Changes in mortality due to Chronic Liver Diseases (CLD) during the COVID-19 pandemic: Data from the United States' National Vital Statistics System.

INTRODUCTION: We assessed chronic liver disease (CLD)-related mortality in the U.S. using death data (2011-2021) obtained from National Vital Statistics System (NVSS). The average annual percentage change (AAPC) from the models selected by Joinpoint regression analysis over the pre-pandemic (2011-2019) and the 2019-2021 were reported because non-linear trend in death rates were observed over the 2011-2021. Liver-specific death was defined as an underlying cause of death and Chronic liver disease (CLD)-related death was defined as any cause of death. During the pre-pandemic, age-standardized HCC- and cirrhosis-specific death rates were annually increased by AAPC = +1.18% (95% confidence interval, 0.34% to 2.03%) and AAPC = +1.95% (1.56% to 2.35%). In contrast, during the 2019-2021, the AAPC in age-standardized cirrhosis-specific death rate (per 100,000) accelerated by up to AAPC +11.25% (15.23 in 2019 to 18.86 in 2021) whereas that in age-standardized HCC-specific death rate slowed to -0.39 (-1.32% to 0.54%) (3.86 in 2019 to 3.84 in 2021). Compared to HCC-specific deaths, cirrhosis-specific deaths were more likely to be non-Hispanic white (72.4% vs. 62.0%) and non-Hispanic American Indian and Alaska native (AIAN) (2.2% vs. 1.1%) and have NAFLD (45.3% vs. 12.5%) and ALD (27.6% vs. 22.0%). During the 2019-2021, the age-standardized HCV- and HBV-related death rate stabilized, whereas the age-standardized NAFLD- and ALD-related deaths rate increased to 20.16 in 2021 (AAPC = +12.13% [7.76% to 16.68%]) and to 14.95 in 2021 (AAPC = +18.30% [13.76% to 23.03%]), which were in contrast to much smaller incremental increases during the pre-pandemic (AAPC = +1.82% [1.29% to 2.35%] and AAPC = +4.54% [3.97% to 5.11%]), respectively). The most pronounced rise in the age-standardized NAFLD-related death rates during the pandemic was observed among AIAN (AAPC = +25.38%), followed by non-Hispanic White female (AAPC = +14.28%), whereas the age-standardized ALD-related death rates during the pandemic were highest among AIAN (AAPC = +40.65%), followed by non-Hispanic Black female (AAPC = +26.79%). CONCLUSIONS: COVID-19 pandemic had a major negative impact on cirrhosis-specific and CLD-related mortality in the U.S. with significant racial and gender disparities.

Liver Transplantation Profile Among Teenagers in the United States.

PURPOSE: Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022. METHODS: The Scientific Registry of Transplant Recipients 2008-2022 provided data (clinical, sociodemographic, indications for LT, outcomes) for all teenagers (13-19 years) waitlisted for LT in the United States. Sociodemographic and clinical characteristics, including primary listing diagnoses, were evaluated and compared by age group (13-16 vs. 17-19 years) among waitlisted teenage candidates. RESULTS: There were 2,813 teenage LT candidates listed between 2008 and 2022. The most common LT indication was acute liver disease (23.5%), followed by biliary atresia or hypoplasia (11.9%), autoimmune hepatitis (11.1%), and primary sclerosing cholangitis (9.7%). In contrast, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease (the most common indications in adults) did not exceed 1% each; 2.8% had hepatocellular carcinoma. Excluding the two most recent years, 67.2% of candidates received a transplant; mean time to transplant was 217.0 days (standard deviation 371.6). Independent predictors of receiving a transplant were a more recent calendar year, younger age, higher model for end-stage liver disease score, and an acute liver disease diagnosis (all p < .05). Among the LT group, 3-year survival was 90%, with an improving survival trend. Higher post-transplant mortality was associated with earlier years of transplantation, older age, having Medicaid, being retransplanted, and having hepatocellular carcinoma (adjusted hazard ratios >1, all p < .05). DISCUSSION: Indications for LT among US teenagers are different from adults or younger children. There is a trend toward improved post-transplant outcomes.

The changing epidemiology of adult liver transplantation in the United States in 2013-2022: The dominance of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

BACKGROUND: The high prevalence of obesity in the United States drives the burden of NASH, recently renamed as metabolic dysfunction-associated steatohepatitis (MASH). We assessed the most recent trends in liver transplantation in the United States. METHODS: The Scientific Registry of Transplant Recipients (SRTR 2013-2022) was used to select adult (18 years or above) candidates who underwent liver transplant. RESULTS: There were 116,292 candidates who underwent liver transplant with known etiology of chronic liver disease. In candidates without HCC, the most common etiology was alcohol-associated liver disease (ALD), increasing from 23% (2013) to 48% (2022), followed by NASH/MASH, which increased from 19% to 27%; the rates of viral hepatitis decreased (chronic hepatitis C: 28%-4%; chronic hepatitis B: 1.8%-1.1%) (all trend p<0.01). The proportion of HCC decreased from 25% (2013-2016) to 17% (2021-2022). Among HCC cohort, the proportion of chronic hepatitis C decreased from 60% (2013) to 27% (2022), NASH/MASH increased from 10% to 31%, alcohol-associated liver disease increased from 9% to 24% (trend p<0.0001), and chronic hepatitis B remained stable between 5% and 7% (trend p=0.62). The rapid increase in the proportion of NASH/MASH in HCC continued during the most recent study years [20% (2018), 28% (2020), 31% (2022)]; the trend remained significant after adjustment for age, sex, ethnicity, obesity, and type 2 diabetes. CONCLUSIONS: Liver transplant etiologies in the United States have changed over the last decade. Alcohol-associated liver disease and NASH/MASH remain the 2 most common indications for transplantation among those without HCC, and NASH/MASH is the most common in patients with HCC.

Slow and Steady: A Slowly Progressing Neuroendocrine Tumor.

Neuroendocrine tumors (NETs) are rare malignant tumors that arise from neuroendocrine cells throughout the body, most commonly in the gastrointestinal and respiratory tracts. We report a case of well-differentiated grade 2 NET with a computed tomography scan showing multiple liver lesions consistent with the liver lesions seen 11 years before diagnosis. This case highlights the possibility of an indolent or prolonged clinical course of metastatic NET with an unknown primary vs primary hepatic NET.

How to Identify Advanced Nonalcoholic Fatty Liver Disease in the Primary Care Setting.

Nonalcoholic fatty liver disease (NAFLD) affects 30 to 40% of the population globally and is increasingly considered the most common liver disease. Patients with type 2 diabetes, obesity, and cardiovascular diseases are at especially increased risk for NAFLD. Although most patients with NAFLD do not have progressive liver disease, some patients progress to cirrhosis, liver cancer, and liver mortality. Given the sheer number of patients with NAFLD, the burden of disease is enormous. Despite this large and increasing burden, identification of NAFLD patients at risk for progressive liver disease in the primary care and diabetology practice settings remains highly suboptimal. In this review, our aim is to summarize a stepwise approach to risk stratify patients with NAFLD which should help practitioners in their management of patients with NAFLD.

Noninvasive Tests Used in Risk Stratification of Patients with Nonalcoholic Fatty Liver Disease.

As the prevalence of obesity and type 2 diabetes increases around the world, the prevalence of nonalcoholic fatty liver disease (NAFLD) has grown proportionately. Although most patients with NAFLD do not experience progressive liver disease, about 15% to 20% of those with nonalcoholic steatohepatitis can and do progress. Because liver biopsy's role in NAFLD has become increasingly limited, efforts have been undertaken to develop non-invasive tests (NITs) to help identify patients at high risk of progression. The following article discusses the NITs that are available to determine the presence of NAFLD as well as high-risk NAFLD.

Sarcopenia Among Patients With Nonalcoholic Fatty Liver Disease (NAFLD) Is Associated With Advanced Fibrosis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and sarcopenia can be associated with advanced liver disease. Our aim was to assess the association between sarcopenia and the risk of fibrosis among patients with NAFLD. METHODS: We used the National Health and Nutrition Examination Survey (2017-2018). NAFLD was defined by transient elastography without other causes of liver disease or excessive alcohol use. Significant fibrosis (SF) and advanced fibrosis (AF) were defined by liver stiffness greater than 8.0 kPa and greater than 13.1 kPa, respectively. Sarcopenia was defined using the Foundation for the National Institutes of Health definition. RESULTS: Of the total cohort (N = 2422), 18.9% had sarcopenia, 9.8% had obese sarcopenia, 43.6% had NAFLD, 7.0% had SF, and 2.0% had AF. Moreover, 50.1% had neither sarcopenia nor NAFLD, 6.3% had sarcopenia without NAFLD, 31.1% had NAFLD without sarcopenia, and 12.5% had NAFLD with sarcopenia. Compared with individuals without NAFLD or sarcopenia, individuals with sarcopenic NAFLD had higher rates of SF (18.3% vs 3.2%) and AF (7.1% vs 0.2%). In the absence of sarcopenia, compared with individuals without NAFLD, individuals with NAFLD have a significantly increased risk of SF (odds ratio, 2.18; 95% CI, 0.92-5.19). In the presence of sarcopenia, NAFLD was associated with an increased risk of SF (odds ratio, 11.27; 95% CI, 2.79-45.56). This increase was independent of metabolic components. The proportion of SF that is attributable to the interaction of NAFLD and sarcopenia was 55% (attributable proportion, 0.55; 95% CI, 0.36-0.74). Increased leisure time physical activity was associated with a lower risk of sarcopenia. CONCLUSIONS: Patients with sarcopenic NAFLD are at risk for SF and AF. Increased physical activity and a healthy diet targeted to improve sarcopenic NAFLD could reduce the risk of significant fibrosis.

Increasing heroin, cocaine, and buprenorphine arrests reported to the Maine Diversion Alert Program.

BACKGROUND: The opioid overdose crisis is especially pronounced in Maine. The Diversion Alert Program (DAP) was developed to combat illicit drug use and prescription drug diversion by facilitating communication between law enforcement and health care providers with the goal of limiting drug-related harms and criminal behaviors. Our objectives in this report were to analyze 2014-2017 DAP for: (1) trends in drug arrests and, (2) differences in arrests by offense, demographics (sex and age) and by region. METHODS: Drug arrests (N=8193, 31.3% female, age=33.1±9.9) reported to the DAP were examined by year, demographics, and location. RESULTS: The most common substances of the 10,064 unique charges reported were heroin (N=2203, 21.9%), crack/cocaine (N=945, 16.8%), buprenorphine (N=812, 8.1%), and oxycodone (N=747, 7.4%). While the overall number of arrests reported to the DAP declined in 2017, the proportion of arrests involving opioids (heroin, buprenorphine, or fentanyl) and stimulants (cocaine/crack cocaine, or methamphetamine), increased (p<.05). Women had significantly increased involvement in arrests involving sedatives and miscellaneous pharmaceuticals (e.g. gabapentin) while men had an elevation in stimulant arrests. Heroin accounted for a lower percentage of arrests among individuals age >60 (6.6%) relative to young-adults (18-29, 22.3%, p<.0001). Older-adults had significantly more arrests than younger-adults for oxycodone, hydrocodone, and marijuana. CONCLUSION: Heroin had the most arrests from 2014 to 2017. Buprenorphine, fentanyl and crack/cocaine arrests increased appreciably suggesting that improved treatment is needed to prevent further nonmedical use and overdoses. The Diversion Alert Program provided a unique data source for research, a harm-reduction tool for health care providers, and an informational resource for law enforcement.

Descriptive, observational study of pharmaceutical and non-pharmaceutical arrests, use, and overdoses in Maine.

OBJECTIVES: The Maine Diversion Alert Program grants healthcare providers access to law enforcement data on drug charges. The objectives of this report were to analyse variations in drug charges by demographics and examine recent trends in arrests, prescriptions of controlled substances and overdoses. DESIGN: Observational. SETTING: Arrests, controlled prescription medication distribution and overdoses in Maine. PARTICIPANTS: Drug arrestees (n=1272) and decedents (n=2432). PRIMARY OUTCOME MEASURES: Arrestees were analysed by sex and age. Substances involved in arrests were reported by schedule (I-V or non-controlled prescription) and into opioids, stimulants or other classes. Controlled substances reported to the Drug Enforcement Administration (2007-2017) were evaluated. Drug-induced deaths (2007-2017) reported to the medical examiner were examined by the substance(s) identified. RESULTS: Males were more commonly arrested for stimulants and schedule II substances. More than two-thirds of arrests involved individuals under the age of 40. Individuals age >60 were elevated for oxycodone arrests. Over three-fifths (63.38%) of arrests involved schedule II-IV substances. Opioids accounted for almost half (44.6%) of arrests followed by stimulants (32.5%) and sedatives (9.1%). Arrests involving buprenorphine exceeded those for oxycodone, hydrocodone, methadone, tramadol and morphine, combined. Prescriptions for hydrocodone (-56.0%) and oxycodone (-46.9%) declined while buprenorphine increased (+58.1%) between 2012 and 2017. Deaths from 2007 to 2017 tripled. Acetylfentanyl and furanylfentanyl were the most common fentanyl analogues identified. CONCLUSIONS: Although the overall profile of those arrested for drug crimes in 2017 involve males, age <40 and heroin, exceptions (oxycodone for older adults) were observed. Most prescription opioids are decreasing while deaths involving opioids continue to increase in Maine.

Trends in Medical Use of Opioids in the U.S., 2006-2016.

INTRODUCTION: The U.S. is experiencing an opioid epidemic which is at least partially iatrogenic and fueled by both prescription and illicit misuse. This study provides a nationwide examination of opioid distribution patterns during the last decade. METHODS: Data were obtained from the U.S. Drug Enforcement Administration's Automation of Reports and Consolidated Orders System for 2006-2016. Analyses include quantities of ten opioids legally dispensed nationwide by weight and converted to Morphine Milligram Equivalents. Geospatial and state-level analyses were also completed in 2017. RESULTS: The total for ten opioids peaked in 2011 (389.5 metric tons Morphine Milligram Equivalents) relative to both 2006 (286.1) and 2016 (364.6). Changes in the volume of opioids by weight over the decade were agent specific. Since 2011, there were decreases in hydrocodone (-28.4%); oxymorphone (-28.0%); fentanyl (-21.4%); morphine (-18.9%); oxycodone (-13.8%); and meperidine (-58.0%) and an increase in buprenorphine (75.2%) in 2016. There were substantial inter-state variations in rates with a fivefold difference between the highest Morphine Milligram Equivalents in 2016 (Rhode Island=2,623.7 mg/person) relative to the lowest (North Dakota=484.7 mg/person). An association was identified between state median age and per capita Morphine Milligram Equivalents (r =0.49, p<0.0005). CONCLUSIONS: With the exception of buprenorphine, used to treat an opioid use disorder, prescription opioid use has been decreasing over the past 5 years in the U.S. Further efforts are needed to continue to optimize the balance between appropriate opioid access for acute pain while minimizing diversion and treating opioid addiction.

Illicit and prescription drug misuse as reported to the Maine Diversion Alert Program.

BACKGROUND: The opioid epidemic is rapidly evolving and new tools are needed to combat drug abuse. The Maine Diversion Alert Program (DAP) is an informational resource that facilitates communication about drug arrests between the criminal justice and healthcare fields. The objectives of this report were to: (1) describe the illegal and prescription pharmaceuticals reported to the DAP; (2) determine if the drugs implicated in arrests changed from the first to latter half of 2016; (3) identify the demographic and other characteristics of arrestees; and (4) outline the strengths and limitations of the DAP for other areas considering implementing similar programs. METHODS: The arrests (N=2,368, 31.4% female, mean age=33.7, SD=9.9, Min=18, Max=71.5) reported to the DAP were examined. Drugs were classified by Drug Enforcement Administration Schedule (I-V, non-controlled prescription) and into families (opioids, stimulants, sedatives, hallucinogens, and other). A comparison between the first and second half of 2016 and arrest by county was completed. RESULTS: Arrests involved 2,957 substances (drugs and paraphernalia). Most arrests (80.6%) involved a single drug. One-third (33.2%) of arrests involved illicit drugs (i.e. Schedule I) and three-fifths (59.8%) were for controlled prescription medical drugs (i.e. Schedule II-V), and a minority (6.8%) involved non-controlled prescription drugs (e.g. gabapentin, bupropion). Opioids (e.g. heroin, buprenorphine, and oxycodone) accounted for over-half (51.3%) of arrests followed by stimulants (29.0%, e.g. cocaine), and sedatives (7.6%). Arrests for oxycodone significantly decreased (51.9%) and alprazolam increased (89.3%) during 2016. Arrestees for non-controlled prescription drugs were older than arrestees for illegal drugs. Arrests, correcting for population, were most common in more urban (e.g. Androscoggin and Cumberland) counties. CONCLUSIONS: Opioids (illicit and prescription) account for over half of all arrests. However, arrests for oxycodone decreased while arrests for benzodiazepines, and especially alprazolam, increased in 2016. The DAP is a novel source of information for healthcare decisions and can empirically inform law enforcement about drug misuse and addiction.