Hepatitis B and C management in context of newer therapies

HBV vs HCV side by side

The exam tests the two viruses side by side. The single most important contrast:

	HBV	HCV
Genome	Partially dsDNA, cccDNA + integration	ssRNA, cytoplasmic only
Curable?	No - suppression only	Yes - >95% SVR
Endpoint	HBsAg loss ("functional cure", ~1%/yr)	SVR12
Therapy	Indefinite nucleos(t)ide analogue	8-12 weeks oral DAA
Vaccine	Yes	No
HCC without cirrhosis	Yes (~20%) - integration	Essentially no
Post-cure surveillance	Continue if male >40 / female >50 at clearance	Only if cirrhotic at cure

~220,000 Australians with chronic HBV; ~120,000 with chronic HCV
HBV: born overseas in endemic areas, and Aboriginal and Torres Strait Islander peoples are the priority populations
HCV: PWID account for 80-90%
HCV prevalence falling steeply with unrestricted DAA access; HBV prevalence static
Both are substantially under-diagnosed - roughly a third of HBV is undiagnosed

HBV liver injury is immune-mediated - so immunosuppression -> high DNA, low ALT; immune reconstitution -> flare
HBV integrates into host DNA -> direct oncogenesis independent of cirrhosis
HCV has no nuclear reservoir -> eradication is permanent (reinfection is a new infection, not relapse)
HBV/HCV, HBV/HDV, HBV/HIV coinfection accelerates fibrosis and multiplies HCC risk

HBV DNA, ALT, HBeAg/anti-HBe, anti-HDV once in every HBsAg-positive person, HIV, anti-HCV
Fibrosis stage (elastography, APRI/FIB-4); liver ultrasound
A single set of bloods cannot assign a phase - phases move

HCV RNA, LFT, FBE, INR, eGFR, Child-Pugh if cirrhotic
HBsAg + anti-HBc + anti-HBs - mandatory, reactivation risk
Genotype no longer required
Assess cirrhosis - it changes regimen choice and post-cure surveillance
DAA failure -> test for resistance-associated substitutions (RAS) to guide the salvage regimen

A. Chronic HBV - who to treat

Immune clearance or immune escape phase (raised ALT with raised HBV DNA)
All cirrhosis - any detectable DNA, regardless of ALT
Early to advanced fibrosis - prevents progression, improves histology
Additional progression risk: raised ALT + viral load; family history of chronic HBV with cirrhosis or HCC
Immune tolerant: treat if age >40, >=F2 fibrosis, or grade 2 inflammation
Extrahepatic manifestations, HCC, coinfection
Before immunosuppression (see below)

Situation	Agent
Renal impairment or decompensated cirrhosis	Entecavir
Pregnancy	Tenofovir
Prior lamivudine exposure	Tenofovir (entecavir has cross-resistance)
HIV co-infection	Tenofovir (within a full ART regimen)
CKD or osteoporosis on TDF	Tenofovir alafenamide (TAF)

TAF vs TDF: same antiviral efficacy, smaller falls in eGFR and bone mineral density, higher rates of ALT normalisation
No resistance with long-term entecavir or tenofovir
Peg-interferon alfa: finite 48-week course, higher HBsAg loss, poorly tolerated; contraindicated in decompensated cirrhosis
Not curable - do not stop before HBsAg loss. Stopping -> ALT flare ~27%

B. HBV reactivation with immunosuppression - risk-stratified

Risk	Agents	HBsAg+	HBsAg- / anti-HBc+
Highest	Rituximab / B-cell depletion, stem cell transplant	30-60%	>10%
High-intermediate	Anthracyclines; moderate-high dose corticosteroid >4 weeks	15-30% / >10%
Moderate	TNF inhibitors, other biological DMARDs, leflunomide, methotrexate, cyclophosphamide, prednisone >7.5 mg/day
Lowest	Calcineurin inhibitors, azathioprine, 6-MP

HBsAg-positive -> prophylax for any significant immunosuppression
HBsAg-negative/anti-HBc-positive -> prophylax if anti-CD20 or stem cell transplant; otherwise monitor HBV DNA
Entecavir or tenofovir, continuing >=12 months after finishing (18 months after rituximab)

C. Pregnancy

HBV: high viral load carries ~10% perinatal transmission despite HBIG + birth-dose vaccine
- Tenofovir from 28-30 weeks until 2-3 months post-partum if HBV DNA >200,000 IU/mL
- Infant: HBIG + vaccine within 12 hours -> transmission <2%
- Breastfeeding not contraindicated
HCV: treatment is not recommended in pregnancy - treat before conception or after delivery

D. Chronic HCV - regimens

Regimen	Composition	Use
Sofosbuvir/velpatasvir (Epclusa)	NS5B polymerase + NS5A inhibitor	First line, 12 weeks
Glecaprevir/pibrentasvir (Maviret)	NS3/4A protease + NS5A inhibitor	First line, 8 weeks. Safe in any renal impairment incl. dialysis
Sofosbuvir/velpatasvir/voxilaprevir (Vosevi)	+ protease inhibitor	Salvage after DAA failure

E. HCV contraindications and cautions

Protease inhibitors (glecaprevir, voxilaprevir) contraindicated in Child-Pugh B or C
Sofosbuvir: avoid if eGFR <30
Not recommended in pregnancy, or life expectancy <1 year
MELD ~18-20 or above: transplant first, then treat - there is no effective salvage regimen if DAA therapy precipitates further decompensation, and clearing HCV can remove the patient's MELD-based transplant priority without improving the liver
Amiodarone + sofosbuvir -> severe bradycardia (contraindicated)
Enzyme inducers (rifampicin, carbamazepine, phenytoin, St John's wort) reduce DAA levels

F. HCC surveillance in both

6-monthly liver ultrasound +/- AFP
All cirrhosis; non-cirrhotic HBV in defined groups (Asian men >40, Asian women >50, African ancestry from diagnosis, family history of HCC); non-cirrhotic HCV with advanced fibrosis
Continue after HCV cure if cirrhotic at the time of SVR - risk falls but does not disappear

HBV: polyarteritis nodosa, membranous GN, MPGN, Guillain-Barre, cryoglobulinaemia (mostly HCV)
HCV: mixed cryoglobulinaemia (strongest), MPGN, porphyria cutanea tarda, lichen planus, sicca, B-cell NHL, T2DM
HDV - only in HBsAg-positive; fastest-progressing viral hepatitis
HIV - shared routes; accelerates both
Alcohol and metabolic liver disease - additive fibrosis in both

HBV: chronicity ~90% if neonatal, 20-30% at age 1-5, <5% in adults
HCV: ~25-35% clear spontaneously; the rest become chronic; cirrhosis at ~20 years, HCC at ~30
HBV-related HCC can occur without cirrhosis (~20%) - surveillance cannot be limited to cirrhotics
HCV cure improves fibrosis, portal hypertension and extrahepatic disease
HBV treatment reduces but does not eliminate HCC risk - surveillance continues on therapy

HBV untreated: HBV DNA + ALT 6-12 monthly, periodic fibrosis staging
HBV treated: HBV DNA for suppression, adherence, renal function and bone on TDF
HCV: HCV RNA at SVR12; then RNA (not antibody) annually if ongoing risk of reinfection

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