Abstract
Swietenia macrophylla seeds (SMS), as a traditional medicine, are widely used against diabetes, hypertension, and malaria. To date, knowledge about the safety of human consumption remains limited. We herein reported two cases of drug-induced liver injury (DILI) caused by SMS. Both patients had positive antinuclear antibodies. Hepatotoxicity of SMS is characterized by elevated alanine aminotransferase and obvious autoimmune-like hepatitis. Furthermore, the 2nd biopsy at the 3rd year of methylprednisolone treatment showed normal liver tissue, and then methylprednisolone was withdrawn. No recurrence occurred during one-year follow-up after methylprednisolone withdrawal. SMS may increase the risk of liver damage for patients with potential immune disorders, and patients with SMS-related DILI may benefit from methylprednisolone.
Keywords: Autoimmune hepatitis, drug-induced liver injury, hepatotoxicity, methylprednisolone, Swietenia macrophylla
Clinical Pearls
Unique Features of the Case: Two cases of drug-induced liver injury (DILI) caused by Swietenia macrophylla seeds (SMS) are presented. Both patients had elevated liver enzymes and autoimmune-like hepatitis. One patient recovered fully with methylprednisolone, with normal liver tissue seen in the second biopsy after three years. No recurrence occurred during one-year follow-up after treatment withdrawal.
Primary Lesson for Clinicians: Clinicians should exercise caution with SMS in patients with potential immune disorders, as it may cause liver damage. Methylprednisolone may be beneficial for SMS-related DILI.
Introduction
Drug-induced liver injury (DILI), which is an adverse drug reaction (ADR), has become a challenging problem worldwide. The annual incidence of DILI is estimated to be 23.8/100,000 in the general population from the mainland of China, and the leading causes of DILI include traditional Chinese medicine, herbal, and dietary supplements.[1]
Swietenia macrophylla, commonly known as sky fruit, is widely distributed in South America, Malaysia, southern China, and west India.[2,3] As a traditional medicine, Swietenia macrophylla seeds (SMS) are widely used for the treatment of diabetes, hypertension, malaria, and even wounds.[4–10] Mi et al.[2] reported that polyacetylenes extracted from the roots of Swietenia macrophylla demonstrated cytotoxicity against human hepatocellular carcinoma cell line, myeloid leukemia cell line, and gastric carcinoma cell line. SMS showed no acute toxicity in Sprague-Dawley rats.[4,11] Tan et al.[12] reported three cases of DILI caused by SMS, all of whom were elderly men aged from 72 to 80 years old. In addition, Shao et al.[13] reported a case of herb-induced autoimmune-like hepatitis associated with SMS. Histological features of autoimmune hepatitis (AIH), including interfacial inflammation, “rosette”-like changes in the hepatocytes, and focal necrosis, were demonstrated in the case of SMS-related liver injury.[13] Thus, immune-mediated DILI and AIH could not be classified clearly by histology. For patients with obvious histologic characteristics of AIH, immunosuppressive therapy can be recommended, and DILI can be established if there is no sign of recurrence after withdrawal of immunosuppressive therapy.[14] To date, the effect and safety of immunosuppressive therapy in patients with SMS-related autoimmune-like hepatitis remain limited.
We herein reported two cases of DILI caused by SMS. Both patients were followed up for four years, and methylprednisolone was administered for three years in one patient.
Case Report
Two patients were admitted to the Third People’s Hospital of Changzhou on October 17, 2018, at the same time. Patient 1 was a 57-year-old Chinese woman who presented with a 6-day history of fatigue and loss of appetite. She had jaundice on the skin and sclera. Liver function parameters were abnormal at the time of admission. She had alanine transaminase (ALT) levels nearly 35 times the upper limit of the normal range (1,402 U/L), whereas aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) were also high (337 U/L, 420 U/L, and 158 U/L, respectively). Total bilirubin (TBIL) was more than 4 times the upper limit of the normal range (92 μmol/L), with the majority being conjugated bilirubin (62.3 μmol/L). She had positive antinuclear antibodies (ANA, 1:100 titers, cytoplasmic granule type) and anti-Ro-52.
Patient 2 was the daughter of the aforementioned woman. She was 35 years old, with an asymptomatic rise in her liver enzymes. Laboratory tests showed elevated ALT (417 U/L), AST (117 U/L), and TBIL (36.5 μmol/L), with normal ALP (64 U/L) and GGT (39 U/L) levels. She had a high ANA titer (1:1000, centromere type) and positive anti-centromere antibody.
Both patients had no history of liver diseases or alcohol abuse, and they had taken SMS as a traditional dietary supplement for two months. Serological markers of HAV, HBV, HCV, HDV, and HEV were all negative. Moreover, both patients had normal immunoglobulin profiles. Informed consent was obtained from the two patients, and the clinical data were collected during the four-year follow-up period.
The two patients were diagnosed with SMS-induced DILI according to the Roussel Uclaf Causality Assessment Method (RUCAM), and the clinical type was classified based on the R value.[1] According to RUCAM, the two patients were given scores of 8 and 7, and thus DILI was diagnosed by the diagnostic tool (http://www.hepatox.org/rucam). Both patients had ALT levels ≥3× the upper limit of normal, and R values of ≥5 (29.95 and 21.99, respectively). Based on this, the hepatocellular type of DILI was classified. SMS was withdrawn instantly at admission, and then glycyrrhizin was administered intravenously every day at a dose of 150 mg. Liver biochemistry improved markedly during the first two weeks after admission (Fig. 1).
Figure 1.
Clinical characteristics of patients with Swietenia macrophylla seeds induced liver injury.
The liver functions of Patient 1 appeared to be normal in the 1st month after admission, and she had a liver tissue biopsy. Histological features, including focal necrosis, interfacial inflammation, “rosette”-like changes in the hepatocytes, and milder fibrosis, were found. Then, AIH was considered, and methylprednisolone was administered at a dose of 24 mg per day. During the 3-year treatment with methylprednisolone, indices of liver function, immunoglobulins, and complements remained at normal levels, and methylprednisolone was reduced gradually. The 2nd biopsy in the 3rd year of treatment showed no significant abnormality in liver tissue, and then methylprednisolone was withdrawn. No recurrence occurred during the one-year follow-up after withdrawal of methylprednisolone (Fig. 2).
Figure 2.
Dynamic changes of immunoglobulins and complements in a patient with Swietenia macrophylla seeds related liver injury.
Discussion
In the present study, two cases of DILI caused by SMS have been reported. Hepatotoxicity of SMS is characterized by elevated ALT and AIH-like inflammation, and these histologic changes could be improved by methylprednisolone.
The clinical presentation of DILI varies widely, ranging from an asymptomatic rise in liver enzymes to liver failure. The severity of DILI is graded as mild, moderate, moderate to severe, severe, and fatal according to liver enzymes, TBIL, international normalized ratio, and complications. This can result from the use of drugs or dietary supplements, especially in patients with multiple drug consumption. However, it remains an exclusive diagnosis. Widespread use of RUCAM is highly recommended to evaluate the causality of suspected drugs. A liver biopsy may help to diagnose DILI when the RUCAM scale is less than 6, or when there is a possibility of autoimmune hepatitis. In cases with hepatocellular DILI, the peak ALT level decreases by >50% at 30–60 days after stopping the suspected offending drug, and then maintains normal levels during the follow-up. This is different from autoimmune hepatitis. However, consistent with Shao et al.,[13] our case report suggested that SMS-induced DILI was difficult to distinguish from AIH by liver biopsy.
According to the positive ANA in the two patients, it is possible that AIH may be a comorbidity with SMS-induced DILI. Although urgent administration of an immunosuppressive agent remains controversial for SMS-induced DILI, histological changes in Patient 1 demonstrated that the patient can benefit from methylprednisolone. On the other hand, SMS should not be recommended to people with positive ANA. Collectively, these data suggest that SMS may increase the risk of liver damage for patients with potential immune disorders.
The mechanisms underlying SMS-induced DILI remain elusive, and new biomarkers for distinguishing SMS-related autoimmune-like hepatitis and AIH need to be further studied in the future.
Conclusion
In conclusion, SMS may increase the risk of liver damage for patients with potential immune disorders, and patients with SMS-related DILI may benefit from methylprednisolone.
Footnotes
How to cite this article: Huang Z-Y, Zhang X-J, Tong X-C, Xue Y. Methylprednisolone for Swietenia macrophylla seeds-induced liver injury: A report of two cases. Hepatology Forum 2026; 7(2):163–166.
Ethics Committee Approval
This is a case report, and therefore ethics committee approval was not required in accordance with institutional policies.
Informed Consent
Informed consent was obtained from the two patients, and the clinical data were collected during the four-year follow-up period.
Conflicts of Interest
The authors declare no conflict of interest.
Financial Disclosure
This work was supported by the Leading Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project (2022CZLJ021), Changzhou Key Medical Discipline, the Science and Technology Project of Changzhou (CE20225040).
Use of AI for Writing Assistance
Artificial intelligence was not used in the preparation of the article.
Author Contributions
Concept: YX; Design: YX; Supervision: YX; Funding: YX; Materials: Z-YH, X-ZJ, X-CT, YX; Analysis and/or Interpretation: Z-YH; Literature Search: Z-YH, X-ZJ, X-CT, YX; Writing: Z-YH, X-ZJ; Critical Reviews: YX.
Peer-review
Externally peer-reviewed.
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