(a) (i) Elaborate the indications for initiating antiviral therapy in a patient with chronic hepatitis B. (ii) Write the…

(a)(i) Indications for antiviral therapy in chronic hepatitis B

Antiviral therapy in Chronic Hepatitis B (CHB) aims to achieve sustained suppression of HBV replication, prevent progression to cirrhosis, decompensation, and hepatocellular carcinoma (HCC). Treatment is indicated in:

1. Immune-active HBeAg-positive CHB: Serum HBV DNA >20,000 IU/mL with elevated serum alanine aminotransferase (ALT >2× upper limit of normal [ULN]).
2. Immune-active HBeAg-negative CHB: Serum HBV DNA >2,000 IU/mL with ALT >2× ULN.
3. Cirrhosis (compensated or decompensated): Detectable serum HBV DNA at any level, regardless of ALT value.
4. Non-invasive markers of liver injury: Significant fibrosis (≥F2 by transient elastography/FibroScan, or APRI >0.5 under WHO 2024; APRI >2 suggests cirrhosis) or moderate-to-severe necroinflammation on biopsy, even if ALT is normal or minimally elevated.
5. High-risk demographics: Patients older than 30 years with persistent replication (HBV DNA >2,000 IU/mL) and a family history of cirrhosis or HCC, or those planned for systemic immunosuppression/chemotherapy (prophylaxis).
6. Other groups: extrahepatic manifestations (glomerulonephritis, vasculitis), HIV or HCV co-infection, acute liver failure or severe acute hepatitis B, and pregnant women with HBV DNA ≥200,000 IU/mL (or HBeAg positive) from 24–28 weeks to prevent mother-to-child transmission.

The WHO 2024 guideline simplified and widened eligibility to reach more people: treat all adults with significant fibrosis (APRI >0.5 or transient elastography >7 kPa) or cirrhosis; those with HBV DNA >2,000 IU/mL and ALT above normal; and, where HBV DNA testing is not available, those with persistently abnormal ALT. India's National Viral Hepatitis Control Programme follows similar criteria and provides free drugs.

(a)(ii) First-line regimens and monitoring

First-line treatment utilizes high-potency oral nucleos(t)ide analogues with a high barrier to resistance:

• Tenofovir Disoproxil Fumarate (TDF): 300 mg once daily orally (preferred in pregnancy and in lamivudine-resistant cases).
• Tenofovir Alafenamide (TAF): 25 mg once daily, preferred where there is renal impairment or osteoporosis.
• Entecavir (ETV): 0.5 mg once daily on an empty stomach in treatment-naïve patients (1.0 mg in decompensated cirrhosis; it is not preferred after lamivudine resistance, where tenofovir is used). It is avoided in pregnancy, and the dose is adjusted for renal function.
• Treatment is usually long-term; stopping is considered only after HBsAg loss, or after HBeAg seroconversion with consolidation of at least 12 months in non-cirrhotics, because withdrawal flares can decompensate cirrhosis. Lamivudine, adefovir and telbivudine are no longer first-line because of resistance.
• Pegylated interferon-α is an alternative in selected patients (e.g., young, high ALT, low HBV DNA), offering a finite course of treatment and a chance of HBsAg seroconversion.

Monitoring Strategy:

• Virologic and biochemical efficacy: ALT and serum HBV DNA quantified every 3 to 6 months until virological suppression (<20 IU/mL), then every 6 months.
• Serology: HBeAg and anti-HBe checked every 6–12 months in HBeAg-positive patients. Quantitative HBsAg checked annually to detect HBsAg loss/seroconversion.
• Drug safety: Serum creatinine, estimated GFR, and serum phosphate assessed at baseline and every 3–6 months for TDF nephrotoxicity and bone loss.
• Resistance: Genotypic resistance testing is mandated if virologic breakthrough (HBV DNA rebound >1 log10 above nadir) occurs during compliant therapy; adherence is checked first.
• HCC surveillance: ultrasound with or without alpha-fetoprotein every 6 months in cirrhosis and other high-risk groups, since therapy reduces but does not abolish HCC risk.
• Peginterferon: complete blood count and TSH monthly to 3-monthly, and monitoring for depression, during a 48-week course.

(b) Respiratory distress syndrome (RDS) in the newborn.

Risk Factors: Primary driver is surfactant deficiency due to prematurity (<34 weeks). Other factors include maternal diabetes mellitus, elective caesarean delivery without prior labour or antenatal corticosteroid coverage, male sex, perinatal asphyxia, and being the second-born twin.

Differential Diagnosis: Transient Tachypnoea of the Newborn (TTN), neonatal sepsis/congenital pneumonia, Meconium Aspiration Syndrome (MAS), Congenital Heart Disease (such as critical cyanotic CHD or large patent ductus arteriosus), and pulmonary haemorrhage.

Management:

• Prevention: antenatal corticosteroids (betamethasone 12 mg IM, two doses 24 hours apart, or dexamethasone 6 mg IM 12-hourly for four doses) to women at risk of preterm birth between 24 and 34 weeks, with delayed cord clamping at birth.
• Resuscitation and Oxygenation: Early application of continuous positive airway pressure (CPAP, 5–6 cm H2O) in the delivery room via nasal prongs to maintain functional residual capacity.
• Surfactant Replacement Therapy: Natural exogenous surfactant (such as Poractant alfa 100–200 mg/kg) administered via catheter (LISA/MIST technique) or endotracheal tube if oxygen requirement rises (FiO2 >0.30 on CPAP).
• Mechanical Ventilation: Synchronised intermittent mandatory ventilation or high-frequency oscillatory ventilation indicated for severe respiratory acidosis (pH <7.20, PaCO2 >60 mmHg) or refractory hypoxaemia.
• Supportive Care: Strict thermoregulation, judicious intravenous fluid management, empirical intravenous antibiotics (ampicillin and gentamicin) pending blood culture clearance, and blood pressure maintenance.

(c)(i) Diagnosis

Impetigo Herpetiformis (a severe form of generalised pustular psoriasis occurring during pregnancy, typically triggered by third-trimester hormonal shifts and associated with hypocalcaemia). Differentials include acute generalised pustular psoriasis (AGPP) and acute generalised exanthematous pustulosis (AGEP).

(c)(ii) Management.

• Multidisciplinary Care: Joint management between dermatology, obstetrics, and neonatology in an intensive care setting.
• Pharmacotherapy: Systemic corticosteroids are first-line (Oral Prednisolone 0.5–1.0 mg/kg/day). In refractory cases, oral Cyclosporine (3–5 mg/kg/day) acts as a rapid, steroid-sparing agent safe in late pregnancy.
• Teratogenic agents such as acitretin and methotrexate are contraindicated. Narrowband UVB may be used as an adjunct in limited disease, and biologics (TNF inhibitors such as certolizumab, which has minimal placental transfer, or the IL-36 receptor antagonist spesolimab) are considered in refractory disease with specialist advice. Secondary infection is treated with appropriate antibiotics.
• Supportive Therapy: Fluid resuscitation, correction of electrolyte derangements, and aggressive parenteral calcium repletion.
• Obstetric Plan: Fetal surveillance via cardiotocography and Doppler. Prompt induction of labour or delivery if near term or in the presence of fetal compromise, which typically leads to rapid maternal resolution.

(c)(iii) Complications.

• Maternal: Severe hypocalcaemia leading to tetany, secondary bacterial sepsis, high-output cardiac failure, and placental insufficiency leading to premature labour.
• Fetal: Intrauterine growth restriction (IUGR), preterm birth, intrauterine fetal demise/stillbirth, and neonatal sepsis. There is a high risk of recurrence in subsequent pregnancies.