Liver Shorts -March 2021. Neonatal liver disease, Hepatitis-Associated Aplastic Anemia & Two

S Kemme et al. JPGN 2021; 72: 194-201. Outcomes of Severe Seronegative Hepatitis-associated Aplastic Anemia: A Pediatric Case Series This small case series (n=4) with HAAA found that this condition was poorly responsive to steroids, azathioprine and tacrolimus; however, Anti-Thymocyte Globulin (ATG) was associated with sustained biochemical remission of the hepatitis. Two patients underwent hematopoietic stem cell transplantation. All patients had extensive investigations. All had evidence of systemic hyperinflammation (with markedly-elevated ferritin and soluble IL-2 R levels) and CD8+ T cell predominant liver tissue infiltration.

C Potter. JPGN Reports 2021; 1: e031. doi: 10.1097/PG9.0000000000000031. Full text: The Role of a NICU Hepatology Consult Service in Assessing Liver Dysfunction in the Premature Infant This was a retrospective observational study of 157 consecutive babies were evaluated by a single hepatologist. The approach outlined by this study:

  1. Workup: In the well and stable premature with elevated DB, “aminotransferases, AP, GGT, glucose, T4, TSH, UC, urine CMV PCR, and US with Doppler evaluation should be obtained…Coagulation studies in well babies with other evidence of good synthetic function are not necessary.” Empiric ursodeoxycholic acid may be given with weekly evaluation.
  2. Genetic testing: “Genetic panels are indicated in babies with no obvious risk factors after the first tier of studies…In critically ill babies with multisystem disease, critical whole exome sequencing (WES) is faster and provides broader results.”
  3. Sepsis: Babies with sudden increase in DB and ALT should be evaluated for sepsis (including urosepsis) and CMV.
  4. Nutritional support: Infants should be “supported with MCT and vitamin supplementation.”
  5. Severe liver disease: “Babies with coagulopathy and marked elevation of aminotransferases who have multiorgan failure in the first few days of life need to be evaluated for perinatal complications, severe metabolic disease, and gestational alloimmune liver disease (GALD). In this period, ischemic shock or infectious disease is much more common than primary liver disease, but the presentations can overlap.”
  6. Liver biopsy: “Liver biopsy should be pursued in babies whose cholestasis is not improving and the diagnosis is unclear.”
  7. Etiology: Infection, genetic disease, cardiac dysfunction, large heme loads, and hypothyroidism are common causes of liver dysfunction in the NICU. Common findings included trisomy 21-associated liver dysfunction (n=12), and thyroid disease. 6 patients had type 2 Abenathy shunts -only one required closure. Two patients had biliary atresia. Other liver diseases identified included GALD (n=2), PFIC2, Alagille, Alpha-one-antitrypsin, Cystic Fibrosis, and Niemann-Pick.

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Wahid N et al. AASLD 2020, Abstract 153. Summary from GI & Hepatology News: Liver-related deaths decline after Medicaid-expansion under ACA. “Beginning around 2015, liver-related deaths began to decline in expansion states by a mean of –0.6%, while they continued on an upward trajectory in the nonexpansion states…“It’s a no-brainer that the lack of insurance accessibility for the most vulnerable people in the United States meant that they were dying of cirrhosis instead of being transplanted,” said Elliot Benjamin Tapper, MD, of the University of Michigan, Ann Arbor.”

W-M Choi et al. Clin Gastroenterol Hepatol 2021; 19: 246-258. Effects of Tenofovir vs Entecavir on Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection: A Systematic Review and Meta-analysis “In a meta-analysis of studies of patients with chronic HBV infection, we found that TDF treatment was associated with a significantly lower (20%) risk of HCC than entecavir treatment. Randomized trials are needed to support this finding.” This analysis comprised 15 studies (61,787 patients; 16,101 patients given TDF and 45,686 given entecavir).

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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.

COVID-19: Excess Mortality in Younger Adults

From NEJM Journal Watch: COVID-19: Excess Mortality in Younger Adults

Excess mortality in younger adults: Among U.S. adults aged 25 to 44, there were 19% more deaths than expected — or 12,000 people — from March through July 2020. In JAMA, the researchers — including Dr. Rochelle Walensky, who has been nominated to lead the CDC — report that 38% of this excess mortality was directly from COVID-19, but that proportion varied by region. Deaths from COVID-19 were similar to or exceeded unintentional deaths from opioids in this age group in 2018 in several areas of the country. The authors write that this may be an underestimate of the COVID-19 mortality burden in younger adults, as they may have been undertested.”

Link to study: All-Cause Excess Mortality and COVID-19–Related Mortality Among US Adults Aged 25-44 Years, March-July 2020

Bariatric Surgery Reduced Obesity’s Premature Death from 8 years to 5 years in SOS Study

A recent study (LMS Carlsson et al. NEJM 2020; 383: 1535-43) was summarized in a quick take. Essentially, obese subjects who underwent bariatric surgery survived three years longer than a control group who had not undergone surgery but lived 5 years shorter than a reference group without obesity.

The authors speculate on the reasons why the bariatric subjects continued to have a lower life expectancy than controls after surgery:

  • Above-normal BMI even after surgery
  • Irreversible effects of obesity-related metabolic dysfunction
  • Surgical complications
  • Higher risk of alcohol abuse, suicide, and trauma (including fall-related); these factors were identified in the SOS study more often than in those who had not undergone bariatric surgery

Since there have been improvements in bariatric surgery since the time of this cohort underwent surgery (1987-2001), it is possible that the average gain in life expectancy would be greater.

Here are a few screenshots:

Phase 3 Trial of Budesonide for Eosinophilic Esophagitis & COVID-19 Deaths in U.S.

NY Times article:  U.S. Coronavirus Cases Are Rising Sharply, but Deaths Are Still Down

This article explains why deaths from COVID-19 have not increased despite increasing number of infections.  Three main reasons: increased testing -detects many with less severe symptoms, younger population are being infected, and new treatment approaches may be helping.  However, “the dip in coronavirus mortality will not necessarily last. As more people socialize, those with milder infections might end up ferrying the pathogen to vulnerable individuals…Recent upswings in coronavirus case numbers leave experts apprehensive of what’s to come. Death, when it occurs, tends to trail infection by about two to four weeks.”


The Budesonide Oral Suspension (BOS) resulted in 62% of BOS patients meeting the threshold of < 15 eos/hpf compared to 1% of placebo patients. From lead author, Ikuo Hirano: “the results of the BOS trial showed that BOS successfully treated both the symptoms and signs of EoE. The positive results will hopefully lead to an approved, safe and effective therapy for EoE.”

Abstract from ACG Meeting October 2019:

Abstract: Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis in Adolescents and Adults: Results From a Phase 3, Randomized, Placebo-Controlled Trial

Introduction: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease for which there is an unmet clinical need for new therapies. The safety and efficacy of budesonide oral suspension (BOS) for the treatment of EoE has been demonstrated in a previous phase 2 study. The current phase 3 study evaluated the efficacy and safety of BOS in a large cohort of patients with EoE. 

Methods: This randomized, double-blind, placebo-controlled trial (SHP621-301; NCT02605837) investigated the safety and efficacy of BOS in patients (11–55 years) with EoE and dysphagia. Patients were randomized 2:1 to 2.0 mg BOS or placebo twice daily (b.i.d.) for 12 weeks (Figure 1). Co-primary endpoints were histologic (peak eosinophil count ≤6 eosinophils/high-powered field [eos/hpf]) and dysphagia symptom (≥30% decrease in symptoms as measured by the Dysphagia Symptom Questionnaire [DSQ]) responses after 12 weeks of therapy. Secondary endpoints included change in DSQ score and change in EoE Endoscopic Reference Score (EREFS) from baseline to final treatment period. Safety was also assessed.

Results: A total of 322 patients were randomized (BOS, n=215; placebo, n=107), of whom 318 patients received at least one dose of double-blind therapy (BOS, n=213; placebo, n=105) (Table). The primary outcomes were achieved, with significantly more histologic and symptom responders in the BOS-treated than the placebo-treated group (53.1% vs 1.0%, p< 0.001; 52.6% vs 39.1%, p=0.024, respectively; Figure 2). Improvements in mean DSQ score from baseline to week 12 were significantly greater in the BOS group (n=197) than the placebo group (n=89) (−13.0 vs −9.1; p=0.015). Similarly, improvements in mean EREFS scores were significantly greater with BOS (n=202) than placebo (n=93) (−4.0 vs −2.2; p< 0.001). In total, 61.0% of patients reported a treatment-emergent adverse event (TEAE) (BOS, 61.0%; placebo, 61.0%). Only 2.5% of patients experienced a TEAE leading to dose discontinuation (BOS, 1.4%; placebo, 4.8%). Few patients had severe or serious TEAEs on BOS or placebo.  No life-threatening TEAEs were reported.

Discussion: This phase 3 trial demonstrated the efficacy of BOS as induction therapy for EoE. BOS resulted in significant improvements in histologic, symptomatic and endoscopic endpoints compared with placebo. The majority of TEAEs were mild to moderate and comparable between placebo and BOS. A double-blind, placebo-controlled maintenance study (SHP621-302) is ongoing.

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Island Ford, Sandy Springs

 

 

 

Updated Outcome Data for Necrotizing Enterocolitis

A recent systematic review (IH Jones, NJ Hall. J Pediatr 2020; 220: 86-92) provides contemporary outcomes for infants with necrotizing enterocolitis (NEC). The authors analyzed from 38 articles (from 1375 abstracts); the authors excluded data from developing countries. This review included 21,349 infants with any stage of NEC and 7540 with Bell stage 2a+.

Key findings:

  • Overall mortality was 23.5% in all neonates with confirmed NEC (Bell stage 2a+), 34.5% for infants who underwent surgery
  • Mortality rates were higher for extremely low birthweight infants (<1000 g) at 40.5%; the rate was 50.9% for surgical NEC in this cohort
  • Neurodevelopmental disability was reported in only 4 studies and ranged between 24.8% and 61.1% (n=1209)
  • Intestinal failure was reported with an incidence of 15.2% to 35.0% (n=1370)

A limitation with this study is the lack of agreement on definitions/diagnosis for necrotizing enterocolitis and intestinal failure.

My take: This study shows that NEC still carries a high mortality.

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Sandy Springs

How The IRS Proved That Health Insurance Saves Lives

NY Times: The I.R.S. Sent a Letter to 3.9 Million People, It Saved Some of Their Lives

Recently, economists have shown that an I.R.S. letter encouraging people to sign up for health insurance saved lives.  This letter was an inadvertent randomized trial as 600,000 people who were eligible for the letter did not receive it due to a budget shortfall.

An excerpt:

Three years ago, 3.9 million Americans received a plain-looking envelope from the Internal Revenue Service. Inside was a letter stating that they had recently paid a fine for not carrying health insurance and suggesting possible ways to enroll in coverage…

Obtaining insurance… reduced premature deaths by an amount that exceeded any of their expectations. Americans between 45 and 64 benefited the most: For every 1,648 who received a letter, one fewer death occurred than among those who hadn’t received a letter.

In all, the researchers estimated that the letters may have wound up saving 700 lives…

The results also provide belated vindication for the much-despised individual mandate that was part of Obamacare until December 2017, when Congress did away with the fine for people who don’t carry health insurance…

The uninsured rate for Americans is rising for the first time in a decade, as states tighten eligibility rules for Medicaid, and as the Trump administration cuts back on health care outreach…

Previous research has found a link between expanded health insurance access and fewer deaths. Multiple studies showed a decline in mortality rates after states expanded Medicaid, but none could tie the outcome directly to the policy change, since states typically cannot randomly pick which residents do and don’t receive Medicaid. That makes the Treasury experiment, an unintended result of a budget shortfall, distinctively useful.

My take: This analysis shows that prompting health care coverage by sending a single letter can save lives.  It is unfortunate that we are currently heading in the opposite direction.

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NY Times: “Our Food is Killing Too Many of Us”

NY Times: D Mozaffarian, D Glickman Our Food is Killing Too Many of Us

“Improving American nutrition would make the biggest impact on our health care”

An excerpt:

“Instead of debating who should pay for all this, no one is asking the far more simple and imperative question: What is making us so sick, and how can we reverse this so we need less health care? … our food…

Poor diet is the leading cause of mortality in the United States, causing more than half a million deaths per year. Just 10 dietary factors are estimated to cause nearly 1,000 deaths every day from heart disease, stroke and diabetes alone…

Taxes on sugary beverages and junk food can be paired with subsidies on protective foods like fruits, nuts, vegetables, beans, plant oils, whole grains, yogurt and fish….Levels of harmful additives like sodium, added sugar and trans fat can be lowered through voluntary industry targets or regulatory safety standards

Nutrition standards in schools, which have improved the quality of school meals by 41 percent, should be strengthened; the national Fresh Fruit and Vegetable Program should be extended beyond elementary schools to middle and high schools…

Coordinated federal leadership and funding for research is also essential. This could include, for example, a new National Institute of Nutrition at the National Institutes of Health. Without such an effort, it could take many decades to understand and utilize exciting new areas, including related to food processing, the gut microbiome, allergies and autoimmune disorders, cancer, brain health, treatment of battlefield injuries and effects of nonnutritive sweeteners and personalized nutrition.”

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Crater Lake, OR

 

Bariatric Surgery Survival – 5 Countries, 500,000 Participants

A recent population-based cohort study (JH Kauppila et al. Gastroenterol 2019; 157: 19-27) examined the effects of bariatric surgery on survival from Nordic countries between 1980-2012.

Link: Effects of Obesity Surgery on Overall and Disease-Specific Mortality in a 5-Country Population-Based Study

Among 505,258 obese individuals, 49,977 had bariatric surgery.

Key findings:

  • Overall mortality rates were lower in the surgery group during the first 14 years but higher after 15 years (HR 1.20 with CI 1.02-1.42).  Thus, overall, obese patients who underwent bariatric surgery had longer survival times than obese patients who did not have surgery.  Both groups had higher mortality than the general population
  • The improved survival compared to those without surgery was related to decreased mortality from cardiovascular mortality, diabetes and cancer.  However mortality due to suicide was increased.
  • Limitations: lack of detailed data including BMI, smoking and alcohol consumption

Graphical abstract (available online)

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Tweet Updates: Nutrients Helpful in Foods Rather Than Supplements, More ID Doctors Needed

 

Yesterday’s post highlighted a study which indicated that low quality diets result in signiificant mortality.  The tweets below refer to a study which indicated that supplements generally do not help one achieve a good diet.  For a diet to be effective, the nutrients need to be present in the diet.

 

Bad Diets –>High Mortality

A recent article in Lancet (“Health effects of dietary risks in 195 countries, 1990–2017:
a systematic analysis for the Global Burden of Disease Study 2017″ -open access) estimated that bad diets lead to 11 million deaths per year. Thanks to Ana Ramirez for sending me this article. “High intake of sodium, low intake of whole grains, and low intake of fruits were the leading dietary risk factors for deaths and DALYs globally and in many countries.”

A summary of this study was reported on NPR: Bad Diets Are Responsible For More Deaths Than Smoking, Global Study Finds

An excerpt:

About 11 million deaths a year are linked to poor diet around the globe…

As part of a new study published in The Lancet, researchers analyzed the diets of people in 195 countries using survey data, as well as sales data and household expenditure data. Then they estimated the impact of poor diets on the risk of death from diseases including heart disease, certain cancers and diabetes. (They also calculated the number of deaths related to other risk factors, such as smoking and drug use, at the global level.)…

“Generally, the countries that have a diet close to the Mediterranean diet, which has higher intake of fruits, vegetables, nuts and healthy oils [including olive oil and omega-3 fatty acids from fish] are the countries where we see the lowest number of [diet-related] deaths,” …

What would happen if everyone around the globe began to eat a healthy diet, filling three-fourths of their plates with fruits, vegetables and whole grains? We’d run out…

Improving diets won’t be easy: A range of initiatives may be needed, including nutrition education and increased access to healthy foods, as well as rethinking agricultural production.

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