Clinical Trials as Topic ; trends ; Humans ; Non-alcoholic Fatty Liver Disease ; drug therapy

OBJECTIVETo evaluate the efficacy of antioxidants in the treatment of non-alcoholic fatty liver.

METHODSThe Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE or PUBMED (1978-2011), EMBASE (1978-2011), ISI, OVID Database (1978-2011), CNKI Net and WANFANG database (1978-2011) were searched for relevant randomized controlled trials, with also manual search of the bibliographies of the retrieved articles. The data were synthesized to assess the histological response of the patients (hepatic steatosis, inflammation and fibrosis) and hepatic biochemical changes after the treatments (alanine aminotransferase responses).

RESULTSFourteen trials involving 1284 patients were included in the Meta-analysis. The quality of the trials was inconsistent. The data were extracted for meta-analysis or descriptive analysis, which did not yield sufficient evidence that antioxidants could improve hepatic steatosis, inflammation, fibrosis or alanine aminotransferase responses.

CONCLUSIONSThe current data do not support a positive therapeutic effect of antioxidants on nonalcoholic fatty liver, and antioxidants are therefore not recommended in the clinical treatment of the condition.

Antioxidants ; therapeutic use ; Fatty Liver ; drug therapy ; Humans ; Non-alcoholic Fatty Liver Disease ; Randomized Controlled Trials as Topic ; Treatment Outcome

Adult ; Fatty Liver ; diagnosis ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Waist-Hip Ratio

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m²; lean, BMI < 24 kg/m²). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.
Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Overweight/drug therapy* ; Insulin Resistance ; Obesity/drug therapy* ; China ; DNA/therapeutic use*

Animals ; Liver Cirrhosis/drug therapy* ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes/pharmacology* ; Signal Transduction

Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Hypoglycemic Agents/therapeutic use* ; Liver Cirrhosis/pathology* ; Biopsy ; Patients ; Liver/pathology* ; Fibrosis

Diabetes Mellitus, Type 2 ; drug therapy ; Humans ; Hypoglycemic Agents ; therapeutic use ; Non-alcoholic Fatty Liver Disease ; drug therapy

OBJECTIVETo evaluate the efficacy and safety of Chinese medicine (CM) intervention in the treatment of nonalcoholic steatohepatitis (NASH) from liver enzyme (ALT), imaging (the liver/spleen CT ratio) and syndrome scores, and to establish standard methods for diagnosis and therapeutic efficacy evaluation with characteristics of CM.

METHODSA multi-center, stratified randomized, parallel controlled, blindness-method evaluated, superiority trial was performed. Totally 204 patients were randomly allocated into two groups, 102 patients in the experimental group (treated with CM) and 102 patients in the control group [treated with Western medicine (WM)]. The alanine aminotransferase (ALT), liver/spleen CT ratio, and clinical symptoms were observed in both groups.

RESULTSOf the randomly allocated 204 cases from 4 hospitals, 3 patients were rejected, and 25 were lost. Totally 176 cases con- formed to the plan with complete follow-ups. After 3 months of treatment, syndrome scores and the improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). After 3 months of follow-up, the syndrome scores and improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). There was no statistical difference in improving liver enzymes or the liver/spleen CT ratio between the two groups (P > 0.05). There were 4 adverse reactions/adverse events in the two groups in the process of treatment, mainly covering drug-induced liver injury, diarrhea, and epigastric distension. Adverse reactions had nothing to do with CM treatment.

CONCLUSIONSJianpi Shugan Recipe had obvious efficacy in treatment of NASH. It could remove the liver fat and play a role in anti-inflammation and liver protection. It also could improve the indices of liver enzymes and the liver/spleen CT ratio effectively, which was superior to Polyene Phosphatidylcholine Capsule (PPC) in improving clinical symptoms, especially for such symptoms as fatigue and sallow complexion.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Phytotherapy

Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. zhuchuanlong@jsph.org.cn.
Adolescent ; Child ; Female ; Glycyrrhizic Acid ; therapeutic use ; Humans ; Male ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Tablets

The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10–20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases. Currently, diet and exercise are chiefly recommended to achieve significant weight loss and improve metabolic dysfunction in patients with NAFLD. However, weight loss remains to be an elusive goal for both clinical practitioners and NAFLD patients. To date, although there has not been any proven pharmacotherapy against NAFLD, numerous promising pipelines with good target engagement are under development. Moreover, given the global landmark phase 3 trials using obeticholic acid (a farnesoid X receptor agonist, REGENERATE trial) and elafibranor (a dual peroxisome proliferator-activated receptor α/δ agonist, RESOLVE-IT trial), the era of specific target therapies focusing on molecular and metabolic pathogenesis of NASH and fibrosis is near at hand. In this paper, we briefly cover the current and future therapeutic options in patients with NAFLD across the entire spectrum of diseases.
Apoptosis ; Carcinoma, Hepatocellular ; Diet ; Drug Therapy ; Fatty Liver ; Fibrosis ; Hand ; Humans ; Inflammation ; Korea ; Non-alcoholic Fatty Liver Disease* ; Obesity ; Peroxisomes ; Prevalence ; Stress, Physiological ; Weight Loss