Hepatitis+B

This is a guide to Adult Hepatitis B Screening, treatment and monitoring. See Pregnancy Page for Hep B infection in pregnancy toc

Screening

 * Transmission: if infected perinatally or as a young child, 90% chance of chronic infection. If infected as an adult, 5% of chronic infection.
 * Who to Test: CDC recommends testing all patients from Asia, Africa, Middle East, Eastern Europe, Amazon Basin, Guatemala, Caribbean for HBV. We should also test all family members - parents, children, and sexual partners of HBV infected pts, as its primarily perinatally and sexually transmitted,
 * Order a **chronic hep panel + Hep B sAb**, checking a Hepatitis B sAb at the same time will help with recommending vaccination if sAg and sAb negative.

Diagnosis:

 * **Diagnosis** || **HepBsAg** || **HepBcAb** || **IgM HepBcAb** || **HepBsAb** || **Notes** ||
 * **Non-Immune, Non-exposed** || Negative || Negative ||  || Negative || Offer Immunization ||
 * **Immune due to Natural Infection** || Negative || Positive ||  || Positive || No IZ necessry ||
 * **Immune due to Vaccination** || Negative || Negative ||  || Positive || No IZ necessary ||
 * **Acute Infection** || Positive || Positive || Positive || Negative || Risk of Chronic Infection ||
 * **Chronic Infection** || Positive || Positive || Negative || Negative || See below for work-up ||
 * **Resolved Infection (Most Common)** || Negative || Positive ||  || Negative || Possibly resolving acute infection or low level chronic infection. Most often false positive OR prior infection w/ HepB SAb levels too low to detect. Likely only 10% have occult (active) hepatitis. But Hep B is covalently bound to DNA, and all previously infected patients can reactivate with chemotherapy or w/ some of the immunotherapy used for autoimmune disease. ||

Initial Work-up (for Chronic Infection):
All patients with a positive hepatitis B surface antigen should be initially tested for:
 * Hepatitis B eAb
 * Hepatitis B eAg
 * Hepatitis B Viral Load
 * Liver Function Panel
 * CBC
 * PT/INR
 * HIV
 * AFP
 * Ultrasound

Who to refer:

 * Signs of liver inflammation elevated AST/ALT or Platelets <140
 * Splenomegaly on Ultrasound
 * Hep B DNA level > 2000.
 * Consider referral for biopsy at time of referral (Please consult)

Routine Monitoring:
Regardless of whether on treatment, patients can change over time including their level of inflammation, viral loads, and fibrosis. Overtime, the major risk of Hepatitis B is cirrhosis and hepatocellular carcinoma (HCC). Patients with inactive disease can reactivate anytime -- many patients periodically go in and out of inactive phases. For this reason, as long as someone is Hep B sAG +, lifelong monitoring is recommended.
 * AST/ALT every 3 months for 1-2 years then every 6-12 months if normal.
 * Hepatitis B Viral Load every 3 months for 1-2 years then every 6-12 months if <2000.
 * Hepatocellular Carcinoma: Screen with US every 6-12 mo +/- AFP q6 mo. Only screen high risk populations:
 * Asian, Men >40 and Women >50
 * African >20 years old
 * Cirrhosis
 * FMHx of HCC
 * All chronic hep B >40 years with persistent ALT elevations and/or viral load >2000

Summary of Stages:
Stages of Hepatitis B are useful to help determine treatment and monitoring. Fluctuating ||= Negative ||= Positive ||= High >200,000 ||= Active Inflammation ||= High (Men >40, Women >50) || Consider if Age >40, DNA >20k, ALT persistently 2x normal, fibrosis on bx or high risk || <2000 ||= Minimal Fibrosis ||= Low || ALT 2x ULN, DNA >20k, bx if DNA >2000, treat fibrosis. ||
 * =  ||= **Hepatitis B sAg** ||= **ALT** ||= **Hepatitis B eAb** ||= **Hepatitis B eAg** ||= **HBV DNA** ||= **Biopsy** ||= **Risk of Cirrhosis/HCC** || **Treatment** ||
 * = **Immune Tolerant Phase** ||= Positive ||= Normal ||= Negative ||= Positive ||= High >200,000 ||= Minimal Fibrosis ||= Low || Not Recommended ||
 * = **Immune Active Phase** ||= Positive ||= Elevated/
 * = **Non-replicative/Inactive "Carrier" Phase** ||= Positive ||= Normal ||= Positive ||= Negative ||= Low

Who benefits from Treatment:
Benefit for Hepatitis B treatment depends on the severity of liver disease and the risk of cirrhosis and hepatocellular carcinoma (HCC).
 * 1) [[file:ccrmc/HepBeAg Positive Treatment.pdf|HepBeAg Positive]]: ALT 2x ULN and viral load >20,000. This should be persistent over 3-6 months. Goal of treatment is conversion to eAb positive and eAg negative status. Discontinue treatment 6 months after conversion.
 * 2) [[file:ccrmc/HepBeAg Negative Treatment.pdf|HepBeAg Negative]]: ALT 2x ULN and viral load >20,000. Consider treatment after biopsy if ALT 1-2x ULN and viral load 2000-20,000 or if biopsy shows fibrosis (stage 2 or greater).
 * 3) [[file:ccrmc/Cirrhosis Hepatitis B treatment.pdf|Cirrhosis]]:
 * Decompensated: Treat patients immediately with progressively worsening liver disease and signs of decompensation (ascites, encephalopathy, portal hypertension, or hemorrhage).
 * Compensated: Treat If viral load >2000. Patients with compensated cirrhosis are at increased risk of HCC and treatment can improve their Child-Pugh score with treatment.
 * 1) Immunosuppressive therapy: Chemotherapy or other immunosuppresants (i.e. biologic agents for autoimmune disorders, etc) can cause reactivation of hepatitis B activty in patients with minimal hepatitis B activity. Regardless of ALT and viral load, start treatment before immunosuppressive therapy.

Who may not benefit from treatment:

 * 1) Young Patients <40 years old
 * 2) Immune tolerant phase with absence of hepatic inflammation (i.e. normal ALT and/or no fibrosis on biopsy) even if they have high DNA levels.
 * 3) Non-replicative Phase with low DNA levels and normal ALT.
 * 4) [[file:ccrmc/Monitoring for patients not on treatment.pdf|Monitoring reccomendations for patients not on treatment]]

First-Line Treatment Options

 * 1) Entecavir
 * 2) Tenofivir
 * 3) Peginterferon alpha-2a: Contraindicated in cirrhosis, pregnancy, immunosuppressive therapy

**Stopping Treatment:**

 * 1) For eAg positive patients, goal of treatment is to achieve eAg negative/eAb positive status. If this is achieved, treatment can be stopped after 6-12 months. Unfortunately, eAg seroconversion only occurs in about 25% of pts.
 * 2) For eAg negative patients, no specific end point is available to stop treatment. Stopping treatment usually results in rebound of viral load and hepatic inflammation. As a result, life long treatment in recommended.

References:
Sorrell et al. "National Institutes of Health Consensus Development Conference Statement: Management of Hepatitis B." //Ann Intern Med//. 2009; 150: 104-110 Kowdley, Kris. "Understanding and Implementing the AASLD's HBV Practice Guidelines and other recent Guidelines and Recommendations on the Diagnosis Managment and Treatment of Hepatitis B." Clinical Care Options [|www.clinicaloptions.com/hepatitis] Accessed July 17, 2011. HepBMoms.org - an online tool for patients and providers about perinatal Hep B.