A full text draft of the case report is available here:
https://sci-hub.tw/https://doi.org/10.1016/j.phymed.2018.08.011
TL/DR: It's possibly this actually is a rare case of liver failure caused by some kind of kava product. But reading the article raises many unanswered questions, and the possibility of drug interactions or preexisting conditions seems more likely to me than the abstract suggests. Also it's not clear what kind of kava product was actually involved here. Obviously it was not traditional kava as we know it.
Description of the patient's initial presentation and other medications:
"Female, 45 years old, admitted to a small hospital on 09/05/2016 with symptoms of nausea and jaundice since 09/03/2016. Computed tomography of abdomen within normality. Total bilirubin: 12.40mg/dl; direct bilirubin: 10.40mg/dl; Alanine methyltransferase: 2459 U/L; international normalized ratio: 1.76(Graph 1). In anamnesis, the patient disclaims alcoholism and smoking. Previous use of continuous drugs: omeprazole 20mg QD for 4 years and bromazepam 3mg QD for 2 years. Patient reports stop using bromazepam and self-medicating with herbal kava medicine 100mg QD at night. The symptoms started 52 days after the onset of kava use. On 09/05/2016, after hospital admission, the kava medication was suspended. Infectious diseases, such as hepatitis A, B, C, cytomegalovirus, Epstein bar virus, leptospirosis, and herpes, were excluded."
So the patient said that she had been taking 2 medications every day ("QD") for several years: omeprazole and bromazepam. The paper doesn't say if the patient had any liver tests done during the prior 2-4 years when she was on those medications. According to the patient's self-report she then stopped taking the bromazepam when she started taking some sort of kava product, and then a couple months later started experiencing severe liver symptoms. The paper doesn't say if she kept taking the omeprazole during this time. The "Concomitant drug/herb" item on the RUCAM form in Fig. 1 is marked in a way that seems to indicate they didn't think the patient's prior use of bromazepam or possibly continuing use of omeprazole was significant. Specifically "Concommitant drug/herb with incompatible time to onset" is marked with 0, but my question is how can they be certain that the onset time was not earlier without having test results from the prior years, in which case that item would be -1 or -2 subtracted from the total.. And both of those meds have had their own reported liver issues:
Omeprazole AKA Prilosec is used for gastric reflux. The NIH Livertox database gives it a rating of
"B (rare but likely cause of clinically apparent liver injury)":
https://livertox.nlm.nih.gov/Omeprazole.htm
Bromazepam is a benzodiazapine that is not available in the US, so there isn't any info on the NIH Livertox site, but the
Wikipedia article on bromazepam has this:
"Leukopenia and liver-damage of the cholostatic type with or without jaundice (icterus) have additionally been seen; the original manufacturer Roche recommends regular laboratory examinations to be performed routinely."
Another thing the paper is not really clear about is what kind of kava product or extract these capsules actually were. It has this confusing description of the chemical analysis:
"The quality control reports indicated extraction with methanol, and all the chemical and microbiological requirements were met. The capsules used by the patient were submitted to constituents and contaminants investigation. Chemo-profiling was performed by HPLC/ESI-MS/MS.The drug used by the patient was compared to a sample purchased at the same pharmacy a few months later. In this study, the drug purchased by the researchers was considered the control. Both medicines were 100-mg kava capsules. For the possible contaminants, Aflatoxins(AfB1, AfB2, AfG1, AfG2 e AfM1) and Ochratoxin A werere searched by HPLC/ESI-MS/MS, with the Multiple Reaction Monitoring method. The results showed that all Kavalactones, Flavocaine B, Pipermetistina, and other specifications were within the standards. Similarly, the research for Aflatoxins and Ochratoxin A was negative. Graph 2 shows that there was some reduction in the concentration of constituents in the patient sample, however, this can be attributed to the natural degradation of the drug. Besides, the environmental conditions in which the plant developed could also contribute to the constituents variation (Graphs2 and 3). We reject the hypothesis that there are high concentrations of the kava active compounds. However, we cannot accurately state that the capsule had 100 mg of kava since the control used was not a standard."
Comments:
"The quality control reports indicated extraction with methanol" - WTF?? Does that mean the product was a methanol-based extract??!! I certainly hope not because methanol is highly toxic and that should not be legal anywhere.. More likely it means the analytical method used methanol extraction, which would be an irrelevant detail and does not answer the question I really want to know of how the product was made.
"
The results showed that all Kavalactones, Flavocaine B, Pipermetistina, and other specifications were within the standards." - So they measured KLs, FKB and PM and found they were "within standards" but what does that mean? How much KL, FKB and PM was there in absolute terms? The paper doesn't say. Does Brazil actually have standards for acceptable levels of FKB and pipermethystin in kava products? Really? Are those levels some number higher than 0?
All this analysis really concludes is that yes, the product contained some kavalactones in proportions suggestive of a non-noble chemotype, but not a lot of those, plus possibly unknown quantities of FKB and pipermethystin that we are assured were within some unknown standard, was free of mold toxins, and the capsules the patient had were the same as some other ones they bought in a store, but did not compare to any real standard references?