An updated assessment of hepatitis delta prevalence among adults in Canada: A meta-analysis.

Foreign-born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta-analysis. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of FB persons in Canada in 2021 from Statistics Canada to estimate total numbers of FB with CHB and HDV, respectively. These estimates were combined with estimates of Canada-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2021, we estimated 0.550 million (M) (95% CI 0.488-0.615) persons with CHB; 0.344 M (95% CI 0.288-0.401) were FB and 0.206 M (95% CI: 0.200-0.214) were Canada-born. The weighted average HDV prevalence among FB persons in Canada was 5.19% (17,848 [95% CI 9611-26,052] persons), among whom 50% emigrated from Asia and 31% from Africa. When combined with estimates of Canada-born persons with HDV, we estimate 35,059 (95% CI: 18,744-52,083) persons with HDV in Canada. In conclusion, we estimate 0.550 M and 35,059 persons living with CHB and HDV, respectively, in Canada in 2021.

Limited Sustained Remission After Nucleos(t)ide Analog Withdrawal: Results From a Large, Global, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

INTRODUCTION: Complete viral suppression with nucleos(t)ide analogs (NAs) has led to a profound reduction in hepatocellular carcinoma and mortality among patients with chronic hepatitis B. Finite therapy yields higher rates of functional cure; however, initial hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) elevations are almost certain after treatment interruption. We aimed to analyze off-treatment outcomes beyond 12 months after NA cessation. METHODS: Patients with well-suppressed chronic hepatitis B who were hepatitis B e antigen-negative at NA cessation and remained off treatment without hepatitis B surface antigen (HBsAg) loss at 12 months were included (n = 945). HBV DNA and ALT fluctuations were allowed within the first 12 months. We used Kaplan-Meier methods to analyze outcomes beyond 12 months. Sustained remission was defined as HBV DNA <2,000 IU/mL and ALT <2× upper limit of normal (ULN) and an ALT flare as ALT ≥5× ULN. RESULTS: Cumulative probability of sustained remission was 29.7%, virological relapse was 65.2% with a mean peak HBV DNA of 5.0 ± 1.5 log 10 IU/mL, an ALT flare was 15.6% with a median peak ALT × ULN of 8.3 (5.7-11.3), HBsAg loss was 9.9% and retreatment was 34.9% at 48 months after NA cessation. A single occurrence of virological relapse or an ALT flare within the first 12 months off-treatment were associated with significantly lower rates of sustained remission beyond 12 months. DISCUSSION: Despite allowing for HBV DNA and ALT fluctuations within the first 12 months off-treatment, most patients without HBsAg loss did not maintain a sustained response thereafter. The best candidates for NA withdrawal are patients with low HBsAg levels at NA cessation, and those without profound or recurrent virological and biochemical relapses in the first off-treatment year.

One-time screening for abdominal aortic aneurysm in Ontario, Canada: a model-based cost-utility analysis.

BACKGROUND: Screening programs for abdominal aortic aneurysm (AAA) are not available in Canada. We sought to determine the effectiveness and costutility of AAA screening in Ontario. METHODS: We compared one-time ultrasonography-based AAA screening for people aged 65 years to no screening using a fully probabilistic Markov model with a lifetime horizon. We estimated life-years, quality-adjusted life-years (QALYs), AAA-related deaths, number needed to screen to prevent 1 AAA-related death and costs (in Canadian dollars) from the perspective of the Ontario Ministry of Health. We retrieved model inputs from literature, Statistics Canada, and the Ontario Case Costing Initiative. RESULTS: Screening reduced AAA-related deaths by 84.9% among males and 81.0% among females. Compared with no screening, screening resulted in 0.04 (18.96 v. 18.92) additional life-years and 0.04 (14.95 v. 14.91) additional QALYs at an incremental cost of $80 per person among males. Among females, screening resulted in 0.02 (21.25 v. 21.23) additional life-years and 0.01 (16.20 v. 16.19) additional QALYs at an incremental cost of $11 per person. At a willingness-to-pay of $50 000 per year, screening was cost-effective in 84% (males) and 90% (females) of model iterations. Screening was increasingly cost-effective with higher AAA prevalence. INTERPRETATION: Screening for AAA among people aged 65 years in Ontario was associated with fewer AAA-related deaths and favourable cost-effectiveness. To maximize QALY gains per dollar spent and AAA-related deaths prevented, AAA screening programs should be designed to ensure that populations with high prevalence of AAA participate.

Incidence of Hepatic Decompensation After Nucleos(t)ide Analog Withdrawal: Results From a Large, International, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

INTRODUCTION: Despite improvements in the management of chronic hepatitis B (CHB), risk of cirrhosis and hepatocellular carcinoma remains. While hepatitis B surface antigen loss is the optimal end point, safe discontinuation of nucleos(t)ide analog (NA) therapy is controversial because of the possibility of severe or fatal reactivation flares. METHODS: This is a multicenter cohort study of virally suppressed, end-of-therapy (EOT) hepatitis B e antigen (HBeAg)-negative CHB patients who stopped NA therapy (n = 1,557). Survival analysis techniques were used to analyze off-therapy rates of hepatic decompensation and differences by patient characteristics. We also examined a subgroup of noncirrhotic patients with consolidation therapy of ≥12 months before cessation (n = 1,289). Hepatic decompensation was considered related to therapy cessation if diagnosed off therapy or within 6 months of starting retreatment. RESULTS: Among the total cohort (11.8% diagnosed with cirrhosis, 84.2% start-of-therapy HBeAg-negative), 20 developed hepatic decompensation after NA cessation; 10 events were among the subgroup. The cumulative incidence of hepatic decompensation at 60 months off therapy among the total cohort and subgroup was 1.8% and 1.1%, respectively. The hepatic decompensation rate was higher among patients with cirrhosis (hazard ratio [HR] 5.08, P < 0.001) and start-of-therapy HBeAg-positive patients (HR 5.23, P < 0.001). This association between start-of-therapy HBeAg status and hepatic decompensation remained significant even among the subgroup (HR 10.5, P < 0.001). DISCUSSION: Patients with cirrhosis and start-of-therapy HBeAg-positive patients should be carefully assessed before stopping NAs to prevent hepatic decompensation. Frequent monitoring of viral and host kinetics after cessation is crucial to determine patient outcome.

Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B.

BACKGROUND AND AIMS: Whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differentially affect relapse and outcomes following treatment discontinuation across different patient subpopulations remains unclear. We aimed to compare rates of off-therapy hepatitis B surface antigen (HBsAg) loss, virological and clinical relapse, and retreatment between chronic hepatitis B (CHB) patients who discontinued TDF or ETV therapy. METHODS: This study included 1402 virally suppressed CHB patients who stopped either ETV (n = 981) or TDF (n = 421) therapy between 2001 and 2020 from 13 participating centers across North America, Europe, and Asia. All patients were hepatitis B e antigen-negative at treatment discontinuation. Inverse probability of treatment weighting was used to balance the treatment groups. Outcomes were analyzed using survival methods. RESULTS: During a median off-treatment follow-up of 18 months, HBsAg loss occurred in 96 (6.8%) patients overall. Compared with ETV, TDF was associated with a higher rate of HBsAg loss (P = .03); however, the association was no longer significant after statistical adjustment (P = .61). Virological relapse occurred earlier among TDF-treated patients (P < .01); nonetheless, rates became comparable after the first year off therapy (P = .49). TDF was significantly associated with a higher clinical relapse rate than ETV throughout follow-up (P < .01). The development of a virological or clinical relapse did not affect the rate of HBsAg loss. Retreatment rates were not significantly different between the treatment groups. CONCLUSIONS: TDF and ETV have differential relapse patterns but are associated with similar rates of HBsAg loss and retreatment following discontinuation. Finite therapy can be considered for CHB patients on either TDF or ETV therapy.

Birth cohort hepatitis C antibody prevalence in real-world screening settings in Ontario.

Background: Widespread screening and treatment of hepatitis C virus (HCV) is required to decrease late-stage liver disease and liver cancer. Clinical practice guidelines and Canadian Task Force on Preventative Health Care recommendations differ on the value of one-time birth cohort (1945-75) HCV screening in Canada. To assess the utility of this approach, we conducted a real-world analysis of HCV antibody (Ab) prevalence among birth cohort individuals seen in different clinical contexts. Methods: Cross-sectional study of individuals born between 1945 and 1975 who completed HCV Ab testing at multiple participating centres in Ontario, Canada between January 2016 and December 2020. Differences in prevalence were compared by year of birth, gender, and setting. Results: Among 16,672 birth cohort individuals tested, HCV Ab prevalence was 3.2%. Prevalence was higher among younger individuals which increased from 0.9% among those born between 1945 and 1956 to 4.6% among those born between 1966 and 1975. Prevalence was higher among males (4.4%) compared with females (2.0%) and differed by test site. In primary care, the prevalence was 0.5%, whereas the prevalence was highest among those tested at drug treatment centres (28.7%) and through community outreach (14.0%). Conclusions: HCV Ab prevalence remains high in the 1945-1975 birth cohort. These data highlight the need to re-evaluate existing Canadian Preventative Task Force recommendations, to consider incorporating one-time birth cohort and/or other population-based approaches to HCV screening into the clinical workflow as a preventative health measure, and to increase training among community providers to screen for and treat HCV.

Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study).

BACKGROUND & AIMS: Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB). METHODS: This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virologic, biochemical, and clinical relapse, alanine aminotransferase flare, retreatment, and liver-related events after NA cessation. RESULTS: Among 1552 patients with CHB, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7-16.8; P < .001) and among patients with HBsAg levels <100 IU/mL at end of therapy (vs ≥100 IU/mL: subdistribution hazard ratio, 22.5; 95% confidence interval, 13.1-38.7; P < .001). At 48 months of follow-up, Whites with HBsAg levels <1000 IU/mL and Asians with HBsAg levels <100 IU/mL at end of therapy had a high predicted probability of HBsAg loss (>30%). Incidence rate of hepatic decompensation and hepatocellular carcinoma was 0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with hepatocellular carcinoma. CONCLUSIONS: The best candidates for NA withdrawal are virally suppressed, HBeAg- negative, noncirrhotic patients with CHB with low HBsAg levels, particularly Whites with <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.

Controversies in Treating Chronic Hepatitis B Virus Infection: Discordant Serologic Results.

Despite effective vaccines and approved therapeutic agents, hepatitis B virus (HBV) remains a prevalent global health problem. Current guidelines rely on a combination of serologic, virological, and biochemical markers to identify the phase in the natural history of chronic HBV infection. Discordant serologic results can occur, which may lead to misclassification. Commonly encountered results that differ from the typical profiles seen in chronic HBV infection are described. For each scenario, the frequency of occurrence, possible explanations, and recommendations for clinical management are discussed. Recognition of discordant serologic findings is crucial for optimal clinical decision.

Effects of on-treatment ALT flares on serum HBsAg and HBV RNA in patients with chronic HBV infection.

As pegylated interferon alpha (PEG-IFN-α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG-IFN-α-based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5 × ULN. The association between flares and HBsAg and HBV RNA changes were examined. On-treatment flares occurred in 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4-12], 7.6 × ULN [IQR 6.2-10.5]). Flare patients were more often Caucasians with genotype A/D and had higher baseline ALT, HBV DNA, HBV RNA and HBsAg levels than the no-flare group. More flares were observed on PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de novo combination (24%) vs. PEG-IFN-α add-on (2%) or NA monotherapy (1%) (p < .001). On-treatment flares were significantly and independently associated with HBsAg and HBV RNA decline ≥1 log10 at the final visit declines started shortly before the flare, progressing towards 24 weeks thereafter. On-treatment flares were seen in 16/22 (73%) patients who achieved HBsAg loss. In conclusion, ALT flares during PEG-IFN-α treatment are associated with subsequent HBsAg and HBV RNA decline and predict subsequent HBsAg loss. Flares rarely occurred during PEG-IFN-α add-on therapy and associated with low HBsAg loss rates. Combination regimens targeting the window of heightened response could be promising.

Ethnicity and Insurance-Specific Disparities in the Model for End-Stage Liver Disease Score at Time of Liver Transplant Waitlist Registration and its Impact on Mortality.

BACKGROUND AND AIMS: Disparities in timely referral to liver transplantation (LT) evaluation persist. We aim to examine race/ethnicity and insurance-specific differences in the Model for End-Stage Liver Disease (MELD) score at time of waitlist (WL) registration and its impact on WL survival. METHODS: We retrospectively evaluated U.S. adults listed for LT using 2005-2018 United Network for Organ Sharing LT registry. Multiple linear regression methods examined factors associated with MELD at listing, and Fine-Gray competing risks regression were used to analyze WL mortality. RESULTS: Among 144,163 WL registrants (median age = 56 years, 65.3% male, 56.4% private insurance, 23.3% Medicare, 15.7% Medicaid), mean WL MELD at listing was higher in African Americans versus non-Hispanic whites (2.57 points higher, 95%CI: 2.40-2.74, P < 0.001). Compared with patients with private insurance, adjusted mean WL MELD was higher among those with no insurance, Medicare, or Medicaid (P < 0.001 for all). After correcting for differences in MELD at listing, Asians had lower risk of WL death versus non-Hispanic whites (subhazard ratio (SHR): 0.92, 95% CI: 0.86-1.00, P = 0.04), but no difference was observed in African Americans or Hispanics. Compared with patients with private insurance, higher risk of WL death was observed in patients with no insurance (SHR: 1.33, 95%CI: 1.14-1.56, P < 0.001), Medicare (SHR: 1.20, 95%CI: 1.16-1.25, P < 0.001), or Medicaid (SHR: 1.22, 95%CI: 1.17-1.27, P < 0.001). CONCLUSION: Higher MELD scores at listing among African Americans did not translate into increased WL mortality. Patients with Medicare, Medicaid, or uninsured had significantly higher WL mortality than privately insured patients, even after correcting for disparities in MELD scores at listing.

Prevalence of hepatitis B surface antigen and hepatitis B core antibody among adults with latent tuberculosis infection.

OBJECTIVE: To evaluate the prevalence of hepatitis B surface antigen (HBsAg) positive or hepatitis B core antibody total (anti-HBc) among adults with latent tuberculosis infection (LTBI) in the USA. METHODS: Using data from the National Health and Nutrition Examination Survey 1999-2000 and 2011-2012 cycles, US adults with LTBI (identified by positive tuberculin skin test or positive QuantiFERON-TB Gold In-Tube test) were evaluated to determine prevalence HBsAg and anti-HBc. Survey-weighted data was used to determine prevalence estimates of HBsAg or anti-HBc, which were further stratified by sex, race/ethnicity, country of birth and age. Trends were analyzed by regressing the outcome over time. Between-group comparisons used chi-squared testing. RESULTS: Overall prevalence of LTBI was 4.2% [95% confidence interval (CI), 3.5-5.1]. Among individuals with LTBI, HBsAg prevalence was 0.9% (95% CI, 0.4-2.1) and anti-HBc prevalence was 12.9% (95% CI, 9.8-16.8), both of which remained stable between 1999-2000 and 2011-2012. While no significant differences in HBsAg prevalence were observed by sex, race/ethnicity, country of birth, age, anti-HBc prevalence was significantly higher in men vs. women (16.8 vs. 7.9%, P < 0.05), blacks vs. non-Hispanic whites (22.9 vs. 5.9%, P < 0.05), non-US born vs. US-born (15.9 vs. 7.2%, P = 0.01) and highest in the oldest age group (age ≥65 years: 17.5%, 95% CI, 10.5-27.8). CONCLUSION: Among US adults with LTBI, overall prevalence of HBsAg was 0.9%. One in eight individuals with LTBI had prior HBV exposure. Effective HBV screening among individuals with LTBI may allow changes in clinical practice to prevent drug-induced liver injury from anti-TB therapies.

Impact of Safety-Net Burden on In-Hospital Mortality and Hospitalization Costs Among Patients with Alcoholic Hepatitis and Alcoholic Cirrhosis.

AIMS: Alcoholic hepatitis (AH) and alcoholic cirrhosis disproportionately affect ethnic minority and safety-net populations. We evaluate the impact of a hospital's safety net burden (SNB) on in-hospital mortality and costs among patients with AH and alcoholic cirrhosis. METHODS: We performed a cross-sectional analysis of 2012-2016 National Inpatient Sample. SNB was calculated as percentage of hospitalizations with Medicaid or uninsured payer status. Associations between hospital SNB and in-hospital mortality and costs were evaluated with adjusted multivariable logistic regression and linear regression models. RESULTS: Among 21,898 AH-related hospitalizations, compared to low SNB hospitals (LBH), patients hospitalized in high SNB hospitals (HBH) were younger (44.4 y vs. 47.4 y, P < 0.001) and more likely to be African American (11.3% vs. 7.7%, P < 0.001) or Hispanic (15.4% vs. 8.4%, P < 0.001). AH-related hospitalizations in HBH had a non-significant trend towards higher odds of mortality (OR 1.27, 95% CI 0.98-1.65, P = 0.07) and higher mean hospitalizations costs. Among 108,669 alcoholic cirrhosis-related hospitalizations, patients in HBH were younger (53.3 y vs. 55.8 y, P < 0.001) and more likely to be African American (8.2% vs. 7.3%, P < 0.001) or Hispanic (24.4% vs. 12.0%, P < 0.001) compared to LBH. Compared to alcoholic cirrhosis-related hospitalizations in LBH, mortality was higher among medium SNB (OR 1.10, 95% CI 1.03-1.17, P = 0.007) and HBH (OR 1.07, 95% CI 1.00-1.15, P = 0.05). Mean hospitalization costs were not different by SNB status. CONCLUSIONS: HBH hospitals predominantly serve ethnic minorities and underinsured/uninsured populations. The higher in-hospital mortality associated HBH particularly for alcoholic cirrhosis patients is alarming given its increasing burden in the USA.

The Effect of Hospital Safety-Net Burden and Patient Ethnicity on In-Hospital Mortality Among Hospitalized Patients With Cirrhosis.

BACKGROUND: Over 2.1 million individuals in the United Stats have cirrhosis, including 513,000 with decompensated cirrhosis. Hospitals with high safety-net burden disproportionately serve ethnic minorities and have reported worse outcomes in surgical literature. No studies to date have evaluated whether hospital safety-net burden negatively affects hospitalization outcomes in cirrhosis. We aim to evaluate the impact of hospitals' safety-net burden and patients' ethnicity on in-hospital mortality among cirrhosis patients. METHODS: Using National Inpatient Sample data from 2012 to 2016, the largest United States all-payer inpatient health care claims database of hospital discharges, cirrhosis-related hospitalizations were stratified into tertiles of safety-net burden: high (HBH), medium (MBH), and low (LBH) burden hospitals. Safety-net burden was calculated as percentage of hospitalizations per hospital with Medicaid or uninsured payer status. Multivariable logistic regression evaluated factors associated with in-hospital mortality. RESULTS: Among 322,944 cirrhosis-related hospitalizations (63.7% white, 9.9% black, 15.6% Hispanic), higher odds of hospitalization in HBHs versus MBH/LBHs was observed in blacks (OR, 1.26; 95%CI, 1.17-1.35; P<0.001) and Hispanics (OR, 1.63; 95% CI, 1.50-1.78; P<0.001) versus whites. Cirrhosis-related hospitalizations in MBHs or HBHs were associated with greater odds of in-hospital mortality versus LBHs (HBH vs. LBH: OR, 1.05; 95% CI, 1.00-1.10; P=0.044). Greater odds of in-hospital mortality was observed in blacks (OR, 1.27; 95% CI, 1.21-1.34; P<0.001) versus whites. CONCLUSION: Cirrhosis patients hospitalized in HBH experienced 5% higher mortality than those in LBH, resulting in significantly greater deaths in cirrhosis patients. Even after adjusting for safety-net burden, blacks with cirrhosis had 27% higher in-hospital mortality compared with whites.

Functional Status at Liver Transplant Waitlisting Correlates With Greater Odds of Encephalopathy, Ascites, and Spontaneous Bacterial Peritonitis.

BACKGROUND & AIMS: Whether higher liver transplant (LT) waitlist mortality in patients with poor functional status (FS) is mediated by higher prevalence of cirrhosis complications is not clear. We aim to evaluate the impact of FS on risk of hepatic encephalopathy (HE), ascites, and spontaneous bacterial peritonitis (SBP) among adults listed for LT. METHODS: Using 2005-2018 United Network for Organ Sharing LT data, we retrospectively evaluated the impact of FS on prevalence of ascites, HE, and SBP among adults listed for LT using Karnofsky Performance Status Score categories (KPSS-1: FS 80-100%, KPSS-2: 60-70%, KPSS-3: 40-50%, KPSS-4: 10-30%), stratified by underlying liver disease etiology. Between-group comparisons used chi-squared methods and adjusted multivariate logistic regression. RESULTS: Among 100,618 adults listed for LT (68.8% male, 72.4% non-Hispanic white) 35.2% were KPSS-1, 36.6% KPSS-2, 15.7% KPSS-3, and 12.6% KPSS-4 at time of LT waitlist registration. Patients with worse FS were significantly more likely to have ascites, HE, and SBP at time of waitlist registration (KPSS-1 vs. KPSS-4: ascites, 66% vs. 93%; HE, 81% vs. 49%; SBP, 4% vs. 16%, p < 0.001 for all). On multivariate regression, compared with patients with KPSS-1, those with KPSS-4 had significantly higher odds of ascites (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.37-1.62, p < 0.01), HE (OR: 1.69, 95% CI: 1.59-1.80, p < 0.01), and SBP (OR: 2.17, 95% CI: 1.98-2.38, p < 0.01), which was observed across all liver disease etiologies. CONCLUSION: Worse FS is associated with higher odds of cirrhosis complications including ascites, HE, and SBP, which was observed across all liver disease etiologies.

Trends in the Burden of Chronic Liver Disease Among Hospitalized US Adults.

Importance: One factor associated with the rapidly increasing clinical and economic burden of chronic liver disease (CLD) is inpatient health care utilization. Objective: To understand trends in the hospitalization burden of CLD in the US. Design, Setting, and Participants: This cross-sectional study of hospitalized adults in the US used data from the National Inpatient Sample from 2012 to 2016 on adult CLD-related hospitalizations. Data were analyzed from June to October 2019. Main Outcomes and Measures: Hospitalizations identified using a comprehensive review of CLD-specific International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes. Survey-weighted annual trends in national estimates of CLD-related hospitalizations, in-hospital mortality, and hospitalization costs, stratified by demographic and clinical characteristics. Results: This study included 1 016 743 CLD-related hospitalizations (mean [SD] patient age, 57.4 [14.4] years; 582 197 [57.3%] male; 633 082 [62.3%] white). From 2012 to 2016, the rate of CLD-related hospitalizations per 100 000 hospitalizations increased from 3056 (95% CI, 3042-3069) to 3757 (95% CI, 3742-3772), and total inpatient hospitalization costs increased from $14.9 billion (95% CI, $13.9 billion to $15.9 billion) to $18.8 billion (95% CI, $17.6 billion to $20.0 billion). Mean (SD) patient age increased (56.8 [14.2] years in 2012 to 57.8 [14.6] years in 2016) and, subsequently, the proportion with Medicare also increased (41.7% [95% CI, 41.1%-42.2%] to 43.6% [95% CI, 43.1%-44.1%]) (P for trend < .001 for both). The proportion of hospitalizations of patients with hepatitis C virus was similar throughout the period of study (31.6% [95% CI, 31.3%-31.9%]), and the proportion with alcoholic cirrhosis and nonalcoholic fatty liver disease showed increases. The mortality rate was higher among hospitalizations with alcoholic cirrhosis (11.9% [95% CI, 11.7%-12.0%]) compared with other etiologies. Presence of hepatocellular carcinoma was also associated with a high mortality rate (9.8% [95% CI, 9.5%-10.1%]). Cost burden increased across all etiologies, with a higher total cost burden among hospitalizations with alcoholic cirrhosis ($22.7 billion [95% CI, $22.1 billion to $23.2 billion]) or hepatitis C virus ($22.6 billion [95% CI, $22.1 billion to $23.2 billion]). Presence of cirrhosis, complications of cirrhosis, and comorbidities added to the CLD burden. Conclusions and Relevance: Over the study period, the total estimated national hospitalization costs in patients with CLD reached $81.1 billion. The inpatient CLD burden in the US is likely increasing because of an aging CLD population with increases in concomitant comorbid conditions.

Alcoholic Liver Disease Epidemiology in the United States: A Retrospective Analysis of 3 US Databases.

OBJECTIVES: Alcoholic liver disease (ALD) prevalence, particularly the subset with advanced liver disease, is not well defined. Herein, we aim to provide a comprehensive assessment of ALD epidemiology across the spectrum of disease severity and across different settings using 3 unique US databases. METHODS: We performed a retrospective, observational study of US adults with ALD using 2001-2016 National Health and Nutrition Examination Survey (NHANES), 2007-2014 Nationwide Inpatient Sample (NIS), and 2007-2017 United Network for Organ Sharing (UNOS) registry. ALD in the NHANES was defined using clinical laboratory data and self-reported alcohol use, among which fibrosis-4 score of >2.67 defined stage ≥3 fibrosis. Alcoholic cirrhosis (AC) in the NIS was identified using International Classification of Diseases, Ninth Revision codes. ALD in the UNOS was identified using UNOS coding. RESULTS: From 2001-2002 to 2015-2016, the overall weighted ALD prevalence was stable from 8.8% to 8.1% (P = 0.102), whereas the proportion of ALD with stage ≥3 fibrosis increased from 2.2% (95% CI: 0.4-4.0) to 6.6% (95% CI: 2.0-9.9; P = 0.007) (NHANES). From 2007 to 2014, the number of hospitalizations among patients with AC per 1,000 increased by 32.8%, and the proportion of hospitalizations among the patients with AC with ≥3 cirrhosis complications increased from 11.6% in 2007 to 25.8% in 2014 (Ptrend < 0.0001) (NIS). From 2007 to 2017, the total number of adults with ALD listed for liver transplant increased by 63.4% and the proportion with concurrent hepatocellular carcinoma increased by 178% (UNOS). DISCUSSION: Among these 3 US databases, consistent observations of increasing ALD severity emphasize the urgent need for greater awareness about the consequences of unhealthy alcohol use and interventions aimed specifically at addressing alcohol use disorders.