Statin-related drug-induced liver injury / 中华肝脏病杂志

Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.

Genetic susceptibility to drug-induced liver injury / 中华肝脏病杂志

Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.

Standardize the diagnosis and treatment of drug-induced liver injury, and strengthen clinical and translational research / 中华肝脏病杂志

As a liver disease with the most complex clinical phenotype, drug-induced liver injury (DILI) poses great challenges in diagnosis and management in clinical practice. Although guidelines based on the latest research advances can provide clinicians with guidance on the identification, diagnosis, and management of DILI, the overall level of evidence in this field is relatively low and high-level evidence is limited. Therefore, we should interpret guidelines with caution and look forward to more clinical and translational research to address the huge unmet clinical needs in DILI.

Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes

We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics. The results revealed that 96 genes, 17 liver metabolites and 4 serum metabolites consistently changed in different NAFLD phenotypes (>2-fold, P<0.05). Gene-metabolite network analysis identified ccl2 and jun as hubs with the largest connections to other genes, which were mainly involved in tumor necrosis factor, P53, nuclear factor-kappa B, chemokine, peroxisome proliferator activated receptor and Toll-like receptor signaling pathways. The specifically regulated genes and metabolites in different NAFLD phenotypes constructed their own networks, which were mainly involved in the lipid and fatty acid metabolism in HFD models, the inflammatory and immune response in MCDD models, and the AMPK signaling pathway and response to insulin in HFD+STZ models. Our study identified networks showing the general and specific characteristics in different NAFLD phenotypes, complementing the genetic and metabolic features in NAFLD with hepatic and extra-hepatic manifestations.

General characteristics and clinical practices of Chinese patients with non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China.</p><p><b>METHODS</b>NAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines.</p><p><b>RESULTS</b>A total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline.</p><p><b>CONCLUSION</b>Data indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.</p>

Validation of transient elastography (Fibroscan) in assessment of hepatic fibrosis in autoimmune hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To validate transient elastography (Fibroscan) in assessment of hepatic fibrosis in autoimmune hepatitis (AIH).</p><p><b>METHODS</b>Liver stiffness was assessed using Fibroscan in totally 30 patients with AIH. We compared the results of Fibroscan with the Scheuer fibrosis stage in liver biopsy in each patient.</p><p><b>RESULTS</b>4 patients were shown as liver fibrosis stage S0, 6 as S1, 5 as S2, 11 as S3 and 4 as S4. Failure of the Fibroscan measurement occurred in 1 case (3.3%) because of her increased body mass index (BMI). The stiffness of Fibroscan was significantly correlated with the liver biopsy fibrosis stage (r = 0.801, P less than 0.001). The liver stiffnesses between mild and moderate fibrosis (S0-2) and advanced fibrosis (S3-4) were significantly different (t = -3.937, P = 0.001).</p><p><b>CONCLUSION</b>Transient elastography (Fibroscan) is a promising non-invasive method for detection of fibrosis in patients with autoimmune hepatitis. Its use for the follow up and management of these patients and should be evaluated further.</p>

Magnesium isoglycyrrhizinate in the treatment of chronic liver diseases: a randomized, double-blind, multi-doses, active drug controlled, multi-center study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Magnesium isoglycyrrhizinate in treatment of chronic liver diseases.</p><p><b>METHODS</b>It is a randomized, double-blind, multi-doses, active drug controlled, multi-center study. 480 proper patients were randomly divided into group A (180 patients), group B (180 patients) or group C (120 patients). Patients in group A received magnesium isoglycyrrhizinate 100 mg once daily. Patients in group B received magnesium isoglycyrrhizinate 150 mg once daily. Patients in group C received compound glycyrrhizin 120 mg once daily. The treatment course was 4 weeks. Patients were followed up 2 weeks after the treatment. Patients visited once every 2 weeks. Clinical symptoms, ALT, AST were evaluated in all the patients before treatment, at week 2, at week 4 and at 2 weeks later after treatment. The other liver function test was done before treatment and at week 4.</p><p><b>RESULTS</b>412 patients completed the study according to the protocol,152 in group A, 160 in group B and 100 in group C. ALT and AST level were significantly decreased in all groups at week 2 and week 4 (P < 0.05). The degree of ALT decrease is greater in group B than in group C at week 2 (P < 0.01). The degree of ALT decrease was not significant different among three groups at week 4 (P > 0.05). The rates of ALT improvement at week 4 in group A, B, C were 92.59%, 91.76%, 88.29%, respectively (P > 0.05). The rates of symptoms improvement at week 4 in group A, B, C were 90.41%, 89.86%, 86.46% and 72.22%, 73.53%, 68.47%, respectively (P > 0.05). No relapse were found in all three groups after treatment. The rate of adverse event in three groups was similar (P > 0.05).</p><p><b>CONCLUSION</b>Magnesium isoglycyrrhizinate is an effective and safe treatment for chronic liver diseases.</p>

Capsule metadoxine in the treatment of alcoholic liver disease: a randomized, double-blind, placebo-controlled, multicenter study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Capsule metadoxine in the treatment of alcoholic liver disease.</p><p><b>METHODS</b>A randomized double blind multicenter placebo-controlled clinical study was performed to evaluate the therapeutic effectiveness and safety of capsule metadoxine. Patients in metadoxine group received capsule metadoxine 500mg tid po. Patients in placebo group received placebo 2 pillows tid po. The treatment duration was 6 weeks. Patients were followed up 2 weeks after the treatment. Patients were visited once every 3 weeks during the treatment period. Clinical symptoms and liver function were evaluated in all the patients before treatment, at week 3, week 6 and 2 weeks after therapy. CT scan was done in some patients before treatment and at the end point of therapy.</p><p><b>RESULTS</b>254 patients were recruited in the study, 126 in metadoxine group and 128 in placebo group. Median ALT, AST, GGT level in metadoxine group were decreased from 80.0 U/L, 59.2 U/L, 123.0 U/L (before treatment) to 41.1 U/L, 36.0 U/L, 57.0 U/L (after 6 weeks therapy). The improvement in liver function was more significant in metadoxine group than in placebo group (P less than 0.05). For the patients who stopped drinking during the study, the total effective rate of improvement in liver function was 82.8% in metadoxine group, much higher than that in placebo group (55.7% , P=0.0000). For the patients who did not stop drinking during the study, the total effective rate of improvement in liver function was 65.4% in metadoxine group, which is not significantly higher than that in placebo group (44.8%, P=0.1767). The CT value ratio of liver to spleen was significantly improved in metadoxine group (P=0.0023), and there was no significant difference between the two groups (P=0.6293). The rate of adverse was 1.6% in both of groups.</p><p><b>CONCLUSION</b>Capsule metadoxine is an effective and safe treatment for alcoholic liver disease.</p>

Pharmacokinetics of single dose intravenous infusion of magnesium isoglycyrrhizinate in patients with chronic hepatic impairment / 上海第二医科大学学报

0.05). Conclusion The elimination half-life of magnesium isoglycyrrhizinate in patients with chronic hepatic impairment is 27 h,and the regiment of 100 mg once a day is recommended.

Effect of magnesium isoglycyrrhizinate on the proliferation and oxidative stress of rat hepatic stellate cells in vitro / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the effect of magnesium isoglycyrrhizinate on the proliferation and oxidative stress of rat hepatic stellate cells (HSCs).</p><p><b>METHODS</b>The effect of various concentrations of maganesium isoglycyrrhizinate on the proliferation of primary rat HSCs and HSCs strains were measured by making cell growth curves and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphennylterazolium bromide (MTT) colorimetric assay. Morphological changes of the rat HSCs were also studied. After rat HSCs were incubated with various concentrations of maganesium isoglycyrrhizinate and ferric nitrilotriacetate (Fe-NTA) for 24 hours, the activity of superoxide dismutase (SOD) and contents of malondialdehyde (MDA) in supernates were measured to observe the effect of magnesium isoglycyrrhizinate on the oxidative stress of rat HSCs.</p><p><b>RESULTS</b>Compared with the control group, the proliferation of rat HSCs was significantly inhibited when the concentration of magnesium isoglycyrrhizinate in the medium reached a certain level range. In the oxidative stress induced by Fe-NTA, magnesium isoglycyrrhizinate, within a certain strength range, obviously enhanced the activity of SOD and decreased the contents of MDA in supernates of rat HSCs culture media.</p><p><b>CONCLUSIONS</b>Magnesium isoglycyrrhizinate could significantly inhibit the proliferation of rat HSCs and it, within a certain strength range, exert protective effects in the oxidative stress induced by Fe-NTA.</p>

Diisopropylamine dichloroacetate in the treatment of nonalcoholic fatty liver disease: a multicenter random double-blind controlled trial / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of diisopropylamine dichloroacetate in the treatment of nonalcoholic fatty liver diseases (NAFLD).</p><p><b>METHODS</b>A randomized, double-blind, dose-paralleled control trial was carried out with NAFLD patients. The patients were randomly assigned to 2 groups treated with either a high dosage (120 mg/d) or a low dosage (60 mg/d) of diisopropylamine dichloroacetate for 8 weeks and the efficacy and safety of the drug were examined.</p><p><b>RESULTS</b>127 cases were recruited for the trial, 63 in the high dosage group, and 64 in the low dosage group. No case dropped out in the trial but four cases were eliminated (4/127, 3.1%). The final number in this trial was 123, with 61 in the high dosage group and 62 in the low dosage group. After 8 weeks of treatment, the overall improvement of clinical symptoms in the high dosage and in the low dosage group was 87.8% and 79.6%, respectively. ALT normalization was found in 55.7% and 69.4% of the cases in the two groups, serum lipids were lowered in 67.2% and 67.7% and ultrasound grading of the liver alteration severity was lowered in 51.7% and 43.5% in the two groups. The differences found between the two groups were of no statistical significance. One case from each group was found having an adverse drug reaction of dryness of the mouth (1.6%). No severe adverse drug reactions were found.</p><p><b>CONCLUSION</b>Diisopropylamine dichloroacetate could be used as a safe and effective drug in the treatment of nonalcoholic fatty liver diseases.</p>

The role of peroxisome proliferators-activated receptor gamma (PPARgamma) during activation of hepatic stellate cells / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To observe the role of PPARgamma during the activation process of hepatic stellate cells (HSC).</p><p><b>METHODS</b>By morphology and RT-PCR, we study the changes of expression of PPARgamma in culture-activated HSC or in vivo activated HSC induced by dimethylnitrosamine (DMN).</p><p><b>RESULTS</b>In vitro, the expression level of PPARgamma in freshly isolated HSC (0.72+/-0.01) significantly reduced to 0.48+/-0.03 on the third day of culture (t = 19.8372, P<0.01), and reduced 70% on the seventh culture-day and could not be detected after the second passage. In vivo, HSC freshly isolated from normal control rats expressed PPARgamma (0.76+/-0.01). During the development of rat liver fibrosis induced by DMN, the expression level significantly reduced to 0.46+/-0.02 after the third injection of DMN (t = 29.5318, P<0.01), and reduced 66% on the end of first week and could not be detected on the end of second and third week.</p><p><b>CONCLUSION</b>The expression of PPARgamma might play an important role on the maintenance of resting-form of HSC, and the reduction of expression of PPARgamma might be an early event during the activation process of HSC.</p>

Oxymatrine in the treatment of chronic hepatitis B for one year: a multicenter random double-blind placebo-controlled trial / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of oxymatrine in the treatment of chronic hepatitis B.</p><p><b>METHODS</b>A multicenter randomized double-blind placebo-controlled trial was conducted. A total of 144 patients with chronic hepatitis B entered the study for 52 weeks; of them 72 received oxymatrine, and 72 received a placebo. Before and after the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reactions were observed.</p><p><b>RESULTS</b>In 144 patients, 14 were dropped and excluded due to inconsistencies in the included standard. Therefore, the efficacy and safety of 130 patients were analyzed. After being treated for 52 weeks, 70.77% of the patients in the study group had a normal ALT level, and in 43.08% and 33.33% their HBV DNA and HBeAg became negative. In the placebo group, 39.68% had normal ALT level, and 12.31% and 3.33% had their HBV DNA and HBeAg become negative. The rates of complete response and partial response in the oxymatrine group were 23.08% and 58.46%, and in the placebo group they were 3.08% and 44.62%. They were significantly higher in the oxymatrine group than in the placebo group. In the oxymatrine treated patients, 12 weeks after its withdrawal, 60.00% had a normal ALT level, 41.54% and 23.33% had both HBV DNA and HBeAg negative. In the placebo group, 31.75% had a normal ALT level, 3.08% and 1.67% had both HBV DNA and HBeAg negative. The rates of complete response and partial response in the oxymatrine group were 21.54% and 47.69%, and in the placebo group they were 0 and 41.54%. They were significantly higher in the study group than in the placebo group. The adverse reaction rates of oxymatrine in the study and the placebo group were 7.69% and 6.15%, respectively, but there was no statistical significant difference between them.</p><p><b>CONCLUSION</b>Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.</p>

Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B in China / 中华传染病杂志

Objective To evaluate the efficacy and safety of Adefovir dipivoxil in the 52-week treatment of chronic hepatitis B in China.Methods We randomly assigned 480 patients with chronic hepatitis B who were positive for hepatitis B e antigen(HBeAg)in China.During the first 12-week period,480 patients were randomly to receive either 10 mg of adefovir dipivoxil(ADV)or placebo once daily in a 2:1 ratio and in the second period,all patients were accepted ADV for 18 weeks.In the last 12-week stage,all patients treated by ADV were randomly to receive either 10 mg of ADV or placebo in a 2:1 ratio and patients treated by placebo were accepted ADV.The primary end point was serum HBV DNA change during the treatment.The secondary endpoints were ALT normalization rate,HBeAg loss rate and HBeAg seroconversion rate.Results At week 12,median serum hepatitis B virus(HBV)DNA levels of group AAA(ADV-ADV-ADV)and group AAP(ADV-ADV-Placebo) were reduced 3.4 and 3.3 log copies per milliliter,significantly greater than group PAA(Placebo- ADV-ADV)of 0.1 log copies/ml reduction(P