Normal Serum Alanine Aminotransferase Research Articles

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000mg/kg/d of PFE for 2weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

Liver inflammation activity in patients with autoimmune hepatitis with normal alanine aminotransferase and immunoglobulin G levels

Background and aimsNormal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. MethodsTwo hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. ResultsOne hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045–1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138–2.014, P = 0.004) were independent factors associated with advanced inflammation. ConclusionsHigh proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

RDW Predicts Fibrosis in Patients with Chronic Hepatitis B Having Persistently Normal ALT Levels.

There are studies on the determination of hepatic fibrosis with noninvasive markers but data about liver biopsy results and noninvasive markers in patients with chronic hepatitis B (CHB) are limited. The aim of this study is to determine the relationship between pathological findings and noninvasive markers, and to determine the marker that predicts fibrosis in patients with consistently normal serum alanine aminotransferase (ALT) levels, diagnosed with CHB and undergoing liver biopsy. A total of 122 patients with CHB, 29 of them with HbeAg (+), aged 30 years and older, HBV DNA > 2000 IU / ml, and serum ALT levels measured four times in the last year, were consistently normal, and 93 of them with HbeAg (-) were included in the study. Demographic characteristics of patients, laboratory parameters, histological activity index (HAI) and fibrosis values obtained in liver biopsy, and noninvasive markers (AP (age-platelet) index, APRI (AST/Platelet ratio) and FIB-4 score, neutrophil/lymphocyte ratio, mean platelet volume (MPV) and erythrocyte distribution width (RDW) were recorded. The relationship between RDW value and fibrosis was statistically significant in the HbeAg (+) group (p<0.001). The relationship between AP index, APRI and FIB-4 score, neutrophil/lymphocyte ratio and MPV with fibrosis was not statistically significant (>0.05 for each). It has been shown that the RDW value can be used to predict fibrosis in CHB patients with normal ALT and HbeAg (+), and the cut-off value for RDW is 12.

Improved on-treatment fibrosis-4 during antiviral therapy and lower hepatocellular carcinoma risk in cirrhotic patients with hepatitis B

Normalization of serum alanine aminotransferase (ALT) levels is one of the goals of hepatitis B treatment. However, ALT levels in cirrhosis patients might be normal or mildly elevated regardless of ongoing inflammation. Therefore, we examined whether on-treatment ALT and other potential on-treatment indicators could be clinical surrogates of antiviral therapy in HBV-related cirrhosis. A total of 911 patients with HBV-related liver cirrhosis who started treatment with entecavir or tenofovir were analyzed. At 1 year of antiviral therapy, we evaluated ‘ALT normalization’, ‘undetectable serum HBV DNA’, ‘fibrosis-4 (FIB-4) index improvement’, and ‘serum HBeAg loss’ as potential biomarkers for HCC development. During 6.6 (3.8–10.2) years of follow-up, 222 patients (24.3%) newly developed HCC. Undetectable HBV DNA levels at 1 year were observed in 667 patients (73.2%), and the HCC incidence was significantly lower in this population (adjusted hazard ratio (HR) 0.66, 95% CI 0.50–0.87). Improvement of the FIB-4 index (< 3.25) was associated with a lower risk of HCC in 478 patients with an elevated FIB-4 index (adjusted HR 0.59, 95% CI 0.55–0.82). However, there was no significant difference in HCC risk between those with and without normalization of ALT levels (p = 0.39) among those with elevated ALT levels or between those with and without HBeAg seroconversion (p = 0.55) among HBeAg-positive patients. Therefore, on-treatment FIB-4 levels at 1 year are clinically useful surrogates of antiviral therapy for HBV-related cirrhosis patients.

The upper limit of normal for ALT in males according to AASLD guideline.

Dear Editor, I read with great interest the editorial paper by Oh and Sinn [1] entitled “Is liver biopsy mandatory to identify immunetolerant phase of chronic hepatitis B?” published online ahead of print. In their paper, Oh and Sinn [1] suggested that the status of patients presumed to be in the immune-tolerant phase without histological information should be carefully evaluated. I would like to draw attention to the following printing error related to the normal serum alanine aminotransferase (ALT) levels according to the American Association for the Study of Liver Disease (AASLD) guidelines. The recommended normal serum ALT level for males was incorrectly written as “&lt;33 U/L” in both the text and Table 1. However, according to the AASLD 2018 hepatitis B guidance [2], the upper limit of normal for ALT in males is 35 U/L. I believe that correcting this printing error will prevent any possible confusion in daily practice guiding management decisions.

Macrophage Depletion Reactivates Fecal Virus Shedding following Resolution of Acute Hepatitis A in Ifnar1-/- Mice.

Although hepatitis A virus (HAV) is associated only with acute hepatitis in humans, HAV RNA persists within the liver for months following resolution of liver inflammation and cessation of fecal virus shedding in chimpanzees and murine models of hepatitis A. Here, we confirm striking differences in the kinetics of HAV RNA clearance from liver versus serum and feces in infected Ifnar1-/- mice and investigate the nature of viral RNA persisting in the liver following normalization of serum alanine aminotransferase (ALT) levels. Fecal shedding of virus produced in hepatocytes declined >3,000-fold between its peak at day 14 and day 126, whereas intrahepatic HAV RNA declined only 32-fold by day 154. Viral RNA was identified within hepatocytes 3 to 4 months after inoculation and was associated with membranes, banding between 1.07 and 1.14 g/cm3 in isopycnic iodixanol gradients. Gradient fractions containing HAV RNA demonstrated no infectivity when inoculated into naive mice but contained neutralizing anti-HAV antibody. Depleting CD4+ or CD8+ T cells at this late point in infection had no effect on viral RNA abundance in the liver, whereas clodronate-liposome depletion of macrophages between days 110 and 120 postinoculation resulted in a striking recrudescence of fecal virus shedding and the reappearance of viral RNA in serum coupled with reductions in intra-hepatic Ifnγ, Tnfα, Ccl5, and other chemokine transcripts. Our data suggest that replication-competent HAV RNA persists for months within the liver in the presence of neutralizing antibody following resolution of acute hepatitis in Ifnar1-/- mice and that macrophages play a key role in viral control late in infection. IMPORTANCE HAV RNA persists in the liver of infected chimpanzees and interferon receptor-deficient Ifnar1-/- mice for many months after neutralizing antibodies appear, virus has been cleared from the blood, and fecal virus shedding has terminated. Here, we show this viral RNA is located within hepatocytes and that the depletion of macrophages months after the resolution of hepatic inflammation restores fecal virus shedding and circulating viral RNA. Our study identifies an important role for macrophages in virus control following resolution of acute hepatitis A in Ifnar1-/- mice and may have relevance to relapsing hepatitis A in humans.

Clinically Meaningful Body Mass Index Change Impacts Pediatric Nonalcoholic Fatty Liver Disease

To investigate the prevalence and characteristics of children with nonalcoholic fatty liver disease (NAFLD) who reduce their body mass index (BMI) z-score (BMIz) by >.25, a goal in obesity medicine, and to determine the BMIz decrease needed for serum aminotransferase normalization. This retrospective, single-center study included patients aged <18years followed for NAFLD. Patients who had undergone weight loss surgery or had other reasons for weight loss/gain were excluded. Logistic regression was used to determine the odds of achieving a BMIz change of >-.25, as well as predictors of this outcome. Of the 784 children who met the study criteria (median age, 13years; 66% male; 24% Hispanic), 541 had a lowest BMIz at >90days following the baseline clinic visit. Of these children, 168 (31%) had a BMIz change of >-.25 from baseline over a median of 367days (IQR, 201-678days). Decreases in serum aminotransferase and lipid levels were seen in both groups (with and without a BMIz change of >-.25); however, these decreases were more pronounced in children who achieved a BMIz drop of >.25. Hemoglobin A1c concentration did not change in either group. Young age (OR, .861; 95% CI, .81-.92; P<.01) and non-Hispanic ethnicity (OR of non-Hispanic vs Hispanic, .61; 95% CI, .38-.97; P<.04) were predictors of a BMIz change>-.25. The BMIz decrease associated with normalization of serum alanine aminotransferase was .27. A BMIz reduction of >.25 is associated with significant changes in serum aminotransferase levels. These findings can further guide the clinical management of children with NAFLD.

A Novel Non-Invasive Approach Based on Serum Ceruloplasmin for Identifying Non-Alcoholic Steatohepatitis Patients in the Non-Diabetic Population.

Background and AimFew non-invasive models were established to identify patients with non-alcoholic steatohepatitis (NASH). Liver biopsy remains the gold standard in the clinic. Decreased serum ceruloplasmin (CP) is reported in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to develop a non-invasive model incorporating CP for identifying NASH from NAFLD without type 2 diabetes mellitus (T2DM).MethodsA total of 138 biopsy-proven patients with NAFLD without T2DM were enrolled. The CP ratio was calculated for standardization as the CP value divided by the lower limit of normal. The clinical, anthropometric, biochemical, and histological parameters were compared between the low and high CP ratio groups divided by the median value. Multivariate logistic regression analysis was performed to develop a model for identifying NASH in patients with NAFLD.ResultsThe medians of the high (n = 69) and low (n = 69) CP ratio groups were 1.43 (1.28–1.61) and 1.03 (0.94–1.12), respectively. A comparison of the two groups showed that the severity of steatosis, hepatocellular ballooning, inflammation activity, fibrosis, and liver iron deposition decreased along with the CP ratio (p < 0.05). The median CP ratio of patients with NASH was significantly lower than those with NAFL [1.15 (1.01–1.41) vs. 1.33 (1.24–1.54), p = 0.001]. A novel model which consists of the CP ratio, BMI, and aspartate aminotransferase (AST) was developed. The AUCs of the model in discriminating NASH from NAFLD was 0.796 (0.694–0.899) and 0.849 (0.713–0.984) in the training and validation groups, and 0.836 (0.659–1.000), 0.833 (0.705–0.962), and 0.821 (0.612–1.000) in patients with normal serum alanine aminotransferase, AST, and both levels, respectively.ConclusionsDecreased CP ratio is associated with more severe histological activity, a diagnosis of NASH, and hepatic iron deposition among patients with NAFLD without T2DM. The CP ratio model could be served as a non-invasive approach to identifying patients with NASH, which might reduce the need for liver biopsy.

Innate-like bystander-activated CD38+ HLA-DR+ CD8+ T cells play a pathogenic role in patients with chronic hepatitis C.

HCV-specific T cells are few and exhausted in patients with chronic hepatitis C (CHC). Whether these T cells are responsible for the liver damage and fibrosis is still debated. However, cluster of differentiation 38-positive (CD38+ ) human leukocyte antigen DR-positive (HLA-DR+ ) CD8+ T cells are regarded as bystander CD8+ T cells that cause liver injury in acute hepatitis. We propose that these innate CD8+ T cells play a pathogenic role in CHC. Lymphocytes from peripheral blood were obtained from 108 patients with CHC and 43 healthy subjects. Immunophenotyping, functional assays, T-cell receptor (TCR) repertoire, and cytotoxic assay of CD38+ HLA-DR+ CD8+ T cells were studied. The percentage of CD38+ HLA-DR+ CD8+ T cells increased significantly in patients with CHC. These cells expressed higher levels of effector memory and proinflammatory chemokine molecules and showed higher interferon-γ production than CD38- HLA-DR- CD8 T cells. They were largely composed of non-HCV-specific CD8+ T cells as assessed by HLA-A2-restricted pentamers and next-generation sequencing analysis of the TCR repertoire. In addition, these CD38+ HLA-DR+ CD8+ T cells had strong cytotoxicity, which could be inhibited by anti-DNAX accessory molecule 1, anti-NKG2 family member D, and anti-natural killer NKp30 antibodies. Lastly, the percentage of CD38+ HLA-DR+ CD8+ T cells was significantly associated with liver injury and fibrosis and decreased significantly along with serum alanine aminotransferase normalization after successful direct-acting antiviral treatment. The TCR-independent, cytokine-responsive bystander CD38+ HLA-DR+ CD8+ T cells are strongly cytotoxic and play a pathogenic role in patients with CHC.

Upper limit of normal serum alanine transaminase ALT and correlation with gender and BMI

Alanine transaminase ALT is considered the most specific marker for hepatocellular membrane damage, once asymptomatic ALT elevation may be the only indicator of some liver diseases such as non-alcoholic fatty liver disease NAFLD which is the most common liver disease in the western world, so it is necessary to define upper limit of normal ULN of ALT accurately to differentiate healthy and asymptomatic patients, many studies were made to evaluate ULN of ALT in different countries, all of which recommended that ULN of ALT should be lower than current reference values with presence of difference between males and females.

Effect of liver steatosis on liver stiffness measurement in chronic hepatitis B patients with normal serum alanine aminotransferase levels: A multicentre cohort study.

Liver steatosis is becoming increasingly common in patients with chronic hepatitis B (CHB), and its effect on liver stiffness measurement (LSM), as assessed by transient elastography, remains controversial. Seven hundred and fifty-five patients with CHB and normal serum alanine aminotransferase levels, who underwent vibration-controlled transient elastography and liver biopsy, were included in the study. We examined whether the histological degree of liver steatosis affects the accuracy of transient elastography-assessed LSM in these patients. Among the 755 CHB patients included in the study, 286 (37.9%) had liver steatosis, of whom 156had grade S1, 74had grade S2, and 56had grade S3 on histology. Presence of liver steatosis was independently associated with greater body mass index (BMI, adjusted-odds ratio [OR]=5.786, 95% CI: 3.998-8.373, p=0.018), and higher serum total cholesterol (adjusted-OR=7.944, 95% CI: 4.731-13.339, p<0.001) and triglyceride levels (adjusted-OR=2.777, 95% CI: 2.050-3.761, p<0.001). There was no significant association between liver steatosis and fibrosis stage (OR=1.016, 95% CI: 0.905-1.140, p=0.790). Age (B-coefficient = 0.020, 95% CI: 0.001-0.040, p=0.044), BMI (B-coefficient=0.060, 95% CI: 0.011-0.127, p=0.019), serum gamma-glutamyl-transpeptidase (GGT, B-coefficient=0.015, 95% CI: 0.001-0.029, p=0.032), positivity for HBeAg (B-coefficient=-0.816, 95% CI: -1.568 to -0.064, p=0.034), as well as liver fibrosis stage (B-coefficient=2.796, 95% CI: 2.501-3.090, p<0.001), and inflammation activity grade (B-coefficient=0.648, 95% CI: 0.162-1.135, p=0.009) were all independently associated with higher LSM, while no significant association was found between degree of liver steatosis and LSM. Among patients with the same histological fibrosis stage, LSM values did not show any significant difference among patients with absent, mild, moderate or severe steatosis. We conclude that liver steatosis has no significant effect on transient elastography-measured LSM in CHB patients with normal serum alanine aminotransferase levels.

Antidiabetic and Hepatoprotective Effects of an Aqueous Extract of Rauwolfia Vomitoria (Apocynaceae) Roots Barkless on Alloxan-Induced Diabetic Rats

In Côte d'Ivoire, people use Rauwolfia vomitoria (Apocynaceae) as traditional medicine for the treatment of diabetes mellitus. The purpose of this study is to bring out the potentiel antidiabetic effect of an aqueous extract of roots devoid of Rauwolfia vomitoria bark (EARv), in rats made diabetic by alloxan monohydrate, a diabetogen substance, compared with the effect of glibenclamide, a reference antidiabetic substance. For this, the blood glucose level and weight evolution of healthy rats (normoglycemic), diabetic control rats and diabetic rats treated with EARv or glibenclamide are measured, as well as variations in transaminase levels during 28 days of experimentation. Administration of alloxan induces in rats made diabetic characterized by a significant and permanent increase in blood sugar, a decrease in body mass, followed by an increase in the level of serum transaminases, a sign of liver toxicity in rats. In rats made diabetic and treated daily with EARv at a dose of 1000 mg/kg body weight (B.W), there is a decrease in blood sugar and an increase in body mass, in the sense of their normalization, during the 28 days of treatment. In diabetes rats, EARv also results in normalization of serum alanine aminotransferase (ALT) concentration and a significant decrease in aspartate aminotransferase (AST). These effects of EARv at 1000 mg/kg B.W are similar to those of glibenclamide at 10 mg/kg B.W. These results show that, just like glibenclamide, EARv is an antidiabetic, hepatoprotective substance and tends to correct body mass loss in diabetic rats. These effects of EARv justify the use of Rauwolfia vomitoria in traditional medicine in the treatment of diabetes mellitus.

Gamma-glutamyl transpeptidase elevation is associated with metabolic syndrome, hepatic steatosis, and fibrosis in patients with nonalcoholic fatty liver disease: A community-based cross-sectional study.

This study aimed to analyze the association between elevated gamma-glutamyl transpeptidase (GGT) and metabolic syndrome (MetS), hepatic steatosis, and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). From August 2013 to August 2018, a community-based study was conducted in the northeastern part of Taiwan. Patients who underwent abdominal ultrasonography (US) and had no history of alcoholic liver disease were included. According to a US examination showing fatty liver degree, 1566 patients with NAFLD were divided into four groups: normal GGT, isolated GGT elevation, isolated alanine aminotransferase (ALT) elevation, and both GGT and ALT elevation groups. Further 1147 participants with normal serum ALT, GGT, and the abdominal US were included as the control group. GGT levels were associated with high sensitivity C-reactive protein, lower adiponectin, diabetes mellitus, and chronic kidney disease. A stepwise increase in odds ratio (OR) for MetS was found in the normal GGT group (OR=1.71), isolated GGT elevation group (OR=3.06), isolated ALT elevation (OR=4.00), and both GGT + ALT elevation group (OR=4.17) than the control group. Linear regression analysis revealed a positive association between GGT/ALT value and hepatic steatosis degree, GGT value, and degree of hepatic fibrosis. Hence, GGT elevation is associated with MetS, hepatic steatosis, and fibrosis in patients with NAFLD.

Comparison of Clinical Characteristics Between Obese and Non-Obese Patients with Nonalcoholic Fatty Liver Disease (NAFLD).

ObjectiveNon-alcoholic fatty liver disease (NAFLD), previously thought to predominantly affect obese individuals, has also been shown to occur in subjects who have a relatively normal body mass index (BMI). Due to the normal BMI, non-obese NAFLD are easily to be ignored and eventually lead to potential liver injuries.MethodsA population-based cross-sectional study was conducted on 1608 cases with normal serum alanine aminotransferase (ALT) levels who were divided into an obese group (BMI ≥25 kg/m2) and a non-obese group (BMI <25 kg/m2). NAFLD was diagnosed by ultrasound and Fibro Scan examination. Non-obese populations were divided into NAFLD group (CAP ≥240 db/m) and non-NAFLD group (CAP <240 db/m). The incidence of NAFLD in the obese and non-obese populations and constituent ratios of genders, age, and serum levels of triglycerides (TG), cholesterol (CHOL), and blood glucose were compared. Risk factors of NAFLD in non-obese people were analyzed by multivariate logistics regression.ResultsThe occurrence of NAFLD was higher in the obese group than in the non-obese group, regardless of gender (P <0.001). In the non-obese group, the occurrence of NAFLD in female patients was lower than that in male (P=0.001). The occurrence of NAFLD increased with age, with 50–59 years being the peak age of incidence in both male and female. The peak age of NAFLD occurrence in non-obese male patients was more delayed than that in obese male patients. BMI (OR=1.311, P=0.000) and TG (OR=2.545, P=0.000) were risk factors for NAFLD in the non-obese population.ConclusionCompared with obese population, the incidence of NAFLD in non-obese population was relatively low and more frequently in male than in female, the peak age of NAFLD occurrence in non-obese male patients was also delayed. BMI and TG should still be controlled to avoid the occurrence of NAFLD although the BMI of such patients is normal.

Fish protein intake is a novel dietary approach for managing diabetes-associated complications in diabetic Wistar rat model.

Diabetes mellitus is a metabolic disorder associated with short term as well as long‐term undesirable complications caused by persistent hyperglycemia. Recently, there has been emerging evidence that natural foods and their bioactive compounds are the key contributors to the treatment of diabetes and associated complications. This study was designed to explore the therapeutic efficacy of a fish protein‐rich diet for managing diabetes and associated complications in the diabetic Wistar rat model. A high‐protein (HP) diet (45% and 55% fish protein rich in ω3 fatty acids) was given to alloxan‐induced diabetic rats for 28 days. Blood samples were collected for monitoring serum glucose, oxidative stress markers, lipid profile, kidney function markers, serum proteins, and liver function markers. Results indicated that there was a noteworthy control (p < .05) of serum glucose, oxidative stress, and lipid profile in HP diet treated diabetic rats. Treatment with 45% and 55% fish diet appreciably improved the concentration of serum creatinine, urea, uric acid and exhibited a vibrant improvement in renal functions. Our results confirmed that the HP diet restored total protein and albumin concentration in blood. The HP diet treatment also restored the normal serum aspartate transaminase and alanine aminotransferase concentration.

THU034 - A substantial number of patients with non-alcoholic fatty liver disease and type 2 diabetes have advanced liver fibrosis with a normal serum alanine transaminase

THU034 - A substantial number of patients with non-alcoholic fatty liver disease and type 2 diabetes have advanced liver fibrosis with a normal serum alanine transaminase

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients.

BACKGROUNDThe presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals.AIMTo examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.METHODSTwo hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models.RESULTSSerum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn’s score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.CONCLUSIONCPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.

Protective Effect of N-Acetyl Cysteine on Moringa Oleifera Aqueous Leaf Extract-Induced Hepatic Toxicity in Wistar Albino Rats

Background: Moringa oleifera (M. oleifera) is a commonly used medicinal and nutritive plant. The aqueous leaf extract from this plant contains a high concentration of alkaloids and they are toxic to body organs especially the liver leading to hepatotoxicity after long term exposure. However, if N-Acetyl cysteine (NAC) is administered together with M. oleifera extract, it may have a hepatotoxic protective effect.&#x0D; Objective: To establish the protective effect of N-Acetyl cysteine against M. oleifera aqueous leaf extract-induced hepatotoxicity in the Wistar albino rats.&#x0D; Methods: An experimental laboratory-based study conducted at department of Physiology Makerere University, College of Health Sciences. Three treatment groups of six Wistar albino rats each, were dosed intragastrically once a day for 28 days. Group I; negative control, received 8.05g/kg bwt of M. oleifera extract plus 1ml of normal saline (NS), Group II; test group, received 8.05g/kg bwt of M. oleifera extract plus 50mg/kg of NAC. Group III; positive control, received 750mg/kg bwt of Paracetamol plus 50mg/kg of NAC. On the 14th and 29th day, three animals selected randomly from each group were sacrificed; blood samples were collected, the liver was harvested for histopathological analysis. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and total protein levels were determined.&#x0D; Results: There was an increase in serum ALT, AST and ALP levels in the M. oleifera extract plus NS group which was a sign of hepatotoxicity. The M. oleifera extract plus NAC group showed normal serum ALT, AST and ALP levels with no significant changes in the bilirubin (P-value = 0.9089) and total protein levels (P-value = 0.8858).&#x0D; Conclusion: The results have provided evidence that NAC administration with M. oleifera extract effectively prevents the occurrence of M. oleifera leaves xtract- induced hepatotoxicity.&#x0D;

The Serum Mac-2-binding Protein Glycosylation Isomer Dynamics in Acute Liver Injury.

Objective We aimed to examine the dynamics of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with acute liver injury. Methods Serum M2BPGi levels at the time of the diagnosis (n=77) and normalization of the serum alanine aminotransferase (ALT) level (n=26) were examined retrospectively. The difference in the serum M2BPGi level according to the etiology, and the correlations with other laboratory parameters were evaluated. Results The serum M2BPGi level at the time of the diagnosis was increased in 59 of 77 patients [2.3 cutoff index (COI); range, 0.31-11.1 COI] and was significantly decreased at the time of serum ALT normalization (0.68 COI; range, 0.15-1.87 COI; p<0.0001). The serum M2BPGi level was positively correlated with the duration for which serum ALT normalization was achieved (n=46, Spearman rho=0.53, p<0.0001). A multivariate analysis identified total bilirubin (T-bil), albumin, ALT, alkaline phosphatase, and etiology (e.g., drug-induced liver injury or etiology unknown) as independent factors for increased serum M2BPGi. In patients with infectious mononucleosis, the serum M2BPGi level was higher relative to the degree of increase of serum ALT or T-bil levels in comparison to other etiologies. Conclusion The serum M2BPGi level in patients with acute liver injury reflects the magnitude and duration of liver injury. However, it should be noted that the degree of increase of serum M2BPGi in patients with acute liver injury may differ according to the etiology.