The majority of acute viral hepatitis infections are asymptomatic or they can cause an anicteric illness that may not be diagnosed as hepatitis.
Hepatitis A generally causes minor illness in childhood with >80% of infections being asymptomatic. Jaundice and intestinal symptoms usually resolve 2-3 weeks after onset. A patient is infectious 1-2 weeks prior to the clinical illness.
Hepatitis B, C, & D may be symptomatic depending on the mode and time of transmission.
Hepatitis A is predominantly transmitted through oral-fecal by person-person direct transmission and contaminated material or food.
Hepatitis B is transmitted perinatal, horizontal spread, percutaneous, sexual, close person-to-person contact.
Majority of hepatitis C infections are identified in children with repeated exposure to blood products.
Hepatitis D is route of transmission is through sexual, percutaneous especially IV drug use.
Hepatitis E is transmitted primarily through contaminated drinking water and oral-fecal transmission.

Hepatitis%20-%20viral%20(pediatric) Treatment

Principles of Therapy

Hepatitis B

  • Children at high risk for disease progression or HCC development should be identified early so that therapy can be started, reducing the risk for antiviral resistance 
  • Initiate treatment in patients with chronic hepatitis B with evidence of fibrosis or alanine aminotransferase (ALT) ≥30 IU/L for boys & ≥19 IU/L for girls obtained from 2 consecutive tests conducted 3 months apart

Hepatitis C

  • Antiviral therapy should be given to HCV-infected patients aged 3-17 years
  • The benefits of treatment need to be weighed against the risk of side effects for children who have mild or no liver disease & are asymptomatic
  • Treatment should start between 3 & 6 months of diagnosis, if the infection has not resolved spontaneously

Consequences of HCV Infection

  • More likely to resolve spontaneously in children
  • Slower rate of progression to end-stage liver disease
  • 50% of cases of HCV infection becomes chronic
    • 70% of transfusion acquired infections persist for >6 months
  • 5-20% of these patients may develop cirrhosis over the next 20-25 years
    • HCV-related cirrhosis is associated with risk of developing end-stage liver disease (30% risk over 10 years) as well as hepatocellular carcinoma (HCC)
  • HCV-infected children should be monitored to determine the minority who are at risk of progressive fibrosis during childhood & who may be candidates for treatment
  • In patients with persistent infection, the evolution to cirrhosis is the primary concern
    • Usually occurs ≥20 years after initial infection & occurs more often in patients at older ages (especially in men), those who drink >50 g of alcohol/day, those who are obese or have substantial hepatic steatosis & in those with HIV infection

Hepatitis B

Patients For Whom Treatment is Not Recommended

  • Negative HBeAg, positive anti-HBe, HBV DNA <105 copies/mL, normal ALT (inactive HBV infection)
  • Positive HBeAg, HBV DNA >105 copies/mL & normal ALT

Patients For Whom Treatment is Recommended

  • Positive HBeAg, HBV DNA >105 copies/mL, persistent or intermittent elevations of ALT
  • Negative HBeAg, HBV DNA >104 copies/mL, elevated ALT

Goals of Treatment

  • Continued viral suppression is necessary to reduce or prevent hepatic disease & disease progression
  • Primary goal of treatment is to permanently suppress HBV or to eliminate it
    • Short-term goal is the sustained suppression of HBV DNA, ALT normalization, to prevent decompensation & to decrease hepatic necroinflammation & fibrosis during & after therapy
    • Long-term goal of therapy is to avoid hepatic decompensation, reduce or prevent progression to cirrhosis &/or HCC & to prolong survival
  • Endpoints used to assess response:
    • Biological response: Normalization of serum ALT
    • Virological response: Undetectable HBV DNA, loss of HBeAg in those initially HBeAg positive
    • Histological response: Decrease in histology activity compared to pretreatment liver biopsy
    • Complete response: Fulfill criteria of biochemical & virological response & loss of HBsAg
    • Anti-HBs positive on 2 consecutive annual tests
  • Current treatments of chronic hepatitis B have limited long-term efficacy

Considerations Prior to Initiation of Treatment

  • Age of patient
  • Severity of liver disease
  • Likelihood of response
  • Potential adverse events & complications
  • HBeAg positive chronic HBV patients with elevated ALT levels & compensated liver disease should be observed for 3-6 months for spontaneous seroconversion from HBeAg to anti-HBe prior to initiation of treatment; initiation of therapy may be delayed
  • Choice of therapy will depend on availability, cost of medication, necessary number of clinic visits, expected duration of treatment & patient/parent/guardian clinician preference
  • Different genotypes may have different prognoses but currently do not imply difference in therapeutic management compared to hepatitis C

Other Considerations

  • In children with high viremia, delay the treatment until viremia decreases
  • Consider Interferon alfa in case of cirrhosis due to chronic HBV in children with Child-Turcotte-Pugh class A & persistent HBe antigenemia
  • Contraindicated in patients with decompensated cirrhosis, coexisting autoimmune diseases & in children with organ transplant, renal or cardiac failure, neurological diseases & severe function disturbances
  • Not recommended for patients with compensated cirrhosis because of risk of hepatic decompensation
  • Prednisone priming prior to Interferon alfa therapy is not recommended
  • Discontinue treatment when HBV DNA levels reach <2 log10 IU/ml &/or HBsAg >20,000 IU/ml
  • Monitor HBV DNA levels, quantitative HBsAg, HBeAg levels at 12, 24, & 48 weeks after initiation of therapy, & every 6 months thereafter
    Test for HBV DNA every 12 weeks in HBeAg-negative patients on Lamivudine treatment for ≥5 years

Hepatitis C

  • Peginterferon/Ribavirin combination therapy with either Telaprevir or Boceprevir is the treatment of choice for chronic hepatitis C genotype 1
  • Peginterferon alfa/Ribavirin combination therapy is the treatment of choice for chronic hepatitis C genotype 2, 3, 4, 5 & 6
  • Assess liver disease severity prior to therapy

Goals of Treatment

  • Prevent complications of HCV infection by eradication of the infection
  • Treatment responses are usually characterized by HCV RNA testing (<15 IU/ml at 12 & 24 weeks post-treatment
  • Eradication of infection is considered when there is sustained virologic response (SVR)
    • SVR is defined as the absence of HCV RNA in serum by a sensitive test at the end of treatment & 6 months later
  • Early virologic response is defined as 2-log drop or loss of HCV RNA 12 weeks into therapy
  • End of treatment response is defined as continued absence of detectable virus at end of treatment
  • Relapse is considered when HCV RNA becomes undetectable on treatment but is detected after discontinuation of therapy
  • Patients in whom HCV RNA levels remain stable while on treatment are considered non-responders while those HCV RNA levels decline but never become undetectable are referred to as partial responders

Individualize treatment based on the following:

  • Severity of liver disease
  • Potential of serious side effects
  • Likelihood of treatment response
  • Presence of comorbid conditions


Hepatitis B
Interferon alfa

  • Interferons have antiviral, antiproliferative & immunomodulatory effects
  • Therapy of choice for pediatric patients >1 year old with chronic hepatitis B & compensated liver disease
  • May be a preferred agent, in the treatment of HBeAg negative chronic hepatitis B & may be used as initial therapy for HBeAg positive chronic hepatitis with elevated alanine aminotransferase (ALT)
  • Action: Suppresses hepatitis B virus (HBV) replication & induces remission of liver disease
  • Effects:
    • Efficacy is similar for adults & children
    • Relapse is a major problem in HBeAg negative chronic hepatitis B
    • Accelerates HBV DNA clearance & HBeAg/anti-HBe conversion
  • Consensus guidelines on optimal selection for Interferon alfa treatment:
    • HBeAg & HBV DNA positive
    • Age >3 years
    • Elevated ALT levels (at least 2x the normal or higher)
    • Intermediate & low levels of HBV DNA in serum (<1000 pg/mL)
  • For HBeAg positive chronic hepatitis B, important predictors of response to therapy are high pretreatment ALT & lower levels of serum HBV DNA
  • Obtain baseline complete blood count (CBC), liver function tests (LFTs) [bilirubin, albumin, ALT], renal function tests (urea, electrolytes), thyroid function test, weight, height, prior to & during therapy
  • Finite duration of therapy associated with Interferon alfa related flares of hepatitis
  • Side effects include mood swings & depression; patient’s mental health should be closely monitored by the clinician
  • Peginterferon, the pegylated form of Interferon, is currently being studied for the treatment of chronic hepatitis B infection in children

Nucleoside/Nucleotide Analogues

  • Eg Adefovir, Entecavir, Lamivudine, Tenofovir
  • Given to HBV DNA-positive pediatric patients unresponsive to Interferon alfa-48 weeks treatment course
  • Obtain baseline CBC, LFTs, renal function tests (with urine protein/creatinine ratio), blood clotting, HBV DNA & HBeAg levels in patients with compensated liver disease prior to & weekly after initiation of Lamivudine or Entecavir therapy
    • Add phosphate level measurement in patients with compensated liver disease who are to be given Tenofovir
  • Adefovir
    • Alternative treatment for HBeAg-positive children >12 years of age with persistently elevated LFTs
    • Studies showed that seroconversion can be achieved after a few years of continuous Adefovir therapy
    • Action: Inhibits DNA synthesis through competitive reverse transcriptase inhibition & viral DNA incorporation
  • Entecavir
    • Treatment option for HBeAg-positive HBV patients >16 year of age with compensated liver disease intolerant or unresponsive to treatment with Interferon alfa or Tenofovir
      • May also be given if HBV DNA is still detectable despite a 96-weeks treatment with Tenofovir & Lamivudine
      • Alternative treatment to Tenofovir in HBeAg-negative HBV patients with compensated liver disease & with detectable HBV DNA even at 48 weeks treatment duration
    • Alternative treatment for HBsAg-negative HBV patients with compensated liver disease previously given Interferon alfa with HBV <2 log IU/ml & HBsAg remains the same
    • Consider in HBV patients with possible HCV coinfection & without history of Lamivudine resistance
  • Lamivudine
    • May be used as initial therapy for HBeAg positive chronic hepatitis with elevated ALT
    • Recommended in viremic patients (HBeAg positive & HBeAg negative patients) aged >2-3 years with ALT >5x ULN especially if there is concern regarding decompensation
    • Good safety profile & ease of administration are its advantages over Interferon alfa
    • Action: Premature termination of viral DNA chain termination thereby inhibiting HBV DNA synthesis
      • Induces histologic improvement & reduction in rate of development of hepatic fibrosis
    • Effects:
      • Pretreatment ALT & active histological disease are the most important predictors of response
      • Response is greatest in patients with an ALT twice the normal value
      • Treatment may be discontinued in patients who have completed 1 year of treatment & have persistent HBeAg seroconversion to anti-HBe
      • Treatment may be continued in patients who have not achieved HBeAg seroconversion & have no evidence of breakthrough infection, because HBeAg seroconversion may occur with continued treatment
    • Lamivudine-resistant HBV
      • Emergence of Lamivudine-resistant HBV is increasingly common with prolonged treatment, together with a decreasing rate of remission
      • Associated with development of Lamivudine-resistant YMDD viral mutants, which appear to be less virulent than wild-type HBV, but have been associated with rapidly progressive liver disease in some patients
      • Lamivudine resistance is usually manifested as breakthrough infection, with reappearance of HBV DNA in serum
      • Factors that may correlate with the emergence of Lamivudine resistance: High pre-treatment HBV DNA levels, high pre-treatment ALT levels, male gender, high body mass index (BMI)
  • Tenofovir
    • Drug of choice for HBeAg-positive HBV patients unresponsive or intolerant to Interferon alfa treatment
    • Alternative treatment for HBsAg-negative HBV patients with compensated liver disease previously given Interferon alfa with HBV <2 log IU/ml & HBsAg remains the same
    • Lamivudine may be added if HBV DNA is still detectable at 96 weeks of treatment
    • Test for HBV DNA, quantitative HBsAg & HBeAg levels prior to, at 12, 24, & 48 weeks during, & every 6 months after initiation of treatment
    • May help evaluate patient’s response & adherence to Tenofovir

Hepatitis C

  • Addition to Interferon alfa/Ribavirin combination yields higher sustained virological response (SVR) rates
  • Recommended triple therapy regimen for the following:
    • Patients with detectable HCV RNA at weeks 8 & 24: stop treatment at 28 weeks
    • Patients with detectable HCV RNA within 8-24 weeks of therapy: stop Boceprevir at week 36 of treatment, then continue Interferon alfa & Ribavirin regimen up to 48 weeks

Interferon alfa with or without Ribavirin

  • The use of Interferon alfa-2b combined with Ribavirin may be considered in patients with HCV infection

Peginterferon alfa-2a with Ribavirin

  • Treatment of choice for treatment-naive chronic HCV patients aged 3-17 years with genotype 2 or 3, & genotype 1 & 4 & high viral load


  • Assess HCV genotype prior to initiation of treatment


  • Added to Interferon alfa/Ribavirin regimen for patients with undetectable HCV RNA at week 4 & 12 of therapy

Hepatitis D

  • Interferon alfa may have a role
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS JPOG - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
21 Feb 2021
The efficacy and safety of the two-bag (TB) system are comparable to those of the one-bag (OB) system in adults with diabetic ketoacidosis (DKA), results of a study have shown. Both approaches can be considered in adult DKA patients.
01 Dec 2020
Tetanus toxoid 5 Lf, diphtheria toxoid 2 Lf, pertussis toxoid 2.5 mcg, filamentous haemagglutinin 5 mcg, fimbriae types 2 and 3 5 mcg, pertactin 3 mcg
Dr. Hsu Li Yang, Dr. Tan Thuan Tong, Dr. Andrea Kwa, 08 Jan 2021
Antimicrobial resistance has become increasingly dire as the rapid emergence of drug resistance, especially gram-negative pathogens, has outpaced the development of new antibiotics. At a recent virtual symposium, Dr Hsu Li Yang, Vice Dean (Global Health) and Programme Leader (Infectious Diseases), NUS Saw Swee Hock School of Public Health, presented epidemiological data on multidrug-resistant (MDR) gram-negative bacteria (GNB) in Asia, while Dr Tan Thuan Tong, Head and Senior Consultant, Department of Infectious Diseases, Singapore General Hospital (SGH), focused on the role of ceftazidime-avibactam in MDR GNB infections. Dr Andrea Kwa, Assistant Director of Research, Department of Pharmacy, SGH, joined the panel in an interactive fireside chat, to discuss challenges, practical considerations, and solutions in MDR gram-negative infections. This Pfizer-sponsored symposium was chaired by Dr Ng Shin Yi, Head and Senior Consultant of Surgical Intensive Care, SGH.
05 Feb 2021

Primary immunodeficiency disease (PIDD) and allergies are two groups of conditions related to the immune system. However, they are uniquely different in terms of symptoms and treatment.