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 serum 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), coinfection with HIV, renal impairment, or in those with treatment
adherence problems.
End of
Therapy
At the end of therapy, induction
of long-term viral suppression is the main endpoint of treatment. HBsAg-negative immune clearance or HBsAg loss
(undetectable HBV DNA with or without anti-HBs) represents the optimal
functional cure endpoint. It is essential to monitor ALT and HBV markers
(including HBV DNA) to detect relapse every 1-3
months for the initial 6 months, then every 3 months for the next 6-12 months,
and then every 3-6 months thereafter. For patients with cirrhosis, the patient
may be monitored monthly for the first 6 months then every 3 months. For
pregnant women in whom treatment is discontinued, monitor for withdrawal flares
every 1-3 months for up to 6 months; treatment is reinitiated for a significant
withdrawal flare (ALT ≥5x
ULN). Monitoring may be done 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 serum AFP. 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. The need for treatment is reassessed at each visit.
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.