Episode 58: Transaminitis.
Elevated aminotransferases can be caused by intrahepatic and extrahepatic causes, Dr Martinez and Dr Civelli explain the workup of transaminitis, distribution of Chantix was stopped by Pfizer, smoking cessation updates
Introduction: Smoking Cessation Updates
By Hector Arreaza, MD, Valeri Civelli, and Yosbel Martinez, MD
On June 25, 2021, Pfizer stopped distribution of some badges of Chantix(r) after high levels of the carcinogen N-nitroso-di-methyl-amine (NDMA) were found in some lots of the pills. “Pfizer told Reuters the distribution pause was ordered out of abundance of caution while further testing is conducted.”
The FDA approved Varenicline in 2006, and there is evidence that Chantix is the most effective anti-smoking medication.
USPSTF Grade A recommendations:
1. All adults should be asked about their tobacco use. Then, if determined to be smokers or tobacco users, advise them to quit, and provide behavioral interventions and FDA-approved medications for cessation. This applies to all adults who are not pregnant and use tobacco.
2. All pregnant patients should be asked about their tobacco use, advised to quit using tobacco, and offer behavioral interventions for cessation.
USPSTF Grade I (I stands for “I don’t know”):
1. The USPSTF does not endorse or discourages the use of pharmacotherapy for smoking cessation in pregnant patients because there is insufficient evidence.
2. E-cigarettes have insufficient evidence to be recommended as an effective way to stop smoking in adults.
This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home.
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Transaminitis.
By Yosbel Martinez, MD
Transaminitis is a way to say elevated aminotransferases. When you see “itis” at the end of a word, it normally means “inflammation” in medical terms, and for that reason transaminitis is not etymologically correct, but it’s easy to use and everyone understands what it means.
What are aminotransferases?
Aminotransferases are intracellular enzymes that are a sensitive indicator of liver cell injury (necrosis or inflammation).
-ALT (alanine aminotransferase) is a more specific measure of liver injury
-AST (aspartate aminotransferase) is less specific because it is also found in striate muscle, heart, brain, kidney and Red and white blood cells.
There is a poor correlation between degree of liver cell damage and level of aminotransferases. Low levels of transaminases may be seen even in some instances when the liver is severely and terminally damaged, for example, in cirrhosis.
General approach of transaminitis > 6 months (asymptomatic patient)
Step 1: Initial evaluation for most common liver conditions.
1. Drugs (herbal or recreational drugs) or medications (acetaminophen, INH, amiodarone, statins)
2. Hepatitis A, B, C
3. Alcoholic hepatitis (AST/ALT ratio above 2:1)
4. Fatty Liver AST/ALT < 1 (may perform RUQ ultrasound to confirm diagnosis)
5. Hemochromatosis (iron/TIBC > 45%)
Hereditary hemochromatosis is an autosomal recessive disorder of the metabolism of iron. It is the most common genetic disease in Caucasians. Women have the protective effect of menstruation, which serves as a monthly phlebotomy until they reach menopause, and hemochromatosis may become symptomatic. Men are more prone to iron-overload disease compared with women.
Hemochromatosis is asymptomatic in early stages. Some common symptoms include arthralgias, low energy, weakness, and erectile dysfunction in men. Later manifestations include arthralgias, osteoporosis, cirrhosis, hepatocellular cancer, cardiomyopathy, dysrhythmia, diabetes mellitus, and hypogonadism.
Screening with iron levels should be ordered in patients with first-degree relatives with classical hemochromatosis.
Diagnosis requires confirmation of increased serum ferritin levels and transferrin saturation, with or without symptoms.
Treatment includes regular phlebotomy guided by serial measurements of serum ferritin levels and transferrin saturation. Iron restriction in diet is normally not needed. Screening for hepatocellular carcinoma is reserved for those with hereditary hemochromatosis and cirrhosis.
Statins
Statins are very important in prevention of treatment of cardiovascular disease. They are safe.
“The risk of hepatic injury caused by statins is estimated to be about 1 percent, similar to that of patients taking a placebo.” Patients with transaminitis below three times the upper limit of normal can continue taking statins safely. Nonalcoholic fatty liver disease and stable hepatitis B and C are not contraindications to statin use. Atorvastatin is contraindicated in active liver disease or in patients with unexplained persistent transaminitis.
Step 2: When you have not determined the source of transaminitis
1. Less common liver conditions:
-Autoimmune hepatitis (more common in women, order SPEP, ANA, ASMA)
-Wilson disease (order ceruloplasmin, look for Kayser-Fleischer rings around the iris of eyes)
-Alfa 1- antitrypsin deficiency (presents with severe emphysema, order AA-1 level)
-Other viral hepatitis: D, E, CMV, EBV, HSV, VZV.
2. Non-Hepatic source.
-Muscle disorder (obtain CK, aldolase)
-Thyroid disease (order TSH, FT4)
-Celiac disease or IBD (obtain IgA anti-tissue transglutaminase, Calprotectin, CRP, P-ANCA, or perform MRCP/ERCP if indicated).
-Adrenal insufficiency (8 am cortisol level and plasma ACTH)
-Anorexia nervosa (assess BMI, recommend psychiatric evaluation, obtain electrolytes and ECHO)
Step 3: Final step of evaluation.
Liver biopsy for diagnostic, staging and grading of liver disease.
Now we conclude our episode number 58 “Transaminitis”. Dr Martinez and Dr Civelli explained what to do when we find elevated aminotransferases. Remember you can have intra-hepatic and extra-hepatic causes. If you cannot determine what’s causing transaminitis, you may need to ask for a liver biopsy. Even without trying, every night you go to bed being a little wiser.
Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Yosbel Martinez, and Valerie Civelli. Audio edition: Suraj Amrutia. See you next week!
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References:
Pfizer Halts Distribution of Stop-Smoking Pill Chantix, WebMD, webmd.com, accessed on Jul 6, 2021. https://www.webmd.com/smoking-cessation/news/20210625/chantix-distribution-halted-pfizer.
Tobacco Smoking Cessation in Adults, Including Pregnant Persons: Interventions, United States Preventive Services Taskforce, uspreventiveservicestaskforce.org, accessed on Jul 6, 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions
Crownover BK, Covey CJ. Hereditary hemochromatosis. Am Fam Physician. 2013 Feb 1;87(3):183-90. PMID: 23418762. https://www.aafp.org/afp/2013/0201/p183.html
Gillett RC Jr, Norrell A. Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. Am Fam Physician. 2011 Mar 15;83(6):711-6. PMID: 21404982. https://www.aafp.org/afp/2011/0315/p711.html
