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.

Gastric bezoar: a case of a patient treated with traditional Chinese medicine.

BACKGROUND: Gastric bezoar is a collection of indigestible material in the stomach. It is a relatively rare disease. In this case report, it is shown that Traditional Chinese Medicine (TCM) was effective in treating a patient with gastric bezoar. SUBJECT AND SETTING: A 47-year-old female patient who had undergone Billroth II gastrectomy for gastric cancer had been experiencing abdominal pain and distension for 1 month. She underwent gastroscopic examination at our outpatient department; the gastroscopy showed a bezoar (7×4×2 cm in size) in her remnant stomach. Treatment using a Chinese herbal decoction was suggested. RESULTS: The gastric bezoar dissolved after 2 weeks of regular therapy with San Jie Pai Shi decoction. No complications or adverse effects were noted during the TCM treatment. CONCLUSIONS: This case showed that TCM was an effective and alternative treatment option for patients with gastric bezoar.

Primary isolated hepatic oval cells maintain progenitor cell phenotypes after two-year prolonged cultivation.

BACKGROUND & AIMS: Although expandable hepatic progenitors provide renewable cell sources for treatment of hepatic disorders, long-term cultivation of hepatic progenitors may affect proliferation and differentiation abilities, and even initiate the formation of malignant cancer stem cells. This study aims to determine characteristics of primary cultured hepatic oval cells after prolonged cultivation in vitro. METHODS: Hepatic oval cells isolated from rats fed with a choline-deficient, ethionine-supplemented diet were continuously propagated every 5-7 days, to 100 passages over two years. Hepatocytic differentiation was induced by sodium butyrate and characterized using western blot, periodic acid Schiff assays, albumin secretion and urea production. Proliferation capacity was evaluated using growth-curve and cell-cycle analysis; anchorage-independent growth and tumorigenicity were determined using soft agar and xenograft assay. RESULTS: After 2 years of serial passages, hepatic oval cells with typical epithelial morphology continuously expressed OV-6, BD-1, BD-2, and Dlk as markers for hepatic progenitors, cytokeratin 19 as a cholangiocyte marker, and alpha-fetoprotein and albumin as hepatocyte markers. Furthermore, sodium butyrate could induce these cells to become glycogen-storage cells with the functions of albumin secretion and ureagenesis from ammonia clearance, indicating hepatocytic differentiation. Although proliferation slightly accelerated after the 50th passage, hepatic oval cells stayed diploid cells with features of chromosomal stability, which did not acquire anchorage-independent growth capacity and caused no tumor in immunodeficient mice, suggesting no spontaneous malignant transformation. CONCLUSIONS: Hepatic oval cells retain the progenitor cell features without spontaneous malignant transformation after prolonged cultivation, and thus may serve as an expandable cell source for future exploitation of stem cell technology.

Treatment of patients with alcoholic liver disease.

BACKGROUND: The proportion of alcoholic liver disease among all kinds of liver diseases in China is increasing. Recent research has elucidated the mechanisms of alcohol-induced liver injury and offered the prospect of advances in the management of alcoholic liver disease. DATA RESOURCES: Searching MEDLINE (1982-July 2004) for papers on alcoholic liver disease, especially those on the treatment of alcoholic liver disease. RESULTS: Abstinence remains the cornerstone of management of all forms of alcoholic liver disease. Nutritional support therapy is also a basal treatment. Corticosteroids may be benefitial for some severe alcoholic hepatitis. None of other measures including anti-inflammatory agents, antioxidants or colchicine has been shown consistently to improve the course of alcoholic liver damage. Ultimately, liver transplantation remains an option for selected patients with liver failure due to chronic alcoholic liver disease. CONCLUSIONS: Abstinence and nutritional support remain the base management of alcoholic liver disease. Corticosteroid is efficient for some severe alcoholic hepatitis. Anti-inflammatory agents and antioxidants may be of benefit but need further studies. The efficacy of other measures including the use of colchicine and propylthiouracil is controversial. Liver transplantation remains an option for selected patients with liver failure.

[Sodium butyrate induces rat hepatic oval cells differentiating into mature hepatocytes in vitro].

OBJECTIVE: To elucidate the effects of sodium butyrate on rat hepatic oval cell differentiation in vitro. METHODS: Hepatic oval cells were isolated from rats fed with a choline-deficient diet supplemented with 0.1% (w/w) ethonine for 4 to 6 weeks. The cultured hepatic oval cells were identified by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). After hepatic oval cells were treated with sodium butyrate, the morphological changes were studied through Giemsa staining and the albumin expression level was tested by Western blot. RESULTS: Immunohistochemical results showed the isolated cells were positive for both mature hepatocyte marker albumin and bile duct cell marker cytokeratin-19. Furthermore, RT-PCR results showed that the cells expressed stem cell marker c-kit, but not hematopoietic stem cell marker CD34. In short, the isolated cells were rat hepatic oval cells. 0.75 mmol/L sodium butyrate induced obvious phenotype changes of hepatic oval cells, including enlargement of the oval cells, a decrease in nucleus to cytoplasm ratio, and a 50% increase in the number of binucleated cells. Western blot results showed that 0.75 mmol/L sodium butyrate markedly raised the expression of albumin. CONCLUSION: Sodium butyrate, a differentiation promoting agent, can induce rat hepatic oval cells (liver progenitor cells) to differentiate into mature hepatocytes in vitro.

[The effect of Cpd 861 on chronic hepatitis B related fibrosis and early cirrhosis: a randomized, double blind, placebo controlled clinical trial].

OBJECTIVES: To further assess the clinical antifibrotic efficacy of Cpd 861 on chronic hepatitis B related fibrosis and early cirrhosis using a randomized, double blind, and placebo controlled clinical trial. METHODS: Total 136 patients with HBV-related fibrosis and early cirrhosis were allocated randomly into Cpd 861 treatment group and placebo group for 24 weeks treatment. Serum fibrosis markers including hyaluronic acid (HA), IV collagen (IV-C), amino terminal propeptide of type III procollagen (PIIIP), and laminin (LN) and serum MMP1, 2, 9, TIMP1, 2 level were determined before and after 24 weeks treatment. Liver biopsies before and after 24 weeks of treatment were assessed according to modified Scheuer and Chevallier's scoring system. RESULTS: Total 52 patients in Cpd 861 treatment group and 50 patients in placebo-controlled group completed the 6 months. ALT level decreased from 68.2 U/L+/-68.6 U/L to 45.9 U/L+/-26.1 U/L, AST level decreased from 60.4 U/L+/-62.6 U/L to 46.7 U/L+/-39.0 U/L (P < 0.05) after 24 weeks treatment, whereas there was no significant change in placebo group (ALT: 65.3 U/L+/-48.3 U/L to 85.4 U/L+/-115.5 U/L; AST: 60.4 U/L+/-44.6 U/L to 77.6 U/L+/-89.6 U/L, P > 0.05). Serum fibrosis markers, including HA, IV-C, PIIIP, and LN were decreased after treatment, but there is no statistically significant compared with placebo group. Compared with placebo group, serum TIMP1 and MMP9 level decreased significantly (TIMP1 172.0 ng/ml+/-79.6 ng/ml vs 133.5 ng/ml+/-66.8 ng/ml; MMP9 116.1 ng/ml+/-88.2 ng/ml vs 80.4 ng/ml+/-79.0 ng/ml), and the ratio of TIMP1/MMP1 (48.3+/-96.3 vs 19.9+/-28.0) were also decreased after 861 treatment. In patients treated with Cpd 861, hepatic inflammatory score (from 14.0+/-6.0 to 10.2+/-6.1), fibrosis score (from 11.9+/-6.5 to 8.2+/-4.5), and relative content of collagen (from 18.9%+/-9.5% to 14.9%+/-8.4%) decreased significantly. In contrast, there was no significant change in placebo group. The reversal (fibrosis score decrease > or = 2) rate of fibrosis in Cpd 861 group was 38.9% in S2, 53.3% in S3 (precirrhotic) and 78.6% in S4 (cirrhosis), significantly higher than those in placebo group (14.3%, 25.0%, and 41.7%, respectively). The overall reversal rate was 52.0% in Cpd 861 group, and 20.0% in placebo group (P < 0.05). No serious adverse effects were observed during Cpd 861 treatment. CONCLUSION: Liver fibrosis and early cirrhosis due to HBV infection in man could be definitely reversed by herbal remedy Cpd 861.