Viral Hepatitis 

Hepatitis is an acute or chronic inflammation of the liver, most commonly due to a viral infection. Two viral types, B and C, are together the leading cause of liver cirrhosis and cancer. Today, viral hepatitis is a major global public health issue. It affects hundreds of millions of people worldwide and is responsible for significant morbidity, mortality and socio-economic losses.

  • The 5 identified forms of viral hepatitis affect about 400 million people worldwide.
  • The viral hepatitis pandemic is responsible for an estimated 1.4 million deaths per year. 47% are attributable to hepatitis B virus and 48% to hepatitis C virus.
  • Viral hepatitis A and E are food- and water-borne infections that can result in acute outbreaks in communities with unsafe water and poor sanitation.
  • More than 95% of people living with chronic hepatitis don’t know they have it.
  • In 2015, less than 1% of people with chronic hepatitis infection were receiving treatment.

Sources:

Definition

Hepatitis is an inflammation of the liver. Acute infection of some types of hepatitis can lead to chronic infection, potentially causing liver diseases including cirrhosis and cancer. It can be developed as a result of alcoholism or medications, but is most commonly caused by viral infection. Five distinct hepatitis viruses have been identified: A, B, C, D and E. Together they affect about 400 million people worldwide. Hepatitis A, B, and C are the most commons types.

Hepatitis B and C, which can lead to chronic hepatitis, are particularly prevalent. They are leading causes of liver cancer, liver cirrhosis and mortality1,2,3. Cirrhosis due to hepatitis is one of the main reasons for liver transplants2.

The means of transmission differs according to the type of viral hepatitis (see chart). Vaccines are available for HAV and HBV; otherwise hygiene and education contribute to prevention.  During the acute phase, hepatitis may cause “flu-like” symptoms (e.g. nausea, vomiting), jaundice, white stools, and dark urine. Yet viral hepatitis is largely asymptomatic nature, so most people don’t know they are affected. That’s why viral hepatitis is called a “silent epidemic”. 
 

Means of potential viral hepatitis transmission

Means

HAV

HBV

HCV

HDV 

HEV

Food and water contamination most common no no HDV infection is linked to HBV infection. most common
Blood e.g. through transfusion; contaminated instruments in healthcare settings; sharing needles among drug users no yes yes rare
Sex with an infected person rare yes yes rare
Mother-to-child transmission rare yes yes rare

 

Diagnosis

Hepatitis can be difficult to diagnose because it can be asymptomatic or symptoms may be non-specific.

  • Non-specific or absent symptoms (90% of cases):
    • pain in right hypochondrium - fever
    • nausea and vomiting - arthralgia
    • urticaria
  • Specific symptom (≤ 10% of cases)4:
    • icterus (jaundice)
  • Severe form: fulminant hepatitis
    • clinical signs: hepatic encephalopathy
    • biological signs: prothrombin level (< 50%) ; transaminase level not correlated with the severity of fulminant hepatitis

When a patient is suspected to have hepatitis knowing their background often helps clinicians orient their diagnosis.1,2 People at higher risk include:

  • HIV-infected individuals are at higher risk of both hepatitis B and C. An estimated ¼ of HIV-infected people in the US are also HCV-infected2
  • Men who have sex with men2
  • Injection drug-users2
  • People in healthcare facilities and correctional facilities2
  • Healthcare workers2
  • Most people from low-resource countries will contract hepatitis A in childhood1,2
  • Asians and Pacific Islanders are at higher risk of hepatitis B2

Because the different types of hepatitis cause similar symptoms during the acute phase, serological tests are important to determine the type of virus and when it was contracted. Once the serology results have been obtained (and possibly a liver biopsy performed to evaluate severity),appropriate treatment and management measures can be implemented. 
 

Viral Hepatitis: Quick Guide to Serologic Markers

Situation

Hepatitis

Serologic markers

Acute hepatitis
A
 
B

 

C
 
D
 
E

Anti-HAV IgM
   
HBsAg / Anti-HBc IgM /Anti-HBc Total /HBeAg/Anti-HBe
    
Anti-HCV*
    
HDV IgM, Ag Delta
    
HEV IgM / HEV IgG

Chronic hepatitis B
 
C

HBsAg / Anti-HBc, then HBe Ag / Anti-HBe
  
Anti-HCV

Prenatal HBV screening B

HBsAg: if HBsAg +  :

• Mother: monitored for HBe Ag / Anti-HBe and

• Newborn: quantitative anti-HBs after vaccination

At-risk groups B
 
 
 
C

Anti-HBc
•  if -   vaccinate
•  if +   quantitative HBsAg / Anti-HBs
  

Anti-HCV*

HBV vaccination B

Pre-vaccination: Quantitative Anti-HBs Total

•  if -   vaccinate

•  if +  → quantitative HBsAg / Anti-HBc Total Post-vaccination: quantitative anti-HBs Total

HAV vaccination A

Patient > 30 years: Total anti-HAV

•  if -  → vaccinate

 

Prevention / Treatment 

Prevention

The incidence of viral hepatitis is not distributed equally around the world. This is mainly due to lack of access to prevention measures in low-resource populations and countries. For this reason, the WHO global policy for the prevention and control of viral hepatitis aims to tailor responses to the specific national or regional context3. In general, this falls into alignment with essential global health strategies. For hepatitis, the most important prevention strategies are universal access to childhood vaccination for hepatitis B; improved hygiene and practices in and out of the healthcare setting; and screening.

Vaccination: Effective vaccines are available for hepatitis A and B2,3. The vaccine for HBV also protects against HDV, since HDV only affects populations already infected with HBV.

  • Universal vaccination in childhood is showing very good results in containing the number ofHBV infections.
  • Vaccination is helping to reduce mother-to-child transmissions (principal transmission for HBV)
  • Awareness and vaccination programs are also part of reducing the spread among adults, in particular at-risk groups. Vaccination is compulsory for some at-risk groups in some countries

Hygiene: Proper hygiene is an important prevention method for all types of viral hepatitis. This includes:

  • Clean drinking water and hygienic food handling
  • Proper hand washing
  • Safer sex
  • Injection drug users: not sharing needles and needle exchange programs
  • Health-care settings: fundamental infection control measures; aseptic techniques; no reuse of needles and syringes; safe injection practices

Screening: Screening of people in at-risk populations and of blood products is helping to reduce the spread of hepatitis2,3.
 

Treatment

Treatment for the various types of hepatitis varies greatly, as does treatment of acute versus chronic illness.

Hepatitis A
Usually resolves on its own. Treatment of symptoms includes rest and elimination of alcohol.

Hepatitis B
Acute HBV infection is not usually treated in immunocompetent adults, as it should resolve naturally.

Current treatments for chronic HBV5:

  • Pegylated Interferon alpha (Peg-IFN)
  • Nucleotides analogues (NAs):
    • First line: Entecavir (ETV), Tenofovir( TDF)
    • Second line: Adefovir, Telbivudine, Lamivudine
  • Liver transplant can be considered for decompensated cirrhosis
  • Therapeutic monitoring recommended during, at the end of treatment, and at a period after end of treatment

Hepatitis C
No specific treatment for acute HCV.

Reference treatment for chronic HCV6:

  • Genotype 1 (60% patients) Pegylated-interferon-α + ribavirin + Direct Antiviral Agent (Boceprévir or Telaprévir)
  • Other genotypes: Peg IFN + ribavirin
  • Treatment duration: 48 weeks for genotype 1, 24 weeks for other genotypes
  • Intermediate criterion to determine therapeutic efficacy: sustained viral response
  • Duration and efficacy of therapy depends on the genotype
  • Treatment monitoring should be done:
    • At T0 before starting therapy,
    • Regularly after several weeks of therapy, generally at weeks 4, 12, 24, 36, 48, etc.
    • Depending on genotype, drugs, viral response
  • New triple therapy treatments to become available in 20147:
    • PegIFN + RBV+ Sofosbuvir or Simeprevir
  • PegIFN-free regimens will also be available in 20147:

Hepatitis D
No specific treatment for acute HDV. See prevention and treatment of its helper virus, HBV.
 

Hepatitis E
Generally, no specific treatment for acute HEV, although treatment with Ribavirin may be effective. For immunocompromised patient, immunosuppressive treatment may be lowered. Otherwise, treatment is usually focused on relieving signs and symptoms. 

 

Guidelines

 

REFERENCES

1)     WHO fact sheets: Hepatitis A (No 328), B (No204), and C (No 164), July 2013

2)     CDC website: http://www.cdc.gov/hepatitis/

3)     WHO: Global policy report on the prevention and control of viral hepatitis in WHO member states. July 2013.

4)     Lefrère JJ, Lunel F, Marcellin P, Pawlotsky JM, Zarski JP. Guide pratique des hépatites virales. MMI Ed, Paris, 1998.

5)     European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection. 2012

6)     European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. 2013 revision. 

7)     American Association for the Study of Liver Disease/Infectious Diseases Society of America. Recommendations for Testing, Managing, and Treating Hepatitis. 14.02.2014
 

 

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