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Other than causing serious problems by themselves, hepatitis B (HBV) and hepatitis C (HCV) can join forces by creating a coinfection which, if untreated, may lead to severe consequences, including cirrhosis and liver cancer.

Hepatitis is an inflammatory disease of the liver that can be caused by external factors (microorganisms, medications, alcohol, or other toxic substances), as well as different immunological or metabolic processes (autoimmune processes and other diseases). However, the major cause of hepatitis is a group of viruses that mainly target the liver, which is why they are called Hepatitis viruses.

There are five different types of hepatitis viruses, called Hepatitis A, B, C, D, and E. We say “different types”, because biologically speaking, they have little in common, except the fact that they primarily attack liver tissue.

Some of these viruses, such as hepatitis A (HAV) and E (HEV), are transmitted via the fecal-oral route (associated with lack of hygiene and sanitation) and these infections almost always end without serious consequences. Hepatitis B (HBV) and C (HCV) are transmitted via blood and mucus membranes, where the most common ways to get infected include direct contact with blood, unprotected sexual intercourse, and during childbirth.

Unlike HAV and HEV, which only cause acute hepatitis, HBV and HCV can also trigger chronic forms of hepatitis. Although Hepatitis D (HDV) is transmitted the same way as Hepatis B and C, HDV infection is never present without HBV already in the organism.

What are the symptoms of hepatitis?

Hepatitis has two main forms, acute and chronic.

Acute hepatitis is characterized by:

  • Jaundice (yellow coloration of the skin)
  • Dark colored urine and lightly colored stool
  • High temperature
  • Fatigue
  • Nausea and vomiting
  • Dull pain under the right side of your rib cage
It’s important to mention that there are forms of acute hepatitis where jaundice is absent, and other symptoms, such as rash, or joint pain are present.

Chronic hepatitis is a form of hepatitis in which the virus is present in your organism for more than six months. Although chronic hepatitis infection is much more malevolent (chronic HBV can cause cirrhosis and liver cancer), it sometimes only manifests as fatigue and an unpleasant sensation on the right side of your upper abdomen.

Fulminant hepatitis is a severe clinical form of hepatitis, characterized by rapid liver failure, coma, and even death.

Hepatitis B and Hepatitis C coinfection: Is it possible?

Both HBV and HBC can cause either acute or chronic hepatitis, although HCV is more likely to advance to the chronic stage. However, if untreated, both viruses can cause severe liver damage, cirrhosis, and liver cancer.

Although these viruses share a similar name and, more importantly, transmission routes and symptoms, HBV and HCV don’t even belong to a same family of viruses. Namely, HBV is a DNA virus from the Hepadnaviridae family, whereas HCV is an RNA virus belonging to the Flavaviridae family. However, they can interact during their replication, causing different types and patterns of infection.

Because these two viruses share the same transmission routes (mainly blood-to-blood contact), it shouldn’t be hard to conclude that there is a chance that both of these viruses can simultaneously infect one individual. This is especially true if that individual belongs to a high-risk population group (such as intravenous drug addicts, HIV positive patients, or people with high numbers of sexual partners).

This is why it is important to check all patients with symptoms of acute hepatitis for every possible viral cause. This presents a challenge on its own, because other than the fact that both diseases share the same symptoms, those symptoms may not exist until further complications develop.

There are many different theories about how the two viruses interact, with no conclusive answer yet, because of the lack of studies done on a massive population.

One of these theories proposes that HCV is the dominant virus, suppressing HBV levels and inhibiting the HBV antigen levels. However, others suggest the opposite, meaning that both viruses may be dominant, depending on the patient. Newer studies propose that there aren’t any direct interactions between the two, and that the main differences are due to variable immune responses in patients.

Dual infection with HBV and HCV may occur via the following mechanisms:

  • Coinfection (both viruses are contracted at the same time) – with symptoms similar to a chronic infection. The disease is shown not to be dangerous, and patients generally recover from at least one, if not both infections.
  • HCV superinfection in patients with an existing HBV infection – which can suppress the HBV infection, but patients have a higher risk of irreparable liver damage and liver cancer than in case of a HCV infection alone.
  • HBV superinfection in patients with an existing HCV infection – the rarest type, shown to suppress, or even completely eliminate, the HCV infection, but causing more severe liver damage than HBV alone. Both types of superinfection show higher rates of the fulminant form of hepatitis.
  • Occult HBV infection in patients with an existing HCV infection – occult infection means that there is proof of HBV DNA, but its antigens are not detectable. This type is shown to damage the liver more than HCV would alone.
A HBV/HCV coinfection is diagnosed via a simple blood test, where elevated liver enzymes (ALT, AST; gamma-globulin) and the existing HBs-antigens and anti-HCV antibodies are detected., along with their DNA (HBV) and RNA (HCV).

What are the complications of a HBV/HCV coinfection?

Although a hepatitis C infection is more likely to become chronic, patients with HBV face a higher risk of liver cirrhosis, liver cancer, and death. Coinfection of the two increases this risk, showing considerably higher rates of liver-related diseases than in HBV or HCV alone.

However, keep in mind that HCV is an extremely diverse disease, counting six types, 74 subtypes, and countless quasispecies. This fact, along with a very different patient population (different in race, amount of alcohol consumption, and already established diseases), makes this classification, as well as treatment, excruciatingly hard.

How do you treat a HBV/HCV coinfection?

Due to many variants of this disease, there aren’t any standard treatment algorithms for this type of infection. The second problem is that many medications are metabolized in the liver, which makes standard treatments pretty complicated.

Knowing what types or subtypes of these viruses a patient is dealing with can help suggesting treatment, which is done with the help of directing acting antivirals (DAA) in HCV, and already established AASLD’s (The American Association for the Study of Liver Diseases) guide for HBV treatment.

Medications such as PEG-Interferon have, alongside ribavirin, been shown to be efficient against both HBV and HCV, because these medications eradicates the HCV infection and may help with the HBV.

This type of treatment, although not very elegant, serves to reduce the rate of cirrhosis, liver cancer, and liver failure in general, which is why it is recommended to start the treatment as soon as possible, before these complications occur in the first place.