Alcohol-related hepatitis: A review article.

Alcohol-related hepatitis (ARH) is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by significant alcohol use. It ranges in severity from mild to severe and carries significant morbidity and mortality. The refinement of scoring systems has enhanced prognostication and guidance of clinical decision-making in the treatment of this complex disease. Although treatment focuses on supportive care, steroids have shown benefit in select circumstances. There has been a recent interest in this disease process, as coronavirus disease 2019 pandemic led to substantial rise in cases. Although much is known regarding the pathogenesis, prognosis remains grim due to limited treatment options. This article summarizes the epidemiology, genetics, pathogenesis, diagnosis and treatment of ARH.

OPTN/SRTR 2021 Annual Data Report: Liver.

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

Risks of digestive diseases in long COVID: Evidence from a large-scale cohort study (preprint)

Objectives: This study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on the long-term risk of digestive diseases in the general population. Design: Large-scale population-based cohort study based on a prospective cohort. Setting: UK Biobank cohort linked to multiple nationwide electronic health records databases. Participants: The cohort consisted of 112,311 individuals who survived the initial 30 days following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as two control groups: a contemporary group (n = 359,671) without any history of COVID-19, and a historical control group (n = 370,979) that predated the COVID-19 outbreak. Main outcome measures: Main outcomes were predefined digestive diseases. Hazard ratios and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. Results: Compared with the contemporary control group, patients with previous COVID-19 infection had higher risks of digestive diseases, including functional gastrointestinal disorders (hazard ratios [HR] 1.95 (95% CI 1.62 to 2.35)); peptic ulcer disease (HR 1.27 (1.04 to 1.56)); gastroesophageal reflux disease (GERD) (HR 1.46 (1.34 to 1.58)); inflammatory bowel diseases (HR 1.40 (1.02 to 1.90)); gallbladder disease (HR 1.28 (1.13 to 1.46)); severe liver disease (HR 1.46 (1.12 to 1.90)); non-alcoholic liver disease (HR 1.33 (1.15 to 1.55)); and pancreatic disease (HR 1.43 (1.17 to 1.74)). The risks of GERD were stepwise increased with severity of the acute phase of COVID-19 infection. The results were consistent when using the historical cohort as the control group. Conclusions: Our study provides important insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing gastrointestinal disorders, with stepwise increased risk with the severity and persisting even after one year follow-up.

Liver transplantation in alcohol-associated liver disease: ensuring equity through new processes.

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients.

The Changing Epidemiology of Alcohol-Associated Liver Disease: Gender, Race, and Risk Factors.

Cases of alcohol-associated liver disease (ALD) are increasing at a steady rate in the United States with more patients presenting with alcohol-associated hepatitis and alcohol-associated cirrhosis. While alcohol use has increased across many demographic groups, women are suffering from a greater increase in alcohol use disorder (AUD), and are at a greater risk of ALD due to pathophysiological differences which include absorption of alcohol, first pass metabolism, and hormonal differences. Differences across race have also been found with Native Americans and Hispanics suffering from some of the largest increases in ALD rates. Younger adults are heavily impacted by rising rates of both AUD and ALD. Comorbidities such as obesity and NASH have been shown to augment the deleterious effects of AUD and ALD, resulting in more advanced liver disease. Finally, COVID-19 and policies related to the pandemic have resulted in increased AUD across many cohorts, which have resulted in marked increases in ALD. In conclusion, ALD rates are rising, with young people and women particularly impacted.

Trends in Etiology-based Mortality From Chronic Liver Disease Before and During COVID-19 Pandemic in the United States.

BACKGROUND & AIMS: During the global coronavirus disease 2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic. METHODS: Population-based analyses were performed on United States national mortality records (2017-2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC). RESULTS: Quarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease before the COVID-19 pandemic (QPC, 1.9%) accelerated during the COVID-19 pandemic (QPC, 6.6%). Although ALD-related mortality increased steeply compared with viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD. CONCLUSION: All-cause mortality for ALD and nonalcoholic fatty liver disease rapidly accelerated during the COVID-19 pandemic compared with the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population.

Covid-19 and alcohol associated liver disease.

The COVID-19 pandemic is having substantial impacts on the health status of individuals with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). AUD and ALD have both been impacted throughout the pandemic, with increases in alcohol use during the early stages of the pandemic, reduced access to treatment during the mid-pandemic, and challenges in managing the downstream effects in the post-COVID era. This review will focus on how the COVID-19 pandemic has impacted AUD and ALD epidemiology and access to treatment, and will discuss to address this rising AUD and ALD disease burden.

Mental Imagery to Reduce Alcohol-related harm in patients with alcohol dependence and alcohol-related liver damaGE: the MIRAGE pilot trial protocol.

INTRODUCTION: In the UK, alcohol use is the main driver of chronic liver disease and each year results in over 1 million unplanned hospital admissions and over 25 000 deaths from alcohol-related liver disease (ArLD). The only effective treatment to prevent progression of liver damage is reducing or ceasing alcohol consumption. Psychological and pharmacological therapies for alcohol misuse are ineffective in patients with ArLD. Functional imagery training (FIT) is a novel psychological therapy that builds on motivational interviewing techniques with multisensory imagery. This pilot trial aims to test the feasibility of training alcohol liaison nurses to deliver FIT therapy and of recruiting and retaining patients with ArLD and alcohol dependence to a randomised trial of FIT and treatment as usual (TAU) versus TAU alone. METHODS AND ANALYSIS: This is a randomised pilot trial of FIT and TAU versus TAU alone in 90 patients with ArLD and alcohol dependence admitted to one of four UK centres. The primary objectives are to estimate rates of screening, recruitment, randomisation, retention, adherence to FIT/TAU and a preliminary assessment of the FIT intervention in the ArLD population. Data from the pilot study will be used to finalise the design of a definitive randomised controlled trial to assess the effectiveness and cost-effectiveness of FIT. The proposed primary outcome measure for the definitive trial is self-reported alcohol use assessed using timeline follow-back. ETHICS AND DISSEMINATION: Research ethics approval was given by the Yorkshire and Humber-Bradford Leeds Research Ethics Committee (reference: 21/YH/0044). Eligible patients will be approached and written informed consent obtained prior to participation. Results will be disseminated through peer-reviewed open access journals, international conferences and a lay summary published on the Trials Unit website and made available to patient groups. TRIAL REGISTRATION NUMBER: ISRCTN41353774.

Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care.

Alcohol use and consequent liver disease are major burdens that have worsened during the COVID-19 pandemic. There are several facets to the pathophysiology and clinical consequences of alcohol-use disorder (AUD) and progression to alcohol-associated liver disease (ALD) that require a concerted effort by clinicians and translational and basic science investigators. Several recent advances from bedside to bench and bench to bedside have been made in ALD. We focused this review on a case-based approach that provides a human context to these important advances across the spectrum of ALD.

Alcohol-Associated Liver Disease Mortality Increased From 2017 to 2020 and Accelerated During the COVID-19 Pandemic.

Alcohol consumption has risen substantially in the United States in the past 2 decades.1,2 Alcohol-associated liver disease (ALD) represents a greater inpatient financial burden than all other etiologies of cirrhosis combined3 and is now the leading indication for liver transplantation.4 A recent study reported that ALD mortality increased between 2006 and 2017.5 Since 2017, alcohol consumption has continued to rise, and more significantly during the COVID-19 pandemic.2 The aim of this research letter is to provide the most updated trends in ALD-related mortality in the United States and to quantify the rate of change of ALD-related mortality over time.

Effect of increased alcohol consumption during COVID-19 pandemic on alcohol-associated liver disease: A modeling study.

BACKGROUND AND AIMS: Alcohol consumption increased during the COVID-19 pandemic in 2020 in the United States. We projected the effect of increased alcohol consumption on alcohol-associated liver disease (ALD) and mortality. APPROACH AND RESULTS: We extended a previously validated microsimulation model that estimated the short- and long-term effect of increased drinking during the COVID-19 pandemic in individuals in the United States born between 1920 and 2012. We modeled short- and long-term outcomes of current drinking patterns during COVID-19 (status quo) using survey data of changes in alcohol consumption in a nationally representative sample between February and November 2020. We compared these outcomes with a counterfactual scenario wherein no COVID-19 occurs and drinking patterns do not change. One-year increase in alcohol consumption during the COVID-19 pandemic is estimated to result in 8000 (95% uncertainty interval [UI], 7500-8600) additional ALD-related deaths, 18,700 (95% UI, 17,600-19,900) cases of decompensated cirrhosis, and 1000 (95% UI, 1000-1100) cases of HCC, and 8.9 million disability-adjusted life years between 2020 and 2040. Between 2020 and 2023, alcohol consumption changes due to COVID-19 will lead to 100 (100-200) additional deaths and 2800 (2700-2900) additional decompensated cirrhosis cases. A sustained increase in alcohol consumption for more than 1 year could result in additional morbidity and mortality. CONCLUSIONS: A short-term increase in alcohol consumption during the COVID-19 pandemic can substantially increase long-term ALD-related morbidity and mortality. Our findings highlight the need for individuals and policymakers to make informed decisions to mitigate the impact of high-risk alcohol drinking in the United States.

Impact of COVID-19 Pandemic on Liver Transplantation and Alcohol-Associated Liver Disease in the USA.

BACKGROUND AND AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30. CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.