26. Alcoholic Hepatitis
• Excessive alcohol use=
• Male- more than 21 standard drinks / week
• Female- more than 14 standard drinks / week
• Binge drinking
• AST/ALT>2
• CAGE test
27. Drug-Induced Hepatitis
• Direct toxic effect
• Dose related effect
• Short latency period
• Acetaminophen hepatotoxicity
• Idiosyncratic reaction
• Immunologically mediated
• Non predictable latency
• Halothane , isoniazid , methyldopa , valproic acid , and
trimethoprim/sulfamethoxazole
31. Wilson Disease
• Less than 40yrs
• Neuropsychiatric symptoms, Kayser-Fleischer ring
• Laboratory findings-
• ↓ceruloplasmin
• ↑urinary copper excretion
• Treatment- D -penicillamine
44. Mildly elevated liver enzymes
• Less than 5 time upper limit?
• Recheck 3-6 months
• If still high- search for uncommon
• Recheck 3-6 months
• If still high- search for rare
45. Mildly elevated liver enzymes
• When to refer?
• Unexplained, persistent liver biochemical
test elevations
• Biopsy is considered
49. References
• Primary Care Medicine, Goroll 8th edition:
• Chapter 62 Evaluation of Jaundice
• Appendix 62-1: Evaluation of the Asymptomatic Patient with an Incidental Elevation in a Liver
Function Test
• Chapter 70 Management of Hepatitis
• Chapter 71 Management of Cirrhosis and Chronic Liver Failure
• AAFP
• Evaluation of Jaundice. Am Fam Physician. 2017 Feb 1;95(3):164-168.
• Cirrhosis. Am Fam Physician. 2019 Dec 15;100(12):759-770.
• Hepatitis B. Am Fam Physician. 2019 Mar 1;99(5):314-323.
• Hepatitis C. Am Fam Physician. 2015 Jun 15;91(12):835-842.
• Hereditary Hemochromatosis. Am Fam Physician. 2013 Feb 1;87(3):183-190.
• Mildly Elevated Liver Transaminase Levels. Am Fam Physician. 2017 Dec 1;96(11):709-715.
• Nonalcoholic Fatty Liver Disease. Am Fam Physician. 2020 Nov 15;102(9):603-612.
• Celiac Disease, Am Fam Physician. 2014 Jan 15;89(2):99-105
50. Thank you!
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Definitions.
In this talk we will discuss an incidental abnormal LFT in the asymptomatic patient.
Image source- https://www.positivelyaware.com/files/7a-your-liver-and-hepatitis-normal-liver-cirrhosis-500x400pxjpg
AST (SGOT) is normally found in a variety of tissues including liver, heart, muscle, kidney, and the brain.
ALT (SGPT) is, by contrast, normally found largely in the liver.
The alkaline phosphatase (ALP) isoenzymes of clinical interest are derived from the liver, bone, first trimester placenta, and kidneys
Image source:
https://www.medicinenet.com/liver_blood_tests/article.htm
https://www.labpedia.net/alkaline-phosphatase-level-alp/
https://www.youtube.com/watch?app=desktop&v=Mall9GEMCXg&ab_channel=MediLabAcademy
Celiac Disease - p99 – 2014
Chronic inflammation of the small intestinal mucosa, gluten mediated
Images sources-
https://share.baptisthealth.com/symptoms-celiac-disease/
https://www.mayoclinic.org/diseases-conditions/celiac-disease/symptoms-causes/syc-20352220
Elevated liver enzyme might be measure in certain contions not involving the liver directly
After sternous activity an intermittent rise in LFT is measured, as in CPK
Thyroid, and especially Hyperthyroidism is related to increased LFT
HBV hepatitis progression to cirrhosis can be effectively monitored using levels of viral DNA.
The viral DNA is also a marker that indicates response to treatment.
2127, 2132, 2145
Hepatitis B - p314 - 2019
Unlike HBC, in HCV the viral load is not related in a predictable manner to the disease progression.
Therefore, blood tests and imaging is used to monitor progression to fibrosis.
2133, 2154,
Hepatitis C - p835 - 2015
FIB-4 is calculated using clinical and blood test values, and gives a first estimate to progression
In patients with high risk FIB-4 score, a Fibrotest lab exam is preformed to increase the accuracy of fibrosis prediction.
A liver biopsy is the only way to truly asses the extent of fibrosis.
2139
https://www.hepatitisc.uw.edu/page/clinical-calculators/fib-4
Cirrhosis - p759 – 2019
https://www.biopredictive.com/he/products/fibrotest-actitest/
Sensitivity and specificity of non invasive methods to asses fibrossis
Cirrhosis - p759 - 2019
According to Israeli guidelines 2013, HCV screening is warranted in high risk groups- hemodyalisis patients, IV drug users, migrants..
https://uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-c-screening
Today, it is highly recommended to screen everybody at least once in a life time for HCV
Since medication is highly effective and change the course of disease
There are many other viruses that might cause an intermittent rise in LFT
Acute= less than 6 months. Chronic= more than 6 months
2167, 2135
NAFLD - p603 – 2020
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/cld.716
While NAFLD is mostly benign condition, NASH is highly related to fibrosis, cirrhosis and primary liver malignancy.
The only way to distinguish NAFLD from NASH is by liver biopsy
2140- NAFLD score
https://nafldscore.com/
NAFLD is diagnosed after using non-invasive modalities (blood tests, imaging) in order to exclude other etiologies for hepatitis.
After that, the risk for fibrosis is evaluated.
High risk patients will be referred to a biopsy, in order to detect NASH and early detect cirrhosis complications
https://www.news-medical.net/health/Esophageal-Varices.aspx
https://www.researchgate.net/figure/Causes-of-liver-cancer-hepatocellular-carcinoma_fig1_329145392
Referral of NASH patient to hepatology follow-up is crucial in order to early detect cirrhosis and its complication, such a s varices and HCC
An example to management algorithm from AAFP, NAFLD 2020
It’s important to screen for alcoholism.
A male patient with drinking problem might drink 3 drinks per day, or 7 drinks during the weekend (3*7=21)
2196
5464
5473
Image source- https://www.niaaa.nih.gov/alcohols-effects-health/overview-alcohol-consumption/what-standard-drink
https://en.wikipedia.org/wiki/Standard_drink
Some drugs cause a dose effective effect- the higher the dose, the higher the liver injury.
Acetaminophen is a classical example to this mechanism of injury.
Idiosyncratic reaction= not dose related. The reaction can be related to the drug or it’s metabolites.
Re-exposure to the drug in this kind of reaction can be more extreme than first exposure.
2129
1947
Mildly Elevated Liver Transaminase - p709 - 2017
Up-to-date, Hepatotoxicity due to herbal medications and dietary supplements
2134, 2164
Image source: https://www.youtube.com/watch?v=eqRLwAKkDoM&ab_channel=MedicosisPerfectionalis
UTD- Overview of autoimmune hepatitis
Both Wilson disease an hereditary hemochromatosis(HH) are autosomal recessive, and will show signs later in life
In HH iron deposition in multiple organs cause diabetes (pancreas), CHF (cardiomyopathy)
1942, 2197, 2020
Image source- https://www.msdmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis
Portal vein thrombosis have a chronic variant, when collateral blood supply is developed
https://www.sciencedirect.com/science/article/abs/pii/S0016508519303725
Some drugs might cause a cholestatic injury in dose related or idiosyncratic manner
2130
https://www.ncbi.nlm.nih.gov/books/NBK547852/
Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis), UTD
1943
2197
2201
The treatment to PSC is Ursodiol. However, unlike PBC, in PSC the treatment does not changes the course of disease.
Most patient will need a liver transplant.
Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis, UTD
1943
Image source- https://www.nejm.org/doi/full/10.1056/NEJMra1506330
Normal MRCP- https://www.dartmouth.edu/~anatomy/HAE/Radiology_Intro/MRI/mri4/mri4d.html
PSC MRCP- https://liveratlas.org/diagnosis/20/?modality=mr
Harrisons’ 20ed
Mildly Elevated Liver Transaminase - p709 - 2017
UTD- Approach to the patient with abnormal liver biochemical and function tests
Israeli preventative medicine guidelines don’t relate to LFT screening
Secondary prevention is relating to the detection of asymptomatic patients with possible liver injury, based on risk factor stratification
Does risk factors for NAFLD are included? No (not yet?)
Currently, there is no recommendation to use LFT in order to screen healthy population.
However, the benefit of screening patients with high risk to develop NAFLD is still unclear.
American guidelines (ACG) do not address screening healthy population.
Evaluation of Jaundice. https://www.aafp.org/afp/2017/0201/p164.html
Cirrhosis. https://www.aafp.org/afp/2019/1215/p759.html
Hepatitis B. https://www.aafp.org/afp/2019/0301/p314.html
Hepatitis C. https://www.aafp.org/afp/2015/0615/p835.html
Hereditary Hemochromatosis. https://www.aafp.org/afp/2013/0201/p183.html Mildly Elevated Liver Transaminase Levels- https://www.aafp.org/afp/2017/1201/p709.html
Nonalcoholic Fatty Liver Disease- https://www.aafp.org/afp/2020/1115/p603.html
Celiac Disease- https://www.aafp.org/afp/2014/0115/p99.html
