Background: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis. Methods: The diagno‐ sis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (r s) were calculated. Results: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (r s =0.61, p ≤ .001), venous total ammonia (r s =0.56, p ≤ .001), arterial partial pressure of ammonia (r s =0.55, p ≤ .001), and venous partial pressure of ammonia (r s =0.52, p≤ .001). Conclusions: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammo‐ nia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels.
Introduction and Aim: Our previous pilot study showed half the cases of drag induced liver injury (DILI) at our unit were due to traditional Chinese medicines (TCM), but their toxic components are unknown. This prospective study aims to evaluate presence of adulterated medications in the herbs in TCM-DILI. We achieved this through a collaborative study between a clinical hepatology unit and a government pharmacological laboratory. Methods: All patients admitted to, or referred to our hepatology unit for suspected DILI from 1 Sept 2004 to 31 August 2005 were recruited and evaluated. Implicated TCMs were sent for further analysis. The test protocol categorized 208 commonly encountered drugs in adulterated herbs into 37 different pharmacological effect groupings. Depending on the volatility of the drugs, the screening protocol used Gas Chromatography/ Mass Spectrometry or High performance liquid chromatography/DiodeArray Detector to screen for common adulterants. Any positive results from HPLC were further confirmed by using Liquid Chromatography/ Mass Spectrometry. Results: Twenty-four patients with suspected DILI were recruited over the 12 months period: median age 53yrs (range 23 79), 12 (50%) male, 18 (75%) Chinese, 20 (84%) were related to TCM, 1 each related to anti-TB drugs, lovastatin, phenytoin, and ketamine. 19 had hepatocellular injury, 2 had cholestatic injury, and 3 had mixed injury. Adulterated substances were found in 5/24 (21%) preparations of TCM: toxic doses of mercury (1), phenylbutazone (1), berberine/codeine (1), berberine/ metformin (1), and dexamethasone (1). 1 died from liver failure from anti-TB drugs related DILI, 1 who took herbs adulterated with toxic doses of mercury developed acute liver failure requiring living donor liver transplant, the other 22 (92%) survived. Of note was that 1 inactive hepatitis B carrier who took herbs adulterated with dexamethasone developed hepatitis B flare requiring lamivudine therapy; and another male patient who took herbs adulterated with phenylbutazone developed autoimmune hepatitis requiring steroids therapy. Conclusion: TCMs could be adulterated with toxins to the liver. Further studies on the safety of TCMs including routine testing for adulterated substances should be considered.
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