Viral Hepatitis: Tackling a silent killer

Viral hepatitis is a major public health problem. In addition to causing loss of 250,000 lives annually, it also causes a huge financial burden due to repeated hospitalizations, particularly in cases of Hepatitis B and C.

BOTH hepatitis A and E are hyper endemic in India and are caused by drinking contaminated water. Both these viruses, in addition to causing sporadic cases of jaundice, also cause large epidemics, particularly during the monsoon, flooding and natural calamities like earthquakes and famine etc.

Global burden

Hepatitis A is the commonest cause of acute viral hepatitis in young children. Over 99 per cent of these children recover fully, acute liver failure can occur in a very small percentage of patients. Hepatitis A has the highest global burden at over 5.5 billion. The mortality of hepatitis A increases with increasing age. With mortality rates of 1 per 1,000 in children and 2 per 100 in adults, treatment is largely symptomatic and supportive.

Hepatitis E shares the same mode of transmission as hepatitis A. This virus affects both older children and adults. Hepatitis E is a more serious infection than hepatitis A, with incidence of acute liver failure exceeding 20 per cent in late stages of pregnancy. Globally hepatitis E causes annual mortality of over 300,000.

Hepatitis E has a global burden of 2.5 billion. Both hepatitis A and E have similar clinical presentation such as fever, loss of appetite, body, muscle and joint pain, weight loss, skin rash and jaundice.

Acute liver failure

Combined hepatitis A and E are the commonest cause of acute liver failure in India. When should one refer a patient to hospital? Rapidly increasing jaundice, severe headache and vomiting, bleeding from the nose or mouth, drowsiness, irrelevant talk and decreased urine output are symptoms that should require hospitalization.

Boiling and chlorination of water effectively kills hepatitis A & E viruses. We must ensure a 24 x 7, safe drinking water supply, repair of leaking sewerage pipes, which are often the main cause of fecal contamination of drinking water. Hepatitis A can effectively be prevented by two doses of hepatitis A vaccine, spaced six months apart. Hepatitis E vaccine has been available in China for almost two years now but this vaccine is still unavailable in India.

Common causes

Hepatitis B and C viruses are common causes of liver cirrhosis and liver cancer. Both are blood-borne viruses with a similar mode of transmission as the HIV/ AIDS virus. Hepatitis B and C rank as the ninth commonest cause of global mortality. Over 1.4 million people across the world die each year from hepatitis B and C. Hepatitis B is a hundred times more infectious than HIV/ AIDS virus. In Asian countries, mother-to-baby transmission (vertical transmission) is quite common, because of a shared mode of transmission, co-infection of hepatitis B, C and HIV/AIDS virus is not uncommon.

India and China combined have well over half-a-billion people chronically infected with hepatitis B; between 15 and 30 per cent of these will develop liver cirrhosis and/ or liver cancer during their lifetime. Hepatitis B causes over 50 per cent of all cases of liver cancer and over 30 of all cases of liver cirrhosis. Hepatitis C infects 2 per cent of the world’s population, with India having more than 14 million people infected with this virus. This is almost twice the burden of hepatitis C in Europe to 20 per cent of all patients of hepatitis C will develop liver cirrhosis and/ or liver cancer in 20 to 30 years.
Combined hepatitis B & C, contribute to 70 per cent of 750,000 new cases of liver cancer diagnosed globally. Liver cancer is a very serious disease with over one-third of patients dying within one year of diagnosis. However, if liver cancer is diagnosed early, curative treatment may be offered by surgery, radio frequency ablation or liver transplantation.

Hepatitis B and C are often referred to as “The Silent Killers”, because symptoms of liver disease appear at a very late stage. These symptoms include jaundice, swelling of feet and abdomen, vomiting of blood or passage of black stools, fatigue, anemia, memory disturbances, decreased urine output, fever etc. Both these can be diagnosed through appropriate blood tests.

In chronic hepatitis C, the risk of liver cancer increases 17-fold, with maximum risk in an elderly male patient who takes moderate to large amount of alcohol. Hepatitis C is responsible for maximum number of liver-related deaths, and is the leading indication for liver transplants in USA and Europe.

Blood tests & treatment

Hepatitis B and C can be diagnosed by blood tests. Chronic hepatitis B is diagnosed if hepatitis B virus persists over six months. Timely and appropriate antiviral therapy will improve patients’ survival, decrease liver-related deaths and improve the quality of life. Therapy for chronic hepatitis C has undergone a paradigm shift.

The standard of care which included prolonged injections with PEG interferon and daily ribavirin has been replaced by all-oral therapy where this standard therapy cannot be given or is ineffective. These all oral drugs are called DAA’s (Directly acting antivirals). These drugs are highly effective, given for a short duration, but are costly and are still unavailable in India. Sofosbuvir and ledipasvir are examples of such new drugs.

Hepatitis B can be prevented by three doses of an excellent vaccine given at day 0, 1 month and six months’ interval. These three doses give a 22 to 25 years protection against hepatitis B.

Safe surgical practices, avoidance of reusable syringes and needles, proper testing of blood and blood products to be transfused, banning of professional blood donors and taking universal precautions are some of the methods to control the spread of hepatitis B and C.

Delta hepatitis is a defective virus which is only seen in patients infected with hepatitis B. This is an extremely difficult-to-eradicate virus and leads to significant liver-related morbidity and mortality. Fortunately, delta virus is uncommon in India.

High-risk groups that must be tested and vaccinated against hepatitis B are:
• All new-born babies
• All pregnant females
• All children and adolescents not vaccinated at birth
• All HIV positive cases
• All patients of chronic liver disease (not caused by hepatitis B)
• All patients of chronic kidney disease with or without hemodialyses
• All healthcare professionals
• All patients being treated for sexually transmitted diseases
• All prison inmates
• All mentally challenged people requiring institutional care
• All intravenous drug abusers
• All spouses of patients who are suffering from hepatitis B.
• All people with high-risk sexual behavior
• All travelers visiting highly endemic areas
• Patients attending STD clinics
• Prison inmates
• All immigrants from highly endemic countries.

ABCDE of the silent killer

• Hepatitis A and E are spread by drinking faecally contaminated water.
• Hepatitis A is the commonest cause of viral hepatitis in children, with the global burden of 5.5 billion as per W.H.O.
• Hepatitis A can be prevented by two doses of vaccine.
• Hepatitis E is a more severe infection than hepatitis A, with mortality rates exceeding 20 per cent in late pregnancy.
• Hepatitis B and C are blood-borne and share a common mode of transmission.
• Hepatitis B and C cause liver cirrhosis and / or liver cancer
• Globally, over 400 million people are infected with hepatitis B and over 180 million with hepatitis C.
• India has over 40 million chronically infected patients of hepatitis B and over 14 million patients infected with hepatitis C.

Prevention & treatment of hepatitis B

HEPATITIS B virus affects over 40 million Indians, with a prevalence rate of 2 to 7 per cent. It shares the same route of transmission as HIV and hepatitis C virus. Hepatitis B can cause acute hepatitis with a 1 per cent mortality rate. Over 95 per cent of the people clear the virus from their blood, unlike 95 per cent infants and children who are unable to do so.

Persistence of hepatitis B for more than six months is defined as chronic hepatitis B. Both vertical and horizontal modes of transmission occur with this virus. About 15-30 per cent of all cases of chronic hepatitis B will develop liver cirrhosis and/or liver cancer.

Liver cancer is the most-dreaded complication of chronic hepatitis B. Liver cancer is invariably fatal as it is often diagnosed at a late stage. If it is diagnosed at an early stage, it may be cured by liver surgery, liver transplantation or radio-frequency ablation (RFA). Hepatitis B is truly an oncogenic (cancer-causing) virus.

The devastating complications of hepatitis B virus can be most effectively prevented with three doses of hepatitis B vaccine given intra-muscularly, in the arm, in three doses of 20 mcg on day zero, one month and six months.

The third dose gives a protection of 20-25 years. In India, less than 50 per cent of all vaccinated people receive their third dose. Globally, only one out of five babies will receive the third dose of this vaccine. A titer of 10 IU/ml is protective.

Hepatitis B immunoglobulin (HbIg) is also used for prevention of hepatitis B in special circumstances — in babies born to hepatitis B positive mothers, after needle-stick injury, and after liver transplantation to prevent re-infection of graft.

Other methods to prevent hepatitis B include testing of all blood and blood products, avoiding reused needles and syringes, practicing safe sex, avoiding the roadside barber, etc. This infection is not spread by casual contact.

Goals of treatment of hepatitis B include the reduction or slowing down of disease progression and prolongation of life. This includes the delaying or prevention of developing the dreaded complications of liver cirrhosis and liver cancer.

Two types of therapies are available

The first includes injections of pegylated interferons given for 48 weeks to patients with early liver cirrhosis and a moderate viral load. About one-third of patients respond to this therapy.

The other therapy used includes oral drugs like entecavir, tenofovir, adefovir, lamivudine and telbivudine.

The first two drugs have a high genetic barrier and are preferred in clinical practice. Therapy is generally continued for few years.

Over all, these drugs are safe but may cause lactic acidosis, kidney toxicity and bone changes.

Keep these in mind:

• Over 33 per cent of all liver cirrhosis is due to this virus.
• 15-30 per cent of all chronically infected people will develop liver cirrhosis and/ liver cancer.
• Three doses of hepatitis B vaccine are the most effective way to prevent hepatitis B.
• Hepatitis B vaccine is truly a cancer-preventive vaccine
• Injections of pegylated interferon are costly, given for 48 weeks, and cause side-effects.
• Oral drugs against hepatitis B are effective, can be given in advanced stages of liver cirrhosis, for long term.
• Testing of blood and blood products by nucleic-acid testing (NAT) is more effective, although costly.
• Hepatitis B and C cause over 50 per cent of all cases of liver cirrhosis and over 75 per cent of 750,000 new cases of liver cancer globally, annually.
• Hepatitis B and C-induced liver cirrhosis and/ or liver cancer is one of commonest indication for doing a liver transplantation.
• W.H.O. recommends universal Hepatitis B vaccination.
• Currently there is no vaccine available against hepatitis C
• Less than 5 per cent of people infected with hepatitis B and C are undergoing treatment.
• Hepatitis C infection can be cured by excellent all-oral drugs known as Directly Acting Antiviral (DAA’s). These drugs are still unavailable in India.

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