Increasing prevalence of cirrhosis among insured adults in the United States, 2012-2018.

BACKGROUND: Liver cirrhosis is a chronic disease that is known as a "silent killer" and its true prevalence is difficult to describe. It is imperative to accurately characterize the prevalence of cirrhosis because of its increasing healthcare burden. METHODS: In this retrospective cohort study, trends in cirrhosis prevalence were evaluated using administrative data from one of the largest national health insurance providers in the US. (2011-2018). Enrolled adult (≥18-years-old) patients with cirrhosis defined by ICD-9 and ICD-10 were included in the study. The primary outcome measured in the study was the prevalence of cirrhosis 2011-2018. RESULTS: Among the 371,482 patients with cirrhosis, the mean age was 62.2 (±13.7) years; 53.3% had commercial insurance and 46.4% had Medicare Advantage. The most frequent cirrhosis etiologies were alcohol-related (26.0%), NASH (20.9%) and HCV (20.0%). Mean time of follow-up was 725 (±732.3) days. The observed cirrhosis prevalence was 0.71% in 2018, a 2-fold increase from 2012 (0.34%). The highest prevalence observed was among patients with Medicare Advantage insurance (1.67%) in 2018. Prevalence increased in each US. state, with Southern states having the most rapid rise (2.3-fold). The most significant increases were observed in patients with NASH (3.9-fold) and alcohol-related (2-fold) cirrhosis. CONCLUSION: Between 2012-2018, the prevalence of liver cirrhosis doubled among insured patients. Alcohol-related and NASH cirrhosis were the most significant contributors to this increase. Patients living in the South, and those insured by Medicare Advantage also have disproportionately higher prevalence of cirrhosis. Public health interventions are important to mitigate this concerning trajectory of strain to the health system.

MELD 3.0 in Advanced Chronic Liver Disease.

The MELD (model for end-stage liver disease) 3.0 score was developed to replace the MELD-Na score that is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the United States. The MELD 3.0 calculator includes new inputs from patient sex and serum albumin levels and has new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is expected that use of MELD 3.0 scores will reduce overall waitlist mortality modestly and improve access for female liver transplant candidates. The utility of MELD 3.0 and PELDcre (pediatric end-stage liver disease, creatinine) scores for risk stratification in cirrhotic patients undergoing major abdominal surgery, placement of a transjugular intrahepatic portosystemic shunt, and other interventions requires further study. This article reviews the background of the MELD score and the rationale to create MELD 3.0 as well as potential implications of using this newer risk stratification tool in clinical practice.

The Diagnosis and Non-pharmacological Management of Acute Kidney Injury in Patients with Cirrhosis.

Acute kidney injury in patients with cirrhosis is quite common, and is seen in up to 50% of patients hospitalized for decompensated cirrhosis. Causes of acute kidney injury include prerenal, renal, or postrenal etiologies. The diagnosis and early institution of nonpharmacologic and pharmacologic management are key to the recovery of renal function. The objective of this review is to provide a practical approach to the use of diagnostic biomarkers and highlight the nonpharmacologic management and prevention of acute kidney injury.

Using Artificial Intelligence to Predict Cirrhosis From Computed Tomography Scans.

INTRODUCTION: Undiagnosed cirrhosis remains a significant problem. In this study, we developed and tested an automated liver segmentation tool to predict the presence of cirrhosis in a population of patients with paired liver biopsy and computed tomography (CT) scans. METHODS: We used a cohort of 1,590 CT scans within the Morphomics database to train an automated liver segmentation model using 3D-U-Net and Google's DeeplLabv3+. Imaging features were then automatically calculated from an external test cohort of patients with chronic liver disease who had a paired liver biopsy and CT within 6 months of each other in January 2004-2012. Using gradient boosting decision trees, we developed multivariate models to predict the presence of histologic cirrhosis and evaluated with 5-fold cross-validated c-statistic. RESULTS: Our cohort had 351 patients; 96 patients had cirrhosis. Of the total cohort, 72 were postliver transplant. Both fibrosis (FIB)-4 and liver morphomics alone performed equally well with area under the receiving operating characteristics of 0.76 (95% confidence interval 0.70-0.81) and 0.71 (95% confidence interval 0.65-0.76), respectively ( P = 0.2). However, the combination of liver morphomics with laboratory values or liver morphomics with laboratory and demographic data resulted in significant improved performance with area under the receiving operating characteristics of 0.84 (0.80-0.89) and 0.85 (0.81-0.90), respectively, compared with FIB-4 alone ( P < 0.001). In a subgroup analysis, we also examined performance in patients without liver transplantation and saw similar augmentation of FIB-4. DISCUSSION: This proof-of-principle study demonstrates that automatically extracted features within CT scans can be combined with classic electronic medical record data to improve the prediction of cirrhosis in patients with liver disease. This tool may be used in both pretransplant and posttransplant patients and has the potential to improve our ability to detect undiagnosed cirrhosis.

Portal Venous Remodeling Determines the Pattern of Cirrhosis Decompensation: A Systems Analysis.

INTRODUCTION: As liver disease progresses, scarring results in worsening hemodynamics ultimately culminating in portal hypertension. This process has classically been quantified through the portosystemic pressure gradient (PSG), which is clinically estimated by hepatic venous pressure gradient (HVPG); however, PSG alone does not predict a given patient's clinical trajectory regarding the Baveno stage of cirrhosis. We hypothesize that a patient's PSG sensitivity to venous remodeling could explain disparate disease trajectories. METHODS: We created a computational model of the portal system in the context of worsening liver disease informed by physiologic measurements from the field of portal hypertension. We simulated progression of clinical complications, HVPG, and transjugular intrahepatic portosystemic shunt placement while only varying a patient's likelihood of portal venous remodeling. RESULTS: Our results unify hemodynamics, venous remodeling, and the clinical progression of liver disease into a mathematically consistent model of portal hypertension. We find that by varying how sensitive patients are to create venous collaterals with rising PSG we can explain variation in patterns of decompensation for patients with liver disease. Specifically, we find that patients who have higher proportions of portosystemic shunting earlier in disease have an attenuated rise in HVPG, delayed onset of ascites, and less hemodynamic shifting after transjugular intrahepatic portosystemic shunt placement. DISCUSSION: This article builds a computational model of portal hypertension which supports that patient-level differences in venous remodeling may explain disparate clinical trajectories of disease.

Identifying and Screening At-Risk Patients for Hepatitis Delta Virus: A Case Report.

Hepatitis Delta Virus (HDV) is associated with one of the most severe forms of viral hepatitis, with rapid progression to cirrhosis and hepatocellular carcinoma. While HDV was thought to be uncommon in the United States, recent data shows that its prevalence may be significantly higher than formerly acknowledged. Early identification of HDV is critical since approved therapeutic options are only available for compensated patients. All patients with a reactive hepatitis B virus surface antigen should undergo HDV screening, especially those with additional risk factors, including migration from an endemic area, immunosuppressed patients, hemodialysis patients, gay and bisexual men, persons who inject drugs, and persons employed in healthcare or public safety professions.

Personality Traits in Patients With Cirrhosis Are Different From Those of the General Population and Impact Likelihood of Liver Transplantation.

BACKGROUND: Personality traits influence clinical outcomes in chronic diseases, but their impact in cirrhosis is unknown. We studied the personality of patients with cirrhosis undergoing liver transplant (LT) evaluation and determined their correlation to clinical outcomes. METHODS: A multicenter' prospective study of adult patients undergoing LT evaluation was performed from January 2018 to October 2019. The "Big Five" personality traits of conscientiousness, extraversion, openness, neuroticism, and agreeableness plus agency were assessed with the Midlife Development Inventory Personality Scale and compared with the general population. Frailty was assessed with the Liver Frailty Index. RESULTS: Two hundred sixty-three LT candidates were enrolled. Twenty-four percent had hepatitis C virus, 25% nonalcoholic steatohepatitis, and 25% ethyl alcohol (mean model for end-stage liver disease = 15.7). Compared with the general population, LT candidates had higher openness (3.1 versus 2.9; P < 0.001), extraversion (3.2 versus 3.1; P < 0.001), agreeableness (3.5 versus 3.4; P = 0.04), agency (2.9 versus 2.6; P < 0.001), neuroticism (2.2 versus 2.1; P = 0.001), and lower conscientiousness (3.3 versus 3.4; P = 0.007). Patients with higher conscientiousness were more likely to receive an LT (HR = 2.76; P = 0.003). CONCLUSIONS: Personality traits in LT candidates differ significantly from the general population, with higher conscientiousness associated with a higher likelihood of receiving a transplant.

Factors Underlying Racial Disparity in Utilization of Hepatitis C-Viremic Kidneys in the United States.

Utilization of hepatitis C (HCV) viremic kidneys is increasing in the United States. We examined racial disparity in this utilization using UNOS/OPTN data (2014-2020) and mixed effects models adjusting for donor/recipient/center factors. Included in the study were 58,786 adults receiving a deceased donor kidney transplant from 191 centers. Two thousand six hundred thirteen (4%) received kidneys from HCV-viremic donors. Of these, 1598 (61%) were HCV seronegative and 1015 (49%) were HCV seropositive. Among seronegative recipients, before adjusting for waiting time and education, Blacks (OR 0.69, 95%CI (0.60, 0.80)), Hispanics (OR 0.63, 95%CI (0.51, 0.79)), and Asians (OR 0.69, 95%CI (0.53, 0.90)) were less likely than Whites to receive HCV-viremic kidneys. In final models, effect of race was attenuated. Notably, shorter waiting time (OR 0.65, 95%CI (0.63, 0.67)) and increasing educational level (grade school less likely compared to high school OR 0.67, 95% CI (0.49, 0.92) and college more likely than high school (OR 1.16 95% CI (1.02, 1.31)) were associated with receipt of HCV-viremic kidneys. Among HCV-seropositive recipients, recipient race was not independently associated with receipt of HCV-viremic kidneys; however, centers with larger populations of Black waitlisted patients were more likely to utilize HCV-viremic kidneys (OR 1.71, 95%CI (1.20, 2.45)) compared to other centers. Our results suggest recipient race does not independently determine who receives HCV-viremic kidneys; however, other underlying factors including waiting time, education (among seronegative), and center racial mix (among seropositive) contribute to the current differential distribution of HCV-viremic kidneys among races.

The answer at our fingertips: Volume status in cirrhosis determined by machine learning and pulse oximeter waveform.

OBJECTIVE: The objective of our study was to determine if the waveform from a simple pulse oximeter-like device could be used to accurately assess intravascular volume status in cirrhosis. METHODS: Patients with cirrhosis underwent waveform recording as well as serum brain natriuretic peptide (BNP) on the day of their cardiac catheterization where invasive cardiac pressures were measured. Waveforms were processed to generate features for machine learning models in order to predict the filling pressures (regression) or to classify the patients as volume overloaded or not (defined as an LVEDP>15). RESULTS: Nine of 26 patients (35%) had intravascular volume overload. Regression analysis using PPG features (R2  = 0.66) was superior to BNP (R2  = 0.22). Linear discriminant analysis correctly classified patients with an accuracy of 78%, sensitivity of 60%, positive predictive value of 90%, and an AUROC of 0.87. CONCLUSIONS: Machine learning-enhanced analysis of pulse ox waveforms can estimate intravascular volume overload with a higher accuracy than conventionally measured BNP.

Predicting mortality among patients with liver cirrhosis in electronic health records with machine learning.

OBJECTIVE: Liver cirrhosis is a leading cause of death and effects millions of people in the United States. Early mortality prediction among patients with cirrhosis might give healthcare providers more opportunity to effectively treat the condition. We hypothesized that laboratory test results and other related diagnoses would be associated with mortality in this population. Our another assumption was that a deep learning model could outperform the current Model for End Stage Liver disease (MELD) score in predicting mortality. MATERIALS AND METHODS: We utilized electronic health record data from 34,575 patients with a diagnosis of cirrhosis from a large medical center to study associations with mortality. Three time-windows of mortality (365 days, 180 days and 90 days) and two cases with different number of variables (all 41 available variables and 4 variables in MELD-NA) were studied. Missing values were imputed using multiple imputation for continuous variables and mode for categorical variables. Deep learning and machine learning algorithms, i.e., deep neural networks (DNN), random forest (RF) and logistic regression (LR) were employed to study the associations between baseline features such as laboratory measurements and diagnoses for each time window by 5-fold cross validation method. Metrics such as area under the receiver operating curve (AUC), overall accuracy, sensitivity, and specificity were used to evaluate models. RESULTS: Performance of models comprising all variables outperformed those with 4 MELD-NA variables for all prediction cases and the DNN model outperformed the LR and RF models. For example, the DNN model achieved an AUC of 0.88, 0.86, and 0.85 for 90, 180, and 365-day mortality respectively as compared to the MELD score, which resulted in corresponding AUCs of 0.81, 0.79, and 0.76 for the same instances. The DNN and LR models had a significantly better f1 score compared to MELD at all time points examined. CONCLUSION: Other variables such as alkaline phosphatase, alanine aminotransferase, and hemoglobin were also top informative features besides the 4 MELD-Na variables. Machine learning and deep learning models outperformed the current standard of risk prediction among patients with cirrhosis. Advanced informatics techniques showed promise for risk prediction in patients with cirrhosis.

Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study.

BACKGROUND AND AIMS: Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/or transplant. APPROACH AND RESULTS: We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P < 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver-related death (subdistribution HR, 1.26; 95% CI, [1.15-1.38]; P < 0.001). CONCLUSIONS: Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology.

Outcomes After TIPS for Ascites and Variceal Bleeding in a Contemporary Era-An ALTA Group Study.

INTRODUCTION: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications. METHODS: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT). RESULTS: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13). DISCUSSION: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.

Amalgamation of cloud-based colonoscopy videos with patient-level metadata to facilitate large-scale machine learning.

Background and study aims Storage of full-length endoscopic procedures is becoming increasingly popular. To facilitate large-scale machine learning (ML) focused on clinical outcomes, these videos must be merged with the patient-level data in the electronic health record (EHR). Our aim was to present a method of accurately linking patient-level EHR data with cloud stored colonoscopy videos. Methods This study was conducted at a single academic medical center. Most procedure videos are automatically uploaded to the cloud server but are identified only by procedure time and procedure room. We developed and then tested an algorithm to match recorded videos with corresponding exams in the EHR based upon procedure time and room and subsequently extract frames of interest. Results Among 28,611 total colonoscopies performed over the study period, 21,170 colonoscopy videos in 20,420 unique patients (54.2 % male, median age 58) were matched to EHR data. Of 100 randomly sampled videos, appropriate matching was manually confirmed in all. In total, these videos represented 489,721 minutes of colonoscopy performed by 50 endoscopists (median 214 colonoscopies per endoscopist). The most common procedure indications were polyp screening (47.3 %), surveillance (28.9 %) and inflammatory bowel disease (9.4 %). From these videos, we extracted procedure highlights (identified by image capture; mean 8.5 per colonoscopy) and surrounding frames. Conclusions We report the successful merging of a large database of endoscopy videos stored with limited identifiers to rich patient-level data in a highly accurate manner. This technique facilitates the development of ML algorithms based upon relevant patient outcomes.

Health Literacy Gaps in Online Resources for Cirrhotic Patients.

BACKGROUND: The average readability level in the USA is a sixth grade level and for patients with chronic disease it is lower. Cirrhosis is a prevalent chronic disease that requires complex knowledge and instructions to manage. No research has been done about the understandability of online educational content for cirrhotic patients. Patients can find online materials curated by both general health platforms and high-volume liver transplant centers, and thus these materials were analyzed. METHODS: After determining exclusion criteria, the websites of the top 20 general health platform results and the websites of the top 20 high-volume hepatology centers were analyzed. Readability was assessed using the Patient Education Materials Assessment Tool (Audiovisual Materials) (PEMAT-A/V), Flesch-Kincaid Grade Level tests, word counts, sentence counts, words per sentence, and time for an average sixth grader to read. RESULTS: The mean grade level readabilities were 12.3 and 11.3 for the general resources and the transplant center resources, respectively. The online resources ranged from 9 to 389 sentences requiring an average of 9.8 min to read. The mean PEMAT-A/V scores were 70.05% for the general resources and 72.45% for the transplant center resources. There was a statistically significant difference in the Flesch-Kincaid grade level, sentence number, words per sentence, word count, and time for an average sixth grader to read the general resources and transplant center resources (P < 0.05). CONCLUSIONS: The online resources both from health platforms and hepatology centers available to patients with cirrhosis are too long and complex and underscore the need for simpler and shorter resources.

Neuropraxia: An Underappreciated Morbidity of Liver Transplantation.

BACKGROUND: Peripheral nerve injuries can be devastating complications of surgery, potentially resulting in severe functional disability and decreased quality of life. Long surgeries with considerable tissue manipulation, for example, liver transplantation, may present increased risk; however, neuropraxia in transplantation has not been well investigated. MATERIALS AND METHODS: This is a retrospective study of all adult patients undergoing liver transplantation at a large academic center between January 2013 and December 2015. Descriptive analyses, logistic regressions, and forward selection procedures were used to determine the odds of developing neuropraxia and associated factors. RESULTS: Of the 283 liver recipients, the mean age was 55.8 y, 35.1% were female, 65.6% were Caucasian, 8.9% were African American, 16.7% were Hispanic, and mean model for end-stage liver disease sodium score at transplant was 24.2 ± 10.9. The underlying etiology was alcohol (26.2%), hepatitis C (34.8%), nonalcoholic steatohepatitis (13.1%), and other (14.2%). The incidence of neuropraxia after liver transplantation was 8.3% (n = 25), with 60% (n = 16) upper extremities, 82% left sided, and 84% male. There was no difference in age, race, body mass index, hypertension, diabetes, hyperlipidemia, or smoking in those with neuropraxia versus those without. In multivariate analysis, neuropraxia was significantly associated with male gender, lower model for end-stage liver disease score, and longer duration of surgery (P < 0.05). Symptoms lasted median 5 d, with a wide range up to 187 d. Neuropraxia-specific treatment (physical therapy or medications) was required in 32% (n = 9). CONCLUSIONS: Peripheral nerve injuries are an unexplored complication of liver transplantation. Although transient, a high number (8.2%) of patients developed neuropraxia, negatively affecting their ability for recovery. Exploration of mechanisms for minimizing risk and intraoperative detection and prevention should be considered to mitigate this complication.

Liver-related mortality is similar among men and women with cirrhosis.

BACKGROUND & AIMS: Sex-based differences are known to significantly contribute to outcomes in patients with chronic liver diseases; however, the role of patient sex in cirrhosis is unclear. We aimed to study the relationship between patient sex and cirrhosis. METHODS: We analyzed a cohort of 20,045 patients with cirrhosis using a Chicago-wide electronic health record database that was linked with the United Network for Organ Sharing and cause of death data from the state death registry. Adjusted Cox survival analyses and competing risk analyses were performed to obtain subdistribution hazard ratios (HRs) for liver-related cause of death. RESULTS: Female and male patients had similar age, racial distribution, insurance status, and comorbidity status by Elixhauser score. Females had higher rates of cholestatic liver disease (17.1% vs. 6.2%, p <0.001) and non-alcoholic steatohepatitis (29.8% vs. 21.2%, p <0.001) than males. They were less likely to have portal hypertensive complications and had lower peak MELD-Na scores during follow-up. Female sex was associated with a decreased hazard of all-cause mortality (adjusted HR 0.85; 95% CI 0.80-0.90). This effect was attenuated when liver-related mortality was examined (subdistribution HR 0.93; 95% CI 0.87-1.00). No significant difference was noted for women who were 'ever-listed' in competing risk analyses for either all-cause mortality (subdistribution HR 1.09; 95% CI 0.88-1.35) or liver-related death (subdistribution HR 1.12; 95% CI 0.87-1.43), despite lower rates of listing (7.5% vs. 9.8%; p <0.001) and transplant (3.5% vs. 5.2%; p <0.001). CONCLUSIONS: In this longitudinal study of patients with cirrhosis, female sex was associated with a survival advantage likely driven by lower rates of non-liver-related death. Women were not at an increased risk of liver-related death despite lower rates of listing and transplantation. LAY SUMMARY: Patient sex is an important contributor in many chronic diseases, including cirrhosis. Prior studies have suggested that female sex is associated with worse outcomes. We analyzed a cohort of 20,045 patients with cirrhosis using a Chicago-wide electronic health record database. Using multivariate competing risk analyses, we found that female sex in cirrhosis is actually associated with a lower risk of all-cause mortality and has no association with liver-related mortality. Our findings are novel because we show that women with cirrhosis have a similar risk of liver-related death as their male counterparts, despite lower rates of listing and transplantation.

A Comprehensive Review of Outcome Predictors in Low MELD Patients.

Risk scoring for patients with cirrhosis has evolved greatly over the past several decades. However, patients with low Model for End-Stage Liver Disease-Sodium scores still suffer from liver-related morbidity and mortality. Unfortunately, it is not clear which of these low Model for End-Stage Liver Disease-Sodium score patients would benefit from earlier consideration of liver transplantation. This article reviews the literature of risk prediction in patients with cirrhosis, identifies which patients may benefit from earlier interventions, such as transplantation, and proposes directions for future research.