Outcomes, Mortality, and Cost Burden of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

BACKGROUND AND AIMS: Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data. METHODS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens. RESULTS: The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay. CONCLUSIONS: AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.

Nonalcoholic Fatty Liver Disease in Lean/Nonobese and Obese Individuals: A Comprehensive Review on Prevalence, Pathogenesis, Clinical Outcomes, and Treatment.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with an estimated prevalence of 25% globally. NAFLD is closely associated with metabolic syndrome, which are both becoming increasingly more common with increasing rates of insulin resistance, dyslipidemia, and hypertension. Although NAFLD is strongly associated with obesity, lean or nonobese NAFLD is a relatively new phenotype and occurs in patients without increased waist circumference and with or without visceral fat. Currently, there is limited literature comparing and illustrating the differences between lean/nonobese and obese NAFLD patients with regard to risk factors, pathophysiology, and clinical outcomes. In this review, we aim to define and further delineate different phenotypes of NAFLD and present a comprehensive review on the prevalence, incidence, risk factors, genetic predisposition, and pathophysiology. Furthermore, we discuss and compare the clinical outcomes, such as insulin resistance, dyslipidemia, hypertension, coronary artery disease, mortality, and progression to nonalcoholic steatohepatitis, among lean/nonobese and obese NAFLD patients. Finally, we summarize the most up to date current management of NAFLD, including lifestyle interventions, pharmacologic therapies, and surgical options.

Alterations of the fecal microbiota in relation to acute COVID-19 infection and recovery.

People with acute COVID-19 due to SARS-CoV-2 infection experience a range of symptoms, but major factors contributing to severe clinical outcomes remain to be understood. Emerging evidence suggests associations between the gut microbiome and the severity and progression of COVID-19. To better understand the host-microbiota interactions in acute COVID-19, we characterized the intestinal microbiome of patients with active SARS-CoV-2 infection in comparison to recovered patients and uninfected healthy controls. We performed 16S rRNA sequencing of stool samples collected between May 2020 and January 2021 from 20 COVID-19-positive patients, 20 COVID-19-recovered subjects and 20 healthy controls. COVID-19-positive patients had altered microbiome community characteristics compared to the recovered and control subjects, as assessed by both α- and ß-diversity differences. In COVID-19-positive patients, we observed depletion of Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae, as well as decreased relative abundances of the genera Faecalibacterium, Adlercreutzia, and the Eubacterium brachy group. The enrichment of Prevotellaceae with COVID-19 infection continued after viral clearance; antibiotic use induced further gut microbiota perturbations in COVID-19-positive patients. In conclusion, we present evidence that acute COVID-19 induces gut microbiota dysbiosis with depletion of particular populations of commensal bacteria, a phenomenon heightened by antibiotic exposure, but the general effects do not persist post-recovery.

Wilson's Disease: An Analysis of Health Care Use and Cost Burden of Commercially Insured Adults in the United States.

The economic and health care use burdens of Wilson's disease (WD) are unknown. In this study, we aimed to quantify this health care resource use and economic burden. We performed a retrospective case-control analysis of individuals in the Truven Health MarketScan Commercial Claims database (2007-2017). Using propensity scores, 424 WD cases were matched 1:1 to chronic liver disease (CLD) controls without WD. Total and service-specific parameters, expressed in monthly averages, were quantified for the 6-month pre-WD diagnosis versus the 12-month period after diagnosis. Wilcoxon signed-rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare health care burdens. Relative to the 6-month pre-WD diagnosis, the 12 months after diagnosis had more claims per patient (2.87 vs. 3.35; P < 0.0001) and increased per patient health care costs (US $2,089 vs. US $3,887; P < 0.0001). WD cases incurred US $1,908 more in total unadjusted costs compared to controls in the 12-month postindex date monthly averages. The increase in claims was primarily due to outpatient visits (1.62 vs. 1.82) and pharmaceutical claims (1.11 vs. 1.37). Cases also had higher health care costs for inpatient admissions (US $559 vs. US $1,264), outpatient visits (US $770 vs. US $1,037), and pharmaceutical claims (US $686 vs. US $1,489). Conclusion: WD is associated with significant health care cost and use burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.

The Spontaneous Regression of Primary Gastrointestinal Malignancies: An Observational Review.

The spontaneous regression or remission (SR) of cancer, often described as the partial or complete disappearance of a malignant tumor in the absence of all medical treatment and therapy, is a well-documented phenomenon. With efforts ongoing to establish cancer treatments that limit undesirable outcomes and adverse effects, these uncommon occurrences of SR carry significant implications for novel therapies and warrant further investigation. While several case studies have reported instances of SR in gastrointestinal (GI) malignancies, a comprehensive review of previous manifestations of SR in the GI tract remains lacking. The inclusion criteria for the rare phenomenon are also in need of an appropriate update that takes recent scientific advancements and emerging new medical technologies into account. Our analysis of 390 cases of SR in the GI tract focuses primarily on neoplasms of the hepatobiliary system and proposes an updated version of the older inclusion criteria for spontaneous regression.

Acute kidney injury and hepatorenal syndrome in cirrhosis.

Acute kidney injury (AKI) in cirrhosis, including hepatorenal syndrome (HRS), is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. AKI is separated into two categories, non-HRS AKI and HRS-AKI. The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease. The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation. The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients; novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models. The overall management of non-HRS AKI and HRS-AKI requires a systematic approach. Although pharmacological treatments have shown mortality benefit, the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation. Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment. This article reviews the current guidelines and recommendations of AKI in cirrhosis.

Training of computational algorithms to predict NAFLD activity score and fibrosis stage from liver histopathology slides.

BACKGROUND: The incidence of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), has been increasing for decades. Since the mainstay is lifestyle modification in this mainly asymptomatic condition, there is a need for accurate diagnostic methods. OBJECTIVES: This study proposes a method with a computer-aided diagnosis (CAD) system to predict NAFLD Activity score (NAS scores-steatosis, lobular inflammation, and ballooning) and fibrosis stage from histopathology slides. METHODS: A total of 87 pathology slides pairs (H&E and Trichrome-stained) were used for the study. Ground-truth NAS scores and fibrosis stages were previously identified by a pathologist. Each slide was split into 224 × 224 patches and fed into a feature extraction network to generate local features. These local features were processed and aggregated to obtain a global feature to predict the slide's scores. The effects of different training strategies, as well as training data with different staining and magnifications were explored. Four-fold cross validation was performed due to the small data size. Area Under the Receiver Operating Curve (AUROC) was utilized to evaluate the prediction performance of the machine-learning algorithm. RESULTS: Predictive accuracy for all subscores was high in comparison with pathologist assessment. There was no difference among the 3 magnifications (5x, 10x, 20x) for NAS-steatosis and fibrosis stage tasks. A larger magnification (20x) achieved better performance for NAS-lobular scores. Middle-level magnification was best for NAS-ballooning task. Trichrome slides are better for fibrosis stage prediction and NAS-ballooning score prediction task. NAS-steatosis prediction had the best performance (AUC 90.48%) in the model. A good performance was observed with fibrosis stage prediction (AUC 83.85%) as well as NAS-ballooning prediction (AUC 81.06%). CONCLUSIONS: These results were robust. The method proposed proved to be effective in predicting NAFLD Activity score and fibrosis stage from histopathology slides. The algorithms are an aid in having an accurate and systematic diagnosis in a condition that affects hundreds of millions of patients globally.

Bariatric Surgery Reduces Cancer Risk in Adults With Nonalcoholic Fatty Liver Disease and Severe Obesity.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and increased risk of cancer. The impacts of bariatric surgery on cancer risk in NAFLD patients are unknown. We investigated the effect of bariatric surgery on cancer risk in patients with NAFLD and severe obesity using the MarketScan database. METHODS: We conducted a retrospective cohort study of 18 to 64 years old newly diagnosed NAFLD patients with severe obesity between 2007 and 2017. We used Cox proportional hazard models to examine the association between bariatric surgery, modeled as a time-varying covariate, and the risks of any cancer and obesity-related cancer, while accounting for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 98,090 patients were included in the study, 33,435 (34.1%) received bariatric surgery. In those without surgery, 1898 incident cases of cancer occurred over 115,890.11 person-years of follow-up, compared with 925 cancer cases over 67,389.82 person-years among surgery patients (crude rate ratio, 0.84; 95% CI, 0.77- 0.91). The IPTW-adjusted risk of any cancer and obesity-related cancer was reduced by 18% (hazard ratio, 0.82; 95% CI, 0.76-0.89) and 25% (hazard ratio, 0.65; 95% CI, 0.56-0.75), respectively, in patients with versus without bariatric surgery. The adjusted risks of any cancer and obesity-related cancer were significantly lower in cirrhotic versus non-cirrhotic patients who underwent surgery. In cancer-specific models, bariatric surgery was associated with significant risk reductions for colorectal, pancreatic, endometrial, thyroid cancers, hepatocellular carcinoma, and multiple myeloma. CONCLUSION: Bariatric surgery was associated with significant reductions in the risks of any cancer and obesity-related cancer in NAFLD patients with severe obesity.

Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS).

PURPOSE: Treatment with antiseizure medications (ASMs) confers a risk of drug-induced liver injury (DILI), especially for older ASMs. We sought to quantify recent reports of DILI attributed to both older and newer generation ASMs and survey newly marketed ASMs for hepatotoxicity in a large post-marketing database. METHODS: We queried over 2.6 million adverse event reports made to the FDA Adverse Event Reporting System (FAERS) database between July 1, 2018 and March 31, 2020 for DILI due to ASMs commonly used in clinical practice. Patient characteristics and outcomes were assessed. We calculated the reporting odds ratio (ROR) of DILI for each individual ASM versus all non-ASM reports. RESULTS: A total of 2175 DILI cases were attributed to an ASM during the study period. 97.2% of these were designated as serious reactions, which include death, hospitalization, disability, and other life-threatening outcomes. A number of older and newer generation ASMs were associated with DILI, specifically: carbamazepine (ROR 2.92), phenobarbital (ROR 2.91), oxcarbazepine (ROR 2.58), phenytoin (ROR 2.40), valproate (ROR 2.22), lamotrigine (ROR 2.06), clobazam (ROR 1.67), levetiracetam (ROR 1.56), and diazepam (ROR 1.53). However, increased odds of DILI were not seen with zonisamide, perampanel, stiripentol, lacosamide, clonazepam, pregabalin, felbamate, eslicarbazepine, cannabidiol, topiramate, gabapentin, ethosuximide, brivaracetam, or primidone. Vigabatrin, tiagabine, and rufinamide all had zero reports of DILI. CONCLUSIONS: The majority of newer generation ASMs were not significantly associated with DILI. Future studies utilizing FAERS in conjunction with other data sources will be critical for the ongoing surveillance of DILI, particularly as newly marketed ASMs continue to enter into widespread clinical use.

Healthcare Utilization and Cost Burden of Porphyria in Commercially Insured Adults in the United States.

OBJECTIVES: The healthcare burden associated with porphyria remains unevaluated despite the associated increased risks of morbidity and mortality. We aimed to assess the healthcare utilization and cost burdens of porphyria in the United States (US) using real-world claims data. METHODS: We performed a case-control analysis of adults in the Truven Health MarketScan® Commercial Claims database (2010-2015). Using propensity scores, 2788 porphyria cases were matched 1:1 to porphyria-free controls with chronic liver disease. Total and service-specific parameters were quantified for the 12 months before porphyria diagnosis versus the 12 months after diagnosis and over the 12 months following a randomly selected date for controls. Wilcoxon signed rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare healthcare burdens for cases versus controls. RESULTS: Relative to the 12 months before porphyria diagnosis, the following 12 months had more claims per patient (35.94 vs 39.67; p < 0.0001) and increased per-patient healthcare costs (US$21,308 vs US$27,270; p < 0.0001). Porphyria cases incurred US$7839 more in total unadjusted costs compared with controls in the 12 months after index date. Compared with controls, cases also had more claims (39.67 vs 34.81), primarily due to inpatient admissions (1.80 vs 0.78) and outpatient visits (21.41 vs 17.98). Cases also had higher healthcare costs for inpatient admissions (US$8882 vs US$4674) and outpatient visits (US$12,378 vs US$9801). CONCLUSION: Porphyria is associated with significant healthcare costs and utilization burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.

Health Care Resource Use and Cost Burden of Chronic Kidney Disease in Patients With Chronic Liver Disease: A Real-World Claims Analysis.

Chronic Liver Disease (CLD) is associated with an increased risk of chronic kidney disease (CKD). However, the health care burden of CKD in the CLD spectrum is unknown. We aimed to evaluate the health care use and cost burdens associated with CKD in patients with CLD in the United States by using real-world claims data. We analyzed data from the Truven Health MarketScan Commercial Claims database from 2010 to 2015. A total of 19,664 patients with CLD with or without comorbid CKD were identified using International Classification of Diseases, Ninth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific unadjusted and adjusted health care parameters were analyzed for the 12 months following an index date selected at random to capture whole disease burdens. In CLD, comorbid CKD was associated with a higher annual number of claims per person (CKD vs. no CKD, 69 vs. 55) and higher total annual median health care costs (CKD vs. no CKD, $21,397 vs. $16,995). A subanalysis stratified by CKD category showed that health care use and cost burden in CLD increased with disease stage, with a peak 12-month median cost difference of $77,859 in patients on dialysis. The adjusted per person annual health care cost was higher for CKD cases compared to controls ($35,793 vs. $24,048, respectively; P < 0.0001). Stratified by the type of CLD, the highest between-group adjusted cost differences were for cirrhosis, viral hepatitis, hemochromatosis, and nonalcoholic fatty liver disease. Conclusion: CKD is a cost multiplier in CLD. The CKD health care burden in liver disease differs by the type of CLD. Improved CKD screening and proactive treatment interventions for at-risk patients can limit the excess burden associated with CKD in patients with CLD.

In-Hospital Mortality and Prediction in an Urban U.S. Population With COVID-19.

Coronavirus disease 2019 (COVID-19) has touched every aspect of society, and as the pandemic continues around the globe, many of the clinical factors that influence the disease course remain unclear. A useful clinical decision-making tool is a risk stratification model to determine in-hospital mortality as defined in this study. The study was performed at Robert Wood Johnson University Hospital (RWJUH) in New Brunswick, New Jersey, USA. Data was extracted from our electronic medical records on 44 variables that included demographic, clinical, laboratory tests, treatments, and mortality information. We used the least absolute shrinkage and selection operator regression with corrected Akaike's information criterion to identify a subset of variables that yielded the smallest estimated prediction error for the risk of in-hospital mortality. During the study period, 808 COVID-19 patients were admitted to RWJUH. The sample size was limited to patients with at least one confirmed in-house positive nasopharyngeal swab COVID-19 test. Pregnant patients or those who were transferred to our facility were excluded. Patients who were in observation and were discharged from the emergency room were also excluded. A total of 403 patients had complete values for all variables and were eligible for the study. We identified significant clinical, laboratory, and radiologic variables determining severe outcomes and mortality. An in-hospital mortality risk calculator was created after the identification of significant factors for the specific cohort, which were abnormal CT scan or chest X-ray, chronic kidney disease, age, white blood cell count, platelet count, alanine aminotransferase, and aspartate transaminase with a sensitivity, specificity, and negative predictive value of 82%, 72%, and 93%, respectively. While numerous reports from around the globe have helped outline the pandemic, demographic factors vary widely. This study is more applicable to an urban, highly diverse population in the United States.

Economic and Health Care Burdens of Hepatitis Delta: A Study of Commercially Insured Adults in the United States.

BACKGROUND AND AIMS: The paucity of data regarding the extent of hepatitis delta virus (HDV) associated health care burden in the United States is an important obstacle to assessing the cost-effectiveness of potential intervention strategies. In this study, we characterized the health care use and cost burdens of HDV in the United States using real-world claims data. APPROACH AND RESULTS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2011-2014. A total of 2,727 HDV cases were matched 1:1 by sociodemographic characteristics and comorbidities to chronic hepatitis B virus (HBV) controls using propensity scores. The HDV group had significantly higher prevalence of substance abuse, sexually transmitted diseases, decompensated cirrhosis, cirrhosis, and hepatitis C virus compared to patients with chronic HBV. First HDV diagnosis was associated with significant increases in the total number of health care claims (25.61 vs. 28.99; P < 0.0001) and total annual health care costs ($19,476 vs. $23,605; P < 0.0001) compared with pre-HDV baseline. The case-control analysis similarly indicated higher total claims (28.99 vs. 25.19; P < 0.0001) and health care costs ($23,605 vs. $18,228; P < 0.0001) in HDV compared with HBV alone. Compared with HBV controls, HDV cases had an adjusted incident rate ratio of 1.16 (95% confidence interval: 1.10, 1.22) times the total number of annual claims and an adjusted incident rate ratio 1.32 (95% confidence interval 1.17, 1.48) times the total annual health care cost. CONCLUSIONS: HDV is associated with higher health care use and cost burden than HBV alone, underscoring the need for improved screening and treatment.

Hepatic Silicone Granulomas Secondary to Ruptured Breast Implants: A Report of Two Cases.

The differential diagnosis of hepatic granulomas is vast and includes infections, drugs, immunologic diseases, foreign material exposure, and neoplasia. Silicone, whether directly injected into tissues or used as a filler in breast implants, is known to cause localized granulomatous reactions. It can also migrate to other anatomic locations resulting in granulomatous inflammation at a distance. We report two cases of unsuspected hepatic silicone granulomas in patients undergoing liver biopsy for isolated elevated alkaline phosphatase levels, both with a history of ruptured breast implants. These cases highlight the need for awareness of hepatic silicone granulomas as an etiology of elevated liver enzymes in patients with a history of surgical interventions utilizing silica, such as cosmetic surgery.

Health Care Utilization and Economic Burdens of Hemochromatosis in the United States: A Population-Based Claims Study.

BACKGROUND: Little is known about the health care burden of hemochromatosis in the United States, despite its increased morbidity and mortality due to associated advanced liver diseases. OBJECTIVE: To evaluate the health care utilization and economic burdens of hemochromatosis in the United States using real-world claims data. METHODS: We performed a case-control analysis of adult participants in the Truven Health MarketScan Commercial Claims database from 2010 to 2015. 37,092 hemochromatosis cases were matched 1:1 by demographics and comorbidities to hemochromatosis-free controls with chronic liver disease using propensity scores. Total and service-specific health care parameters were quantified for the 12 months following versus the 12 months before the first date of hemochromatosis diagnosis and over the 12 months following a randomly selected date for controls. Incremental differences in health care burdens between cases and controls were examined using Wilcoxon signed rank tests and McNemar tests for continuous and dichotomous measures, respectively. Adjusted multivariable regression analyses using generalized linear models were used to compare the health care burdens for cases with controls. RESULTS: In comparison with the year before, the 12 months following first hemochromatosis diagnoses had a higher total number of claims per patient (34.37 vs. 29.99; P < 0.0001) and an increase in the per-patient total health care costs ($20,023 vs. $16,905; P < 0.0001). After hemochromatosis diagnosis, health care costs were 2%, 8%, 23%, and 43% higher for inpatient admissions, emergency department visits, outpatient visits, and pharmaceutical prescriptions, compared respectively with the 12 months before diagnosis. In the 12 months following the index date, hemochromatosis cases incurred $2,732 more in total unadjusted costs compared with controls. Compared with controls, cases had adjusted incident rate ratio (IRR) 1.26 (95% CI = 1.30-1.77) times the total number of claims (IRR = 1.40, 95% CI = 1.38-1.43) more outpatient visits and IRR = 1.10 (95% CI = 1.08-1.11) excess pharmaceutical claims. Compared with controls, cases had significantly higher adjusted mean health care costs for inpatient services ($6,484 vs. $7,854), outpatient services ($7,032 vs. $11,005), and pharmaceutical claims ($2,520 vs. $2,822; all P values < 0.05). The annual health care costs among type 2 diabetes, hypertension, arthritis, and chronic kidney disease (CKD) patients with hemochromatosis were $6,968, $7,424, $2,967, and $43,847, respectively, higher than type 2 diabetes, hypertension, arthritis, and CKD patients without hemochromatosis (P < 0.0001). CONCLUSIONS: Hemochromatosis in the United States is associated with significant health care utilization and economic burdens driven by outpatient visits, pharmaceutical claims, and a high number of comorbidities DISCLOSURES: No outside funding supported this study. The authors have no relevant financial or other relationships to disclose. An abstract containing some of the results from this study was accepted for the American Association for the Study of Liver Diseases Meeting; November 9-13, 2018; San Francisco, CA.