Ocrevus, known generically as ocrelizumab, is a monoclonal antibody used to treat multiple sclerosis (MS). While it is an effective disease-modifying therapy, like all medications, it is associated with potential side effects. A critical concern for patients and healthcare providers is the medication's impact on liver health, specifically the question: can Ocrevus damage the liver?
Recent data and regulatory updates confirm that liver injury is a potential risk associated with ocrelizumab, identified through post-marketing surveillance. It is important to understand the different ways this liver damage can occur and the necessary precautions taken to manage this risk.
Mechanisms of Ocrevus-related liver injury
Liver injury from Ocrevus can occur through two distinct pathways. A healthcare provider must evaluate the patient's full medical history and current health status to determine their individual risk profile.
Hepatitis B virus (HBV) reactivation
One of the most well-documented risks associated with B-cell depleting therapies like Ocrevus is the potential for reactivating the hepatitis B virus. For individuals who have previously been infected with HBV, the virus can remain dormant in the body. When a patient receives an immunosuppressive medication like Ocrevus, which targets and depletes B cells, their immune system is weakened. This suppression can allow the dormant HBV to become active again, leading to a severe and potentially fatal form of liver inflammation known as fulminant hepatitis.
To prevent this, healthcare providers are required to screen all patients for current or past HBV infection before starting Ocrevus. Patients who are carriers of the virus or have markers of previous infection are carefully managed, often involving consultation with a liver disease specialist and potentially prophylactic antiviral treatment.
Idiosyncratic drug-induced liver injury (DILI)
In addition to HBV reactivation, reports have emerged of clinically significant, idiosyncratic liver injury directly linked to ocrelizumab, even in patients with no viral hepatitis. An idiosyncratic reaction is an unpredictable adverse effect unrelated to the drug's intended action or dose.
The FDA and other regulatory bodies have noted cases of severe DILI with markedly elevated liver enzymes and bilirubin levels, sometimes requiring temporary addition to a liver transplant list. In many of these cases, the injury showed a temporal association with the first or second dose of Ocrevus. The liver injury typically resolved after the medication was discontinued, though recovery time varied. These findings have prompted explicit warnings in the drug's prescribing information.
Monitoring and mitigating liver risk
Proactive screening and monitoring are essential for managing the risk of liver damage associated with Ocrevus. This involves specific laboratory tests and a vigilant approach to monitoring symptoms.
- Pre-treatment screening: Before starting Ocrevus, patients undergo baseline liver function tests (LFTs), which include checking liver enzymes like alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), as well as bilirubin levels. A full hepatitis B virus (HBV) panel is also conducted to determine the patient's HBV status.
- Monitoring during treatment: Regular LFTs are recommended throughout treatment, particularly if symptoms of liver injury arise. Any signs indicating a potential problem, such as elevated liver enzymes with elevated total bilirubin, would prompt further investigation and potentially treatment discontinuation.
- Recognizing symptoms: Patients should be informed about the symptoms of liver damage and instructed to contact their healthcare provider immediately if they experience any.
Symptoms of liver injury
Early identification of liver injury is key to a positive outcome. Watch for the following signs and symptoms:
- Jaundice: A yellowing of the skin and whites of the eyes
- Fatigue: Unusual or severe tiredness
- Gastrointestinal issues: Nausea, vomiting, or loss of appetite
- Abdominal pain: Discomfort or pain in the upper right side of the abdomen
- Changes in urine and stool: Unusually dark urine and light-colored (clay-colored) stool
- Itching: Generalized skin itching without a visible rash
HBV Reactivation vs. Idiosyncratic DILI
| Feature | HBV Reactivation | Idiosyncratic DILI |
|---|---|---|
| Mechanism | Reactivation of a dormant Hepatitis B virus due to immunosuppression. | Unpredictable, adverse drug reaction not caused by an infection. |
| Risk Factor | Prior or chronic Hepatitis B infection. | Can occur in patients without pre-existing liver disease or HBV. |
| Time of Onset | Can occur during or after discontinuation of treatment. | Often noted in temporal association with the first or second infusion. |
| Monitoring | Requires pre-screening for HBV and careful monitoring in susceptible patients. | Regular LFT monitoring and symptom awareness are key for all patients. |
| Incidence | A rare but known risk in susceptible individuals. | Considered a rare, post-marketing risk, exact incidence is unknown. |
Conclusion
Can Ocrevus damage the liver? Yes, although it is a rare occurrence. The risk is primarily associated with two different mechanisms: the reactivation of dormant Hepatitis B virus in susceptible patients and, less commonly, an idiosyncratic drug-induced liver injury. Because of these identified risks, comprehensive liver function monitoring and hepatitis B screening are standard procedures before and during Ocrevus therapy. Patients should have an open conversation with their healthcare team about their liver health, potential risks, and what to look for regarding symptoms of liver injury. Prompt reporting of any concerning symptoms is essential for ensuring patient safety while on Ocrevus.
An example of a case highlighting the risk of DILI with ocrelizumab can be found in the American Journal of Gastroenterology at https://journals.lww.com/ajg/fulltext/2022/10002/s2916_a_rare_case_of_refractory_drug_induced_liver.2916.aspx. This resource provides detailed insights into a documented case of severe drug-induced liver injury following Ocrevus treatment, illustrating the importance of continuous monitoring and reporting.
