A Single-Center Experience on Outcomes of Complementary and Alternative Medicine Use Among Patients With Cirrhosis

Abstract

Drug-induced liver injury (DILI) due to complementary and alternative medicine (CAM) use is on the rise throughout the world by patients looking for "safer" alternatives. However, data on acute-on-chronic liver failure (ACLF) due to CAM are lacking. In a large cohort of patients with cirrhosis, we retrospectively studied CAM-related health-seeking behavior and attempted to identify those who developed possible CAM-DILI-related ACLF. In this study, we examine the clinical, biochemical, and liver histopathologic characteristics of possible CAM-DILI-related ACLF, describe implicated CAM agents, and discuss predictors of patient outcomes. Out of 1,666 patients with cirrhosis, 68% used CAM at some point. A total of 35.7% (n = 30/84) patients presented with CAM-related DILI leading to ACLF in the whole CAM-DILI-related decompensation cohort. The most common CAM was unlabeled polyherbal Ayurvedic formulations. Of possible patients with ACLF, 63% self-medicated with CAM based on social media sharing. Mean age ± SD was 51.9 ± 9.9 years, 83% were male patients, median follow-up duration was 173 (range, 14-584) days, median Child-Turcotte-Pugh score was 13 (range, 10-14), Model for End-Stage Liver Disease-sodium score was 30.1 ± 4.8, median chronic liver failure-organ failure (CLIF-C-OF) score was 11 (range, 8-14), and median CLIF-C-ACLF score was 98 (range, 87-127). Portal-based neutrophilic predominant mixed inflammation, hepatocyte ballooning, autoimmune-like features, and severe cholestasis were seen on liver biopsy. Overall, 53% of patients died (median survival 194 days). Baseline overt hepatic encephalopathy and CLIF-C-OF score, total bilirubin, hyponatremia and leukocytosis, and grade of ACLF predicted 1-, 3-, 6- and 12-month mortality, respectively. Conclusion: Possible CAM-DILI-related ACLF has a high mortality. Strict monitoring and identification of CAM use among people with cirrhosis and an integrative public health educational practice can help ameliorate this modifiable risk factor that potentiates heavy liver disease burden and resource use.

Figure 1

Consolidated Standards of Reporting Trials diagram. Abbreviation: HBV, hepatitis B virus.

Figure 2

Liver biopsy findings of patients with possible CAM‐related ACLF. Cirrhosis with mild to moderate neutrophilic predominant mixed inflammation with periportal hepatocyte destruction. (A) Aloe vera extract along with unlabeled polyherbal powder, (H&E, magnification ×20) and (B) advanced fibrosis with irregular nodule formation with marked ductular reaction (white arrows) within areas of fibrosis (MT stain, magnification ×10). (C) Cirrhosis with moderate to severe lymphoplasmacytic inflammation of the portal tracts without interface hepatitis but with severe siderosis; unlabeled polyherbal powder, multi‐herb syrup, and unlabeled Ayurvedic tablets (H&E, magnification ×10). (D) Cirrhosis with severe plasma cell‐rich portal inflammation, few lymphocytes, mild to moderate neutrophilic infiltrates, and canalicular cholestasis, and areas of macrovesicular steatosis are also seen; aloe vera and Malabar nut tree leaf extract (H&E, magnification ×20). (E) Extensive and severe sinusoidal fibrosis; gold‐containing Siddha metallomineral ash and gale of the wind herb (MT, magnification ×20). (F) Marked infiltration of portal tract with neutrophils, lymphocytes, and eosinophils, with cholangiolar cholestasis; bitter oleander and unlabeled polyherbal powder (H&E, magnification ×20). Abbreviations: H&E, hematoxylin and eosin; MT, Masson‐Trichrome.

Figure 3

Liver biopsy findings of patients with possible CAM‐related ACLF. (A) Liver biopsy showing interface hepatitis with lymphoplasmacytic cells, extensive feathery degeneration, and ballooning of hepatocytes; passion fruit leaf concoction, aloe vera extract, and gale of the wind herb (H&E, magnification ×20). (B) Portal inflammation with severe siderosis in the absence of human hemochromatosis protein gene mutation; polyherbal powder and unlabeled Ayurvedic tablets (H&E, magnification ×20). (C) Extensive fibrosis with dissection of fibrotic strands into islands of hepatocyte nodules; magnesium sulfate and sweet broom weed (MT, magnification ×20). (D) Severe intracanalicular and hepatocellular cholestasis; metallomineral Ayurvedic preparations and unlabeled polyherbal powders (H&E, magnification ×40). (E,F) Marked ballooning of hepatocytes with multinucleation, feathery degeneration with extensive fibrosis, irregular hepatocyte nodules, and lymphoplasmacytic cellular inflammation and interface hepatitis; Malabar nut tree leaf extract (H&E and MT, magnification ×10 and ×20, respectively). Abbreviations: H&E, hematoxylin and eosin; MT, Masson‐Trichrome.

Figure 4

Overall survival in patients with possible CAM‐related ACLF. (A) Overall survival in patients with CAM‐related DILI and (B) lower and higher grades of ACLF.

Figure 5

Survival of patients with possible CAM‐related ACLF. (A) Proportion of patients with possible CAM‐related ACLF surviving at 1 month, grouped according to CLIF scores. (B) Proportion of patients with CAM‐related DILI and lower and higher grades of ACLF surviving at the end of 1 year.

Figure 6

Proportion of patients with possible CAM‐related ACLF compared to those with prescription drug‐related ACLF surviving at 180 days and characteristics of both groups with respect to liver disease severity.