Liver-related Hospitalizations Research Articles

Association of circulating Z-polymer with adverse clinical outcomes and liver fibrosis in adults with alpha-1 antitrypsin deficiency.

Circulating polymerized mutant Z-alpha-1 antitrypsin (Z-polymer) constitutes a characteristic feature in alpha-1 antitrypsin deficiency (AATD), but there is limited knowledge about its association with adverse clinical outcomes and liver fibrosis. We explored this association using data from a large cohort of adults with AATD. A total of 836 (431 PiZZ, 405 PiMZ) adults with AATD and 312 controls (PiMM) from the European Alpha-1 Liver Cohort (2015-2020) were included. Time-to-event analyses were conducted for adults with the PiZZ genotype followed for adverse clinical outcomes (earliest occurrence of liver-related hospitalization, liver transplant or all-cause mortality). Cox proportional hazard models were used to describe the association between binary circulating Z-polymer levels and adverse clinical outcomes. Correlations between baseline circulating Z-polymer levels and baseline liver fibrosis (liver stiffness measurement [LSM] determined by transient elastography [FibroScan®]) were evaluated. The analyses were stratified by augmentation therapy status. Of 324 adults with the PiZZ genotype and longitudinal follow-up data, 28 reported adverse clinical outcomes. Higher baseline circulating Z-polymer levels were associated with an increased risk of adverse clinical outcomes in both crude (hazard ratio [95% confidence interval, CI], 2.88 [1.21, 6.87]) and age-adjusted (1.96 [0.78, 4.94]) analyses. In adults with the PiZZ genotype, circulating Z-polymer levels were weakly positively correlated with baseline LSM (Spearman's rho [95% CI]: 0.21 [0.11, 0.31]). Similar results were observed after stratification by augmentation therapy status. In adults with the PiZZ genotype, higher circulating Z-polymer levels were associated with a shorter time to adverse clinical outcome, and positively correlated with baseline LSM. Circulating Z-polymer levels may be a prognostic biomarker of clinically relevant disease in AATD.

The clinical and economic burdens of metabolic dysfunction-associated steatohepatitis

Aims This study aimed to assess and compare the health care resource utilization (HCRU) and medical cost of metabolic dysfunction-associated steatohepatitis (MASH) by disease severity based on Fibrosis-4 Index (FIB-4) score among US adults in a real-world setting. Materials and methods This observational cohort study used claims data from the Healthcare Integrated Research Database (HIRD) to compare all-cause, cardiovascular (CV)-related, and liver-related HCRU, including hospitalization, and medical costs stratified by FIB-4 score among patients with MASH (identified by International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code K75.81). Hospitalization and medical costs were compared by FIB-4 score using generalized linear regression with negative binomial and gamma distribution models, respectively, while controlling for confounders. Results The cohort included a total of 5,104 patients with MASH and comprised 3,162, 1,343, and 599 patients with low, indeterminate, and high FIB-4 scores, respectively. All-cause hospitalization was significantly higher in the high FIB-4 cohort when compared with the low FIB-4 reference after covariate adjustment (rate ratio, 1.63; 95% CI, 1.32-2.02; P<.0001). CV-related hospitalization was similar across all cohorts; however, CV-related costs were 1.26 times higher (95% CI, 1.11-1.45; P<.001) in the indeterminate cohort and 2.15 times higher (95% CI, 1.77-2.62; P<.0001) in the high FIB-4 cohort when compared with the low FIB-4 cohort. Patients with indeterminate and high FIB-4 scores had 2.97 (95% CI, 1.78-4.95) and 12.08 (95% CI, 7.35-19.88) times the rate of liver-related hospitalization and were 3.68 (95% CI, 3.11-4.34) and 33.73 (95% CI, 27.39-41.55) times more likely to incur liver-related costs, respectively (P<.0001 for all). Limitations This claims-based analysis relied on diagnostic coding accuracy, which may not capture the presence of all diseases or all care received. Conclusions High and indeterminate FIB-4 scores were associated with significantly higher liver-related clinical and economic burdens than low FIB-4 scores among patients with MASH.

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking. To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D). This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD. Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days. The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks. In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas. The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.

Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies.

Non-alcoholic fatty liver disease (NAFLD) is by far the most prevalent form of liver disease worldwide. It's also the leading cause of liver-related hospitalizations and deaths. Furthermore, there is a link between obesity and NAFLD risk. A projected 25% of the world's population grieves from NAFLD, making it the most common chronic liver disorder. Several factors, such as obesity, oxidative stress, and insulin resistance, typically accompany NAFLD. Weight loss, lipid-lowering agents, thiazolidinediones, and metformin help prominently control NAFLD. Interestingly, pre-clinical studies demonstrate gut microbiota's potential causal role in NAFLD. Increased intestinal permeability and unhindered transport of microbial metabolites into the liver are the major disruptions due to gut microbiome dysbiosis, contributing to the development of NAFLD by dysregulating the gut-liver axis. Hence, altering the pathogenic bacterial population using probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) could benefit patients with NAFLD. Therefore, it is crucial to acknowledge the importance of microbiota-mediated therapeutic approaches for NAFLD and comprehend the underlying mechanisms that establish a connection between NAFLD and gut microbiota. This review provides a comprehensive overview of the affiliation between dysbiosis of gut microbiota and the progress of NAFLD, as well as the potential benefits of prebiotic, probiotic, synbiotic supplementation, and FMT in obese individuals with NAFLD.

Characteristics and Outcomes of Black and White Patients Hospitalized With Nonalcoholic Steatohepatitis: A Nationwide Analysis.

Nonalcoholic steatohepatitis (NASH) is an increasingly common etiology for liver-related hospitalizations in the United States. The aim of this study was to examine the differences of disease characteristics and outcomes between hospitalized Black and White patients with NASH. We used the National Inpatient Sample (NIS) to identify all adult hospitalizations with NASH (ICD-10 code: K75.81) from 2016 to 2018. We compared demographic and clinical characteristics between Black and White patients. Multivariable models were computed to compare all-cause mortality, length of stay (LOS), and total hospital costs between the groups. There were 43,409 hospitalizations with NASH (41,143 White, 2266 Black). Black patients were less likely to have cirrhosis (33.6%) compared with Whites (56.4%), P <0.0001. Black patients were less likely to have esophageal variceal bleeding (1.2% vs. 3.5%), ascites (17.1% vs. 28.8%), and acute liver failure (16.2% vs. 28.9%) compared with Whites (all P <0.0001). These findings were consistent among patients with cirrhosis. Mortality was higher among Blacks compared with Whites (3.9% vs. 3.7%, adjusted odds ratio=1.34; 95% confidence interval: 1.05-1.71, P =0.018). Compared with Whites, Blacks had a longer LOS (6.3 vs. 5.6, P <0.001), and higher hospital costs ($18,602 vs. $17,467; P =0.03). In this large population of inpatients with NASH, Black patients were less likely to have cirrhosis and liver disease-related complications, but had overall worse hospital mortality, longer LOS, and higher hospital costs. Further research is warranted to elaborate on factors that generate the health inequities in NASH outcomes between Black and White patients.

HIV-HBV Coinfection-Current Challenges for Virologic Monitoring.

HIV-HBV coinfected patients have higher rates of liver-related morbidity, hospitalizations, and mortality compared to HBV or HIV mono-infected ones. Clinical studies have shown an accelerated progression of liver fibrosis and an increased incidence of HCC, resulting from the combined action of HBV replication, immune-mediated hepatocytolysis, and HIV-induced immunosuppression and immunosenescence. Antiviral therapy based on dually active antiretrovirals is highly efficient, but late initiation, global disparities in accessibility, suboptimal regimens, and adherence issues may limit its impact on the development of end-stage liver disease. In this paper, we review the mechanisms of liver injuries in HIV-HBV coinfected patients and the novel biomarkers that can be used for treatment monitoring in HIV-HBV coinfected persons: markers that assess viral suppression, markers for liver fibrosis evaluation, and predictors of oncogenesis.

The Impact of Supportive Housing on Liver-Related Outcomes Among Persons With Hepatitis C Virus Infection.

BackgroundHepatitis C virus (HCV) infection disproportionately impacts people experiencing homelessness. Hepatitis C virus can lead to negative health outcomes, including mortality. We evaluated the impact of a permanent supportive housing (PSH) program (ie, “treatment”) on liver-related morbidity and mortality among persons with chronic homelessness and HCV infection.MethodsWe matched records for persons eligible for a New York City PSH program (2007–2014) with Heath Department HCV and Vital Statistics registries and Medicaid claims. Among persons diagnosed with HCV before or 2 years posteligibility, we added stabilized inverse probability of treatment weights to negative binomial regression models to compare rates for liver disease-related emergency department visits and hospitalizations, and hazard ratios for mortality, by program placement 2 and 5 years posteligibility.ResultsWe identified 1158 of 8783 placed and 1952 of 19 019 unplaced persons with laboratory-confirmed HCV infection. Permanent supportive housing placement was associated with significantly reduced liver-related emergency department visits (adjusted rate ratio [aRR] = 0.76, 95% confidence interval [CI] = .61–.95), hospitalizations (aRR = 0.62, 95% CI = .54–.71), and all-cause (adjusted hazard ratio [aHR] = 0.65, 95% CI = .46–.92) and liver-related mortality (aHR = 0.72, 95% CI = .09–.83) within 2 years. The reduction remained significant for hospitalizations after 5 years.ConclusionsPlacement into PSH was associated with reduced liver-related morbidity and mortality among persons with HCV infection and chronic homelessness.

Standardized Criteria Increases Palliative Care Consultation Utilization in Patients With End-Stage Liver Disease: A Pilot Study.

Context: Patients with end-stage liver disease have high symptom burden and high healthcare utilization, which may be improved by palliative care consultation. Objectives: We sought to determine if implementing standardized palliative care consultation criteria in hospitalized patients with end-stage liver disease would increase palliative care utilization and improve patient outcomes. Methods: We conducted a retrospective cohort study of hospitalized patients with end-stage liver disease. Patients under the age of 18, received a previous liver transplant, or admitted for liver transplantation were not included. Patients with end-stage liver disease meeting two or more of the following criteria were included: (i)Child Pugh C cirrhosis, (ii)2 or more liver related hospitalizations within 6months, (iii) current alcohol use with alcoholic cirrhosis, and (iv) unsuitable for transplantation work up. We compared consults before and after implementation of the criteria, and we compared outcomes in patients who did and did not see palliative care. Results: With implementation, consults increased (2/25 (8%) vs 11/33 (33%), p = .020). Palliative care was associated with higher completion of health care representative documentation (66.7% vs 35.7%, P = .20) and physician orders for scope of treatment forms (16.7% vs 0%, P = 0.13). Patients seen by palliative care had a higher rate of discharges with hospice (30.8% vs 0, P = .002). Conclusions: Implementation of standardized palliative care consultation criteria for patients with end-stage liver disease increased palliative care utilization. Patients seen by palliative care had increased discharges with hospice services and a trend towards higher completion rates of advanced directives.

The impact of rifaximin on the hospital burden and infections in patients with hepatic encephalopathy: a retrospective observational study.

Advanced liver disease frequently culminates in hepatic encephalopathy (HE), which can be classified as covert or overt HE, with subtle or clinically obvious changes respectively. 30-40% of patients with cirrhosis develop overt HE, which negatively affects the patients' quality of life. Next to lactulose, rifaximin-α has been prescribed as a second line therapy to treat and reduce the risk of recurrence of overt HE. In this study, we aimed to evaluate the effect of rifaximin-α therapy, both on the number of occurring infections and on the evolution in hospital admissions of patients with overt HE. A total of 66 cirrhotic patients, treated for at least 6 months with rifaximin-α at AZ Maria Middelares, between October 1st 2014 and January 1st 2020, were included in the study analysis. Medical records of all patients were evaluated over a period of 6 months prior and after initiation of rifaximin-α therapy. Data analysis revealed that the included cirrhotic patients were severely ill, with a mean model for end-stage liver disease (MELD) score of 21, and a median Child Pugh score of 11. Among these patients, rifaximin-α treatment significantly downgraded the total number of infections, with a main effect on respiratory infections. Furthermore, rifaximin-α therapy led to a significant decrease in HE-related, as well as in other liver-related hospital admissions. This study confirms the potential value of rifaximin-aα in reducing the number of developing infections and hospital admissions in a severely ill cirrhotic patient population.

Lower Rates of Emergency Department Visits and Hospitalizations Among Patients With Chronic Hepatitis C With Sustained Virological Response to Interferon-Free Direct-Acting Antiviral Therapy (2014-2018).

We compared rates of emergency department visits and hospitalizations between patients with hepatitis C virus who achieved sustained virological response after direct-acting antiviral therapy (case patients) and matched controls. Among 3049 pairs, case patients demonstrated lower rates of liver-related emergency department visits (P = .01) than controls; all-cause and liver-related hospitalization rates and number of hospitalized days were also lower in case patients (P < .001).

Impact of the COVID-19 Pandemic on Hospitalizations for Alcoholic Hepatitis or Cirrhosis in Alberta, Canada

Background & AimsCoronavirus disease 2019 (COVID-19) pandemic lockdown and restrictions had significant disruption to patient care. We aimed to evaluate the impact of COVID-19 restrictions on hospitalizations of patients with alcoholic and nonalcoholic cirrhosis as well as alcoholic hepatitis (AH) in Alberta, Canada.MethodsWe used validated International Classification of Diseases (ICD-9 and ICD-10) coding algorithms to identify liver-related hospitalizations for nonalcoholic cirrhosis, alcoholic cirrhosis, and AH in the province of Alberta between March 2018 and September 2020. We used the provincial inpatient discharge and laboratory databases to identify our cohorts. We used elevated alanine aminotransferase or aspartate aminotransferase, elevated international normalized ratio, or bilirubin to identify AH patients. We compared COVID-19 restrictions (April–September 2020) with prior study periods. Joinpoint regression was used to evaluate the temporal trends among the 3 cohorts.ResultsWe identified 2916 hospitalizations for nonalcoholic cirrhosis, 2318 hospitalizations for alcoholic cirrhosis, and 1408 AH hospitalizations during our study time. The in-hospital mortality rate was stable in relation to the pandemic for alcoholic cirrhosis and AH. However, nonalcoholic cirrhosis patients had lower in-hospital mortality rate after March 2020 (8.5% vs 11.5%; P = .033). There was a significant increase in average monthly admissions in the AH cohort (22.1/10,000 admissions during the pandemic vs 11.6/10,000 admissions before March 2020; P < .001).ConclusionsBefore and during COVID-19 monthly admission rates were stable for nonalcoholic and alcoholic cirrhosis; however, there was a significant increase in AH admissions. Because alcohol sales surged during the pandemic, future impact on alcoholic liver disease could be detrimental.

S1122 Rifaximin When Delivered at the Bedside Prior to Discharge, Reduces Liver-Related Hospitalization Rates in Patients With Hepatic Encephalopathy: A Single Institution’s Experience

S1122 Rifaximin When Delivered at the Bedside Prior to Discharge, Reduces Liver-Related Hospitalization Rates in Patients With Hepatic Encephalopathy: A Single Institution’s Experience

Minimal Hepatic Encephalopathy and Biejia-Ruangan Are Associated with First Hospital Readmission in Nonalcoholic Cirrhosis Patients.

Introductionand Aim. Patients with cirrhosis are often hospitalized repeatedly for a variety of complications. This retrospective study aimed to assess the effects of minimal hepatic encephalopathy (MHE) and Biejia-Ruangan (BR) on first hospital readmission in nonalcoholic cirrhosis patients without previous overt hepatic encephalopathy (OHE) or hepatocellular carcinoma (HCC). Materials and Methods. A total of 176 hospitalized patients with nonalcoholic cirrhosis were included in this retrospective study. Patients who were first admitted to Beijing Ditan Hospital of Capital Medical University from January 2017 to September 2019 were enrolled. The primary endpoint was their first liver-related hospital readmission. The risk factors for readmission were analyzed by Cox proportional hazard regression analysis. Results. A total of 176 nonalcoholic cirrhosis patients without previous OHE or HCC were included; 57 patients (32.4%) were diagnosed with MHE, and 63 patients (35.8%) were administered BR (2 g, three times a day). Multivariate analysis revealed that nonalcoholic cirrhosis patients with MHE (HR, 5.805; 95% CI, 3.007–11.206; x, P < 0.001) and a higher Model for End-Stage Liver Disease (MELD) score (HR, 1.145; 95% CI, 1.068–1.227; P < 0.001) had an increased risk of first hospital readmission, and patients treated with BR (HR, 0.318; 95% CI, 0.151–0.670; P=0.003) had a decreased risk of first hospital readmission. Conclusion. MHE increased the risk of hospital readmission in nonalcoholic cirrhosis patients without previous OHE or HCC, and this risk was decreased by BR administration.

The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization

The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

BackgroundThe rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies.ObjectiveThe primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories.MethodsRADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit.ResultsThis trial is currently open for recruitment. The anticipated completion date for the study is December 2020.ConclusionsThis randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies.Trial RegistrationClinicalTrials.gov NCT03289897 https://clinicaltrials.gov/ct2/show/NCT03289897International Registered Report Identifier (IRRID)DERR1-10.2196/19189

Racial and Socioeconomic Disparities in Hospitalization of Pediatrics with Liver Disease from 2005 to 2015.

Adult liver-related hospitalizations have recently increased in the USA, but data are limited for the pediatric population. Utilizing the Office of Statewide Health Planning and Development hospital claims database (covering > 98% of all California hospitalizations), we aimed to characterize the demographic, clinical, and socioeconomic factors of liver disease-associated admissions among children between 2005 and 2015. We used ICD-9 codes to identify admissions associated with liver disease in patients up to 21years of age. Patient characteristics were described as percentages and evaluated using the χ2 test. We used linear regression to examine changes over time. We analyzed 37,372 eligible admissions. Overall, close to one-third (28%) and one-half (48.0%) of admissions occurred in the age group 0-5years and 16-21years, respectively, with the remaining 23.1% occurring in the age group between 5 and 15years. Over half (54.9%) were in males. By race, blacks made up half of the admission (49.7%), while by ethnicity, Hispanic also accounted for half of the admission (49.7%). Medicaid and Medicare payors were also disproportionately represented (54.6%). The most common liver disease was Alagille syndrome (29.2%) in 2005. Between 2005 and 2015, both the number of pediatric liver-associated admissions and the proportion of pediatric liver admissions over total admissions increased from 3130 to 3429 and 1.2% to 1.6%, respectively (both p = 0.001). By 2015, while Alagille syndrome admissions decreased to 26.4% (p = 0.004), NAFLD admission increased to 19.7% (p < 0.001). Major disparities exist in inpatient liver disease burden for blacks and Hispanics with liver disease, while NAFLD emerged as a rapidly rising liver disease in pediatrics.

Changes in Characteristics of Patients with Liver Cirrhosis Visiting a Tertiary Hospital over 15 Years: a Retrospective Multi-Center Study in Korea.

BackgroundLiver cirrhosis has become a heavy burden not only for patients, but also for our society. However, little is known about the recent changes in clinical outcomes and characteristics of patients with cirrhosis-related complications in Korea. Therefore, we aimed to evaluate changes in characteristics of patients with liver cirrhosis in Daegu-Gyeongbuk province in Korea over the past 15 years.MethodsWe retrospectively reviewed the medical records of 15,716 liver cirrhotic patients from 5 university hospitals in Daegu-Gyeongbuk province from 2000 to 2014. The Korean Standard Classification of Diseases-6 code associated with cirrhosis was investigated through medical records and classified according to the year of first visit.ResultsA total of 15,716 patients was diagnosed with cirrhosis. A number of patients newly diagnosed with cirrhosis has decreased each year. In 2000, patients were most likely to be diagnosed with hepatitis B virus (HBV) cirrhosis, followed by alcoholic cirrhosis. There was a significant decrease in HBV (P < 0.001), but alcohol, hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD) showed a significant increase during the study period (alcohol, P = 0.036; HCV, P = 0.001; NAFLD, P = 0.001). At the time of initial diagnosis, the ratio of Child-Turcotte-Pugh (CTP) class A gradually increased from 23.1% to 32.9% (P < 0.001). The most common cause of liver-related hospitalization in 2000 was hepatocellular carcinoma (HCC) (25.5%); in 2014, gastrointestinal bleeding with esophageal and gastric varices (21.4%) was the most common cause. Cases of hospitalization with liver-related complication represented 76.4% of all cases in 2000 but 70.9% in 2014. Incidence rate of HCC has recently increased. In addition, HCC-free survival was significantly lower in CTP class A than in classes B and C. Finally, there was significant difference in HCC occurrence according to causes (P < 0.001). HBV and HCV cirrhosis had lower HCC-free survival than alcoholic and NAFLD cirrhosis.ConclusionIn recent years, the overall number of cirrhosis patients has decreased. This study confirmed the recent trend in decrease of cirrhosis, especially of cirrhosis due to HBV, and the increase of HCV, alcoholic and NAFLD cirrhosis. Targeted screening for at-risk patients will facilitate early detection of liver diseases allowing effective intervention and may have decreased the development of cirrhosis and its complications.

A Smartphone App for Patients With End-Stage Liver Disease Can Detect Behavioral Changes That Predict Liver-Related Events

Background Patients with end-stage liver disease have significant morbidity and mortality. The 90-day readmission rate for these patients is up to 53% at a cost of $4.45 billion annually. Healthcare delivery for these patients is often fragmented and inadequate. Smartphone-based remote health monitoring may reduce hospitalizations by earlier detection of premonitory warning signs associated with liver-related complications. Hepatic encephalopathy which is a common cause of hospitalization and sleep disturbance and subtle/sub-clinical behavioral changes are early warning signs. Objective In this pilot study of patients with end-stage liver disease, we assessed the feasibility of our smartphone app to detect physiologic and behavioral changes during the 7 days prior to liver-related hospitalizations or urgent visits. Methods This is a prospective multicenter pilot study of patients with end-stage liver disease who were enrolled at three academic centers to receive our smartphone app for a 180-day period. English speaking patients age ≥18 years who receive liver care at one of the study sites, do not actively use alcohol or drugs, have had a liver-related complication in the previous 3 months (ascites, hepatic encephalopathy, variceal bleeding, bacterial peritonitis), and own an Android smartphone with internet connectivity were eligible. The smartphone app solicits emotions daily and collects passive data on activity, sleep, and social interactions. Patients received monthly in-app questions about how many liver-related events they had over the preceding month. Surveys on sociodemographic characteristics and health status were collected at baseline, 90 days, and 180 days. Clinical data on liver-related hospitalizations or urgent visits (“events”) were collected prospectively through chart review. Smartphone data on activity, sleep, social interactions, and emotions were analyzed during the 7-day period preceding a liver event and compared to the average over the study period. Statistical analyses were performed with Mann-Whitney U test. Results An interim analysis of the 40 enrolled patients who met all eligibility criteria found that 15 patients had 27 liver-related events during the study period. These patients were predominantly men with a median age of 56 years. 61% of these patients responded to the monthly in-app question about hospitalizations and did so with 100% accuracy. In the 7-day period prior to the event, these patients had more sleep disturbances and changes in activity score (P=.04; P=.04). There was no statistically significant difference in social scores during the 7-day period prior to the event. Emoji selection among this group was too small for analysis. Conclusions The interim analysis of this pilot study suggests that passive data collected from our smartphone app can detect behavioral changes that could be used to predict liver-related events. Specifically, significant changes in smartphone activity and sleep disturbances were identified during the 7-day period prior to a liver-related event. Smartphone-based remote health monitoring appears to be feasible in this patient population and has the potential to reduce hospitalizations through early detection of early warning signs.

Development of Quality Measures in Cirrhosis by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

Health care delivery is increasingly evaluated according to quality measures, yet such measures are underdeveloped for cirrhosis. The Practice Metrics Committee of the American Association for the Study of Liver Diseases was charged with developing explicit process-based and outcome-based measures for adults with cirrhosis. We identified candidate measures from comprehensive reviews of the literature and input from expert clinicians and patient focus groups. We conducted an 11-member expert clinician panel and used a modified Delphi method to systematically identify a set of quality measures in cirrhosis. Among 119 candidate measures, 46 were identified as important measures to define the quality of cirrhosis care, including 26 process measures, 7 clinical outcome measures, and 13 patient-reported outcome measures. The final process measures captured care processes for ascites (n = 5), varices/bleeding (n = 7), hepatic encephalopathy (n = 4), hepatocellular cancer (HCC) screening (n = 1), liver transplantation evaluation (n = 2), and other care (n = 7). Clinical outcome measures included survival, variceal bleeding and rebleeding, early-stage HCC, liver-related hospitalization, and rehospitalization within 7 and 30 days. Patient-reported outcome measures covered physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The final list of patient-reported outcomes was validated in 79 patients with cirrhosis from nine institutions in the United States. Conclusion: We developed an explicit set of evidence-based quality measures for adult patients with cirrhosis. These measures are a tool for providers and institutions to evaluate their care quality, drive quality improvement, and deliver high-value cirrhosis care. The quality measures are intended to be applicable in any clinical care setting in which care for patients with cirrhosis is provided.

Correction: Economic and clinical burden of viral hepatitis in California: A population-based study with longitudinal analysis.

[This corrects the article DOI: 10.1371/journal.pone.0196452.].