Viral hepatitis is the inflammation of the liver caused by hepatitis viruses A, B, C, D, or E. Out of these, chronic hepatitis caused by hepatitis B virus, or HBV, and hepatitis C virus, or HCV, can be treated with antiviral medications.
Now, chronic HBV infection can be treated with a class of antiviral medications called NRTIs, which include nucleotide reverse transcriptase inhibitors like adefovir and tenofovir, as well as nucleoside reverse transcriptase inhibitors like entecavir; these medications are administered orally.
On the other hand, chronic HCV infection can be treated with antiviral medications that target different components of the virus, so they’re typically used in combination; these include nucleotide polymerase inhibitors like sofosbuvir, as well as nucleoside analogues like ribavirin, both of which are taken orally.
Finally, there’s a third class of medications that can be used to treat both chronic HBV and HCV; these include interferons like peginterferon alfa-2a, which is administered by subcutaneous injection.
Now, once administered, all of these antivirals have a different mechanism of action. NRTIs used to treat hepatitis B act by inserting into the replicating viral DNA. As a result, viral DNA synthesis is halted, ultimately stopping viral replication. On the other hand, medications used to treat hepatitis C work in different ways, inhibiting different viral proteins or enzymes required for viral replication. Interferons, on the other hand, induce the innate antiviral immune response that helps kill off cells that are infected by the virus.
Now, clients taking NRTIs for hepatitis B infection can have side effects. All these medications come with a boxed warning for severe, acute hepatitis exacerbations on discontinuation of therapy. These medications also cause lactic acidosis, which is a boxed warning for adefovir and entecavir, as well as severe hepatomegaly with steatosis; and a risk for individuals with concurrent HIV infection, that refers to the risk of developing HIV resistance to these agents. Other common side effects for these medications include hepatotoxicity and increased serum transaminase levels, as well as hematuria. Finally, adefovir can also cause fatigue; headache; muscle weakness; back pain and joint pain; and gastrointestinal toxicity, which can manifest as nausea, abdominal pain, diarrhea or vomiting; while tenofovir may cause nephrotoxicity.
Now let’s switch gears and look at the side effects of medications used to treat hepatitis C. All these medications come with a boxed warning for HBV reactivation in clients with concomitant HBV infections, which can cause potentially life-threatening fulminant hepatitis. Ribavirin also has two more boxed warnings, for use during pregnancy and for an increased risk of causing hemolytic anemia.
Another thing to bear in mind is that hepatitis C medications are usually part of a multi-drug regimen, so common side effects refer to those occurring with combination therapy. These include neurotoxicity, like fatigue, headache, insomnia and dizziness; dermatological reactions, like rashes, pruritus and eczema; as well as flu-like symptoms, myalgia and muscle weakness. Multidrug regimens containing ribavirin can also cause alopecia. Gastrointestinal toxicity is also a common side effect of these medications, and it can manifest as nausea, diarrhea, anorexia and subsequent weight loss.
Finally, let’s go over the side effects of peginterferon alfa 2a. First up, it comes with a boxed warning for aggravating life-threatening neuropsychiatric, autoimmune, infectious and ischemic conditions. Other common side effects include flu-like symptoms, fatigue, fever, myalgia, and headache, as well as injection site reaction; but it can also cause gastrointestinal toxicity, with nausea, vomiting, diarrhea or abdominal pain; and dermatological side effects like rashes, pruritus or alopecia.
As far as contraindications go, NRTIs should be used cautiously during breastfeeding, pregnancy, in children and the elderly, as well as those with severe renal disease. Entecavir in particular should be used with caution in clients with impaired hepatic function. Also remember that all clients with hepatitis B should be tested for an HIV infection before starting treatment with an NRTI.
Medications used to treat hepatitis C should be used cautiously during pregnancy, breastfeeding, and in clients with hepatic disease, renal disease or diabetes. Ribavirin is also contraindicated in clients with autoimmune hepatitis and decompensated cirrhosis. Now, since sofosbuvir is metabolized by cytochrome P450 in the liver, they shouldn’t be used with potent cytochrome inducers like rifampin or St. John’s wort, since they can decrease the medications’ level and effectiveness. Finally, be extra careful when sofosbuvir is used in combination with amiodarone, since the combo could cause severe bradycardia.
