Table 1.
A summary of all Ayurvedic herbs implicated in liver injury with potential mechanisms of toxicity, liver injury pattern, histopathology patterns and clinical outcomes
| Ayurvedic herb | Author/study /country | Pattern of liver injury (hepatocellular, cholestatic or mixed type) | Liver biopsy features | Suspected potential toxic component (s) | Clinical outcomes and comments |
| Withania somnifera (Ashwagandha) | Inagaki et al[10]/report/Japan | Cholestatic type | Intrahepatic cholestasis, canalicular bile plugs | Unclassified triterpenoids | Resolved, survived |
| Björnsson et al[11]/series (n = 5)/Iceland and United States | Cholestatic and mixed type | Cholestatic hepatitis | Resolved, survived | ||
| Bacopa monnieri, Centella asiatica (Brahmi or Gotu-kola) | Teschke et al[14]/report/Germany | Hepatocellular type | Not performed | Saponin triterpenoids. phytoglycosides, autoantibody or immune-mediated | Resolved, survived. However, multiple other associated herbals used |
| Jorge et al[17]/series (n = 3)/Argentina | Mixed type | Granulomatous cholestatic hepatitis | One patient progressed to cirrhosis and acute decompensation on repeat herb intake; in another, complete resolution noted | ||
| Dantuluri et al[18]/report/United Kingdom | Hepatocellular type | Not performed | Acute liver failure, spontaneous resolution, survived | ||
| Curcuma longa (Turmeric) | Lukefahr et al[22]/ report/United States | Hepatocellular type | Autoimmune hepatitis | Immunomodulatory polyphenolic compounds, drug triggered autoantibodies related liver injury | Complete resolution |
| Suhail et al[23]/report/United States | Hepatocellular type | Acute panlobular hepatitis with early parenchymal collapse | Complete resolution in 3 wk | ||
| Lee et al[24]/report/United States | Hepatocellular type | Autoimmune hepatitis with additional eosinophilic and neutrophilic interface hepatitis | Complete resolution | ||
| Imam et al[25]/report/United States | Hepatocellular type | Not performed | Complete resolution | ||
| Luber et al[26]/two patient report/Australia | Mixed type in first case and hepatocellular type in second patient | Biopsy performed in first case showed mixed lobular inflammation and severe interface hepatitis; biopsy not performed in case two | Complete resolution in both patients, autoantibodies positive in second patient | ||
| Chand et al[27]/report/Australia | Hepatocellular type | Acute hepatitis with mixed inflammatory infiltrate of lobules and interface hepatitis with focal necrosis and mild cholestasis | Complete resolution, no autoantibodies noted, but high immunoglobulin G was remarkable | ||
| Guggul / Guggulipids (as part of polyherbal formulations and weight loss supplements) | Grieco et al[29]/report/Italy | Hepatocellular type | Necroinflammation with lobular eosinophilic inflammation | Guggul sterols associated herb-herb and herb-drug interaction; no direct hepatotoxicity described | Complete resolution |
| Yellapu et al[30]/report/United States | Hepatocellular type | Massive hepatic necrosis | Acute liver failure necessitating cadaveric liver transplantation | ||
| Polavarappu et al[31]/report/United States | Hepatocellular type | Not performed | Spontaneous resolution on drug withdrawal | ||
| Dalal et al[32]/report/United States | Hepatocellular type | Mixed portal inflammation, interface hepatitis, eosinophilic lobular inflammation with ceroid laden macrophages | Spontaneous resolution on drug withdrawal | ||
| Psoralea corylifolia (Bakuchi, Babchi seeds) | Nam et al[34]/report/South Korea | Mixed type | Zone 3 necrosis, cholestasis and severe mixed inflammatory infiltration of lobules | Terpenoids like bakuchiol and coumarinoids | Complete clinical resolution |
| Cheung et al[35]/series (n = 3)/ | Hepatocellular type | Not performed | All three patients had uneventful recovery after drug withdrawal | ||
| Smith et al[36]/report/United Kingdom | Hepatocellular type | Cholestatic acute hepatitis | Clinical resolution on drug withdrawal | ||
| Cassia angustifolio (Indian Senna) | Beuers et al[41]/report/Germany | Mixed type | Perivenular necrosis, lymphohistiocytic portal and lobular inflammation | Anthracoid sennoside and rhein anthron metabolites | Complete resolution, recurrence on rechallenge |
| Sonmez et al[42]/report/Turkey | Mixed type | Bridging hepatocellular necrosis and canalicular cholestasis | Complete resolution | ||
| Seybold et al[43]/report/Germany | Hepatocellular type | Not performed | Complete resolution | ||
| Vanderperren et al[44]/Belgium | Hepatocellular type | Not performed | High amounts of cadmium on toxicology evaluation | Acute liver failure with renal failure, resolved on aggressive supportive care | |
| Aloe vera | Rabe et al[52]/report/Germany | Cholestatic type | Portal and lobular lymphoplasmacytic inflammation, eosinophilic granulomas, bridging necrosis and bilirubinostasis | Aloe alkaloids, anthraquinones | Complete resolution on herbal drug withdrawal |
| Parlati et al[53]/report and review series (n = 9)/France | Hepatocellular type | All patients had portal and lobular inflammation with neutrophils and lymphoplasmacytes along with granulomas, acidophil bodies, ballooning of hepatocytes, extensive bridging necrosis and bilirubinostasis | All cases had clinical resolution of symptoms, no acute liver failure and no chronicity noted on follow up | ||
| Manso et al[56]/series on Herbalife® products/Spain | Hepatocellular type | Cholestatic hepatitis | Complete resolution after supplement withdrawal | ||
| Vázquez-Fernández et al[57]/report/Spain | Cholestatic type | Cholestatic hepatitis with lymphocyte predominant portal inflammation | Acute decompensation of cirrhosis (underlying HCV related infection); outcome not reported | ||
| Morinda citrifolia (Noni juice) | Millonig et al[59]/report/Austria | Hepatocellular type | Severe mixed inflammatory infiltration of portal tracts with lobular eosinophilic inflammation and hepatocellular cholestasis in zone 3 | Suspected noni anthraquinones | Complete resolution on herbal medicine withdrawal |
| Stadlbauer et al[60] / two cases report/Austria | Both cases hepatocellular type | First case, confluent necrosis, second case centrilobular necrosis and mild inflammatory infiltration in both | First patient progressed to acute liver failure and underwent successful liver transplantation; second patient had complete clinical recovery on conservative care | ||
| Yu et al[61]/report/United States | Hepatocellular type | Acute hepatitis with portal inflammation and periportal necrosis, hepatocellular cholestasis and numerous eosinophils in lobules | Paediatric case (14-year-old boy) with complete recovery on supportive care | ||
| Heliotropium sp., Trichodesma sp., Eupatorium sp., Senecia sp., Crotalaria sp. Chelidonium majus sp., Castilleja sp. Holarrhena antidysenterica | Neuman et al[66]/review series > 30 cases/Canada | Hepatocellular and mixed type | Early pathologic changes include the deposition of fibrinogen and factor VIII within the venular walls and liver sinusoids. In acute stage, haemorrhage into markedly dilated sinusoids with hepatocyte atrophy is noted, the sinusoids become denuded, parenchymal collapse is evident followed by the constriction and obliteration of small central veins by subendothelial swelling or fibrosis. The sinusoidal fibrosis and nodular regeneration may occur leading to cirrhosis and portal hypertension at later stages | Pyrrolizidine alkaloids | The acute form is rapidly fatal in 20% to 40% of patients. Adults have worse prognosis that the paediatric age group. Approximately 15% with acute disease will progress to subacute or chronic injury, and develop end-stage liver disease in a few years. |
| Garcinia cambogia (Malabar Tamarind) | Crescoli et al[71] and Kothadia et al[72]/case series review, n = 66/ | Hepatocellular type | Acute hepatitis with necroinflammation and parenchymal collapse is commonly noted on histopathology | Hydroxycitric acid and adulteration with heavy metals and other toxic ingredients | Commonly self-limiting even after a prolonged course; acute liver failure and acute on chronic liver failure leading to death described; in liver failure, transplantation has been performed to increase survival; chronic and prolonged DILI has been described leading to cirrhosis and portal hypertension |
| Gymnema sylvestre (Gurmar or sugar destroyer) | Shiyovich et al[74] and Dara et al[75]/series of patients including those consuming herbal and dietary supplements such as Hydroxycut® containing Gymnema | Mixed type | Necroinflammation of the lobules and portal regions with marked ductular proliferation and neutrophilic infiltration of the portal areas | Triterpene saponins, gymnemic acids and polyalkaloids | Usually self-limiting with complete resolution after herbal drug withdrawal |
| Tribulus Terrestis (Gokshura or Puncture vine) | Talasaz et al[77] and Ryan et al[78] /reports / Iran and United States respectively | Hepatocellular type | Not performed | Phylloerythrin and beta-carboline alkaloids are suspected toxins | Associated with seizures and acute kidney injury (mostly bile cast nephropathy); usually self-limiting and responsive to conservative care |
| Valeriana officinalis (Valerian) | MacGregor et al[81] series (n = 4) /Edinburgh | Hepatocellular type | Not performed | Suspected toxins include valerian alkaloids and sesquiterpenes | All patients had uneventful recovery after drug withdrawal and supportive care |
| Cohen et al[82]/report/United States | Cholestatic type | Not performed | |||
| Vassiliadis et al[83] /report/Greece | Hepatocellular type | Lymphocytic and eosinophilic portal inflammation with perivenular necrosis and small bile duct damage | |||
| Duoros et al[84]/series (n = 5)/Berlin | Hepatocellular and mixed type | Extensive necrosis, lobular and portal severe necroinflammation with neutrophils, lymphocytes and eosinophils |
HCV: Hepatitis C virus; DILI: Drug-induced liver injury.