Favipiravir Inhibits Mayaro Virus Infection in Mice.

Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipiravir treatment post-MAYV infection did not result in a reduction in viral replication. Interestingly, Favipiravir strongly decreased the blood levels of the liver disease markers aspartate- and alanine aminotransferase in the pre- and concurrently treated MAYV-infected mice. Taken together, these results suggest that Favipiravir is a potent antiviral drug when administered in a timely manner.

Protective effects of chitosan and chitosan oligosaccharide against oxidative damage in liver tissue of rats with fluorine poisoning.

Fluorine toxicity has negative effects on soft tissue besides skeletal and dental tissues. In the present study, we have investigated the protective effect of chitosan (CS) and chitosan oligosaccharide (COS) on liver tissue of fluorine-intoxicated rats taking the antioxidant characteristics of chitosan and its derivatives into consideration. In this study, 42 male Wistar albino rats were randomly selected to determine the control and experimental fluorosis groups. Our study lasted for 12 weeks. As a consequence of the study, MDA significantly increased in the liver tissue of NaF group while some antioxidant values significantly decreased. It was detected that serum AST and LDH levels increased significantly while ALB and TP values significantly decreased in NaF group. The degenerations were identified in the liver histopathology of all fluoride-treated groups. We have concluded according to the results that chitosan oligosaccharide can be more effective compared with chitosan.

Protective effect of Phaeoporus obliquus polysaccharide against acute liver injury induced by carbon tetrachloride and alcohol in mice.

Studied the optimum extraction process of polysaccharide from Phaeoporus obliquus and the effect of Phaeoporus obliquus polysaccharide on carbon tetrachloride (CCl4)- or alcohol-induced acute liver injury in mice. The main factor in influencing the extraction rate of Phaeoporus obliquus polysaccharide were extraction power and time, which was a kind of pyran glucose by infrared spectroscopy. CCl4 and alcohol were employed respectively to establish CCl4 and alcohol-induced acute liver injury mouse models. Compared with model groups mice, Phaeoporus obliquus polysaccharide treatment at the doses of 100mg/kg and 200mg/kg exhibited an obvious reduction liver index, ALP, ALT, AST levels, MDA content and TNF-α level (p<0.01) and SOD activity was increased, which was in a dose-dependent manner. Compared with the model group, the necrosis degree of hepatocytes was obviously reduced and the small fat droplets were formed in some cytoplasm, especially in high dose group, which the liver cells recovered to the level of normal group. Rt-PCR results showed that the expression of CYP2E1 mRNA in liver tissues of Phaeoporus obliquus polysaccharide groups were significantly reduced, and the difference were statistically significant compared with the model group (p<0.05). These results demonstrated that Phaeoporus obliquus polysaccharide has significantly hepatoprotective effect on CCl4 and alcohol-induced acute liver injury in mice.

Cardioprotective effect of boswellic acids against doxorubicin induced myocardial infarction in rats.

The aim of the present study was to evaluate the cardioprotective activity of boswellic acids in doxorubicin (DOX) induced cardiotoxicity. DOX (2.5mg/kg) was used intraperitoneally in rats to induce cardiotoxicity in six divided doses every alternate day over a period of two weeks. Dexrazoxane (10:1) was used as a standard drug. Boswellic acids (250, 500 and 750 mg/kg) were orally administered to rats for 14 days. After 14 days, rats were sacrificed, and blood was withdrawn through cardiac puncture. The blood lipid profile and cardiac biomarkers including LDH, CK-MB, CPK, SGOT and troponin T were measured. The heart of rats was isolated for histopathological studies. Graphpad Prism was used for statistical analysis. There was a significant increase in the level of cardiac enzymes and complete lipid profile parameters in diseased group as compared to control group. Pre-treatment with boswellic acids decreased level of all the measured parameters and decreased the severity of myocardial damage as supported by histopathological studies. It was concluded that boswellic acids possess cardioprotective potential by lowering cardiac biomarkers and blood lipid profile. Thus, boswellic acids might act as cardioprotective agent against doxorubicin induced cardiotoxicity.

The effect of melatonin supplementation on liver indices in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials.

Several randomized clinical trials (RCTs) evaluated the effect of melatonin supplementation on liver enzymes in patients with non-alcoholic fatty liver disease (NAFLD) and reported conflicting results. To meet these discrepancies, a meta-analysis was conducted to evaluate the eff ;ect of melatonin on liver indices in patients with NAFLD. To collect the required data, a thorough search was conducted through Web of science, Pubmed, Cochrane database, Embase, Google Scholar, ProQuest, and Scopus databases. The aim was to find clinical trials over the effect of melatonin supplementation on liver indices up to 16 May 2019. As a result, five eligible articles were selected and analysed in this meta-analysis using a fixed-effects model. Heterogeneity test was performed by I2 statistics and Cochrane Q test. The results showed that melatonin had a significant effect on aspartate aminoteransferase (AST) (WMD = 2.29, [95 %CI: 1.14, 3.43] IU/L, p = <0.001), alkaline phosphatase (ALP) (WMD = -8.40, [95 %CI -11.33, -5.48] IU/L, p < 0.001), and gamma-glutamyltransferase (GGT) (WMD = -33.37, [95 %CI: -37.24, -29.49] IU/L, p= < 0.001). Melatonin had no significant effect on alanine aminotransferase (ALT) regarding the overall effect size. Based on this meta-analysis, melatonin supplementation can improve liver indices. However, more RCTs are required with larger sample sizes and better control of confounding variables such as weight, body mass index, and gender to determine the effect of melatonin on patients with non-alcoholic fatty acid disease.

Benefits and harms of ginseng supplementation on liver function? A systematic review and meta-analysis.

OBJECTIVE: Existing evidence on the possible effects of ginseng on liver function has not been fully established. Therefore, the present review was undertaken to evaluate the overall effects of ginseng supplementation on liver enzymes in adults. METHODS: A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google scholar databases was conducted up to May 2019. All RCTs using ginseng supplements in adults were included in this systematic review and meta-analysis. RESULTS: Overall, 14 randomized trials (with 20 arms) including 992 subjects were identified. Pooled analysis did not illustrate any significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin (ALB) levels, however, it showed a minor significant increase in bilirubin (BIL) levels. Subgroup analysis by dosage and study population revealed significant increase of bilirubin after ginseng supplementation ≥3 g/day or in unhealthy individuals. CONCLUSION: Ginseng appears to have neither hepatoprotective nor hepatotoxic effects in conventional doses and duration. It is noteworthy that this seems applicable only for individuals with healthy liver function. Further largescale studies are warranted to confirm present findings.

EX-527 Prevents the Progression of High-Fat Diet-Induced Hepatic Steatosis and Fibrosis by Upregulating SIRT4 in Zucker Rats.

Sirtuin (SIRT) is known to prevent nonalcoholic fatty liver disease (NAFLD); however, the role of SIRT4 in the progression of hepatic fibrosis remains unknown. We hypothesize that EX-527, a selective SIRT1 inhibitor, can inhibit the progression of high-fat diet (HFD)-induced hepatic fibrosis. We found that SIRT4 expression in the liver of NAFLD patients is significantly lower than that in normal subjects. In this study, EX-527 (5 µg/kg), administered to HFD rats twice a week for ten weeks, reduced the serum levels of triglyceride (TG), total cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and attenuated hepatic fibrosis evidenced by Masson's trichrome and hepatic fat by oil red-O staining. EX-527 upregulated SIRT2, SIRT3, and SIRT4 expression in the liver of HFD fed rats but downregulated transforming growth factor-ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expression. It decreased proinflammatory cytokine production and hydroxyproline levels in the serum and SMAD4 expression and restored apoptotic protein (Bcl-2, Bax, and cleaved caspase-3) expression. These data propose a critical role for the SIRT4/SMAD4 axis in hepatic fibrogenesis. SIRT4 upregulation has the potential to counter HFD-induced lipid accumulation, inflammation, and fibrogenesis. We demonstrate that EX-527 is a promising candidate in inhibiting the progression of HFD-induced liver fibrosis.

Effect of L-Carnitine Supplementation on Liver Enzymes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Possible Hepato-protective effects of L-carnitine have been reported in previous studies. Present study was conducted to systematically review the efficacy of L-carnitine supplementation on liver enzymes. METHODS: The following databases were searched up to December 2018: PubMed, Scopus, ISI Web of Science, and the Cochrane library. Only randomized controlled trials (RCTs) evaluating the effects of L-carnitine supplementation on liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were included. Pooled effect size measured using random effect model (Dersimonian-Liard). RESULTS: A total of 16 studies (including 1025 participants) were included in the present meta-analysis. Pooled analysis indicated that L-carnitine supplementation significantly decreased ALT (weighted mean difference (WMD): -10.729 IU/L, 95% CI: -13.787, -7.672, p <0.001; I2 = 95.9%), AST (WMD: -7.149 IU/L, 95% CI: -9.202, -5.096, p <0.001; I2 = 93.5%) and GGT (WMD: -7.395: IU/L, 95% CI: -9.171, -5.619, p <0.001; I2 = 80.1%). Subgroup analysis revealed that effect of L-carnitine supplementation on liver enzymes was not significant in normal weight and healthy subjects. Baseline BMI and health status were the potential source of heterogeneity. CONCLUSION: L-carnitine supplementation showed beneficial hepato-protective effects on circulating liver enzymes.

Effects of garlic supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.

Current evidence on the beneficial effects of garlic on liver enzymes is contradictory. Therefore, the aim of this systematic review and meta-analysis is to evaluate the effect of garlic supplementation on human liver enzymes, such as Alanine Transaminase (ALT/SGPT) and Aspartate Transaminase (AST/SGOT). To collect the required data, PubMed, Scopus, ISI Web of Science, and Google scholar databases were systematically searched from inception to June 2019. A meta-analysis was conducted using the random-effects model to evaluate the effects of garlic supplementation on ALT and AST levels. The Cochran's Q-test and inconsistency index were also used to evaluate heterogeneity among the studies. Among a total of 15,514 identified articles, six studies (containing 301 participants) met the inclusion criteria. Results of the meta-analysis showed that garlic supplementation significantly decreased AST level (Hedges' g = -0.36, 95% confidence interval [CI]: -0.72, -0.004, p = .047); whereas, it had no significant effect on ALT level (Hedges' g = -0.22, 95% CI: -0.64, 0.20, p = .310). Results showed that garlic supplementation reduced AST levels significantly; however, had no significant effect on ALT levels. Further studies are still needed to confirm the results.

Effects of green tea or green tea catechin on liver enzymes in healthy individuals and people with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials.

The therapeutic potential of green tea as a rich source of antioxidants and anti-inflammatory compounds has been investigated by several studies. The present study aimed to systematically review and analyze randomized clinical trials (RCTs) assessing the effects of green tea, catechin, and other forms of green tea supplementation on levels of liver enzymes. PubMed, SCOPUS, EMBASE, and Cochrane databases were searched until February 2019. All RCTs investigating the effect of green tea or its catechin on liver enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin were included. A total of 15 RCTs were included. The overall effect of green tea on liver enzymes was nonsignificant (ALT [Standardized mean difference (SMD)= -0.17, CI -0.42 to 0.08, p = .19], AST [SMD = -0.07, CI -0.43 to 0.29, p = .69], and ALP [SMD = -0.17, CI -0.45 to 0.1, p = .22]). However, subgroup analyses showed that green tea reduced the levels of liver enzymes in participants with nonalcoholic fatty liver disease (NAFLD) but in healthy subjects, a small significant increase in liver enzymes was observed. In conclusion, the results of this study suggest that the effect of green tea on liver enzymes is dependent on the health status of individuals. While a moderate reducing effect was observed in patients with NAFLD, in healthy subjects, a small increasing effect was found.

Hepatoprotective and hematological effects of Justicia secunda Vahl leaves on carbon tetrachloride induced toxicity in rats.

Justicia secunda Vahl is an exotic plant that is used to treat medical problems. We investigated the hepatoprotective and hematological effects of aqueous extracts of J. secunda leaves on carbon tetrachloride induced toxicity in rats. Leaf extracts were prepared using hot and cold extraction methods to obtain a hot extract of J. secunda leaves (JSHAE) and a cold extract of J. secunda leaves (JSCAE). Total phenol and flavonoid measurements and antioxidant assays were performed to determine the extract with the greater antioxidant activity. JSHAE was the more effective extract for treatment of carbon tetrachloride (CCl4) induced hepatotoxicity and hepatotoxicity in rats. Silymarin was used as a standard for comparison. We found that JSHAE contained more total phenol and flavonoid than JSCAE. JSHAE exhibited significantly greater ferric reducing antioxidant power and 1,1-diphenyl-2-picryl hydrazyl and thiobarbituric acid scavenging activity than JSCAE. We also found that in vivo, 100 and 200 mg/kg JSHAE significantly reduced plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total bilirubin levels following CCl4 induced toxicity compared to untreated rats. JSHAE treated animals exhibited white blood cell, red blood cell, hemoglobin, hematocrit, platelet and procalcitonin levels that were comparable to control animals. Liver sections of rats treated with 200 mg/kg. JSHAE exhibited no abnormalities.

The effects of chronic oxytocin administration on body weight and food intake in DHT-induced PCOS model rats.

Polycystic ovary syndrome (PCOS) is commonly associated with metabolic disorders, which are exacerbated by obesity. Recent studies have revealed that oxytocin contributes to metabolic, appetite, and body weight regulation. In the present study, we evaluated the effects of chronic administration of oxytocin on body weight, food intake, and fat mass in a dihydrotestosterone-induced rat model of PCOS. Body weight, body weight change, and relative cumulative food intake were significantly lower in the oxytocin-treated PCOS rats than in the vehicle-treated control PCOS rats. Similarly, visceral adipocyte size was significantly smaller in the oxytocin-treated PCOS rats than in the vehicle-treated control PCOS rats. On the other hand, the numbers of cystic follicles in the ovary did not differ between the two groups. The chronic administration of oxytocin did not affect the rats' serum aspartate aminotransferase, alanine aminotransferase, or lactate dehydrogenase levels, indicating that it does not have adverse effects on hepatic function. These findings suggest that oxytocin could be a candidate drug for preventing the onset of obesity-related metabolic disorders in PCOS patients.

EPA plus DHA improves survival related to a decrease of injury after extended liver ischemia in Sprague-Dawley rats.

INTRODUCTION AND OBJECTIVES: The omega-3 fatty acids (ω3), EPA and DHA, have been described for their beneficial effects on metabolism and inflammation. In addition, they are interesting tools in the treatment of acute liver disease. This investigation was conducted to assess the effect of EPA+DHA administration before partial ischemia (IR) on survival and liver injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were supplemented for 7 days with ω3 [EPA (270mg/kg) and DHA (180mg/kg)]; controls received saline solution. After EPA+DHA supplementation, liver IR was induced by temporarily occluding the blood supply for 1h, followed up by 48h of reperfusion. Control animals were subjected to sham laparotomy. RESULTS: Previous to IR, the EPA+DHA administration improved the rate and prolonged the survival time by decreasing the AST and ALT levels and improving liver degenerative changes generated by the IR, which decreased TNF-α and IL-1ß. In addition, IL-10 increased at 20h with a tendency to normalize at 48h. The IR group had no differences in the IL-10 levels compared to controls. CONCLUSIONS: The ω3 supplementation could prevent and promote the restoration of the liver tissue and significantly improve the survival rate in rats at 48h.

The GLP-1 analog liraglutide attenuates acute liver injury in mice.

INTRODUCTION AND OBJECTIVES: Acute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective and curative potential of the glucagon-like peptide-1 analog liraglutide against carbon tetrachloride (CCl4)-induced hepatotoxicity. MATERIALS AND METHODS: Male Swiss mice were subjected to two protocols. The first protocol (Pretreatment) consisted of intraperitoneal (i.p.) treatment with liraglutide (0.057 and 0.118mgkg-1) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl4 (5mgkg-1, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl4 (5mgkg-1, i.p.) and subsequent treatment with liraglutide (0.057mgkg-1) or vehicle (distilled water) for 1 day. In both protocols, 24h after the last administration, blood and bile were collected from anesthetized animals, followed by euthanasia and liver collection. Plasma and bile underwent biochemical analyses, and histological, oxidative stress, and metabolic parameters were evaluated in the liver. RESULTS: Both liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl4, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl4 tended to reduce bile lipid excretion, but liraglutide did not influence this parameter. CONCLUSIONS: The present results demonstrated the hepatoprotective and therapeutic effects of liraglutide, which may be attributable to a decrease in liver oxidative stress and the preservation of metabolism. Liraglutide may have potential as a complementary therapy for acute liver injury.

Hepatotoxicity and renal toxicity induced by gamma-radiation and the modulatory protective effect of Ficus carica in male albino rats.

It is well-known that gamma radiation initiates generation of free radicals which prompting serious cellular damages in biological systems. In the present study, we investigated the role of Ficus carica, a natural antioxidant substance, in modulating changes in liver and kidney functions, antioxidant enzyme's gene expression, and apoptosis, in male albino rats exposed to gamma radiation. A total of 40 rats were used in this experiment and divided equally into 4 groups: Group 1, rats administered distilled H2O (Control); Group 2, rats administered F. carica; Group 3, rats irradiated; and Group 4, rats treated with F. carica and irradiated. Groups 3 and 4 were exposed to whole-body gamma radiations at a dose level of 8 Gy and with a dose rate of 0.762 Gy/min. F. carica was administered to rats by gavage, for 3 consecutive weeks, before exposure to radiation. Five rats were sacrificed from each group at intervals of 24 and 72 h after cessation of treatment. The results revealed marked increases in alanine aminotransferase and aspartate aminotransferase levels in liver, a decrease in albumin level and increase in urea level in kidney. Irradiation resulted in cytotoxic effects as indicated by elevation in antioxidant enzyme's gene expression at 24 h, the opposite was observed at 72 h. Immunohistochemical analysis revealed that cytochrome c and p53 expressions significantly increased following exposure to radiation. Oral administration of F. carica pre-irradiation as a natural product plays a modulatory protective and anti-apoptotic role against cells damaged by free radicals induced by whole-body irradiation.

Sufentanil Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury by Suppressing Inflammation.

BACKGROUND Inflammation is one of the most significant mechanisms of hepatic ischemia-reperfusion injury (IRI). Sufentanil has a protective effect against liver injury by reducing inflammatory response. In this study, we used a cellular hepatic ischemic/reoxygenated (IR) model to determine whether sufentanil preconditioning protects against hepatic IRI. MATERIAL AND METHODS The human normal liver cells line L-O2 was studied. The levels of glutamic oxaloacetic transaminase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), and superoxide dismutase (SOD) were measured using corresponding assay kits. The protein levels of total and phosphorylated ERK1/2, JNK, and p38, and the expression of p65 and COX2 genes, were measured by Western blotting. The levels of inflammatory factors were examined by ELISA. The Cell Counting Kit-8 (CCK-8) was used to determine if the viability of L-O2 cells was affected by sufentanil. The effects of sufentanil on IR-induced cell apoptosis were examined by flow cytometry. RESULTS IR-induced caused L-O2 cells to become rounded and to have a lower adhesive rate than normal cells. The levels of AST, LDH, and MDA were higher but the level of SOD was lower in the IR group than in the control group. The phosphorylated protein levels of ERK1/2, JNK, and p38, along with the expression of p65 and COX2, were upregulated in the IR group compared to the normal group. In addition, a variety of inflammatory factors were secreted in L-O2 cells after IR. The viability of L-O2 cells decreased and cell apoptosis increased significantly after IR treatment. All indexes of cell injury were reversed by sufentanil in a concentration-dependent manner. CONCLUSIONS Sufentanil stimulation triggers downregulation of inflammatory factors such as HIF-1alpha, TNF-alpha, IL-1ß, and IL-6, possibly through suppressing the p38/ERK/JNK/NF-kappaB-p65/COX2 pathways, and thereby reduces the damage to IR hepatic cells.

A possible biomarker of neurocytolysis in infantile gangliosidoses: aspartate transaminase.

Gangliosidoses (GM1 and GM2 gangliosidosis) are rare, autosomal recessive progressive neurodegenerative lysosomal storage disorders caused by defects in the degradation of glycosphingolipids. We aimed to investigate clinical, biochemical and molecular genetic spectrum of Turkish patients with infantile gangliosidoses and examined the potential role of serum aspartate transaminase levels as a biomarker. We confirmed the diagnosis of GM1 and GM2 gangliosidosis based on clinical findings with specific enzyme and/or molecular analyses. We retrospectively reviewed serum aspartate transaminase levels of patients with other biochemical parameters. Serum aspartate transaminase level was elevated in all GM1 and GM2 gangliosidosis patients in whom the test was performed, along with normal alanine transaminase. Aspartate transaminase can be a biochemical diagnostic clue for infantile gangliosidoses. It might be a simple but important biomarker for diagnosis, follow up, prognosis and monitoring of the response for the future therapies in these patients.

Dynamic Changes of the Aspartate Aminotransferase-to-Platelet Ratio and Transient Elastography in Predicting a Histologic Response in Patients With Chronic Hepatitis B After Entecavir Treatment.

OBJECTIVES: To evaluate the dynamic changes of the aspartate aminotransferase (AST)-to-platelet ratio and transient elastography (FibroScan; Echosens, Paris, France) in predicting a histologic response in patients with chronic hepatitis B (CHB) after entecavir treatment. METHODS: A total of 148 patients with CHB were enrolled. Patient information was collected. All patients received liver biopsy and FibroScan before and after 96 weeks of entecavir treatment. RESULTS: Baseline liver biopsy results showed that there were 7 patients without liver fibrosis (fibrosis stage F0; 4.7%), 51 patients with mild liver fibrosis (F1; 34.5%), and 90 patients with advanced liver fibrosis (>F1; 60.9%). The liver stiffness value and AST-to-platelet ratio increased significantly as the METAVIR score of the patients increased from F0 to F4 (P < .001). After antiviral therapy for 96 weeks, the average liver stiffness value measured by FibroScan and the AST-to-platelet ratio showed a significant decrease. When we use a decreased liver stiffness value to predict a histologic response, the area under the receiver operating characteristic curve was 0.70 (95% confidence interval, 0.61-0.79; P < .001), and the sensitivity and specificity were 74.3% and 68.8%, respectively. The decrease of the AST-to-platelet ratio also could predict the histologic response of patients with CHB; the area under the receiver operating characteristic curve was 0.77 (95% confidence interval, 0.69-0.86; P < .001) with sensitivity of 76.2% and specificity of 70.2%. A multivariate analysis indicated that a high hepatitis B virus DNA viral load (odds ratio, 1.44; P = .04) and high METAVIR score (odds ratio, 1.38; P = .02) were independent risk factors for the histologic response. CONCLUSIONS: Both the AST-to-platelet ratio and FibroScan value can effectively predict a histologic response in patients with CHB during entecavir treatment. Therefore, they can be used to monitor these patients during antiviral treatment to avoid multiple liver biopsies.

Effects of high-dose dexamethasone in postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.

This study was performed to investigate the effectiveness of dexamethasone in the management of postpartum women with class 1 haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. This retrospective study was conducted on 18 women with class 1 HELLP syndrome at the Shiga University of Medical Science. They were divided into two groups: Group A comprised participants who did not receive dexamethasone, and Group B comprised participants that intravenously received dexamethasone. The main outcomes were the serum laboratory values, mortality and morbidity. The only significant difference between the two groups in baseline characteristics was the aspartate aminotransferase levels. The linear regression analysis showed a significant difference between the two groups in the recovery of platelet counts (p = .046) and aspartate aminotransferase (p = .009). These findings support the use of high-dose dexamethasone to promote recovery of the platelet counts and aspartate aminotransferase levels in postpartum women with class 1 HELLP syndrome. Impact statement What is already known on this subject? Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is one of the most dangerous complications that can occur during pregnancy and is considered a particularly serious variant of severe preeclampsia. Several clinical trials have been performed since 1994 because it was expected that corticosteroid therapy, primarily with dexamethasone, accelerates recovery after delivery. However, the effect of dexamethasone therapy on class 1 HELLP syndrome is unclear. What do the results of this study add? In this retrospective study, we demonstrated that dexamethasone administration significantly improved the recovery of the platelet count in postpartum women with class 1 HELLP syndrome, and did not increase the rate of maternal postpartum complications. What are the implications of these findings for clinical practice and/or further research? The use of high-dose dexamethasone in postpartum women with class 1 HELLP syndrome might be effective to promote recovery of the platelet count, and contributes a shorter duration of hospitalisation. Because the number of patients with class 1 HELLP syndrome is small, it is important to confirm these findings with well-designed multicentre prospective studies.

Vitamin E protects against hepatocyte ultrastructural damage induced by high fat diet in a rat model of pre-diabetes / La vitamina E protege contra el daño ultraestructural de los hepatocitos inducido por la dieta alta en grasas en un modelo de pre-diabetes en ratas

SUMMARY: We sought to investigate the potential protective effect of Vitamin E supplementation against hepatocyte ultrastructural alterations induced by high fat diet (HFD) in a rat model of pre-diabetes. Therefore, rats were either fed with HFD (model group) or a standard laboratory chow (control group) for 12 weeks before being sacrificed. The protective group fed on a HFD and started the treatment with vitamin E (100 mg/kg/day, i.p) from day 1 until being sacrificed at week 12. The harvested liver tissues were examined using transmission electron microscopy (TEM) and blood samples were assayed for biomarkers of liver injury and prediabetes. TEM images showed that HFD induced profound pathological changes to the hepatocyte ultrastructure as demonstrated by degenerated hepatocytes with damaged cytoplasm that have mitochondrial swelling, dilation of endoplasmic reticulum, blebbing of plasma membranes, and cytoplasmic accumulations of lipid droplets and vacuoles, which were substantially but not completely protected with vitamin E. In addition, HFD significantly (p<0.05) augmented biomarkers of liver injury and pre-diabetes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C), which were significantly (p<0.05) reduced with vitamin E except TNF-α and TC. Furthermore, none of these biomarkers were reduced to the control level by vitamin E. We conclude that vitamin E is a partial protective agent against HFD-induced liver injury and pre-diabetes.

RESUMEN: El objetivo de este estudio fue investigar el posible efecto protector de la administración de suplementos de vitamina E contra las alteraciones ultraestructurales de los hepatocitos inducidas por una dieta rica en grasas (DRG) en un modelo de prediabetes en ratas. Antes de ser sacrificadas las ratas fueron alimentadas con DRG (grupo modelo) o un alimento estándar de laboratorio (grupo control) durante 12 semanas. El grupo protector se alimentó con una DRG y comenzó el tratamiento con vitamina E (100 mg/kg/día, i.p) desde el día 1 hasta sacrificarlo en la semana 12. Los tejidos hepáticos recolectados se examinaron mediante microscopía electrónica de transmisión (MET) y se tomaron muestras de sangre y se analizaron los biomarcadores de daño hepático y prediabetes. Las imágenes de MET mostraron que el DRG indujo cambios patológicos profundos en la ultraestructura de los hepatocitos, como lo demuestran los hepatocitos degenerados con citoplasma dañado e hinchazón mitocondrial, dilatación del retículo endoplasmático, formación de ampollas en las membranas plasmáticas y acumulaciones citoplásmicas de gotas de lípidos y vacuolas, los que fueron sustancialmente protegidas con vitamina E. Además, DRG aumentó significativamente (p <0,05) los biomarcadores de daño hepático y prediabetes como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), factor de necrosis tumoral alfa (TNF-α), malondialdehído (MDA), colesterol total (CT), triglicéridos (TG) y lipoproteína de colesterol de baja densidad (LDL-C), la cual se redujo significativamente (p <0,05) con vitamina E, excepto TNF-α y CT. Ninguno de estos biomarcadores se redujo al nivel de control por la vitamina E. Concluimos que la vitamina E es un agente protector parcial contra la lesión hepática inducida por DRG y la prediabetes.