acute liver failure ( alf ) is often a life - threatening disease   and , in some cases of alf , the etiology is not clear . because it is difficult to specifically treat those patients with an unknown etiology , their prognosis seems poor compared with patients with a known etiology such as hepatitis a virus , hepatitis b virus , or an autoimmune mechanism . it is possible that drug - induced liver injury ( dili ) could occur with the use of any drug . dili could cause alf , occasionally leading to death [ 2 , 3 , 4 ] . moreover , it is difficult to identify the drug causing the liver injury , and so there is a lack of reliable markers to facilitate and establish the diagnosis of dili [ 5 , 6 ] . due to an increase in health consciousness and internet use , complementary and alternative medicine is readily available . complementary and alternative medicine also occasionally causes liver injury [ 7 , 8 , 9 , 10 ] . recent reports of dili by complementary and alternative medicine are increasing in the united states   and japan . we describe a 24-year - old male patient who had dili associated with complementary and alternative medicine . a 24-year - old japanese man visited our hospital after several days of fatigue and signs of jaundice . he had no previous history of liver diseases , rheumatic diseases , surgeries , transfusions , abuse of illegal drugs , or drug allergies . he was a graduate student and did not work . at the end of august 2015 , he was first admitted to our hospital for a careful examination of his liver disease ( fig 1 ) . on admission , his body length , body weight , and body mass index were 1.75 m , 60.0 kg , and 20.0 , respectively . on physical examination , no ascites or leg edema a first liver biopsy specimen showed that the hepatic architecture was preserved and the histology was compatible to that of acute hepatitis . because conservative treatment made his transaminases lower , he was discharged from our hospital 1 month after the first admission ( aspartate aminotransferase [ ast ] 23 iu / l , alanine transaminase [ alt ] 33 iu / l , and -glutamyltransferase [ -gtp ] 111 iu / l ) ( fig 1 ) . two months after the first admission , his laboratory data were almost normal ( ast 20 3 months after his first admission , his liver function tests were abnormal ( ast 70 iu / l , alt 65 iu / l , and -gtp 30 4 months after his first admission , his liver function tests were worse ( ast 133 iu / l , alt 294 iu / l , and -gtp 46 , we suspected a chronic active hepatitis such as autoimmune hepatitis and introduced prednisolone 15 mg daily and ursodeoxycholic acid 600 mg daily ; however , his liver tests were not improved at 1 week ( ast 438 iu / l , alt 1104 iu / l , and -gtp 119 iu / l ) . in january 2016 , he was admitted to our hospital for a second time for further examination of his liver disease ( fig 1 ) . on admission , his body length , body weight , and body mass index were 1.75 m , 59.0 kg , and 19.3 , respectively . laboratory findings on his second admission are shown in table 2 . during the medical interview , his mother accidentally told us that he took complementary and alternative medicine ( levercol , nippo - yakuhin , tokyo , japan , and jacko , nippo - yakuhin ) temporarily for a single use before the first admission . however , before finding out his liver dysfunction at an outcome clinic and before his second admission , interestingly , this patient did not admit to use of the drugs . a liver biopsy was re - performed , and the results were compatible with acute hepatitis due to a drug ( fig 3 ) . we diagnosed him as dili with complementary and alternative medicine ( levercol and jacko ) . his condition gradually improved with the use of temporary corticosteroids and he was discharged 2 months after the second admission ( ast 15 iu / l , alt 32 iu / l , and -gtp 131 six months after the second admission , his liver function tests had completely returned to normal ranges without any medication ( ast 20 iu / l , alt 21 iu / l , and -gtp 15 the presented case took complementary and alternative medicine ( levercol and jacko ) before every appearance of his liver dysfunction . discontinuation of levercol and jacko could have led to improvement of his condition and liver dysfunction . this patient did not admit the use of these medicines as drugs , but his mother told us about them , resulting in the accurate diagnosis . levercol is an herbal preparation containing fish liver extract that is available only in japan and used for analeptics , weak constitution , and nutritional supplementation [ 11 , 12 ] . it is reported that an 84-year - old male patient who developed subacute fulminant hepatitis was taking levercol with other drugs . we do not know which drugs were responsible for his liver dysfunction . in asian communities , the majority ( 74% ) of patients with hepatotoxicity associated with the use of complementary and alternative medicine were above 40 years of age and 49% were male , although the present case was a 24-year - old man . also reported that traditional chinese medicine , health supplements , and other traditional medicines , including malay jam and indian ayurveda products , caused liver injury in 62 , 28 , and 11% , respectively . they also report that 60% and 5% of patients developed an acute hepatitis type or cholestatic hepatitis type , respectively , corresponding with the present report that levercol and jacko induced acute hepatitis . in the united states , out of 647 adults with liver disease , 41% reported using complementary and alternative medicine , compared with 33% in adults without liver disease . the majority of users believe that complementary and alternative medicine could improve their health . of interest , in the present case , the use of complementary and alternative medicine caused liver dysfunction , such as chronic active hepatitis , although we excluded autoimmune hepatitis by liver biopsy . clinicians should consider dili in patients with repeated liver dysfunction . our report suggests that it is important to perform a medical interview with the patients , as well as their family , even if the patient is an adult . many factors cause liver dysfunction , including fatty changes , drugs , viruses , and autoimmune mechanisms . if the cause is unclear , ultrasound - guided liver biopsy should be performed . in spite of its limitations , the liver biopsy still remains invaluable and can provide important information for diagnosis and management . in the present patient , both liver biopsy specimens were compatible with acute hepatitis due to drugs . in japan , the digestive disease week japan ( ddw - j ) 2004 score is widely used for confirmation of the causality of dili . less than 2 points is a low possibility , 3 - 4 points is possible , and more than 5 points is potentially high . levercol and jacko both had 10 points , but it is difficult to identify which one of them was the cause . it has been reported that complementary and alternative medicine - induced dili is at least as severe in presentation as that observed in prescription medicine - induced dili , with higher rates of transplantation and lower transplant - free survival in those who progress to alf . in general , it is possible that patients may not report taking complementary or alternative medicine as a drug . it may be difficult to determine the cause of liver dysfunction in these patients . in conclusion , attention should be paid to complementary and alternative medicines in patients possessing liver dysfunction with an unknown etiology . a medical interview should be performed with the patients , as well as with their family , to lead to the accurate diagnosis . tatsuo kanda received a research grant from chugai pharmaceutical and msd ; osamu yokosuka received a research grant from chugai pharmaceutical , bayer , msd , daiichi - sankyo , tanabe - mitsubishi , bristol - myers squibb , taiho pharmaceutical , and gilead sciences ; koji takahashi , shin yasui , yuki haga , junichiro kumagai , reina sasaki , shuang wu , shingo nakamoto , masato nakamura , and makoto arai declare that they have no conflict of interest .
a 24-year - old man was admitted due to acute hepatitis with unknown etiology . 
 after his condition and laboratory data gradually improved with conservative therapy , he was discharged 1 month later . 
 two months after his discharge , however , liver dysfunction reappeared . 
 after his mother accidentally revealed that he took complementary and alternative medicine , discontinuation of the therapy caused his condition to improve . 
 finally , he was diagnosed with a recurrent drug - induced liver injury associated with japanese complementary and alternative medicine . 
 it is important to take the medical history in detail and consider complementary and alternative medicine as a cause of liver disease .