Heart-leaved Moonseed- Innocuous or Baneful

We read with great interest the case series by Nagral et al regarding herbal immune booster medication-induced liver injury. It has been long considered that ayurvedic herbal medicines (AHM) are harmless and are hence used in various ailments due to their believed beneficial effects. The study endorses our belief that AHM or complementary and alternative medicines (CAM) are not completely safe and are known to cause serious liver injury in a subset of the population that consumes them. The incidence of drug-induced liver injury (DILI) related to AHM or CAM has been reported in 1.3–10% from various single centers across the country.^{,  ,}  A recent Indian national study on DILI found that AHM comprised about 13.9% of all causes of DILI. The indiscriminate use of herbal medicine has recently increased due to the ongoing COVID pandemic. In India, such medicines are easily available over the counter. A few of them are often unlabeled and do not carry information about the amount of herbal extract. Often, herbal mixtures are prepared at home using various plant parts. In the current pandemic, there has been an upsurge in the usage of certain immunity-boosting natural ingredients like Giloy extract, cinnamon, turmeric, black pepper, aloe vera, ginger, honey, and lemon. Many Indian families make a mixture (Kadha) that consists of varying amounts of these ingredients. This makes it extremely difficult to identify the culprit agent in patients with suspected AHM-related DILI. Furthermore, it is a challenge to ascertain the amount of molecule that caused the adverse outcome.

The recent APASL consensus guidelines have mentioned various ayurvedic herbs causing DILI. In the study by Nagral et al Giloy (Tinospora cordifolia) also known as heart leaved moonseed in English language is a common ingredient used in many herbal preparations, has been invoked as the cause of liver injury. However, the study lacks analysis of ingredients or potential toxins, which the author has mentioned as a limitation of the study. Prior to this, Karousatas et al reported a single patient of Tinospora cordifolia causing liver injury.

We would like to advocate the above series by reporting three patients diagnosed with DILI recently managed by our team. All of them had hepatocellular jaundice (R > 5.0) after consumption of the same herbal medicine. In our patients (two females, one male), one consumed a branded pack of Giloy tablets (2 tablets/day for 30 days) and each of the other two consumed a glass of boiled Giloy stem mixed with cinnamon or honey daily for 60 and 90 days, respectively. The peak value of bilirubin was 24.99 mg/dl; 4.3 mg/dl and 11 mg/dl in the three patients, peak AST/ALT values were 1198/1044 IU/L, 360/610 IU/L, and 987/1045 IU/L whereas peak alkaline phosphatase values were 351 IU/L, 145 IU/L and 210 IU/L. All patients had a normal prothrombin time. On evaluation, two patients had positive autoimmune markers (antinuclear antibody-ANA, antismooth muscle antibodies-ASMA), one had hypersensitivity skin reaction which resolved on the consumption of anti-allergic medications, and one patient had diabetes mellitus (male patient). All of them were thoroughly evaluated for other causes of liver injury, which were negative. After stopping the consumption of the herbal medicine, liver function tests normalized within 30–60 days. The Roussel Uclaf Causality Assessment Model score (RUCAM) was 6–7, which suggested a probable association; however, we did not re-challenge the drug for reasons similar as given by Nagral et al. None of the patients underwent a liver biopsy, as the patients were reluctant and their liver function tests had started improving after cessation of the herbal medicine. This is a major limitation of our case series, as liver biopsy is useful in such patients to confirm the DILI or DILI-related Autoimmune hepatitis. We did not use corticosteroids in any of the cases.

Giloy has well-known immunomodulatory properties, but in certain subgroups of patients, it might lead to an autoimmune-like illness that needs to be further evaluated. The risks involved in the consumption of immunomodulatory herbal medicines need to be carefully evaluated in patients with an underlying autoimmune disease, diabetes, and chronic liver disease. More controlled studies need to be performed to elucidate the efficacy and safety of AHM and CAM. Regulatory bodies need to be formed to keep a check on unlabeled and potentially harmful AHM and CAM. In conclusion, awareness about Giloy extract consumption as a cause of AHM-related DILI can help physicians recognize and take corrective steps to stop the consumption of the extract and thereby prevent serious liver injury, especially in high-risk patient populations.