Abnormal liver function tests
- 1. General Approach: Abnormal Liver Function Tests Itamar Tzadok, MD 24/02/2021
- 2. History • Exposure to hepatotoxins • Medications • OTC / dietary supplements • Drugs, alcohol • Risk for viral hepatitis • Related medical conditions • Obesity, DM, metabolic syndrome • IBD, celiac, thyroid • CHF (cardiomyopathy) • Occupational/recreational exposure • Family history
- 3. Physical examination • Stigmata of liver disease
- 4. Terminology • Abnormal liver biochemical and function tests • Hepatitis • Cirrhosis • Jaundice
- 5. Liver functions tests (LFT) Synthetic Cholestatic Hepatocellular Bilirubin ALP AST Albumin GGT ALT PT
- 6. Classification of LFT patterns (Goroll) • Isolated Elevation in Serum Aminotransferase (Hepatocellular) • Isolated Elevation of Alkaline Phosphatase (Cholestatic) • Isolated Bilirubin Elevation (Synthetic)
- 7. Classification by etiology • Hepatocellular pattern • Non-hepatic • Infectious • Non-Infectious • Cholestatic pattern • Non-cholestatic • Dilated biliary tree • Non-dilated biliary tree
- 9. Celiac disease • Related condition- Autoimmune thyroid disease, DM1 • Manifestations- • Iron deficiency anemia • Lactose intolerance • Osteoporosis • Laboratory findings: • Tissue Transglutaminase (TTG), HLA DQ2, DQ8 • Small bowel biopsy • Treatment- gluten free diet
- 10. More conditions • Thyroid dysfunction (Hyperthyroidism) • Muscle related • Myocardial infarction, heart failure • Adrenal insufficiency
- 12. Chronic Viral Hepatitis B (HBV) • Diagnosis- serologies • Progression to cirrhosis- level of replication (HBV DNA), HBeAg • Treatment- no biopsy needed • Pegylated interferon alfa-2a • Nucleoside analogs- Entecavir • Nucleotide analogs- Tenofovir
- 14. Chronic Viral Hepatitis C (HCV) • Episodic bursts of hepatitis • Quantitative HCV RNA- • Monitors response • Does not monitor progression to cirrhosis • Estimate fibrosis before treatment • Sustained virologic response (SVR12, 24)
- 15. Fibrosis estimation • Fibrosis-4 (FIB-4) Calculator • Fibrotest • Fibroscan • Liver biopsy
- 18. Screening for HCV cont.
- 19. Acute viral hepatitis • Herpes simplex virus • Varicella zoster virus • Epstein-Barr virus (EBV) • Cytomegalovirus (CMV)
- 21. Nonalcoholic fatty liver disease (NAFLD) • Two forms: • Nonalcoholic fatty liver (NAFL) • Nonalcoholic steatohepatitis (NASH) • Risk factors: • Obesity • Metabolic syndrome • DM2
- 22. Nonalcoholic fatty liver disease (NAFLD) cont. • Exclude other etiologies • Asses fibrosis- • NAFLD fibrosis score • Fibrosis-4 (FIB-4) score • Fibroscan, MRI
- 23. Nonalcoholic fatty liver disease (NAFLD) cont. • Biopsy & referral • Treatment: • Weight loss, stop alcohol • Bariatric surgery • Vitamin E (?) • Liraglutide (Victoza), Pioglitazone (Actos) (?)
- 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
- 28. Herbal medications and dietary supplements • Maté (Paraquay) tea • Mistletoe • Kava Kava
- 29. Autoimmune Hepatitis (“lupoid hepatitis”) • Females, 20-40 yrs old • Extrahepatic manifestations- arthritis, thyroiditis, glomerulonephritis • Laboratory findings- IGG, ANA, ASMA • False positive HCV immunoassay • Treatment- Azathioprin/Imuran
- 30. Hereditary Hemochromatosis • Mostly men, 40-50yrs • Arthralgia, “bronze diabetes” • HFE gene mutation C282Y • Laboratory findings- • ↑Serum ferritin • ↑Serum ferritin • Treatment- phlebotomy
- 31. Wilson Disease • Less than 40yrs • Neuropsychiatric symptoms, Kayser-Fleischer ring • Laboratory findings- • ↓ceruloplasmin • ↑urinary copper excretion • Treatment- D -penicillamine
- 34. Drug-induced cholestasis • Bland cholestasis= dose related • Oral contraceptives • Inflammatory cholestasis= idiosyncratic cholestasis • Erythromycin • Chlorpromazine • Amoxicillin–clavulanic acid, and oxacillin • Anabolic steroids (17α-substituted androgens)
- 35. More conditions • Bone related- • Growth • Fracture • Paget disease • Placenta • Vitamin-D deficiency
- 37. • Within the liver • Outside the liver • Biliary system related • Treatment- surgical / ERCP
- 40. Primary biliary cholangitis (PBC) • Women:Men – 10:1 • Middle aged women • Related conditions- Hashimoto thyroiditis, Sjögren syndrome • Laboratory findings- • Antimitochondrial antibodies (AMA) • Antinuclear antibodies (ANA) • Treatment- Ursodiol (ursodeoxycholic acid)
- 41. Primary sclerosing cholangitis (PSC) • Men:Women- 3:2 • Underlying ulcerative colitis (80%) • Overlapping autoimmune hepatitis (5%) • Laboratory findings- • Hypergammaglobulinemia • Serum immunoglobulin G4 (IgG4) • MRCP • Treatment- Ursodiol, liver transplant
- 42. Primary sclerosing cholangitis (PSC) cont.
- 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
- 46. Screening LFT?
- 48. Thank you!
- 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
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Editor's Notes
- #2: Image source- https://www.internalmedicineforpetparents.com/blog/what-makes-a-liver-sick
- #4: https://www.grepmed.com/images/5225/findings-symptoms-physicalexam-cirrhosis-liverfailure
- #5: 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
- #6: 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
- #10: 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
- #11: 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
- #13: 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
- #15: 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
- #16: 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/
- #17: Sensitivity and specificity of non invasive methods to asses fibrossis Cirrhosis - p759 - 2019
- #18: According to Israeli guidelines 2013, HCV screening is warranted in high risk groups- hemodyalisis patients, IV drug users, migrants..
- #19: 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
- #20: There are many other viruses that might cause an intermittent rise in LFT Acute= less than 6 months. Chronic= more than 6 months
- #22: 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
- #23: 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
- #24: 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
- #25: An example to management algorithm from AAFP, NAFLD 2020
- #27: 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
- #28: 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
- #29: Up-to-date, Hepatotoxicity due to herbal medications and dietary supplements
- #30: 2134, 2164 Image source: https://www.youtube.com/watch?v=eqRLwAKkDoM&ab_channel=MedicosisPerfectionalis UTD- Overview of autoimmune hepatitis
- #31: 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
- #32: 1942, 2198, 2203 Image source: https://medsphere.wordpress.com/2017/06/21/wilson/
- #33: Portal vein thrombosis have a chronic variant, when collateral blood supply is developed https://www.sciencedirect.com/science/article/abs/pii/S0016508519303725
- #35: Some drugs might cause a cholestatic injury in dose related or idiosyncratic manner 2130 https://www.ncbi.nlm.nih.gov/books/NBK547852/
- #38: Images sources: https://www.michaelbickford.com.au/bile-duct-surgery.html https://www.msdmanuals.com/home/liver-and-gallbladder-disorders/manifestations-of-liver-disease/cholestasis
- #40: Image source- https://onlinelibrary.wiley.com/doi/10.1111/apt.12581
- #41: Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis), UTD 1943 2197 2201
- #42: 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
- #43: Normal MRCP- https://www.dartmouth.edu/~anatomy/HAE/Radiology_Intro/MRI/mri4/mri4d.html PSC MRCP- https://liveratlas.org/diagnosis/20/?modality=mr
- #44: Harrisons’ 20ed
- #45: Mildly Elevated Liver Transaminase - p709 - 2017
- #46: UTD- Approach to the patient with abnormal liver biochemical and function tests
- #47: 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?)
- #48: 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.
- #50: 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