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Its use increased rapidly during the COVID-19 pandemic. It is taken in form of drink called locally as kadha in India. We came across multiple cases of T. cordifolia-induced liver injury during July 2020–June 2021.
In the last one year, we saw more than 25 cases with suspected T. cordifolia-induced liver injury. Here we discuss three of them in whom the liver injury was severe, requiring transjugular liver biopsy to aid the diagnosis.
Patient 1
A 49-year-old known hypothyroid female presented in October 2020 with complaints of jaundice of 7 days duration. Her labs showed severe transaminitis of more than 20 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) > alanine aminotransferase (ALT). Her viral markers for HAV, HBV, HEV, and IgM EBV/HSV and CMV were negative. She had a significant history of Giloy intake in the form of kadha (3–4 twig pieces boiled with cinnamon and cloves in a glass of water, once daily) for the past 84 days. USG of the abdomen was unremarkable. Her IgG level was 2120 mg/dl and ANA IF was positive (1:160). Her INR was 2.2, and hence, she underwent transjugular liver biopsy (TJLB). Biopsy showed features of the hepatocellular pattern of liver injury — with lymphoplasmacytic infiltrates and eosinophilic infiltrate, interface hepatitis, and foci of necrosis — suggesting the diagnosis of DILI with autoimmune features. She was given a course of oral prednisolone at 40 mg per day, which was tapered over 12 weeks. Her IgG levels and LFTs normalized 3 months after treatment. Subsequently, she continues to be fine with normal LFTs 3 months after stopping steroids (Table 1, Figure 1).
Table 1Clinical Characteristics, Autoimmune Profile and Liver Biopsies of Patients.
Patient 1
Patient 2
Patient 3
Age
49
36
68
Sex
F
F
F
Clinical presentation
Acute liver injury, INR > 1.5
Acute liver injury, INR > 1.5
Acute liver injury, INR > 1.5
Total bilirubin (peak) mg/dl
16
23
17.8
Latent period (days)
84
21
72
AST/ALT (IU) peak
2300/2150
670/560
450/380
RUCAM
Probable (score 6)
Highly probable (score 9)
Probable (score 6)
IgG (mg/dl)
2120 mg/dl
2230 mg/dl
1913 mg/dl
ASMA
Negative
Negative
Negative
ANA
Positive
Negative
Positive
Liver biopsy
Hepatocellular
Mixed injury
Hepatocellular
Interface hepatitis
interface hepatitis,
Interface hepatitis
Lymphoplasmacytic
lymphocytic infiltrates with
Lymphoplasmacytic
infiltrates
numerous eosinophils and
infiltrates
Numerous eosinophils
few plasma cells. Moderate
Numerous eosinophils
Lobular damage
ductular proliferation and ductular bile plugs seen.
Figure 1Liver Biopsy (H &E stain) of Patient 1 shows lymphocytes and plasma cell infiltration with interface hepatitis and hepatic rosettes formation (A & B). There are also numerous eosinophils infiltrating the portal tracts (C).
A 36-year-old female presented in November 2020 with complaints of jaundice and itching of 2 months duration. The patient gave a history that she developed jaundice in July 2020, and there was a history of intake of 2 twigs of T. cordifolia in the form of kadha since 60 days prior to the onset of jaundice. She was thoroughly worked up elsewhere and was advised to stop T. cordifolia intake. Her jaundice improved and normalized in August 2020, but she started taking T. cordifolia twigs again in mid-October 2020 and presented with severe acute hepatitis at our center after 21 days of restarting it. Her typical and atypical viral markers were negative. Serum ceruloplasmin level was normal. Her Autoimmune markers ANA, AMA, and ASMA were negative but her IgG level was 2230 mg/dl. In view of INR of 2.3, TJLB was done, which showed a mixed pattern of liver injury-interface hepatitis, lymphocytic infiltrates, with numerous eosinophils, and few plasma cells. Moderate ductular proliferation and ductular bile plug seen. Hepatocytes showed mild cytoplasmic and canalicular cholestasis.
She was managed with supportive treatment NAC infusion for 5 days and ursodeoxycholic acid. She did well after the withdrawal of T. cordifolia twigs and with supportive management. Her liver functions and IgG levels normalized within 3 months.
Patient 3
Our third patient was a 68-year-old known diabetic, hypothyroid female with a past history of SLE, diagnosed 20 years back and in remission for 15 years. She was not on any immunosuppressants, including steroids, for last 12 years. She presented with complaints of jaundice of 12 days duration. There was a history of T. cordifolia intake in the form of kadha (2–3 twigs per day) for the last 72 days. Her viral markers were negative. Her IgG was 1913 mg/dl ANA-IF was positive (1:160), and ASMA was negative. In view of INR 1.7, TJLB was done, which showed moderate lymphoplasmacytic infiltrates admixed with fair numbers of eosinophils, lobular damage, and interface hepatitis was seen. Portal and septal fibrosis was present. She was diagnosed of DILI-associated AIH. She was started on prednisolone in 40 mg dosage and tapered to 10 mg once daily. Her liver functions improved after 4 months. In view of underlying liver fibrosis, she is being continued on low-dose prednisolone of 10 mg once daily.
Two of our patients had associated autoimmune diseases, hypothyroidism in patient 1 and (SLE and hypothyroidism) in patient 3. There is a strong possibility that the immune-stimulant effects of T. cordifolia could lead to autoimmune-like hepatitis as in our first patient, or the unmasking of latent chronic auto-immune liver disease as in our third patient. We agree with Nagral et al that there is a need to urge caution and a warning about T. cordifolia-related liver toxicity, especially in high-risk subjects with associated autoimmune disorders.
Credit authorship contribution statement
Dr Amrish Sahney: Data collection and written manuscript draft. Dr Manav Wadhawan: Review, supervision and draft editing. Dr Ajay Kumar: Final review of draft, supervision and editing.
References
Nagral Aabha, Adhyaru Kunal, Rudra Omkar S, et al. Herbal immune booster-induced liver injury in the COVID-19 pandemic - A case series.
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