ABSTRACT
Tinospora cordifolia (Guduchi/Giloy) is a relatively common herbal supplement whose use has recently become prominent in Southeast Asia. It was promoted to the public in India as an immunity booster, especially against the novel COVID-19. There have been reports, mostly from India, of an association between Guduchi/Giloy and liver injury. We present a 50-year-old female with a history of Hashimoto thyroiditis, who presented with abdominal discomfort and nausea of two weeks duration, which coincided with starting HistaEzeTM supplement containing Tinospora cordifolia. The vital signs upon presentation showed no significant abnormalities. Labs were significant for severely elevated transaminases; however, viral panels, autoimmune serologies, and imaging studies were unremarkable. Roussel Uclaf causality assessment method (RUCAM) score was at 6, which was indicative of probable drug/herb-induced liver injury. HistaEzeTM was discontinued, and the patient took a three-day course of oral steroids with significant interval improvement in clinical status, as evidenced by progressive normalization of the transaminases level. The transaminases decreased by greater than 50% within two weeks of discontinuation and trended back to baseline within three months. This case highlights the worldwide availability and use of Tinospora cordifolia, which can cause liver injury that appears to be idiosyncratic and possibly immune-mediated. Further research on the precise mechanism of its hepatotoxicity is warranted.
ABSTRACT
Background: Tinospora cordifolia (TC) is being increasingly consumed in India for its health and suggested immune-enhancing benefits in preventing and countering COVID-19. We previously published our experience of hepatotoxicity with self-medication of TC in six individuals. Since herb-induced liver injury (HILI) has been described with Tinospora crispa (TCR) consumption, it was contested that our patients may have mistakenly self-medicated with TCR which is similar in appearance to TC. Methods: We collected the four plant samples and two commercial preparations that were consumed by our patients for further analysis. The six samples underwent high performance thin layer chromatography phytochemical analysis and DNA barcoding studies for the confirmation of the genus and species. The four plant part samples which included stems and leaves were also analysed by a botanist for the characteristic morphological and microscopic features. Results: Based on morphological, microscopic, phytochemical and DNA studies, the four plant part samples were identified as TC. The two commercial preparations could not be analysed on phytochemical analysis or DNA barcoding studies due to other ingredients that most likely interfered with the analysis. The herb consumed by our study subjects was confirmed to be Tinospora cordifolia. Conclusion: We have highlighted the key morphological and phytochemical differences between these two species. We propose an algorithmic approach to accurately identify the implicated herb in cases of HILI. Future studies on causality need to focus on the serological/histopathological identification of active herb/metabolites in human tissues.
ABSTRACT
The COVID-19 pandemic has resulted in widespread use of complementary and alternative medicines. Tinospora cordifolia is a widely grown shrub which has been commonly used in India's traditional system of Ayurveda for its immune booster properties and has been extensively used as prophylaxis against COVID-19. Six patients (4 women, 2 men) with a median (IQR) age of 55 years (45-56) and with an history of Tinospora cordifolia consumption presented with symptoms of acute hepatitis during the study period of 4 months in the COVID-19 pandemic. The median (IQR) duration of Tinospora cordifolia consumption was 90 days (21-210). The median (IQR) peak bilirubin and AST were 17.5 mg/dl (12.2-24.9) and 1350 IU/ml (1099-1773), respectively. The patients had either a definite (n = 4) or probable (n = 2) revised autoimmune hepatitis score with an autoimmune pattern of drug-induced liver injury on biopsy. Four of these patients (all women) had underlying silent chronic liver disease of possible autoimmune etiology associated with other autoimmune diseases - hypothyroidism and type 2 diabetes mellitus. One of the three patients treated with steroids decompensated on steroid tapering. The other five patients had resolution of symptoms, liver profile, and autoimmune serological markers on drug withdrawal/continuing steroid treatment. The median (IQR) time to resolution from discontinuing the herb was 86.5 days (53-111). Tinospora cordifolia consumption seems to induce an autoimmune-like hepatitis or unmask an underlying autoimmune chronic liver disease, which may support its immune stimulant mechanism. However, the same mechanism can cause significant liver toxicity, and we recommend that caution be exercised in the use of this herb, especially in those predisposed to autoimmune disorders. Besides, in patients presenting with acute hepatitis, even in the presence of autoimmune markers, a detailed complementary and alternative medicine history needs to be elicited.
ABSTRACT
Causality assessment in liver injury induced by drugs and herbs remains a debated issue, requiring innovation and thorough understanding based on detailed information. Artificial intelligence (AI) principles recommend the use of algorithms for solving complex processes and are included in the diagnostic algorithm of Roussel Uclaf Causality Assessment Method (RUCAM) to help assess causality in suspected cases of idiosyncratic drug-induced liver injury (DILI) and herb-induced liver injury (HILI). From 1993 until the middle of 2020, a total of 95,865 DILI and HILI cases were assessed by RUCAM, outperforming by case numbers any other causality assessment method. The success of RUCAM can be traced back to its quantitative features with specific data elements that are individually scored leading to a final causality grading. RUCAM is objective, user friendly, transparent, and liver injury specific, with an updated version that should be used in future DILI and HILI cases. Support of RUCAM was also provided by scientists from China, not affiliated to any network, in the results of a scientometric evaluation of the global knowledge base of DILI. They highlighted the original RUCAM of 1993 and their authors as a publication quoted the greatest number of times and ranked first in the category of the top 10 references related to DILI. In conclusion, for stakeholders involved in DILI and HILI, RUCAM seems to be an effective diagnostic algorithm in line with AI principles.