CSH guidelines for the diagnosis and treatment of drug-induced liver injury.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

Correlation between circulating miR-122 and prognosis of chronic HBV-related liver failure.

OBJECTIVE: To assess the correlation between circulating microRNA (miR)-122 level and the prognosis of chronic hepatitis B-related liver failure (CHBLF). METHODS: Serum miR-122 from CHBLF patients (n = 6) and healthy controls (n = 6) was quantified using an Exiqon locked nucleic acid microarray. Quantitative real-time polymerase chain reaction was utilized to determine serum miR-122 expression in 102 patients with different liver diseases [CHBLF (n = 58), acute hepatitis B (n = 10), chronic hepatitis B (n = 22) and hepatitis B-related cirrhosis (n = 12)] and 23 healthy controls. The correlations between miR-122 and disease stages based on prothrombin activity (PTA) and model for end-stage liver disease (MELD) scores were further analyzed. RESULTS: Microarray showed that miR-122 was significantly upregulated among 148 significantly modified miRNAs in CHBLF patients. Serum level of miR-122 in CHBLF patients was significantly upregulated at early stage based on PTA or stages I-II based on MELD score. Interestingly, there was a significant correlation between the MELD score and circulating miR-122 level in patients with an MELD score of <30 (r = 0.521, P = 0.001). Moreover, serum level of miR-122 was significantly decreased at discharge compared with that at admission as shown in the same group of CHBLF patients (P < 0.05). CONCLUSIONS: Serum level of miR-122 is correlated with the severity of liver injury at an early stage. miR-122 may be a potential biomarker for both the diagnosis at an early stage of CHBLF and the prognosis for recovery.

[Clinical and pathological features in 138 cases of drug-induced liver injury].

OBJECTIVE: To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury (DILI), in order to gain insights into potential diagnostic factors for DILI. METHODS: A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed. The responsible drug for each DILI case was recorded. The Roussel Uclaf Causality Assessment Method (RUCAM) had been used to diagnose DILI. Only cases that had scored as highly probable or probable (more than or equal to 6 points by RUCAM) were included in this study. The patients' general condition, clinical manifestations, and serum biochemical and immunological parameters were assessed. Sixty-six of the patients underwent liver biopsy, and were assessed for liver pathological changes. Clinical and laboratory test data were collected and used to classify the total 138 cases as hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types. RESULTS: Within our patient population, the leading cause of DILI was Chinese herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in 7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy (more than or equal to 3 days after laboratory results) (kappa = 0.63, P less than 0.05) than at the onset of DILI (kappa = 0.25, P less than 0.05). All modified hepatic activity index (HAI) necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type (P less than 0.01 and P less than 0.05, respectively). CONCLUSION: Chinese herbal medicine, dietary supplements and antibiotics were the main causes of DILI in our patient population. The clinical and histological features correlated well, especially at later stages of DILI. The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic injury types than in the hepatocellular injury type. Assessment of both clinical and pathological features may represent a more accurate diagnostic method for DILI.

[Set up drug lymphocyte stimulation test (3H-TdR) and observe its application in drug-induced liver injury].

OBJECTIVE: To set up the drug lymphocyte stimulation test (DLST), as a diagnosis means for DILI which was immunity idiosyncrasy, improve the Diagnosis, level of DILI. METHOD: For the 59 patients who diagnosed as DILI, we separated their PBMC, exploring to the suspicious drug which caused DILI, then use the methods 3H-TdR to test, according to the mixed degree to clear the PBMC count which specific activated by drug.We also set up drug group, negative control and Positive control at the same time. Preliminary experiments was including the best dose of PHA and the best concentration of the drug. We set up 40 healthy group in our experiments as a control, and explore them on the same drug every time. We test the two groups at the same time. We handled the results use t-test. RESULTS: The methods 3H-TdR could be exactly reflect the PBMC's proliferation degree nearly the same when they were be stimulation by PHA or the sensitive drug. When the DILI patients were explore to the suspicious drug, their stimulation index (SI) Obviously higher than 1.8. Form this test, there were 28 in 59 patients of DILI's group were positive (47.46%), SI was from 1.9 to 43.08, the average was 22.49, the healthy group SI was lower than 1.8, the SI of DILI's group was significantly higher than healthy group (5.78+/-0.75/1.16+/-0.25, P less than 0.05). Our test suggested DLST has Higher specificity (94.92%) and sensitivity (47.46%). CONCLUSION: DLST was significance for the patients who diagnosed as immunity idiosyncrasy's DILI, it's reflected these patients' Proliferation of PBMC when explored to the suspicious drug for the second time.