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  The Liver Meeting
Digital Experience
November 13 - 16 - 2021
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Persistent COVID Symptoms, Weight Gain, Alcohol Use With Long COVID and Chronic Liver Disease
  AASLD, The Liver Meeting, November 12-15, 2021
Mark Mascolini
Acute liver injury resolved in most of the 321 members of a US cohort with chronic liver disease and COVID-19, reported the University of Minnesota's Elizabeth Aby and the COVID-19 in Chronic Liver Disease (COLD) Study group* [1,2]. But overall morbidity in this group was high, and symptoms related to COVID-19, alcohol use, and excess weight persisted after resolution of acute COVID-19. Almost 1 in 5 alcohol users reported new or worsening alcohol use after recovery from their initial bout of COVID-19.
When people with chronic liver disease acquire COVID-19, the COLD team found earlier, they endure high rates of hospital admission (60%), intensive care unit admission (23%), and all-cause mortality (14%) [3]. COLD study researchers also determined that alcohol-related liver disease, hepatic decompensation, and hepatocellular carcinoma predict adverse outcomes with COVID-19.
The new COLD analysis aimed to explore long-term clinical outcomes of adults with chronic liver disease diagnosed with COVID-19 in the United States. At 15 centers across the country,* COLD investigators used electronic medical records to identify people with chronic liver disease and COVID-19, either inpatients or outpatients. The 321 people included all got diagnosed with COVID before May 30, 2020 to ensure a reasonable follow-up time. Researchers defined long COVID as symptoms starting at COVID diagnosis and lasting more than 12 weeks without another clear explanation.
COLD study participants had a median age of 56.5 years, and 45% were women. Cohort proportions by race or ethnicity were white 55.9%, black 24.7%, Asian 4.3%, and Hispanic 32%. Median follow-up lasted 364 days and ranged from 31 to 450 days; 80% of the cohort had more than 6 months of follow-up.
Nonalcoholic steatohepatitis (NASH) accounted for 52% of chronic liver disease cases, chronic hepatitis C virus (HCV) infection for 28%, alcohol for 7%, and chronic hepatitis B virus (HBV) infection for 4%. While 16% of the study group had compensated cirrhosis, 10% had decompensated cirrhosis.
During follow-up, 38% of the group got admitted to the hospital. Among people who survived more than 30 days from their COVID diagnosis, 7% had long-term mortality and 3% had "delayed COVID-19-related mortality" (median survival 96 days).
About one quarter of study participants, 26.5%, reported symptoms that suggested COVID-19 and lasted more than 12 weeks after diagnosis with no clear cause other than COVID: persistent dyspnea (difficulty breathing) in 11%, severe fatigue in 9.8%, depression in 7.2%, cough in 6.2%, arthralgias (joint stiffness) in 5.2%, and chest pain in 3.6%.
Multivariate analysis linked three factors to long COVID: Hospital admission for COVID-19 doubled the odds of long COVID: odds ratio (OR) 1.9, 95% confidence interval (CI) 1.0 to 3.5 (P = 0.03). Hispanic ethnicity boosted odds of long COVID 80% (OR 1.8, 95% CI 1.0 to 3.4, P = 0.05), while obesity cut the odds 40% (OR 0.6, 95% CI 0.3 to 0.9, P = 0.04). Gender, age over 65, HCV infection, or nonalcoholic fatty liver disease (NAFLD) did not affect odds of long COVID.
After the initial COVID bout resolved, standard liver tests all improved significantly, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and Hepatitis C international normalized ratio (INR). COVID-19 resolution also heralded significant improvement in white blood cell count, lymphocytes, and neutrophils.
One quarter of cohort members (24.3%) rated their alcohol use moderate to heavy after they recovered from their initial COVID-19 episode. Among people with moderate to heavy alcohol use, 18% confirmed new or worsening alcohol drinking after recovery from COVID-19, and 18% reported alcohol-related medical complications. One third of participants, 32%, gained a median of 10 pounds in body weight.
The COLD investigators believe their findings show "the impact of COVID-19 in patients with chronic liver disease extends beyond the acute infection," including long COVID symptoms in 25% and unhealthy alcohol use and diet. The researchers noted that the COVID pandemic resulted in "massive collateral damage" caused by deferred care, faulty adherence to medication schedules, and heavier alcohol drinking. Heavier drinking is a particularly worrisome outcome in people who already have chronic liver disease or risk liver disease. "Early anecdotal reports," the researchers warned, suggest "an increasing number of hospitalizations for alcohol-related liver disease during the pandemic."
1. Aby E, and COLD Study investigators. Long-term clinical outcomes of patients with COVID-19 and chronic liver disease: US multicenter study COLD study. AASLD, The Liver Meeting, November 12-15, 2021. Parallel session 9: COVID-19 Translational and Clinical. 2. ClinicalTrials.gov. COVID-19 in Patients With Chronic Liver Diseases (COLD).
ClinicalTrials.gov identifier NCT04439084. https://clinicaltrials.gov/ct2/show/NCT04439084 3. Kim D, Adeniji N, Latt N, et al. Predictors of outcomes of COVID-19 in patients with chronic liver disease: US multi-center study. Clin Gastroenterol Hepatol. 2021;19:1469-1479.e19. doi: 10.1016/j.cgh.2020.09.027. Epub 2020 Sep 17.
*The COLD Study principal investigator is Renumathy Dhanasekaran of Stanford University. Other study sites are the Mayo Clinic in Arizona; the University of Arizona; University of California San Francisco, Fresno; University of Southern California; Oschner Medical Center, Louisiana; Beth Israel Deaconess Medical Center, Boston; Massachusetts General Hospital, Boston; University of Michigan; University of Minnesota; Hennepin County (Minnesota) Medical Center; University Hospitals Cleveland Medical Center; University of Pennsylvania; University of Pittsburgh; and the VA Medical Center, Washington, DC.