Summary of liver-related screening and monitoring recommendations before and after HA gene therapy
| . | Screening and monitoring recommendations . | |
|---|---|---|
| Before HA gene therapy . | After HA gene therapy . | |
| Liver inflammation | ||
| ALT, AST | At baseline; repeated tests may be required to establish reliable baseline | Not receiving corticosteroids: monitor weekly until week 26, then every 6-12 mo Receiving corticosteroids: monitor weekly until ALT levels return to baseline |
| FVIII | At baseline | Monitor weekly until week 26, then every 6-12 mo |
| Liver fibrosis (see Table 3 for available modalities) | At baseline (F3, F4, ineligible for gene therapy) | If positive at baseline (F1 or F2), monitor every 6-12 mo |
| HCC screening | At baseline | Monitor every 6 mos by ultrasound or MRI, and α-fetoprotein |
| Liver biopsy | - | Use only to investigate tumors and as part of a research protocol directed by the gene therapy manufacturer |
| Exposure to hepatoxicity | Monitor discontinuation compliance | Up to week 26: monitor weekly for use of alcohol and hepatotoxic drugs, and emphasize importance of avoidance After week 26: monitor for use of alcohol and hepatotoxic drugs, and emphasize importance of avoidance |
| Alcohol use: discontinue 6-8 wk before gene therapy | ||
| Hepatotoxic drugs: discontinue 4-6 wk before gene therapy | ||
| When to consult with a hepatologist: any patient with severe HA considering gene therapy; abnormal liver function test (>1.25× upper limit of normal); international normalized ratio of ≥1.4; radiologic liver abnormalities; or discordant results of liver fibrosis tests. | ||
| . | Screening and monitoring recommendations . | |
|---|---|---|
| Before HA gene therapy . | After HA gene therapy . | |
| Liver inflammation | ||
| ALT, AST | At baseline; repeated tests may be required to establish reliable baseline | Not receiving corticosteroids: monitor weekly until week 26, then every 6-12 mo Receiving corticosteroids: monitor weekly until ALT levels return to baseline |
| FVIII | At baseline | Monitor weekly until week 26, then every 6-12 mo |
| Liver fibrosis (see Table 3 for available modalities) | At baseline (F3, F4, ineligible for gene therapy) | If positive at baseline (F1 or F2), monitor every 6-12 mo |
| HCC screening | At baseline | Monitor every 6 mos by ultrasound or MRI, and α-fetoprotein |
| Liver biopsy | - | Use only to investigate tumors and as part of a research protocol directed by the gene therapy manufacturer |
| Exposure to hepatoxicity | Monitor discontinuation compliance | Up to week 26: monitor weekly for use of alcohol and hepatotoxic drugs, and emphasize importance of avoidance After week 26: monitor for use of alcohol and hepatotoxic drugs, and emphasize importance of avoidance |
| Alcohol use: discontinue 6-8 wk before gene therapy | ||
| Hepatotoxic drugs: discontinue 4-6 wk before gene therapy | ||
| When to consult with a hepatologist: any patient with severe HA considering gene therapy; abnormal liver function test (>1.25× upper limit of normal); international normalized ratio of ≥1.4; radiologic liver abnormalities; or discordant results of liver fibrosis tests. | ||
Recommendations are based on the authors’ expert opinions (see main text for details).
MRI magnetic resonance imaging.