liver disease is challenging given disease burden and variable progression. The aim of this study was to assess primary care physician and referring physician practice patterns regarding non-alcoholic fatty liver disease. METHODS: An anonymous nationwide survey was administered to primary care physicians, endocrinologists, and cardiologists in a: (1) tertiary academic hospital, (2) community hospital, and (3) the American College of Physicians Insider Panel. Survey domains assessed non-alcoholic fatty liver disease knowledge, recommendations for screening, risk stratification, treatment, and referral patterns. RESULTS: A total of 440 providers completed the survey (35.2% completion rate; N = 82 academic hospital, N = 21 community hospital, N = 337 American College of Physicians). Half were male (51.7%), 78% from internal medicine, with 5% subspecialists. Providers were knowledgeable regarding prevalence and risk factors for non-alcoholic fatty liver disease. 58% would support screening for non-alcoholic fatty liver disease and used liver enzymes to do so. Only 22.5% used serum biomarkers and 23% used transient elastography for risk stratification. Primary reason for referral was advanced fibrosis/cirrhosis. 80% reported barriers to treating non-alcoholic fatty liver disease. There was no consistent diet recommended. CONCLUSION: In this nationwide survey, we demonstrated that while overall disease knowledge was good, there was an important disconnect between current guidelines and real-world clinical practice. There is also significant heterogeneity in practice patterns for first-line therapy of non-alcoholic fatty liver disease and the majority of provider's report barriers to treating non-alcoholic fatty liver disease. These findings highlight the potential role for reevaluating screening and risk stratification recommendations in primary care to better align with needs in that setting.

Prevalence and Patterns of Opioid Use Before and After Liver Transplantation.

BACKGROUND: Opioid use in liver transplantation is poorly understood and has potential associated morbidity. METHODS: Using a national data set of employer-based insurance claims, we identified 1257 adults who underwent liver transplantation between December 2009 and February 2015. We categorized patients based on their duration of opioid fills over the year before and after transplant admission as opioid-naive/no fills, chronic opioid use (≥120 d supply), and intermittent use (all other use). We calculated risk-adjusted prevalence of peritransplant opioid fills, assessed changes in opioid use after transplant, and identified correlates of persistent or increased opioid use posttransplant. RESULTS: Overall, 45% of patients filled ≥1 opioid prescription in the year before transplant (35% intermittent use, 10% chronic). Posttransplant, 61% of patients filled an opioid prescription 0-2 months after discharge, and 21% filled an opioid between 10-12 months after discharge. Among previously opioid-naive patients, 4% developed chronic use posttransplant. Among patients with pretransplant opioid use, 84% remained intermittent or increased to chronic use, and 73% of chronic users remained chronic users after transplant. Pretransplant opioid use (risk factor) and hepatobiliary malignancy (protective) were the only factors independently associated with risk of persistent or increased posttransplant opioid use. CONCLUSIONS: Prescription opioid use is common before and after liver transplant, with intermittent and chronic use largely persisting, and a small development of new chronic use posttransplant. To minimize the morbidity of long-term opioid use, it is critical to improve pain management and optimize opioid use before and after liver transplant.

Diagnostic and interventional circulating biomarkers in nonalcoholic steatohepatitis.

INTRODUCTION: In the setting of the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent forms of chronic liver disease worldwide. Approximately 25% of adults globally have NAFLD which includes those with NAFL, or simple steatosis, and individuals with nonalcoholic steatohepatitis (NASH) where inflammation, hepatocyte injury and potentially hepatic fibrosis are found in conjunction with steatosis. Individuals with NASH, particularly those with hepatic fibrosis, have higher rates of liver-related and overall mortality, making this distinction of significant clinical importance. One of the core challenges in current clinical practice is identifying this subset of individuals with NASH without the use of liver biopsy, the gold standard for both diagnostics and staging disease severity. Identifying noninvasive biomarkers, an accurately measured and reproducible parameter, would aide in identifying patients eligible for NASH pharmacotherapy clinical trials and to help tailor intensity of monitoring required. METHODS RESULTS AND CONCLUSIONS: In this review, we highlight both the currently available and novel diagnostic and interventional circulating biomarkers under investigation for NASH, underscoring their accuracy and limitations relevant to our patient population and current clinical practice.

Prevalence and staging of non-alcoholic fatty liver disease among patients with heart failure with preserved ejection fraction.

Insulin resistance and altered energy metabolism is common in non-alcoholic fatty liver disease (NAFLD) and appears to also be associated with myocardial dysfunction. We aimed to evaluate prevalence, staging and clinical features correlated with NAFLD among patients with heart failure with preserved ejection fraction (HFpEF). Adults with HFpEF were prospectively enrolled. Demographic and clinical data were collected. NAFLD was defined based on liver biopsy, abdominal imaging or ICD-coding and the absence of other liver diseases. Descriptive, bivariate and multivariable analyses were performed. 181 patients were analyzed. The median age was 70 with 89% white, 59% female, median BMI 35.1, and 48% with diabetes. NAFLD was present in 27% of the full cohort and 50% of those with imaging. In patients with imaging, multivariable analysis identified diabetes (OR 3.38, 95% CI 1.29-8.88) and BMI (OR 1.11, 95% CI 1.04-1.19) as independent correlates of NAFLD. 54% of NAFLD patients had a NAFLD fibrosis score consistent with advanced fibrosis. Cirrhosis was present in 6.6% of patients overall and 11.5% with imaging. NAFLD patients had a higher frequency of advanced heart failure (75% vs 55%, p 0.01). NAFLD has a two-fold higher prevalence in HFpEF compared to the general population and is independently associated with BMI and diabetes. Patients with HFpEF and NAFLD also appeared to have more advanced fibrosis including cirrhosis suggesting a potential synergistic effect of cardiac dysfunction on fibrosis risk in NAFLD. This data supports consideration for evaluation of underlying liver disease in HFpEF patients.

Assessment of a Deep Learning Model to Predict Hepatocellular Carcinoma in Patients With Hepatitis C Cirrhosis.

Importance: Deep learning, a family of machine learning models that use artificial neural networks, has achieved great success at predicting outcomes in nonmedical domains. Objective: To examine whether deep learning recurrent neural network (RNN) models that use raw longitudinal data extracted directly from electronic health records outperform conventional regression models in predicting the risk of developing hepatocellular carcinoma (HCC). Design, Setting, and Participants: This prognostic study included 48 151 patients with hepatitis C virus (HCV)-related cirrhosis in the national Veterans Health Administration who had at least 3 years of follow-up after the diagnosis of cirrhosis. Patients were identified by having at least 1 positive HCV RNA test between January 1, 2000, to January 1, 2016, and were followed up from the diagnosis of cirrhosis to January 1, 2019, for the development of incident HCC. A total of 3 models predicting HCC during a 3-year period were developed and compared, as follows: (1) logistic regression (LR) with cross-sectional inputs (cross-sectional LR); (2) LR with longitudinal inputs (longitudinal LR); and (3) RNN with longitudinal inputs. Data analysis was conducted from April 2018 to August 2020. Exposures: Development of HCC. Main Outcomes and Measures: Area under the receiver operating characteristic curve, area under the precision-recall curve, and Brier score. Results: During a mean (SD) follow-up of 11.6 (5.0) years, 10 741 of 48 151 patients (22.3%) developed HCC (annual incidence, 3.1%), and a total of 52 983 samples (51 948 [98.0%] from men) were collected. Patients who developed HCC within 3 years were older than patients who did not (mean [SD] age, 58.2 [6.6] years vs 56.9 [6.9] years). RNN models had superior mean (SD) area under the receiver operating characteristic curve (0.759 [0.009]) and mean (SD) Brier score (0.136 [0.003]) than cross-sectional LR (0.689 [0.009] and 0.149 [0.003], respectively) and longitudinal LR (0.682 [0.007] and 0.150 [0.003], respectively) models. Using the RNN model, the samples with the mean (SD) highest 51% (1.5%) of HCC risk, in which 80% of all HCCs occurred, or the mean (SD) highest 66% (1.2%) of HCC risk, in which 90% of all HCCs occurred, could potentially be targeted. Among samples from patients who achieved sustained virologic response, the performance of the RNN models was even better (mean [SD] area under receiver operating characteristic curve, 0.806 [0.025]; mean [SD] Brier score, 0.117 [0.007]). Conclusions and Relevance: In this study, deep learning RNN models outperformed conventional LR models, suggesting that RNN models could be used to identify patients with HCV-related cirrhosis with a high risk of developing HCC for risk-based HCC outreach and surveillance strategies.