Hepatic Disease

• Hepatitis Disease
  • Acute Viral Hepatitis
  • Alpha-1-Antitrypsin Deficiency (AAT)
  • Autoimmune Hepatitis
  • Hepatocellular Carcinoma (HCC)
  • Primary Biliary Cholangitis (PBC)

 

 

• Acute Viral Hepatitis

Definition:

Hepatitis viruses A, B, and C cause 95% of viral hepatitis cases in the U.S. Less common hepatitis viruses include D, E, and G (HGV or GBV-C). Generally, patients meeting the indications for testing should be screened for hepatitis A, B, and C concurrently, unless a specific exposure is known.

 

Hepatitis A Virus (HAV)

Definition:

Hepatitis A virus (HAV) is the most common cause of viral hepatitis worldwide. However, the targeted use of the HAV vaccine in the U.S. since 1995 has led to a 92% decrease in the number of reported cases. Testing for acute hepatitis by panel allows for identification of viral etiology.

Panel test:

• Hepatitis A Virus Antibody, IgM
• Hepatitis A Virus Antibodies (Total)

 

Hepatitis B Virus (HBV)

Definition:

Hepatitis B (HBV) is a bloodborne virus and one of the most common infectious diseases in the world. HBV can cause acute or chronic infection. Chronic HBV infection can lead to cirrhosis or liver cancer. Laboratory testing involves serology, which allows for differentiation of acute versus chronic disease.

Panel test:

• HBV surface antigen
• HBV surface antibody
• HBV core antibody Total
• HBV core antibody IgM
• HBe antibody
• HBe antigen

 

Hepatitis C Virus (HCV)

Definition:

Hepatitis C virus (HCV) is a virally mediated disease of the liver with a propensity to cause chronic infection, leading to cirrhosis and an increased risk of hepatocellular carcinoma. Adults born between 1945 and 1965 should be screened for HCV infection; individuals with certain risk behaviors (eg, injection drug use) or risk exposures (eg, healthcare workers) should also be screened. Laboratory testing involves screening for HCV antibodies followed by confirmatory RNA testing for positive results.

 

Panel test:

• HCV antibody

 

 

 

Hepatitis Delta Virus (HDV)

Definiton:

Hepatitis delta virus (HDV) is a subviral agent that is dependent on the hepatitis B virus (HBV) surface antigen (HBsAg) for its life cycle. HDV infection cannot occur in the absence of HBV, but occurs as an acute coinfection with HBV or as a superinfection. Acute infection will cause an early increase in alanine aminotransferase (ALT).

 

Panel test:

• HDV antibody

 

References

 

1. Aggarwal R, Jameel S. Hepatitis E. 2011; 54(6): 2218-26. PubMed
2. Clemente MG, Schwarz K. Hepatitis: general principles.Pediatr Rev. 2011; 32(8): 333-40. PubMed
3. Degertekin B, Lok AS. Update on viral hepatitis: 2007.Curr Opin Gastroenterol. 2008; 24(3): 306-11. PubMed
4. Denk H. What is expected from the pathologist in the diagnosis of viral hepatitis?Virchows Arch. 2011; 458(4): 377-92. PubMed
5. Sharapov UM, Hu DJ. Viral hepatitis A, B, and C: grown-up issues.Adolesc Med State Art Rev. 2010; 21(2): 265-86, ix. PubMed
6. Suriawinata AA, Thung SN. Acute and chronic hepatitis.Semin Diagn Pathol. 2006; 23(3-4): 132-48. PubMed
7. Centers for Disease Control and Prevention. Atlanta, GA [Updated: Apr 2018; Accessed: Jul 2019]
8. US Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW, Kemper AR, Kubik M, Landefeld S, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng C, Wong JB. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. 2019; 322(4): 349-354. PubMed
9. S. Department of Health and Human Services, Centers for Disease Control and Prevention. Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger. United States, 2019. Centers for Disease Control and Prevention. Atlanta, GA [Last updated: Jan 2019; Accessed: Apr 2019]
10. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015.MMWR Recomm Rep. 2015; 64(RR-03): 1-137. PubMed

1. BJ, Chang K, Hwang JP, Jonas MM, Brown RS, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018; 67(4): 1560-1599. PubMed
2. Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection. World Health Organization. Geneva, Switzerland [Accessed: Aug 2018]
3. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. AASLD/IDSA HCV Guidance Panel. [Updated: May 2018; Accessed: Aug 2018]

 

14. Farci P, Niro GA. Clinical features of hepatitis D.Semin Liver Dis. 2012; 32(3): 228-36. PubMed
15. Guo Z, King T. Therapeutic strategies and new intervention points in chronic hepatitis delta virus infection.Int J Mol Sci. 2015; 16(8): 19537-52. PubMed
16. Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. 2011; 378(9785): 73-85. PubMed
17. Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery.Curr Gastroenterol Rep. 2014; 16(1): 365. PubMed
18. Olivero A, Smedile A. Hepatitis delta virus diagnosis.Semin Liver Dis. 2012; 32(3): 220-7. PubMed
19. Pascarella S, Negro F. Hepatitis D virus: an update.Liver Int. 2011; 31(1): 7-21. PubMed
20. Romeo R, Perbellini R. Hepatitis delta virus: Making the point from virus isolation up to 2014.World J Hepatol. 2015; 7(22): 2389-95. PubMed

 

 

• Alpha-1-Antitrypsin Deficiency (AAT)

Definition:

Alpha-1-antitrypsin (AAT) is the chief protease inhibitor (PI) in human serum. Alterations in the production of this PI may result in the degradation of the connective protein elastin in lung alveoli, which increases the risk for developing lung disease. Additionally, severe AAT deficiency may cause improper folding of the AAT protein leading to deposition in hepatocytes and corresponding liver disease. Chronic obstructive pulmonary disease (COPD) caused by AAT deficiency (AATD-COPD) is the fourth most common factor associated with lung transplantation. Pooled plasma AAT infusions can be used to treat lung disease in patients with AATD-COPD; however, this treatment does not address liver disease caused by AAT deficiency.

Panel test:

• Alpha-1-Antitrypsin (SERPINA1) Enzyme (plasma concentration) (immunoturbidimetry)
• Alpha-1-Antitrypsin (SERPINA1) (immunohistochemistry)

 

References

Guidelines

1. Sandhaus RA, Turino G, Brantly ML, Higgins VS, Make BJ, Marvel J, Yu T, Wood R, Campos M, Cross CE, Goodman K, Hogarth K, Knight SL, Stocks JM, Stoller JK, Strange C, Teckman J. Clinical Guidelines for the Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult.Chronic Obstr Pulm Dis. 2016; 3(3): 668-682. PubMed
2. Alpha-1 antitrypsin deficiency. National Institutes of Health. Bethesda, MD [Reviewed: Jan 2013; Accessed: Jun 2017]
3. Global Strategy for Diagnosis, Management, and Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease. [Accessed: Jun 2017]

 

• Autoimmune Hepatitis

Definition:

Autoimmune hepatitis (AIH) is a chronic and inflammatory liver disease with unknown etiology. AIH can trigger as acute hepatitis and go forward to chronic liver disease and cirrhosis. Clinical symptoms and biochemistry tests are very different in acute hepatitis and cirrhosis.

Autoimmune hepatitis is identified two types:

Type 1: it’s more common type and the first onset occur at all age. This type is more related to other autoimmune disorders like celiac disease, rheumatoid arthritis and ulcerative colitis.

Type 2: it’s happened in children and young individuals.

 

 

Panel test:

• Liver function testing:
  • Transaminases (AST and ALT)

 

• Hepatitis testing: important to rule out acute or chronic hepatitis
  • Hepatitis A virus [HAV]
  • Hepatitis B virus [HBV]
  • Hepatitis C virus [HCV])

 

• Quantitative immunoglobulins:
  • IgG usually elevated

 

• Antibody testing:
  • Antinuclear antibody (ANA)
  • Antineutrophil cytoplasmic antibody (ANCA)
  • Antismooth muscle antibody (anti-SMA)
  • Anti-F-actin (smooth muscle) antibody
  • Antimitochondrial antibody (AMA)
  • Antisoluble liver antigen antibody (anti-SLA)
  • Antiliver-kidney microsomal-1 antibody (anti-LKM-1; cytochrome P450 2D6)
  • Antiliver cytosol (anti-LC-1)

 

Comment: Serum titers of antibodies do not appear to correlate with disease activity. Titers may vary during course of disease without activity correlation.

 

References

Guidelines

1. Mieli-Vergani G, Vergani D, Baumann U, Czubkowski P, Debray D, Dezsofi A, Fischler B, Gupte G, Hierro L, Indolfi G, Jahnel J, Smets F, Verkade HJ, Hadzic N. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement.J Pediatr Gastroenterol Nutr. 2018; 66(2): 345-360. PubMed
2. Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM, American Association for the Study of Liver Diseases. Diagnosis and management of autoimmune hepatitis 2010; 51(6): 2193-213. PubMed
3. International Autoimmune Hepatitis Group. Simplified criteria for the diagnosis of autoimmune hepatitis. 2008; 48(1): 169-76. PubMed
4. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, Gores GJ, American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. 2010; 51(2): 660-78. PubMed
5. Gleeson D, Heneghan MA, British society of Gastroenterology. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. 2011; 60(12): 1611-29. PubMed
6. European Association for the Study of the Liver.. EASL Clinical Practice Guidelines: Autoimmune hepatitis.J Hepatol. 2015; 63(4): 971-1004. PubMed

 

 

• Hepatocellular Carcinoma (HCC)

Definition:

Hepatocellular carcinoma (HCC) tumors are among the most common in the world, particularly in populations with chronic viral hepatitis, such as those of Asian or sub-Saharan African ancestry. Most occur in individuals with chronic liver disease.

 

Panel test:

AFP total

AFP-L3%

DCP

Beta-Catenin

Hepatocyte specific antigen

Arginase 1

Cytokeratin 8,18 low molecular weight

Reticulin

Glypican 3

 

References

Guidelines

1. NCCN Clinical Practice Guidelines in Oncology, Hepatobiliary Cancers. 2.2018. National Comprehensive Cancer Network. Fort Washington, PA [Update: Jun 2018; Accessed: Sep 2018]
2. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69(1): 182-236. PubMed
3. Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, Okusaka T, Miyayama S, Tsuchiya K, Ueshima K, Hiraoka A, Ikeda M, Ogasawara S, Yamashita T, Minami T, Yamakado K, Liver Cancer Study Group of Japan. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014; 3(3-4): 458-68. PubMed
4. Heimbach J, Kulik LM, Finn R, Sirlin CB, Abecassis M, Roberts LR, Zhu A, Murad H, Marrero J. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2017; PubMed
5. Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. World Health Organization. Geneva, Switzerland [Accessed: Mar 2018]
6. Cong W, Bu H, Chen J, Dong H, Zhu Y, Feng L, Chen J, Committee G. Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol. 2016; 22(42): 9279-9287. PubMed
7. National Cancer Institute. Adult Primary Liver Cancer Treatement (PDQ)—Health Professional Version. Rockville, MD [Updated: Feb 2018; Accessed: Feb 2018]

 

 

 

• Primary Biliary Cholangitis (PBC)

Definition:

Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is an autoimmune and chronic liver disorder in which bilary ducts are damaged. PBC is more common in women than in men, and usually arises at 40-50 years of age. Symptoms of PBC may include chronic itchy skin, fatigue, dry eyes and mouth, abdominal pain, jaundice, and arthralgia. The combination of the following factors could increase incidence of PBC:

genetics, sex, age, environmenta factors such as smoking, infections, toxic materials.

Panel Test:

• Hepatic Function tests:
• Albumin
• ALP, AST, ALT,
• bilirubin direct and total
• protein
• CBC and Automated Differential
• Prothrombin Time/INR

 

• Autoantibodies:
• AMA, IgG
• liver-kidney microsome-1 antibody, IgG
• F-actin (smooth muscle) antibody, IgG
• SMA, IgG
• Mitochondrial M2 antibody, IgG
• Antinuclear antibody (ANA) with HEp-2
• Centromere antibody, IgG

 

• Immunoglobulin Tests
• Immunoglobulin M and G (IgG, IgM)

 

• Other Serologic Tests:
• HBV antigen
• HCV antibody
• Hyaluronic Acid, Serum
• Cholesterol
• Thyroid Stimulating Hormone
• Vitamin A (Retinol)
• Vitamin D, 25-Hydroxy
• Vitamin E, Serum or Plasma
• Prothrombin Time/International Normalized Ratio

 

References

1. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. 2019; 69(1): 394-419. PubMed
2. Hirschfield GM, Dyson JK, Alexander GJ, Chapman MH, Collier J, Hübscher S, Patanwala I, Pereira SP, Thain C, Thorburn D, Tiniakos D, Walmsley M, Webster G, Jones DE. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. 2018; 67(9): 1568-1594. PubMed
3. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis.J Hepatol. 2017; 67(1): 145-172. PubMed
4. Bowlus CL, Gershwin E. The diagnosis of primary biliary cirrhosis.Autoimmun Rev. 2014; 13(4-5): 441-4. PubMed
5. Liberal R, Grant CR, Sakkas L, Bizzaro N, Bogdanos DP. Diagnostic and clinical significance of anti-centromere antibodies in primary biliary cirrhosis.Clin Res Hepatol Gastroenterol. 2013; 37(6): 572-85. PubMed
6. Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries.Am J Gastroenterol. 2017; 112(1): 18-35. PubMed