Unusual Case of Liver Damage Linked to Yearlong Use of Tegsedi
Spike in liver enzymes, indicating organ damage, seen in 71-year-old man
Tegsedi (inotersen) helped to stabilize familial amyloid polyneuropathy (FAP) symptoms in a 71-year-old man, but its use also was associated with a rare case of liver damage after one year of treatment.
His liver enzymes, a marker of damage to the organ, rose well beyond the normal range, scientists reported. Enzyme levels returned to normal shortly after treatment was stopped.
While FAP patients with severe liver impairment are advised not to use Tegsedi, treatment-induced liver damage is rare. This case suggests that, despite an unusual finding, “liver function should be carefully monitored” in people using the therapy, the scientists wrote.
The report, “A case of severe increase of liver enzymes in a ATTRv patient after one year of inotersen treatment,” was published as a brief communication in the journal Neurological Sciences.
Regular testing of liver enzymes advised with Tegsedi’s use
FAP is a form of hereditary transthyretin amyloidosis that occurs when amyloid fibrils of misshapen transthyretin protein build in tissues across the body, including nerves, and interfere with how they work.
Tegsedi, by Ionis Pharmaceuticals, is an antisense oligonucleotide — a very short molecule that’s been designed to attach and inactivate the genetic material that contains the instructions for making transthyretin. This lowers the amount of transthyretin produced, reducing the buildup of amyloid fibrils and relieving the symptoms of FAP.
Tegsedi is contraindicated for people with low platelet counts (thrombocytopenia) and those with severe kidney problems, such as damage to the kidneys’ filtering units, a condition known as glomerulonephritis.
Its use also is not advised in people with severe liver problems, and liver enzymes should be measured prior to starting with the treatment and tested regularly once it’s in use. Here, the man’s liver enzyme levels were checked four months after he started with Tegsedi and then every six months.
Scientists in Italy reported the case of a 71-year-old man with a history of a worsening loss of balance while walking and unintended weight loss.
A nerve conduction study, which measures how fast an electrical impulse moves through a nerve, showed widespread nerve damage, known as a sensorimotor polyneuropathy.
Genetic testing revealed the presence of a mutation in the TTR gene, called Val30Met, which is the most common FAP-causing mutation. TTR is the gene that encodes the transthyretin protein.
Based on these findings, the man was diagnosed with FAP, stage 1, meaning he had a mild sensorimotor polyneuropathy that mostly affected the lower limbs, yet he was still able to move about.
Blood and urine tests revealed no contraindication for Tegsedi, and he started on the treatment.
After some six months of treatment, his transthyretin levels were about four times lower than initial levels, and those lower levels were maintained in a one-year test.
Also at the one-year mark, his total Neuropathy Impairment Score had not worsened, and his scores on the Norfolk quality of life questionnaire declined by almost 20 points, indicating better quality.
However, levels of liver enzymes known as transaminases were abnormally high at one year. As this rise could be a side effect of Tegsedi, his doctors immediately stopped the treatment. Investigations also excluded other causes of liver damage, such as a viral infection or an autoimmune disorder.
His transaminase levels returned to normal 45 days (about 1.5 months) after Tegsedi was stopped.
The patient then started on Onpattro (patisiran), also approved to treat adults with FAP. Six month later, his condition continued to be stable and his liver enzymes remained within the normal range.
“Our case highlighted that inotersen [Tegsedi]-related liver damage, although uncommon as reported in scientific literature, is a possible event and liver function should be carefully monitored, to avoid a drug-related hepatic dysfunction,” the scientists wrote.
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