Viral Hepatitis

 

• Causes and epidemiology

  Acute infection

  • Duration <6 months.
  • Causes: hepatitis A (commonest), hepatitis B, hepatitis E.
  • Faecal-oral transmission: food, water, sexual.
  • Incubation: 2-5 weeks (HAV), 2-9 weeks (HEV).

  Chronic infection

  Overview:

  • Causes: hepatitis B, hepatitis C.
  • Incubation: 1-6 months.
  • HDV can co-infect with HBV.

  Transmission:

  • IVDU: common in HCV.
  • Vertical (mother-to-child): common in HBV
  • Child-to-child: contact of broken skin or mucosa e.g. during playing, fighting, biting. Common in HBV.
  • Sex
  • Needlestick injury. Transmission probabilities: HIV 0.3%, HCV 3%, HBV 30%.
  • Blood products, especially in the developing world.
  • Unhygienic piercings or tattoos.

  Prevalence:

  • HCV: 1/200 UK.
  • HBV: 1/20 worldwide. Relatively common in Asian migrants in the UK.

  HBV natural history:

  • Asymptomatic through childhood. LFTs normal, ↑HBV DNA, eAg +ve.
  • Immune system attempts to clear infection in 20s causing acute hepatitis (↑ALT). HBV DNA levels drop and eAg becomes eAb. Infectees become inactive carriers, though can reactivate later.

• Signs and symptoms

  Acute hepatitis (HAV, HBV, HEV):

  • Prodrome/pre-icteric phase: fever, malaise, anorexia, nausea, arthralgia.
  • Icteric phase: jaundice, pale poo and dark pee, itch, RUQ pain, hepato±splenomegaly, lymphadenopathy. Less likely to occur if <30 years old.
  • Usually self-resolves in 2-6 weeks.

  HBV:

  • Acute symptoms are similar to HAV but with more extrahepatic features e.g. arthralgia, urticaria.
  • Adults are more often symptomatic during an acute infection than kids, who are usually asymptomatic.
  • But babies (90%) and kids (30%) are more likely than adults (5%) to become chronically infected.

  HCV:

  • Acute infection is usually asymptomatic or mild.
  • 80% become chronically infected.

• Differential diagnosis

  Other infectious hepatitides:

  • Viral: EBV, CMV, HSV, yellow fever.
  • Bacterial: Leptospira, Brucella, Coxiella, mycobacteria.

  Non-infectious hepatitis:

  • Obesity and alcohol: NASH, alcoholic hepatitis.
  • Autoimmune hepatitis.
  • Drugs: rifampicin, isoniazid, NSAIDs.
  • Ischaemic hepatitis.
  • Wilson's

• Investigations

  Hepatitis serology:

  • Tests in bold are used for diagnosis.
  • HAV: HAV IgM, IgG +ve for life.
  • HBV: HBs Ag, PCR monitoring of DNA levels, check HDV if +ve.
  • HCV: HCV Ab (screening), PCR (confirmation). HCV genotyping if +ve: G1 commonest in UK, then G3 and G2; informs treatment, not prognosis. LFT rises usually less than in HAV and HBV.
  • HEV: HEV IgM, IgG +ve for life, RNA.

  Chronic hepatitis monitoring:

  • Bloods: LFTs, coag, AFP.
  • Liver US.
  • Transient elastography (FibroScan) to detect cirrhosis.

  Investigate other causes:

  • EBV and CMV IgM.
  • Auto-antibodies.
  • Ferritin and ceruloplasmin.

• Hepatitis B serology

  • Incubation: HBs Ag, HBe Ag (=infective).
  • Acute infection: HBs Ag, HBc IgM, HBc IgG, HBe Ag (=infective), ↑↑LFTs.
  • Chronic infection: HBs Ag, HBc IgG, ↑LFTs. Sometimes, HBe Ag (=infective), HBc IgM (acute insult).
  • Recovered: HBs Ab, HBc IgG.
  • Vaccinated: HBs Ab.

• Management

  Infection control

  • Notify Public Health England.
  • Screen and vaccinate contacts (HAV and HBV).

  Acute infection

  • Supportive treatment.
  • Avoid alcohol.
  • Lamivudine, tenofovir, or entecavir can be used if acute liver failure develops in acute HBV.

  Chronic infection

  Advice and support:

  • Avoid alcohol, especially in HCV.
  • Prevent transmission: avoid unprotected sex and toothbrush sharing.
  • HCV progression worsened by continuing IVDU, alcohol use, obesity, and HIV co-infection, so all of these should be addressed.

  Monitoring for complications:

  • Cirrhosis detection: 2-yearly transient elastography in untreated hep C.
  • Hepatocellular carcinoma screening: 6-monthly US and AFP in hep B/C cirrhosis.
  • Varices detection: 3-yearly OGD in hep B/C cirrhosis.

  HBV medication

  Overview:

  • Start treatment if LFTs change, HBV DNA rises, or cirrhosis develops.
  • Rarely cures but lowers complications risk.
  • Aims for seroconversion from HBe Ag +ve to -ve, and HBe Ab -ve to +ve.

  Options:

  • Peginterferon alpha 2a, subcutaneous once-weekly for 48 weeks.
  • Tenofovir or entecavir: PO once-daily until 6 months after seroconversion.

  HCV medication

  Huge range of effective oral direct-acting antiviral (DAA) regimens given for 12 weeks, including:

  • Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for all genotypes ('pan-genotypic').
  • Sofosbuvir/ledipasvir for genotypes 1 and 4-6.
  • Grazoprevir/elbasvir for genotypes 1 and 4.

  Effect of cirrhosis:

  • The above regimens are suitable for both those without cirrhosis and those with Child-Pugh A (compensated) cirrhosis.
  • Glecaprevir/pibrentasvir can be given for 8 weeks (instead of 12) if no cirrhosis.
  • Protease inhibitors are contraindicated in Child-Pugh B-C, so consider sofosbuvir/velpatasvir or sofosbuvir/ledipasvir.

  Confirm cure ('sustained virologic response') with HCV RNA PCR 12 weeks after completion of course.

• Complications and prognosis

  Acute infection:

  • Acute liver failure. ↑Risk if HDV co-infection.
  • Glomerulonephritis with HBV.
  • 20% mortality with HEV in pregnancy, but otherwise very rare.

  Chronic HCV:

  • 20% develop cirrhosis (especially if alcoholic), after around 20 years.
  • 2% develop HCC, after around 30 years.
  • 15% will die from it, usually due to decompensated cirrhosis.

• Hepatitis vaccination

  Hepatitis A vaccine

  • Contains inactivated hep A.
  • Give 2-4 weeks before potential exposure and repeat at 6-12 months for >10 years protection.
  • Indications: sexual and household contacts, foreign travellers, men who have sex with men, haemophiliacs, IVDU, sewage workers, chronic liver disease, chronic HBV/HCV infectees.

  Hepatitis B vaccine

  • Contains recombinant inactive HBsAg.
  • 3-dose series (0, 1, 6 months) or, for the new Heplisav-B, 2-dose series (1 month apart).
  • Aim for HBsAb >100 mIU/mL.
  • Protection is likely lifelong for most who are vaccinated as adults.
  • Indications: sexual and household contacts inc. children of affected mothers, men who have sex with men, HIV +ve individuals, healthcare workers, and those with chronic liver disease.
  • Post-exposure prophylaxis within 48 hours, even if already immunised. May be given to healthcare workers, babies, or sexual contacts. Add HBV Ig (HBIG) if non-immune.