Hepatitis C And Fibrosis

Introduction

Hepatitis C is a viral infection that can lead to inflammation and damage to the liver. Over time, this inflammation and damage can cause a buildup of scar tissue in the liver. This scar tissue is commonly referred to as fibrosis. As liver fibrosis worsens, it can prevent the liver from functioning normally.¹ Severe fibrosis caused by hepatitis C infection cannot be undone, however, further damage can be limited by treating the underlying hepatitis C infection.

Currently, the World Health Organisation estimates 58 million people are living with a chronic hepatitis C infection.

Understanding hepatitis C (HCV)

Hepatitis means inflammation of the liver. It can be caused by a viral infection of the liver with the hepatitis C virus (HCV). Following infection with HCV the illness will either be acute (short-term) or become chronic (long-term). In 15- 25% of people infected by HCV, their body can clear the virus without any need for treatment within 4 to 8 weeks. This acute infection is not associated with fibrosis. However, 55-85% of people will not clear the acute HCV infection by themselves and the infection will then become chronic, this will require further treatment.²

Causes and risk factors

Hepatitis C is always caused by infection with the hepatitis C virus. It is a blood-borne virus, which means it is spread by the contaminated blood of an infected person entering the bloodstream of an uninfected person. Therefore, HCV is commonly transmitted through:

• Inadequately sterilising or reusing medical equipment within a healthcare setting
• Contaminated blood or organ transplantation
• Sharing drug-injecting equipment
• Childbirth: from an infected mother to their baby
• Sexual practices that lead to blood exposure
• Getting tattoos or body piercing with non-sterile instruments
• Sharing items such as toothbrushes or razors which contain contimnated fluids

According to the Centers for Disease Control and Prevention, those most at risk for hepatitis C include:

• People who do or have previously injected or inhaled drugs
• People living with HIV
• People who have received organ transplants or blood transfusions before 1992
• People who have received clotting factor concentrates prior to 1987
• People who have been exposed to the blood of someone with hepatitis C
• Children born to mothers infected with hepatitis C
• People who have been in prison

Symptoms and diagnosis

Most patients living with either an acute or a chronic hepatitis C infection show no real symptoms. This can result in the illness going undiagnosed for many years.³ When symptoms are present in the acute phase of the infection they can include fatigue, nausea, aching muscles, fever and jaundice. Usually, chronic hepatitis C symptoms develop once the liver has been damaged to an extent that mimics liver disease. These symptoms include:

• Fatigue (tiredness)
• Jaundice (yellow appearance of the skin and eyes)
• Fluid buildup in your abdomen (ascites)
• Blood vessels that may resemble spiders on your skin
• Bleeding/ bruising easily
• Unintentional weight loss
• Dark-coloured urine
• Reduced appetite
• Itchiness
• Swollen legs
• Confusion, slurred speech and/or drowsiness

You should make an appointment with your doctor if you are concerned that you have been exposed to the hepatitis C virus or if you have symptoms of hepatitis infection. Screening for the hepatitis C virus is recommended, particularly in those that have a higher risk of exposure.  

Most commonly your doctor will perform blood tests to determine whether you have or have had hepatitis C.

Treatment options

Following diagnosis of a hepatitis C infection, your doctor will discuss the treatment options available to you. 

If the infection is caught at an early stage, your doctor may decide that treatment is not immediately required. This is because some patients infected with hepatitis C will only have an acute infection.² This type of infection can spontaneously clear itself and does not require medical intervention. Instead, your doctor will order another blood test after a few months to assess whether the virus is still present. 

If the virus persists after several months treatment is normally recommended. 

Chronic hepatitis C infections are treated with direct-acting antivirals (DAAs). This type of drug is highly effective and is the safest group of medicines currently available for treating a chronic hepatitis C infection. The use of DAAs in the treatment of chronic hepatitis C have resulted in a hepatitis C cure rate of almost 100%.⁴

DAAs are oral tablets usually taken once daily over the course of several weeks.⁴

Liver fibrosis

Fibrosis refers to the thickening and scarring of tissue. Cirrhosis is the word used to describe severe fibrosis of the liver. The scar tissue buildup is caused by the liver attempting to heal itself from either repetitive or long-lasting inflammation or injury. When an excessive amount of scar tissue (fibrosis) builds up in the liver it can prevent the liver from functioning normally, and in severe cases lead to liver failure. Fibrosis can be caused by most types of chronic liver disease. Those with chronic liver disease should be tested for fibrosis.

Assessing the severity of liver fibrosis

Previously, a liver biopsy was the most useful tool for assessing the extent of liver fibrosis. However, due to progression in the development and accuracy of non-invasive tests which include blood tests and imaging techniques, non-invasive tests are normally favoured by both doctors and patients.⁵ Knowing the severity of fibrosis aids prognosis by providing an understanding of the extent of liver damage, which in turn helps guide the urgency of treatment against possible viral causes of liver disease (including treatment of hepatitis C). A general practitioner (GP) will usually refer a patient with liver cirrhosis to a specialist doctor in liver issues (hepatologist).

Fibrosis blood tests

Liver fibrosis can be detected in a blood test. These blood tests usually take just a few minutes and the results should be available within a few weeks.⁶

Imaging techniques for detecting fibrosis

Imaging tests a doctor may use to confirm a diagnosis of fibrosis include ultrasounds, CT, MRI or a transient elastography scan (this is used to measure liver ‘stiffness’).⁷

Noninvasive scoring systems for liver fibrosis

There are a variety of systems used for scoring liver fibrosis. The scoring systems most commonly used are the Knodell Histological Activity Index, the METAVIR score and the Ishak score. The Knodell score has stages 1-4, the METAVIR score has stages 1-5 and the Ishak score has stages 1-6. All of these scoring systems take into account the amount of inflammatory activity and the severity of the fibrosis, although some are more sensitive than others.

Fibrosis treatments

The treatment a doctor suggests for liver fibrosis depends on the underlying cause of fibrosis, and the extent of the fibrosis. As fibrosis is essentially a scarring of the liver, it cannot currently be cured. Therefore, the treatment options focus on treating the cause of fibrosis, managing the symptoms and preventing the worsening of fibrosis. 

Medications

For example, if the cause of a patient's fibrosis is a hepatitis C infection, a doctor may prescribe DAAs or other antiviral medications that will treat this infection and prevent it from causing further damage to the liver.⁴ Examples of NHS approved DAA’s include sofosbuvir, ledipasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, elbasvir, grazoprevir, velpatasvir, voxilaprevir, glecaprevir, pibrentasvir and ribavirin. These are usually used in combination with the exception of sofosbuvir and ribavirin. 

In addition, a doctor may also prescribe medicines within a group of drugs known as ‘antifibrotics’. Antifibrotics are used to help prevent permanent liver scarring by reducing inflammation.

Surgical options for advanced fibrosis

If a patient has end-stage liver disease caused by severe fibrosis, the only treatment option available at this point is a liver transplant. It is important to remember there is a long waiting list for liver transplants and in some cases, surgery may not be possible.⁸

Lifestyle changes and diet

A doctor may also recommend either stopping drinking or reducing your alcohol intake, exercising and losing weight if needed.

Regardless of the cause of your cirrhosis, alcohol consumption speeds up the rate of cirrhosis progression.  

Hepatitis C and fibrosis relationship

How hepatitis C (HCV) causes fibrosis

Hepatitis C infects cells of the liver (hepatic cells). Chronic infection with HCV in these cells causes hepatic inflammation. The body's natural response to inflammation and injury is to attempt to heal, however, the chronic inflammation caused by HCV results in an excessive and chronic attempt to heal. This exacerbated attempt to heal leads to an excess of scar formation on the liver. This scar formation is what is referred to as ‘fibrosis’.¹

Progression of fibrosis in HCV patients

According to the Hepatitis C Trust HCV infection takes on average about 20 years for significant fibrosis to develop. However, this progression can vary significantly between infected individuals.  

Stages of liver fibrosis

As stated previously, there are many different scoring systems used to describe the extent of fibrosis of the liver. Different healthcare professionals may use different classification systems. Therefore, it is perhaps easiest for your healthcare professional to explain the exact meaning of your stage/score. 

The most important terminology you should be aware of when discussing more severe liver fibrosis is compensated cirrhosis and decompensated cirrhosis. Compensated cirrhosis is normally confirmed via a liver biopsy as blood tests may come back normal. It is normally asymptomatic and has an estimated survival of 9-12 years. Decompensated cirrhosis is much more severe, symptoms are present, it can be detected via blood work and often requires the patient to be admitted to the hospital. The average survival for this type is around 2 years. 

Managing HCV and fibrosis

Following diagnosis with HCV, it is important your doctor establishes whether fibrosis is or is not present. If you have chronic hepatitis C the first course of action would be to treat the infection to prevent it from worsening fibrosis. To do this, you should take the medications prescribed by your doctor and take them as described. 

If you have cirrhosis caused by HCV it is important you reduce any additional damage. Lifestyle changes that should be made include: 

• Stop drinking alcohol: Alcohol is known to cause damage to the liver. Not drinking alcohol prevents further damage to the liver
• Eat healthily: Malnutrition is more likely to develop in those with cirrhosis. To reduce this risk, eat a healthy diet and omit all raw seafood
• Reduce salt intake: Salt causes your body to retain fluids. This can worsen the symptom of swelling in your legs. It is advised to season food with herbs where possible and opt for prepared food that has a low sodium content
• Check with your healthcare provider before using over-the-counter medicines: The damage to your liver caused by cirrhosis makes it difficult for your liver to process medicine. You should check with a doctor before taking any medicine, and avoid aspirin and ibuprofen
• Protect against infection: It is more difficult to fight off infection with cirrhosis. Make sure you are up to date with your vaccines (including hepatitis A and B). Avoid contact with people that are sick and make sure to practice good hygiene

Summary

To conclude hepatitis C is a viral form of hepatitis caused by the hepatitis C virus. This virus is blood-borne and is spread through the contaminated blood of an infected person entering the bloodstream of an uninfected person. Hepatitis C is a treatable virus, and timely treatment can prevent liver damage. If the infection becomes chronic and is left untreated it can cause fibrosis of the liver, which progresses over time. Severe fibrosis of the liver is also called cirrhosis, and this can prevent normal liver function. Cirrhosis is not usually reversible and is classified as a liver disease. The only treatment option for end-stage liver disease is a liver transplant, which may always not be a viable option.