Chronic Hepatitis B

Chronic hepatitis B is persistent infection with hepatitis B virus defined by HBsAg detectable for more than 6 months, with a spectrum from inactive carriage to cirrhosis and hepatocellular carcinoma.

• About 250 million people are infected worldwide; sub-Saharan Africa has a high burden, with HBsAg prevalence of 5 to 8 percent in Kenya in adults.
• Natural history phases: immune tolerant (HBeAg positive, high HBV DNA above 1 million IU/mL, normal ALT), immune active HBeAg positive, inactive carrier (HBeAg negative, HBV DNA below 2000 IU/mL, normal ALT), immune active HBeAg negative (HBV DNA above 2000 IU/mL, raised ALT), and resolved or occult infection.
• Lifetime risk of cirrhosis is 15 to 40 percent in untreated chronic infection; carcinoma may develop without cirrhosis, particularly in Africans at younger ages.

Usually asymptomatic for decades; fatigue, mild right upper quadrant discomfort during flares.

• Cirrhosis: spider naevi, palmar erythema, splenomegaly, ascites, jaundice, oedema, gynaecomastia, coagulopathy, encephalopathy.
• Extrahepatic: polyarteritis nodosa, membranous or membranoproliferative glomerulonephritis, cryoglobulinaemia, arthralgia.
• Differential diagnosis: other chronic liver disease (hepatitis C, D, alcohol-related, metabolic associated fatty liver disease, autoimmune hepatitis, haemochromatosis, Wilson disease, drug-induced), hepatitis B reactivation, hepatitis D superinfection.
• Complications: decompensated cirrhosis (ascites, variceal bleeding, encephalopathy), hepatocellular carcinoma (risk 0.5 to 1 percent per year in non-cirrhotic, 3 to 5 percent in cirrhosis), hepatic flares, reactivation with chemotherapy or immunosuppression, hepatorenal syndrome, hepatitis D coinfection acceleration.

HBsAg positive on two occasions at least 6 months apart; total anti-HBc positive and IgM anti-HBc negative.

• HBeAg, anti-HBe, quantitative HBV DNA, ALT (normal below 35 IU/L in men and 25 IU/L in women, repeated every 3 months for a year to define phase), AST, platelets, albumin, INR.
• Fibrosis assessment: transient elastography (liver stiffness above 12 kPa suggests cirrhosis; above 9 kPa with normal ALT suggests advanced fibrosis), APRI or FIB-4 score where elastography is unavailable; liver biopsy if indeterminate.
• Abdominal ultrasound, alpha-fetoprotein.
• Screen for HIV, hepatitis C, hepatitis D (anti-HDV, then HDV RNA), hepatitis A immunity; creatinine and eGFR before drug choice.
• Viral genotyping is not needed for routine care.

Supportive: abstain from alcohol, healthy weight, vaccinate against hepatitis A, avoid herbal and hepatotoxic remedies, screen household contacts and vaccinate those non-immune.

Treatment indications (any of the following):

• Cirrhosis (clinical or elastographic) with detectable HBV DNA of any level.
• HBV DNA above 2000 IU/mL with ALT above twice the upper limit of normal.
• HBV DNA above 2000 IU/mL with moderate fibrosis, even with normal ALT.
• Age above 30 years in the immune tolerant phase with persistently high DNA, or family history of hepatocellular carcinoma or cirrhosis.
• HIV coinfection (treat all with tenofovir-based antiretroviral therapy), or hepatitis D coinfection with active replication, extrahepatic manifestations, or pregnancy with HBV DNA above 200,000 IU/mL.

Pharmacological

• Preferred agents: tenofovir disoproxil fumarate 300 mg once daily (eGFR 30 to 49 mL/min: 300 mg every 48 hours; 10 to 29: every 72 to 96 hours) or tenofovir alafenamide 25 mg once daily (preferred with renal or bone disease), or entecavir 0.5 mg once daily on an empty stomach (1 mg daily if lamivudine resistant or decompensated; eGFR 30 to 49: 0.25 mg daily; 10 to 29: 0.15 mg daily).
• Duration is long term, indefinitely for cirrhosis; HBeAg positive non-cirrhotic patients may stop after HBeAg seroconversion plus 12 months consolidation therapy with monitoring.
• Pegylated interferon alfa-2a 180 microgram SC once weekly for 48 weeks in selected non-cirrhotic, young HBeAg positive patients with low DNA and genotype A or B; contraindicated in decompensated cirrhosis, autoimmune disease, psychiatric illness and pregnancy.
• Hepatitis D coinfection: pegylated interferon alfa-2a 180 microgram weekly for 48 weeks; bulevirtide 2 mg SC daily where available.
• Prophylaxis during chemotherapy or immunosuppression: start tenofovir or entecavir before therapy in every HBsAg positive patient (and in anti-HBc positive patients with rituximab or stem cell transplant), continue for 6 to 12 months (18 months after rituximab) after stopping.
• Pregnancy: tenofovir 300 mg daily from 28 to 32 weeks if HBV DNA is above 200,000 IU/mL, with infant hepatitis B immunoglobulin 100 to 200 IU and vaccine within 12 hours of birth; breastfeeding is safe.
• Decompensated cirrhosis: tenofovir or entecavir with transplant referral; never interferon.

Procedures: endoscopic variceal screening and band ligation for varices; liver transplantation for decompensation or hepatocellular carcinoma that is within transplant selection limits; treatment of carcinoma by resection, ablation, transarterial chemoembolisation or systemic therapy.

Surveillance: abdominal ultrasound with or without alpha-fetoprotein every 6 months for cirrhosis, family history of hepatocellular carcinoma, Africans aged above 20 years, and Asian men above 40 years and women above 50 years.

Special groups: children (treat when persistent ALT elevation with DNA above 2000 IU/mL), HIV coinfected (tenofovir based regimen; do not stop tenofovir abruptly), renal disease (tenofovir alafenamide or adjusted entecavir).

Red flags: jaundice, ascites, encephalopathy, rising bilirubin with ALT flare, alpha-fetoprotein above 400 ng/mL, hepatic mass, hepatitis flare after stopping therapy.

Follow-up: ALT, HBV DNA and creatinine every 3 months for the first year of treatment then every 6 months; HBsAg, HBeAg and anti-HBe annually; HBsAg loss is rare (1 percent per year) but is the endpoint; inactive carriers have ALT and HBV DNA tested every 3 to 6 months for life (every 12 months if stable).