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Effect of vitamin E in non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomised controlled trials

Amanullah I, Khan YH, Anwar I, Gulzar A, Mallhi TH, Raja AA

Postgrad Med J, 2019 Nov;95(1129):601-611.
PMID: 31434683 DOI: 10.1136/postgradmedj-2018-136364

The efficacy of vitamin E among patients with non-alcoholic fatty liver disease (NAFLD) is unclear. The current qualitative and quantitative analyses aimed to ascertain the efficacy of vitamin E on clinical outcomes of patients with NAFLD. A systematic search of randomised controlled trials (RCTs) was performed using databases (PubMed, ProQuest, Scopus, EBSCOhost and Ovid) from inception to July 2018. Trials meeting the inclusion criteria were subjected to quality assessment using the Jadad Scoring. All trials meeting the prerequisites information for meta-analysis were subjected to quantitative synthesis of results. Nine RCTs (five in adults and four in children) were included. Four of the five RCTs on adults demonstrated significant improvements in alanine transaminase and other liver function surrogates in patients with NAFLD. On the other hand, only one of the four RCTs conducted on children showed significant improvements in liver functions with the use of vitamin E. Although quantitative synthesis of available data revealed insignificant differences between vitamin E and placebo, still the use of vitamin E improves the level of alanine transaminase and aspartate transaminase by -1.96 and -0.59, with heterogeneity of I2=67% and I2=0%, respectively. Adjuvant vitamin E therapy provides significant biochemical and histological improvements in adult patients with NAFLD, while paediatric patients showed insignificant efficacy compared with placebo. Lifestyle interventions along with vitamin E can provide much better results. Data, including the impact of vitamin E on hepatic histology, are still lacking. Moreover, the short duration of trials limits the conclusion on the safety and efficacy of proposed treatments.

Matched MeSH terms: Non-alcoholic Fatty Liver Disease/drug therapy*
Fulltext Comparative efficacy of interventions on nonalcoholic fatty liver disease (NAFLD): A PRISMA-compliant systematic review and network meta-analysis

Sawangjit R, Chongmelaxme B, Phisalprapa P, Saokaew S, Thakkinstian A, Kowdley KV, et al.

Medicine (Baltimore), 2016 Aug;95(32):e4529.
PMID: 27512874 DOI: 10.1097/MD.0000000000004529

The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best.

Matched MeSH terms: Non-alcoholic Fatty Liver Disease/drug therapy*
Fulltext Hepatoprotective Effects of a Novel Trihoney against Nonalcoholic Fatty Liver Disease: A Comparative Study with Atorvastatin

Alfarisi HAH, Ibrahim MB, Mohamed ZBH, Azahari N, Hamdan AHB, Che Mohamad CA

ScientificWorldJournal, 2020;2020:4503253.
PMID: 33132768 DOI: 10.1155/2020/4503253

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide with no curative therapy. The aim of this study was to investigate the hepatoprotective effects of a novel Trihoney against biochemical and histological manifestations of NAFLD in hypercholesterolemic rabbits. Methodology. Forty-eight male New Zealand white (NZW) rabbits were grouped into normal diet (C), normal diet with 0.6 g/kg/day of Trihoney (C + H), 1% cholesterol diet (HCD), 1% cholesterol diet with 0.3 g/kg/day of Trihoney (HCD + H1), 1% cholesterol diet with 0.6 g/kg/day of Trihoney (HCD + H2), and 1% cholesterol diet with 2 mg/kg/day of atorvastatin (HCD + At.). Animals were sacrificed after 12 weeks of treatment. Serum lipids and liver function test (LFT) were measured prior to and at the endpoint of the experiment for total cholesterol (TC), low-density lipoprotein (LDL-c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (T. Bil.). Liver was processed for histopathology study. Liver homogenate was analysed for oxidative stress parameters: superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Results. Lipid analysis approved the induction of hypercholesterolemia. A significant elevation (p < 0.01) of serum AST and ALT levels showed by the HCD group was compared to C and C + H groups. Trihoney exhibited a significant reduction (p < 0.001) of AST and ALT compared to the HCD group. Likewise, AST and ALT reduced significantly in the HCD + At. group (p < 0.001). Trihoney supplementation induced significant (p < 0.05) enhancement of SOD and GPx activities. Atorvastatin treatment was associated with significant (p < 0.05) reduction of SOD and GPx activities in the liver. Trihoney and atorvastatin showed marked (p < 0.001) reduction of hepatic lipid peroxidation. Trihoney showed histological protection against progression of NAFLD to nonalcoholic steatohepatitis (NASH). Atorvastatin exhibited no beneficial impact on hepatic architecture. Conclusion. Trihoney was able to maintain normal liver function and showed hepatoprotection against progression of NAFLD to NASH probably through hypocholesterolaemic and antioxidant functions.

Matched MeSH terms: Non-alcoholic Fatty Liver Disease/drug therapy*
Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus

Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK

Dig Dis Sci, 2020 02;65(2):623-631.
PMID: 30684076 DOI: 10.1007/s10620-019-5477-1

BACKGROUND AND AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of drugs that lower glucose by inducing renal glycosuria. We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology.
METHODS: In this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial.
RESULTS: There was a significant reduction in body mass index (median change, Δ = -0.7 kg per m2, p = 0.011), waist circumference (Δ = -3 cm, p = 0.033), systolic blood pressure (Δ = -9 mmHg, p = 0.024), diastolic blood pressure (Δ = -6 mmHg, p = 0.033), fasting blood glucose (Δ = -1.7 mmol/L, p = 0.008), total cholesterol (Δ = -0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Δ = -19 U/L, p = 0.013), volumetric liver fat fraction (Δ = -7.8%, p = 0.017), steatosis (Δ = -1, p = 0.014), ballooning (Δ = -1, p = 0.034), and fibrosis (Δ = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo.
CONCLUSION: This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients. Trial registry number ClincialTrials.gov number, NCT02964715.

Matched MeSH terms: Non-alcoholic Fatty Liver Disease/drug therapy*
Fulltext Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats

Al Zarzour RH, Ahmad M, Asmawi MZ, Kaur G, Saeed MAA, Al-Mansoub MA, et al.

Nutrients, 2017 Jul 18;9(7).
PMID: 28718838 DOI: 10.3390/nu9070766

Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.

Matched MeSH terms: Non-alcoholic Fatty Liver Disease/drug therapy*