Write the first-line antivirus treatment regimen for the management of chronic hepatitis B along with the recommended monitoring strategy during therapy.

First-Line Antiviral Treatment Regimen for Chronic Hepatitis B

The primary goal of antiviral treatment for chronic hepatitis B is to achieve sustained suppression of HBV replication, reduce liver inflammation and fibrosis, prevent progression to cirrhosis and HCC, and ultimately improve long-term survival. Current international guidelines strongly recommend the use of highly potent nucleos(t)ide analogues (NAs) that possess a high genetic barrier to drug resistance.

Recommended First-Line Agents:

• Tenofovir Disoproxil Fumarate (TDF): This is a nucleotide analogue that inhibits HBV reverse transcriptase. It is highly effective and generally well-tolerated. The recommended dosage for adults is 300 mg once daily.
• Tenofovir Alafenamide (TAF): A newer prodrug of tenofovir, TAF delivers the active antiviral agent to hepatocytes more efficiently, resulting in lower systemic drug exposure. This leads to improved renal and bone safety profiles compared to TDF, making it a preferred option for patients with or at risk for renal or bone disease. The recommended dosage is 25 mg once daily.
• Entecavir (ETV): A guanosine analogue, entecavir is a potent inhibitor of HBV DNA polymerase. It has a high barrier to resistance in treatment-naïve patients. The recommended dosage is 0.5 mg once daily for treatment-naïve patients and 1 mg once daily for those with prior lamivudine resistance.

Key Considerations in Treatment Selection:

• Patient-Specific Factors: The choice among TDF, TAF, and ETV is individualized based on factors such as age, renal function, bone mineral density, pre-existing comorbidities (e.g., HIV co-infection), and potential for drug interactions.
• Co-infection with HIV: For individuals co-infected with HBV and HIV, antiretroviral therapy (ART) regimens that include agents active against both viruses (e.g., TDF or TAF with lamivudine or emtricitabine) are preferred.
• Pregnancy: Tenofovir (TDF) is generally recommended for HBsAg-positive pregnant women with high HBV DNA levels (typically ≥200,000 IU/mL or HBeAg positive) starting from the 28th week of pregnancy until at least birth, to prevent mother-to-child transmission.
• Decompensated Liver Disease: Patients with decompensated cirrhosis should initiate treatment promptly, with ETV, TDF, or TAF considered viable options.

Recommended Monitoring Strategy During Therapy

Regular and systematic monitoring during antiviral therapy for chronic hepatitis B is essential to assess treatment efficacy, detect potential adverse effects, identify drug resistance, and screen for disease progression.

Parameters for Monitoring:

Monitoring should encompass virological, biochemical, and serological markers, as well as safety parameters.

1. Virological Response:
   • HBV DNA Levels: Quantitative HBV DNA levels should be measured at baseline, then typically every 3 months for the first 6-12 months of therapy to establish initial efficacy, and subsequently every 6-12 months once viral suppression is achieved. The goal is undetectable HBV DNA.
2. Biochemical Response:
   • Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST): Liver transaminases should be monitored at baseline, then every 1-3 months during the initial phase of treatment, and every 6-12 months thereafter, to assess liver inflammation. Normalization of ALT is a key indicator of biochemical response.
   • Liver Function Tests: Regular assessment of bilirubin, albumin, and INR, especially in patients with advanced liver disease, is crucial to monitor synthetic liver function.
3. Serological Response:
   • HBeAg and anti-HBe: For HBeAg-positive patients, these markers should be monitored every 6-12 months to detect HBeAg seroconversion (loss of HBeAg and development of anti-HBe), which indicates a more favorable immune response and can guide treatment duration.
   • HBsAg and anti-HBs: Quantitative HBsAg levels can be monitored periodically (e.g., every 6-12 months), particularly in HBeAg-negative patients with persistently undetectable HBV DNA. HBsAg loss (with or without anti-HBs seroconversion) represents a "functional cure" and is the ultimate treatment endpoint, though it is rarely achieved with current NAs.
4. Safety Monitoring:
   • Renal Function: Serum creatinine and estimated glomerular filtration rate (eGFR) should be monitored at baseline and periodically (e.g., every 6-12 months, or more frequently if abnormalities are detected or with TDF use), especially for patients on TDF or TAF, due to potential for renal toxicity.
   • Bone Health: Bone mineral density (BMD) should be considered for patients at risk of bone disease or on long-term TDF therapy.
   • Other Adverse Effects: Patients should be counselled on potential side effects and monitored for their occurrence.
5. Hepatocellular Carcinoma (HCC) Surveillance:
   • Patients with cirrhosis or other risk factors for HCC (e.g., family history, older age, male gender) should undergo regular surveillance with abdominal ultrasound and alpha-fetoprotein (AFP) every 6 months, even while on antiviral therapy, as treatment reduces but does not eliminate the risk of HCC.

Monitoring Frequency Table:

Parameter	Initial Phase (First 6-12 months)	Maintenance Phase (After 6-12 months, stable response)	Special Considerations
HBV DNA	Every 3 months	Every 6-12 months	More frequent if partial response or suspected resistance
ALT/AST	Every 1-3 months	Every 6-12 months	More frequent if abnormal or fluctuating
HBeAg/anti-HBe	Every 6-12 months (HBeAg-positive only)	Annually (HBeAg-positive only)	To assess for seroconversion
HBsAg/anti-HBs	Annually	Annually	To monitor for HBsAg loss (functional cure)
Renal Function (Creatinine, eGFR)	Every 6-12 months (TDF/TAF)	Every 6-12 months (TDF/TAF)	More frequent if pre-existing renal impairment or TDF use
HCC Surveillance (USG, AFP)	Every 6 months (for at-risk patients)	Every 6 months (for at-risk patients)	Regardless of treatment status

Discontinuation of NA therapy should only be considered in non-cirrhotic HBeAg-positive adults who achieve HBeAg seroconversion and complete an additional 12-18 months of consolidation therapy, or in patients who achieve HBsAg loss. Close monitoring for relapse is crucial after stopping therapy.