Dealing with Deadly Disease

Chronic Hepatitis B virus (HBV) and chronic Hepatitis C virus (HCV) infections cause devastating damages to the liver. Though there are effective treatment modalities available for it more emphasis should be given for the prevention, especially in pregnant women to protect the newborn of vertically transmitted hepatitis infection.
By Dr Neelam Mohan

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Around 250 million people in the world have chronic Hepatitis B virus (HBV) infection with prevalence range of 2% to 8% with regional variation and chronic Hepatitis C virus (HCV) to be around 71 million. The prevalence is decreasing in several highly endemic regions due to improvements in the socio-economic status, universal vaccination programmes for HBV and perhaps effective antiviral treatments.
In India the total number of HBV carriers is about 40 million with an average prevalence of 3% to 4% and around 6-12 million people are estimated to have chronic Hepatitis C. Chronic HBV infection accounts for 40-50% of HCC and 20-30% cases of cirrhosis in India. Chronic HCV infection accounts for 12-32% of hepatocellular carcinoma (HCC)
and 12-20% of cirrhosis. There are few states like Punjab which has high burden of hepatitis infection owing to high prevalence of risk factors such as unsafe medical practices including unsafe medical injections, blood transfusions and intravenous drug abuse.
Today Hepatitis B & C combined contribute to more than 1.2 million deaths per year which is more than 1.3 times total deaths from HIV as all three of the diseases have same modes of transmission i.e.
• Vertical transmission (from infected mother to baby during birth)
• Sharing needles and syringes, tattooing
• Sharing items such as toothbrushes, razor with infected person
• Direct contact with blood or open sores of an infected person
• Exposure to blood from needle sticks or other sharp instruments of an infected person
• Sex with an infected partner

Clinical Symptoms:
Most people with Hepatitis B or C do not experience any symptoms during the acute infection phase. However, some people have acute illness with symptoms that last several weeks, including yellowing of the skin and eyes (jaundice), dark urine, extreme fatigue, nausea, vomiting and abdominal pain.
80–90% of infants infected with Hepatitis B during the first year of life develop chronic infections; and 30–50% of children infected before the age of 6 years develops chronic HBV.
After acute HCV infection around 20% get resolved of infection and remaining 80% go on to develop chronic HCV of which around 20% will develop cirrhosis leading to hepatocellular cancer or death.
Major difference in mechanism of infection by Hepatitis B virus is integration of HBV DNA into the cell genome leading to production of unknown protein which is important in the replication cycle of HBV. The present treatment modalities are all able to reduce the replication of virus but not able to remove it from the body. This makes it more difficult for the infection to be cleared from the body as compared to Hepatitis C virus which can be successfully treated with newly available drugs.

Structure of Viruses
• Hepatitis B is a DNA virus whereas Hepatitis C is an RNA virus.
• Hepatitis B surface antigen (HBsAg): positive during acute infection or chronic infection (if persists beyond 6 months)
• Hepatitis B core antigen (HBcAg): Presence of anti HBc IgM antibody suggests acute infection
• Hepatitis B e antigen (HBeAg): marker of high level of replication of the virus and indicates highly infectious state
• HBV DNA: suggests viral load in hepatitis B infected patients
• Anti HCV antibody: Its presence indicates hepatitis C infection
• HCV RNA: suggests viral load in hepatitis C infected patients

Acute HBV infection – Diagnosis is based upon the detection of hepatitis B surface antigen (HBsAg) and IgM hepatitis B core antibody (anti-HBc). Hepatitis B infection with Hepatitis B surface antigen (HBsAg) positive and IgM hepatitis B core antibody (anti-HBc) positive
Past HBV infection — presence of anti-HBs and IgG anti-HBc. Immunity to HBV infection after vaccination is indicated by the presence of anti-HBs only.
Chronic hepatitis – Persistence of HBsAg for more than 6 months
Occult HBV infection – presence of detectable HBV DNA by polymerase chain reaction (PCR) in patients who are negative for HBsAg

Chronic Hepatitis in Hepatitis B
Immune tolerant phase – the initial phase with high levels of HBV replication, HBeAg positive, HBV DNA (high levels) – but no evidence of active liver disease as manifested by lack of symptoms, normal serum ALT concentrations, and minimal changes on liver biopsy. No treatment needed.
Immune active, HBeAg positive (clearance) phase – HBeAg and HbsAg both positive, increased ALT and elevated HBV DNA. Consider treatment in this phase.
Inactive Chronic HBV – HBeAg negative and anti-HBe positive, normal ALT, liver biopsy showing no necrosis or inflammation and HBV DNA may be undetectable. No treatment but regular monitoring required in this phase.
Immune active, HBeAg-negative (reactivation) phase – HBeAg negative, elevated ALT, chronic inflammation on liver biopsy. They have a residual wild-type virus or HBV variants that cannot produce HBeAg due to precore or core promoter genetic variations. This phase is rare in children.
Resolved HBV (loss of HBsAg) – clearance of HBsAg and appearance of antibody to Hepatitis B surface antigen (anti-HBs antibody).

Treatment:
The primary goal of treatment is to improve survival and quality of life by preventing disease progression. The basic aim is to reduce the viral replication, reduce infectivity and reduce the incidence of liver related complications like cirrhosis and Hepatocellular carcinoma. The treatment of Hepatitis has been revolutionised in the last decade. We have virtually overcome the infection of Hepatitis C with newer oral available agents.

Hepatitis B Management
Currently, pegylated interferon alfa (PEG-IFN-a), entecavir (ETV), and tenofovir/tenofovir disoproxil fumarate (TDF) are the first-line agents in the treatment of hepatitis B disease. In children Enticavir is approved for >2 years of age and Tenofovir for >12 years of age. These are the main treatment drugs approved globally for this disease, although ongoing trials are investigating new types of medications, such as tenofovir disoproxil in combination with emtricitabine (FTC). Encapsidation inhibitors, entry inhibitors, TLR7 agonists, and therapeutic vaccines are all in development.

Hepatitis C Management
Though PEG IFN and Ribavirin are approved with the availability of newer Direct Acting Agent (DAAs), and due to the poor safety profile of PEG IFN, PEG-IFN is no longer recommended in combination regimens.
The World Health Organization (WHO) recommends the use of DAAs regimens to treat chronic HCV-infected individuals aged 18 years and older. These pangenotypic regimens include glecaprevir-pibrentasvir, sofosbuvir-daclatasvir and sofosbuvir-velpatasvir for 12 -24 weeks depending on presence of cirrhosis. WHO recommendations for chronic HCV-infected teens aged 12-17 years is Sofosbuvir/Ledipasvir and Sofosbuvir Rribavirin depending on genotype and cirrhosis for 12 -24 weeks.
Follow up: Follow up should be regular due to high likelihood of progression to cirrhosis and likely higher incidence of HCC. It should be done with pediatric gastroenterologist and Hepatologist for children.
As both these infections are preventable, more emphasis should be given for the prevention of infection, especially in pregnant women to protect the newborn of vertically transmitted hepatitis infection. Other modes of infection should be taken into consideration for decreasing the burden of infection in the community.

(The author is Director, Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta Hospital, Gurugram)