Chronic Hepatitis B Treatment

SUMMARY:

Chronic hepatitis B (CHB) is caused by the persistent infection and failure to develop sustained immunity to the hepatitis B virus (HBV), a double-stranded DNA virus transmitted through blood and other bodily fluids. Following infection with HBV, most immunocompetent adults will clear the virus, but roughly 1 to 5% of adults will go on to develop CHB. Nearly a quarter of a billion people in the world have CHB, with estimates in America ranging from 700,000 to 2.2 million adults living with CHB. Chronic hepatitis B infection can lead to cirrhosis, hepatocellular cancer, fulminant liver failure, and death. While immunization remains a cornerstone of HBV and thus CHB prevention, treatment options are available for select patients with CHB to reduce the morbidity and mortality associated with chronic hepatitis B infection.

CHB Disease Phases

CHB is defined as HBsAg positivity for ≥ 6 months along with measurable HBV DNA
CHB is a dynamic and variable disease that is traditionally split into four different phases based on viral replication and the host immune response
- Immune tolerant phase: Normal ALT | Elevated HBV DNA | + HBeAg | Minimal fibrosis and inflammation
- Immune active phase: Elevated ALT | Elevated HBV DNA | + HBeAg | Moderate to severe fibrosis or inflammation
- Inactive CHB phase: Normal ALT | Low or undetectable HBV DNA | -ve HBeAg | Minimal inflammation | Variable fibrosis
- Immune reactivation phase: Elevated ALT | Mildly elevated HBV DNA | -ve HBeAg | Moderate to severe fibrosis or inflammation
Approximately 0.5% of patients with inactive CHB will clear their HBsAg yearly, with most developing HBsAb consistent with immunity
- Clearance of HBsAg improves survival and decreases risk of hepatic decompensation

Evaluation

Initial evaluation in patients with CHB should include
- Thorough history with emphasis on risk factors such as: Alcohol use | Family history of liver cancer | Risk factors for co-infection (e.g., IV drug use) | Metabolic risk factors | Vaccination status
- Physical exam, with special attention paid to signs and symptoms of cirrhosis (e.g., Ascites | Palmar erythema | Splenomegaly | Encephalopathy | Asterixis)
- Laboratory testing: CBC | LFTs | INR | Albumin | Serum fibrosis panel (e.g., APRI | FIB‐4 | FIbroTest)
- Imaging: Abdominal ultrasound | Vibration‐controlled transient elastography
- Serology: HBeAg/anti‐HBe | HBV DNA quantitation | Anti‐HAV Ab (for vaccination) | HBV genotype | HCV | HIV

When to Treat

The goal of antiviral treatment in HBV is to reduce the morbidity and mortality related to CHB via immunological cure
- Immunological cure is defined by HBsAg loss and sustained HBV DNA suppression
- Virological cure, defined as the complete eradication of HBV, is not currently attainable
Elevated serum ALT and HBV DNA are associated with increased morbidity and mortality from CHB
- Additional risk factors for CHB morbidity and mortality include: Older age | Male sex, | Family history of HCC | Alcohol use | HIV infection | Diabetes | HBV genotype C | HBV precore and core promoter variants
Patients that should undergo HBV treatment include
- Patients with immune active CHB: Defined as ALT > 2x upper limit of normal or evidence of significant histological disease + elevated HBV DNA above 2,000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive)
- Patients with cirrhosis and detectable HBV DNA
- Select patients over the age of 40 years with elevated HBV DNA and evidence of liver fibrosis or inflammation
- Select patients with risk factors for increased morbidity and mortality from CHB
- Health care providers who preform exposure-prone procedures
- Patients with hepatocellular carcinoma
Prophylactic treatment should be given to patients with CHB who
- Are undergoing HBV related liver transplantation to prevent recurrence
- Pregnant patients with elevated viremia in the final trimester to prevent vertical transmission
- Patients undergoing immunosuppressive therapy or chemotherapy to prevent the reactivation of HBV

Treatment

Patients should be counseled prior to treatment that therapy for CHB will be long term and likely lifelong
- Exception to lifelong treatment includes: Patients with CHB in the absence of cirrhosis who seroconvert to anti-HBe while on therapy
Treatment for HBV includes pegylated interferon (e.g, Peg-IFN-a-2a (Pegasys)) and various nucleos(t)ide analogs (NAs), four of which are available in the United States
- NAs available in the United States include: Entecavir (Baraclude) | Tenofovir (Viread) | Lamivudine (Epivir) | Adefovir (Hepsera)
In patients with HIV coinfection, treatment of HBV needs to be coordinated with HIV therapy
- Several HBV drugs have anti‐HIV activity (e.g., Tenofovir | Entecavir | Lamivudine)
Preferred initial therapies for adults with immune active CHB include
- Peg-IFN-a-2a (Pegasys): 180 mcg weekly
- Entecavir (Baraclude): 0.5mg daily
- Tenofovir (Viread): 300mg daily
NAs are generally better tolerated than peg-interferon, which is associated with common side effects (e.g., Flu-like symptoms | Cytopenias | Fatigue | Mood disturbances)
NAs can cause lactic acidosis, and lactic acid levels should be checked if there is clinical concern

Monitoring

All patients with CHB should have regular follow up and blood work including
- CBC | LFTs | Albumin | Creatinine | INR
Patients on interferon therapy should additionally have their TSH checked every 3 months
Liver function tests should be repeated at least every 6 months in patients with immune tolerant CHB to monitor for transition to another phase of CHB

KEY POINTS:

Chronic hepatitis B infection is caused by the continued replication of HBV DNA without the development of lasting immunity by the host, and can lead to cirrhosis, hepatocellular carcinoma, and death
Treatment is indicated in select patients who CHB to decrease morbidity and mortality, and is often continued lifelong as there is yet no cure for HBV
The preferred initial treatment for CHB includes: Peg-IFN-a-2a (Pegasys) | Entecavir (Baraclude) | Tenofovir (Viread)
Patients with CHB should be monitored regularly for the development of cirrhosis and HCC