We reviewed an approach to transaminitis in Morning Report on September 28th – we discussed a fictional case of a patient with acute hepatitis B. This was the referral that I showed you on the first slide “Please see this 32-year-old man who presented to the Emergency Department with fever and non-specific symptoms and found to have elevated transaminases – AST 580, ALT 644, ALP 160, bilirubin 40. Please assess. thanks.”

This blog post will recap the differential diagnosis that we outlined on transaminitis, tests to send, and a summary of hepatitis B serology, management of hepatitis B, and hepatocellular carcinoma screening recommendations.

1. Approach to Transaminitis

Below is an approach to elevated transaminases. Remember hepatocellular enzymes are AST ALT, cholestatic are ALP, GGT, bilirubin).

Infectious	Drugs	Autoimmune	Metabolic	Vascular	Infiltrative
Viral hepatitis EBV CMV HSV Sepsis Liver abscesses	Statins Amiodarone Antifungals Anticonvulsants Antibiotics Tylenol Alcohol Herbal medications	Autoimmune hepatitis (There are many serologic tests, some include ANA, anti-smooth muscle)	Alpha-1 antitrypsin deficiency Wilson’s disease (send 24 hour urine copper or serum ceruloplasmin) Hereditary hemachromatosis (ferritin, transferrin saturation) NAFLD	Shock liver (portal vein thrombosis or shock) CHF Hepatic vein occlusion (Budd Chiari) Veno-occlusive disease	Sarcoid Amyloid Hepatocellular carcinoma Metastases

Remember that there are non-hepatic causes of transaminitis including celiac disease, hypo/hyper-thyroidism, rhabdomyolysis, strenuous exercise, cardiac muscle damage, adrenal insufficiency.

We discussed that a few of these etiologies that can contribute to liver enzymes being in the 1000s?

• Acute viral hepatitis
• Acetaminophen toxicity
• Shock liver (ischemic hepatitis/Budd Chiari)
• Autoimmune hepatitis
• Acute bile duct obstruction
• Wilson’s disease

There are specific causes that cause a cholestatic picture (elevated ALP, bilirubin +/- GGT). Extra hepatic causes include biliary stones, strictures (PSC), benign obstruction (IgG4/AIP, AIDS cholangiopathy), malignant obstruction. Intrahepatic drugs (antibiotics, TPN, estrogens), Primary Biliary Cirrhosis (anti-mitochondrial antibodies, ANA), infections, Intra hepatic cholestasis of pregnancy, infiltrative disease

Work up might include U/S, CT, MRCP, EUS (for stones), ERCP NOT for diagnosis, generally only for therapeutic.

In many situations for diagnosis a liver biopsy may be pursued.

I want to clarify that there is a difference between acute hepatitis and acute liver failure. In liver failure, one will have:
– Elevated aminotransferases (often with abnormal bilirubin and alkaline phosphatase levels)
– Hepatic encephalopathy
– Prolonged prothrombin time (INR ≥1.5)

In our fictional case, our patient’s serology revealed Hepatitis B surface Ab -ve, Hepatitis B Core IgM Ab +ve, Hepatitis B surface Antigen +ve.

We then reviewed an approach to hepatitis B.

2. Risk factors for Hepatitis B

Interesting fact, approximately 70% of patients with acute hepatitis B infection have subclinical or anicteric hepatitis. Risk factors include:

• Born in countries with higher hepatitis B prevalence – higher prevalence in parts of sub-Saharan Africa (e.g. Western Africa, South Sudan)
• Screen in pregnancy
• Persons who are HIV positive or have hepatitis C
• Using injection drugs
• Men who have sex with men
• Patients with end stage renal disease (and or undergoing dialysis)
• Household and sexual contacts of those with Hep B
• Living or having lived at correctional facility
• Individuals with chronic liver diseases

3. Decrypting Hepatitis B Serology

We then moved our discussion to review hepatitis B serology – hepatitis B serology can be confusing! Let’s try to break it down.

There are antigens and antibodies. The surface antigen (HBsAg) is positive in infection and is also what is given when we give someone the vaccine for hepatitis B. The equivalent antibody is the surface antibody (HBsAb) and is positive in those who are vaccinated or who have an infection (it is the response to HBsAg).

The Hepatitis eAg (HBeAg) is released during viral replication and would be positive in acute phase of infection – the level correlates with infectivity. HBeAb (e Antibody) is the response to HBeAg and if positive it means that the host has been through active phase of infection as it’s the body’s response to HBeAg. Finally, the core Antigen (HBcAg) is not found in the blood as it’s in the middle of the virus (core). However, the core Antibody is found in the blood and is the response to HBcAg. The IgM is high in acute infection. The core IgG is positive in chronic infection or if immunized related to past infection.

	Surface Ag	Surface Ab	Core IgM	Core IgG	eAg	eAb	HBV DNA
Acute infection	✅	—	✅	—	✅	—	✅
Window period	—	—	✅	—	+/-	+/-	+/-
Chronic infection	✅	—	—	✅	+/-	+/-	✅
Immunity from vaccination	—	✅	—	—	—	—	—
Immunization from previous infection	—	✅	—	✅	—	✅	—

The window period is a specifically a period of time after a few months of acute infection when the surface Ag is negative and surface Ab is also negative. See the reference section below to go over a helpful Youtube video explaining hepatitis B serology.

4. Management of Hepatitis B

The four key principles for managing hepatitis B infection are as follows:

1. Supportive care
   1. More than 90-95% of immunocompetent adults with acute hepatitis B do not require specific treatment because they will fully recover spontaneously.
2. Treat in specific circumstances
   1. Severe or fulminant acute hepatitis B can be treated with nucleoside antagonists if they are being considered for liver transplantation
3. Household contacts
   1. Ensure household and sexual contacts are immune and provide hepatitis B immune globulin and hepatitis B vaccine if they are not immune
4. HCC screening (this is more relevant to chronic Hepatitis B) – see next section below.

5. Chronic Hepatitis B

This is a whole different entity and is categorized into a few different groups summarized below. Remember to make a diagnosis of chronic hepatitis B infection, the surface Ag is positive, core IgG positive (NOT core IgM). The key features that are important when determining whether or not this needs treatment is the ALT (often fluctuating or elevated) and whether or not there is fibrosis on assessment of this/biopsy.

In those with chronic hepatitis B, you should follow them with regular monitoring of ALT (every 6 months) and HBV DNA (every 6–12 months), or at less frequent intervals, depending on individual baseline assessment and risk of liver disease progression. Repeat fibrosis assessment may be indicated if persistent ALT elevation and HBV DNA are present to assess the need for treatment.

US is required every 6 months for HCC surveillance in the following populations:

• Asian men above age 40 years
• Asian women above age 50 years
• Persons of African ethnicity over age 20 years
• All patients with cirrhosis
• Fam Hx of hepatocellular carcinoma starting age 40
• Patients with HIV co-infection starting at age 40

That was a whirlwind on transaminitis and hepatitis B. Please do not hesitate to reach out with questions or comments at cmr@wchospital.ca

References:

• Helpful Youtube Video to understand hepatitis B serology: https://www.youtube.com/watch?v=21eVTf0otUw
• Guidelines for Reference on Hepatitis B:
• https://hepatology.ca/publications/guidelines/2018-ammi-casl-hbv-guidelines/