Discussion and conclusion
Hepatic injury caused by both prescription and non-prescription, is
termed drug-induced liver injury (DILI) [5]. DILI ranges in severity
from mild, asymptomatic, elevations in liver enzymes to severe hepatic
injury culminating in acute liver failure resulting and death [5].
Up to now, there are currently just under a thousand drugs that have
been suspected of causing DILI clinically. Research showed that TCM or
herbal and dietary supplements (HDS) are one of the leading causes of
drug-induced liver injury (DILI) [6].
Kedaling tablets is an extract of
with Corydalis yanhusuo W.T. Wang and used to coronary heart disease,
angina pectoris, myocardial infarction with no previously well
documented hepatotoxicity. We report a case of a 64-year-old man who had
hypertension, coronary disease and fatty liver. After 1 year on related
antihypertensive and anti-coronary heart disease treatments, his liver
enzymes in standard conditions. But he was initially treated with
kedaling
tablets and other drugs, and approximately one month later, his liver
enzymes were elevated, but doctors did not know the DILI was caused by
the kedaling tablets. Over the next month, the patient still experienced
serious DILI after being on kedaling tablets and other drugs. Doctors
analyzed the patient’s medication for nearly a year and suspected that
DILI may relate to kedaling tablets
therapy.
Thus, during a follow-up of 12 months, his liver enzymes remained normal
without
kedaling
tablets, though he had fatty liver. However, when he took kedaling
tablets again, his liver enzymes rebounded. More importantly, after 8
months of follow-up without kedaling tablets, liver enzymes remained
normal.
In
our patient’s case, we attributed liver injury to kedaling tablets on
the basis of the facts that drug exposure preceded the onset of liver
injury, though the patient suffered from fatty liver, cessation of the
drug led to improvement in liver enzymes, and symptoms recurred rapidly
when the patient was re-challenged (Figure 1 and 2). Extensive testing
for other causes of acute liver injury was negative and the patient did
not endorse signs, symptoms or imaging findings suggestive of outflow
obstruction, hepatic ischemia or biliary obstruction. Although the
patient was discovered to be anti-HBs positive and fatty liver, these
were very unlikely to be an acute infection. DILI may be classified into
three categories based upon the pattern of liver injury observed,
including acute hepatocellular injury, cholestatic injury and mixed
liver injury [7]. Hepatocellular injury is due to substantial damage
to the hepatocytes and is characterized by elevations in the serum AST
and ALT levels, with lesser elevations in the ALP level [8]. In the
case of our patient, he demonstrated a predominantly hepatocellular
injury that occurred with substantially elevated AST and ALT levels and
a mildly elevated ALP level (Table1).
It is found that the toxicity of TCM generally depend on their basic
substances [6].
Because
dehydrocorydaline is the main active ingredient in kedaling tablets, we
suspected that the mechanism of kedaling tablets-induced DILI may relate
to dehydrocorydaline in the case report presented here. We searched the
PubMed database to identify literature with the
dehydrocorydaline-induced DILI, but there are not publications. But
studies have reported that dehydrocorydaline could inhibit the
tumorigenesis of breast cancer MDA‑MB‑231 cells through downregulating
cell proliferation, anti-apoptosis, metastasis‑associated proteins CDK1,
CCND1, BCL2 and metastasis‑associated proteins MMP2 and MMP9, and
upregulating the expression of proapoptotic proteins caspase 3/8/9,
suggesting dehydrocorydaline is a multi-target cytotoxic drug and it has
the potential to damage liver cells [9]. Dehydrocorydaline also
could inhibit cell proliferation, migration and invasion via suppressing
MEK1/2-ERK1/2 cascade in melanoma [10]. Besides, the structure of
dehydrocorydaline is similar to that of the hepatotoxic pyrrodines
alkaloids. Therefore, the case of DILI may relate to dehydrocorydaline
therapy in our study.
In summary, this patient presented DILI with substantially elevated AST
and ALT levels following introduction of
kedaling
tablets. To our knowledge, this is the first case of documented
hepatotoxicity induced by kedaling tablets and the exact mechanisms of
how kedaling tablets causes liver injury require further research.
Conflicts of Interests
The authors declare that there are no competing interests
Acknowledgements
None
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