Introduction

The liver plays a crucial role in processing nutrients, filtering blood, and fighting infections within the body. If the liver undergoes inflammation or damage, it can adversely impact its functioning. Chronic hepatitis is a medical condition where the liver is constantly inflamed. This condition is a significant global health challenge and affects millions of people worldwide. Interferon therapy, a type of treatment, has become an important way to manage this condition. This article aims to unravel the intricacies of interferon therapy and its role in chronic hepatitis.

What is hepatitis?

The word hepatitis means inflammation of the liver (hepa = liver, itis = inflammation). It can be caused by infectious agents, i.e. viruses, as well as non-infectious agents, including drugs, alcohol, toxins and some autoimmune diseases. However, the most common cause of hepatitis is viral agents. A list of various types of viral hepatitis and their causative agents is given below:

Acute and chronic hepatitis

Based on the duration of inflammation of the liver, hepatitis can be classified into two types:

Acute (short-term) hepatitis

If the inflammation of the liver lasts for less than six months, it is called acute hepatitis. Acute hepatitis is usually self-resolving, but in a few cases, it could be severe (fulminant) and cause liver failure. However, patients with hepatitis A and E usually fully recover from it.¹

Chronic (long-term) hepatitis

Inflammation that persists for more than six months is referred to as chronic hepatitis. It is characteristic of only hepatitis B, C and D.¹ Chronic liver infection can later develop into cirrhosis (a scarring of the liver) or liver cancer. There is a risk of death for these patients.

Symptoms of hepatitis

Many people with hepatitis may be asymptomatic (do not have any symptoms) and remain unaware of their infection. If symptoms arise during an acute infection, they develop within 2 weeks to 6 months of exposure. Symptoms of acute hepatitis can include: 

• Fever 
• Fatigue
• Nausea
• Vomiting
• Jaundice
• Joint pain
• Dark urine
• Abdominal pain
• Loss of appetite
• Light-coloured stools

It can take several decades for the symptoms of chronic viral hepatitis to manifest. It can cause liver damage that includes: 

• Liver fibrosis 
• Cirrhosis (scarring of the liver) 
• Hepatocellular carcinoma (liver cancer)
• Portal hypertension (a condition where there is high blood pressure in the veins that carry blood from the digestive system organs to the liver). This results in severe health complications and may even lead to death.

Understanding interferons

Interferon (IFN) is a substance that occurs naturally in the body and is produced by white blood cells. It plays a crucial role in helping the immune system fight against viral infections and other diseases, including cancer. Interferons can also be artificially produced in laboratories and are used to treat various conditions. There are three main types of interferons:²

1. Interferon-alpha (IFN-α)
2. Interferon-beta (IFN-β)
3. Interferon-gamma (IFN-γ)

An improved version of interferons called pegylated interferons (PEG-INF), are now given as shots under the skin (subcutaneously). In many cases, these new types have taken the place of the older, standard interferons.⁵

Standard interferon therapy vs pegylated interferon therapy

Standard interferons stay for a shorter period in the body. When administered through subcutaneous or intramuscular injections, standard interferon requires frequent dosing, often several times a week. 

However, pegylated interferons, like peginterferon alfa-2a (PEG-IFN alfa-2a) and peginterferon alfa-2b (PEG-IFN alfa-2b), stay in the body longer, have fewer chances of causing an immune response, work better in the body, and are more potent compared to regular interferons. 

People find it easier to stick to their treatment plan because pegylated interferon is only needed once a week. The side effects are mostly similar between the two, but pegylated interferons have better effects on the body and are at least as easy to handle as compared to standard interferons due to their improved features.⁴

How does interferon therapy work for chronic hepatitis?

As mentioned earlier, interferons are special proteins that help our body fight against infections caused by viruses. Interferons do not exert a direct antiviral effect but trigger an immune response that allows the body to resist viral infections. They promote an antiviral state by activating various immune functions that help combat the virus.⁵ They act as messengers to trigger and boost our immune system, which is responsible for defending our body against harmful invaders.²

Interferon therapy for chronic hepatitis B

Two medications, PEG-IFN alfa-2a and PEG-IFN alfa-2b, are approved to treat chronic hepatitis B infection. To see if the treatment is working, doctors check for the disappearance of HBV DNA using the HBVQN test and hepatitis B envelope antigen (HBeAg) from the blood, especially in patients who initially tested positive for HBeAg. Additionally, improvements in blood tests and liver biopsies are considered.^3,5 

Interferon therapy for chronic hepatitis C

For over twenty years, the preferred medication for treating hepatitis C has been a combination of pegylated interferon alfa-2a or alfa-2b with ribavirin. The duration of this therapy typically lasts between 24 to 48 weeks, depending on the genotype of the virus causing the disease. PEG-IFN and ribavirin treatments had many side effects and were difficult for patients to stick to.³

However, PEG-IFNs alone are no longer the first-choice treatment for most types of hepatitis C, though they might still be considered in specific situations. Research shows that combining direct-acting antivirals (DAAs) with PEG-IFNs and ribavirin leads to better success rates than using just pegylated interferon and ribavirin for chronic hepatitis C.^5,6 

Interferon therapy for chronic hepatitis D

When someone has both hepatitis B and hepatitis D, they are usually treated with PEG-INFs. Other medications that are taken by mouth do not work well for this. Unfortunately, no new treatments have been developed for hepatitis D in a long time, so pegylated interferon remains the best option.^7,8 

Ropegylated interferon to treat chronic viral hepatitis

A new type of medicine called ropeginterferon alfa-2b is being developed to treat chronic viral hepatitis. This medicine is a special kind of interferon that stays in the body for a longer time, and you only need to take it every two to four weeks. This is less frequent than other conventional pegylated interferons, which are usually taken every week. Ropeginterferon alfa-2b provides a promising treatment option for people with chronic viral hepatitis, including those with chronic hepatitis B, C, and D.⁹

Side effects of interferon therapy

The following are the side effects of interferon therapy:³

• Fatigue
• Joint pain
• Flu-like symptoms
• Emotional irritability
• Hair loss
• Depression
• Bone marrow suppression

Summary

Interferon therapy is crucial for managing chronic hepatitis caused by viral agents like HBV, HCV, and HDV. Chronic hepatitis, lasting over 6 months, can lead to severe complications. Interferons boost the immune system's response against viruses, with pegylated versions being more effective and causing fewer side effects. Treatment for hepatitis B involves PEG-IFN alfa-2a and PEG-IFN alfa-2b, while hepatitis C is treated with PEG-IFN alfa-2a or PEG-IFN alfa-2b in combination with ribavirin. Hepatitis D is also primarily treated with pegylated interferons. A novel ropeginterferon alfa-2b offers a longer-lasting option. Despite advancements, interferon therapy has side effects, including fatigue and joint pain. Ongoing research aims to enhance the effectiveness and tolerability of interferon therapy for chronic hepatitis.

FAQs

What is the purpose of interferon therapy for chronic hepatitis B?

Interferon therapy for chronic hepatitis B aims to treat the infection using medications such as PEG-IFN alfa-2a and PEG-IFN alfa-2b.

How does interferon work in the context of hepatitis?

Interferon boosts the immune system's antiviral response by inducing an antiviral state and activating immune functions.

Why is interferon used in hepatitis?

Interferon is used to fight viral infections, particularly in chronic hepatitis B, C, and D because it can trigger and enhance the body's immune defence system.

Are there alternative treatments for interferon therapy for chronic hepatitis?

While interferon therapy is a common approach, there are now direct-acting antiviral drugs available for hepatitis C, and ongoing research explores various treatment options for different types of viral hepatitis.

What are the common side effects of interferon therapy for chronic hepatitis?

Interferon therapy may lead to side effects such as fatigue, joint pain, flu-like symptoms, emotional irritability, hair loss, depression, and bone marrow suppression.