Hepatitis B Follow Up

Monitoring

Goals of Monitoring During Treatment  

Goals of monitoring during treatment include assessing effectiveness of therapy response, assessing treatment adherence, evaluating for therapy adverse effects, and assessing for progression of liver disease and HCC development.  

During Therapy  

During therapy, it is essential to monitor the patient’s ALT, HBeAg, anti-HBe, and/or HBV DNA at least every 3-6 months; and HBsAg every 6-12 months. Monitor the patient’s renal function (eg creatinine, phosphate) if Tenofovir, Entecavir, or Adefovir is used. Monitor for adverse effects (ie CBC, thyroid stimulating hormone) if Interferons are used. Monitor blood phosphorus levels and renal function every 6-12 months if Tenofovir disoproxil fumarate is used. Enhanced computed tomography (CT) and magnetic resonance imaging (MRI) may be performed for early detection of HCC, abdominal ultrasound and AFP every 6 months for cirrhosis-free patients, and every 3 months for patients with cirrhosis, during treatment with nucleos(t)ide analogue therapy. It is also important to assess disease stage and progression of fibrosis or cirrhosis using APRI score or transient elastography annually, and to monitor adherence to treatment during each follow-up. Monitoring every 3-6 months during the first year of treatment is recommended in patients with more advanced diseases (eg compensated or decompensated cirrhosis), co-infection with HIV, renal impairment, or in those with treatment adherence problem.

End of Therapy  

At the end of therapy, induction of long-term viral suppression is the main endpoint of treatment. It is essential to monitor ALT and HBV markers (including HBV DNA) to detect relapse every 3-6 months for the first year then every 6-12 months. For patients with cirrhosis, the patient may be monitored monthly for the first 6 months then every 3 months, or every 6 months in patients who responded to therapy. Further monitoring of HBV DNA every 3-6 months in non-responders is recommended to recognize delayed response and to plan retreatment if required. Monitor for HCC in high-risk (patients with cirrhosis or family history of liver cancer or cirrhosis) patients every 6-12 months using ultrasound and alpha-fetoprotein. Enhanced CT scan and MRI may be performed for early detection.

Viral Resistance

Testing for viral resistance may be done in patients who have undergone treatment, those with persistent viremia despite nucleos(t)ide analogue therapy, or those who had a virological breakthrough (a 10-fold increase from nadir in serum HBV DNA during therapy after an initial virological response) while on therapy.

Primary antiviral therapy failure is defined as failure of an antiviral agent to reduce HBV DNA by levels >1 log within 3 months. Secondary antiviral therapy failure is defined as rebound HBV DNA levels of >1 log increase from the nadir in patients with an initial antiviral therapy effect. 

Chronic Hepatitis B Patients who are Not Treated but Need Continuous Monitoring

The goal of monitoring in this group of patients is to determine when intervention is needed to reduce the risk of progression to liver cirrhosis and HCC. For these patients, monitor ALT and HBV DNA every 3-6 months for the first year or until treatment is initiated, then every 6-12 months thereafter, depending on the disease phase. HBV DNA testing should be done if ALT and AST levels are elevated, and the interval for ALT monitoring should be reduced. This includes patients age <30 years without cirrhosis, with persistently normal alanine transaminase (PNALT), HBV DNA >20,000 IU/mL, and HBeAg-negative patients age <30 years without cirrhosis, intermittently abnormal ALT levels, and HBV DNA between 2,000 and 20,000 IU/mL. 

Monitoring for disease progression including ALT and HBV DNA levels is recommended annually in patients who have persistently normal serum aminotransferase results and HBV DNA >2,000 IU/mL and does not meet the criteria for antiviral therapy. Monitoring HBsAg levels every 12 months is recommended. Testing for HBsAg and anti-HBe is recommended every 12 months or when there is significant change in ALT or HBV DNA levels. Assessment of liver fibrosis progression using non-invasive methods is recommended with intervals based on factors such as disease phase and presence of comorbidities. 

Chronic Hepatitis D Patients who are Not Treated but Need Continuous Monitoring  

Chronic hepatitis D patients who are not treated but need continuous monitoring include patients with mild or without fibrosis and with persistently normal ALT levels. Clinical and laboratory monitoring (eg ALT levels, HDV RNA) for signs of disease progression is recommended every 6-12 months to determine the need for treatment.

Prognosis

Predictors of Progression of HBV-related Liver Disease

• Age
• Alcohol use
• Diabetes
• Family history of HCC
• HIV infection
• Male sex
• Mode of HBV transmission
• Serum ALT levels
• Steatotic liver disease
• Viral factors (ongoing HBV replication measured by HBV DNA level, HBV genotype and HBV pre-core and core promoter variants)

Complications

Chronic HBV infection increases the patient's risk for liver failure, portal hypertension, liver cirrhosis, and HCC.