COVID-19, Vaccines and Liver Disease Plus AAP Declares Mental Health Emergency

OK Fix et al. Hepatology 2021; 74: 1049-1064. Open Access. American Association for the Study of Liver Diseases Expert Panel Consensus Statement: Vaccines to Prevent Coronavirus Disease 2019 Infection in Patients With Liver Disease

“Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.”

A Saviano et al. Hepatology 2021; 74: 1088-1100. Open Access (Review) Liver Disease and Coronavirus Disease 2019: From Pathogenesis to Clinical Care

  • “The presence of liver injury is a surrogate marker for more severe disease and higher mortality in patients with COVID-19. An elevated AST level is the most robust predictor of poor outcome.”
  • “Liver injury and mortality in COVID-19 are likely multifactorial, driven by a sustained and excessive systemic release of proinflammatory and prothrombotic cytokines following SARS-CoV-2 infection, iatrogenic injury caused by DILI, hemodynamic changes associated with mechanical ventilation or vasopressor use, and worsening of underlying liver injury in those with CLD.”
  • “Risk of de novo liver injury appears limited in patients without CLD, and only rare cases of COVID-19–related ACLF [acute-on-chronic liver failure] were observed.”

Related blog post: Aspen Webinar 2021 Part 1: COVID-19 and the Liver (William Balistreri)

“COVID-19–related liver injury and mortality in patients who were hospitalized with and without chronic liver disease (CLD). Patients without CLD usually present with AST elevation, which correlates with ICU admission and mortality. Among patients with CLD, NAFLD has the highest risk of severe illness, ICU admission, and need for mechanical ventilation. Patients with cirrhosis are at risk for decompensation, and patients who are decompensated have a high risk of acute-on-chronic liver failure (ACLF) and mortality.”Abbreviations: CTP, Child-Turcotte-Pugh; ICU, intensive care unit.

Link to AAP News: AAP, AACAP, CHA declare national emergency in children’s mental health (Thanks to Ben Gold for passing this along)

  • “We are caring for young people with soaring rates of depression, anxiety, trauma, loneliness, and suicidality that will have lasting impacts on them, their families, their communities, and all of our futures,” said AACAP President Gabrielle A. Carlson, M.D. “We cannot sit idly by. This is a national emergency, and the time for swift and deliberate action is now.”
  • These organizations make several recommendations to policy makers including more access for mental health services. (I worry that we do not have sufficient numbers of qualified mental health practitioners to meet the challenge.)

COVID Booster Advice for IBD from Dr. David Rubin (@IBDMD)

On Friday, our office started fielding questions regarding COVID-19 booster shots in our IBD population. Currently, I agree with the advice for patients as detailed by Dr. Rubin in the screenshots that follow. Key points:

  • Studies have shown that IBD patients are not at increased risk of COVID-19 infections compared to the general population. 
  • Except for those on high-dose prednisone, it appears that our patient population with IBD does mount an adequate response to vaccination.  That is, they are not considered severely immunocompromised. 
  • In short, it is reasonable, but not a clear recommendation, to give a booster mRNA vaccine dose to patients who are receiving anti-TNF agents and those receiving immunomodulators; this is a patient choice.

Also, from CDC 8/13/21:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Risks of Vaccines Compared to COVID-19 Infection in 12-17 Year Olds

NY Times: Covid Is a Greater Risk to Young People Than the Vaccines (July 4, 2021)

This article elaborates on the risks of vaccination, especially due to myocarditis, compared to the risks posed by COVID-19 infection. Even using very cautious estimates, the authors find that the risks of hospitalizations, cardiac morbidity, and deaths are likely to be much lower in those who receive the vaccine.

Key points:

  • “Among the 6.14 million Americans 17 and under who have been fully vaccinated, there have been 653 possibly related hospitalizations lasting a day or longer…. If that rate holds, it means that if all 73 million Americans ages 17 and under are eventually vaccinated, there will be around 7,700 hospitalizations.”
  • “So far, 326 Americans age 17 and younger have died of Covid-19.”
  • “If the coronavirus were eventually to infect all 73 million children in the United States, we would conservatively expect Covid-19 to be responsible for around 14,600 hospitalizations….[and] lead to over 27,000 additional hospitalizations from the [MIS-C] syndrome.”
  • Unlike hospitalizations related to vaccines which have typically been brief and uneventful, “Covid-related hospitalizations in adolescents can be long and complicated, with nearly one-third requiring patients to enter the intensive care unit.”
  • “Bad things inevitably happen to a small number of people after any vaccination, a few caused by the vaccines, but most not…The virus is more dangerous.”

My take: 12-17 year olds are at less risk from COVID-19 infection than other age groups, however, this risk is still greater risk than the risk of vaccination. Protecting them with immunizations also protects other vulnerable populations and may decrease the risk of vaccine-resistant variants.

Related article: Eric Topol NY Times: It’s Time for the F.D.A. to Fully Approve the mRNA Vaccines An excerpt: “Now more than 180 million doses of the Pfizer vaccine and 133 million of Moderna’s have been administered in the United States, with millions more doses distributed worldwide. In the history of medicine, few if any biologics (vaccines, antibodies, molecules) have had their safety and efficacy scrutinized to this degree…it’s frankly unfathomable that mRNA vaccines have been proved safe and effective in hundreds of millions of people and yet still have a scarlet “E”.”

COVID-19 Vaccine in Israel: Rapid Reduction in Risk of Death

N Dagan et al. NEJM 2021;384:1412-23. DOI: 10.1056/NEJMoa2101765. PDF: BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

Each study group (vaccinated and unvaccinated) included 596,618 persons. Key finding:

  • Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose.

Persistent Symptoms After COVID-19, FAQs, and New Strain

A large study from Wuhan showed that after 6 months following hospitalization, most still had lingering symptoms.

Full text: C Huang et al. Lancet DOI:https://doi.org/10.1016/S0140-6736(20)32656-8; 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Key point: At 6 months after acute infection, COVID-19 survivors (n=1733 enrolled in study) were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations

NY Times analysis (Jan 8, 2021): 6 Months After Leaving the Hospital, Covid Survivors Still Face Lingering Health Issues

  • The most common issue was ongoing exhaustion or muscle weakness, experienced by 63 percent of the patients
  • About one-quarter of the patients reported difficulty sleeping
  • 23 percent said they experienced anxiety or depression
  • “Some of the sickest patients were excluded, so perhaps some of the outcomes that were reported would be worse if those patients were included”

NEJM Link: COVID-19 Vaccine: Frequently Asked Questions

NY Times (1/15/21): C.D.C. Warns the New Virus Variant Could Fuel Huge Spikes in Covid Cases “The new variant, called B.1.1.7, was first identified in Britain, where it rapidly became the primary source of infections, accounting for more than 80 percent of new cases diagnosed in London and at least a quarter of cases elsewhere in the country.”

COVID-19 -Now #1 Cause of Death in U.S.

S Woolf et al. JAMA. Published online December 17, 2020. doi:10.1001/jama.2020.24865: Full text: COVID-19 as the Leading Cause of Death in the United States

  • Between November 1, 2020, and December 13, 2020, the 7-day moving average for daily COVID-19 deaths tripled, from 826 to 2430 deaths per day
  • As occurred in the spring, COVID-19 has become the leading cause of death in the United States (daily mortality rates for heart disease and cancer, which for decades have been the 2 leading causes of death, are approximately 1700 and 1600 deaths per day, respectively)

Related blog posts:

Vaccine Strategy: Nate Silver’s twitter feed suggests that after vaccination of medical personnel, focus of vaccine efforts should rely on age rather than at-risk conditions (which could affect 100 million in U.S). Using an age-based system would also be easier; it would minimize influence and wealth in the distribution of the vaccine.

Treating Pediatric Hepatitis C Infections is Cost-Effective. Plus COVID-19 mRNA Vaccine Study

E Greenaway et al. J Pediatr 2020; DOI:https://doi.org/10.1016/j.jpeds.2020.08.088. Free full text: Treatment of Chronic Hepatitis C in Young Children Reduces Adverse Outcomes and Is Cost-Effective Compared with Deferring Treatment to Adulthood

Methods: A state-transition model of chronic HCV was developed to conduct a cost-effectiveness analysis comparing treatment at age 6 years vs delaying treatment until age 18 years

Key findings:

  • After 20 years, treating 10 000 children early would prevent 330 cases of cirrhosis, 18 cases of hepatocellular carcinoma, and 48 liver-related deaths
  • The incremental cost-effectiveness ratio of early treatment compared to delayed treatment was approximately $12 690/quality-adjusted life-years gained and considered cost-effective

My take (=conclusion from authors): Delaying treatment until age 18 years results in an increased lifetime risk of late-stage liver complications. Early treatment in children is cost effective. Our work supports clinical and health policies that broaden HCV treatment access to young children.

Related blog posts:


FP Polack et al. NEJM Full text link: Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Published data on the Pfizer/BioNTech vaccine

Expert Update on COVID-19 Pandemic and Vaccine Rollout

Our hospital system has been arranging frequent staff meetings to provide situational updates amid the pandemic. On 12/2/20, Evan Anderson (infectious disease) provided an ​an excellent update on COVID-19​/rollout of vaccines.

Key Points:

  • mRNA vaccines​ have been remarkably effective, both ~95% and also effective against severe disease (>90%)
  • Severe reactogenicity occurs >2%. Systemic symptoms like fatigue, myalgia, and chills are more common after 2nd dose
  • Local reactions are typically more pronounced than flu vaccine but less pronounced compared to shingles vaccine (Shingrix)
  • Not wise to vaccinate entire care areas at same time
  • No need to check antibody titers after vaccination
  • Current contraindications: Pregnant women and children due to lack of data (Pfizer vaccine may be approved for those older than 12 yrs)
  • Study participants were allowed to take antipyretics
Slides used with permission.

Current pandemic situation in metro Atlanta (slide from Dan Salinas)

Top curve is total cases and bottom curve is ICU beds –both thru 11/27/20

Related blog posts:

New Information on Hepatic Artery Thrombosis in Pediatric Liver Transplantation & COVID-19 Vaccine Timeline

NE Ebel et al. J Pediatr 2020; 226: 195-201. Decreased Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation Using Technical Variant Grafts: Report of the Society of Pediatric Liver Transplantation Experience

This study used multicenter data from the Society of Pediatric Liver Transplantation on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada (1995-2016).

Key findings:

  • 7.4% developed HAT within the first 90 days of transplantation.
  • Of those who were retransplanted, 20.7% developed recurrent HAT.
  • Those less than 1 year had the highest risk OR 1.20).
  • Lower Risk for HAT:
    • Recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts)
    • Adolescents aged 11-17 years (OR, 0.53; P = .03).
  • HAT increased risk of graft failure and mortality:
    • Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62)
    • Mortality risk (w/in 90 days after transplantation): adjusted hazard ratio, 6.18 (95% CI, 4.01-9.53).

The finding that split grafts had lower rates of HAT may be related to the fact that these grafts more typically come from larger donors with larger vessels. Historically, split grafts had been described as a risk factor for HAT. The authors note that high-performing centers with the lowest incidence of HAT “also tend to have high rates of living and split transplants, suggesting that surgical expertise may play a role in the decreased risk of HAT in select recipients with technical variant grafts.”

Increased rates of HAT among those who were retransplanted, in some, could be related to thrombophilic conditions; thus, consideration of anticoagulation protocol could be needed

My take: Continued efforts are needed to reduce HAT due to its impact on liver transplantation outcomes. One of the biggest risk factors is age. While this would seem to be a nonmodifiable factor, improving recognition and treatment of biliary atresia could help.

Related blog posts: