Normal Serum Alanine Aminotransferase Levels Research Articles

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.

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.

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.

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.

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.

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;

Determination of the upper limits of normal serum alanine aminotransferase (ALT) level in healthy Turkish population.

Background and AimRecent studies have reported that the widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN<40U/L) is high for the healthy population. We aimed to find the correct ULN level for men and women in a presumed healthy liver population group.Materials and MethodsThe data of 7410 healthy subjects visiting the check-up clinics were retrospectively analysed in this study. Patients were divided in to “healthy liver group” (n=2694) and “high-risk liver group” (n=4716) based on fatty liver on ultrasound, existing of chronic liver disease, ongoing significant alcohol consumption, diabetes mellitus and dyslipidaemia. Receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) was calculated at the 95th percentiles for both men and women.ResultsThe AUC score of ALT for men was 0.92, and the ULN for the serum ALT in men was found as 32.10 U/L (sensitivity of 0.89, specificity 0.85). The AUC score of ALT for women was 0.90, and the ULN for serum ALT was found as 23.15 U/L (sensitivity of 0.90, the specificity of 0.88).ConclusionULN for serum ALT level should be lowered and different cut-off values should be used for men (32.10 U/L) and women (23.15 U/L).

Mechanism of Cinnamomi Ramulus improving rat model of intrahepatic cholestasis induced by ANIT by regulating FXR pathway

To study the mechanism and action of Cinnamomi Ramulus in ameliorating intrahepatic cholestasis induced by α-isothiocyanate( ANIT) in rats by regulating FXR pathway. Forty SD rats were randomly divided into normal group,model group,positive control( ursodeoxycholic acid) group( 60 mg·kg~(-1)),Cinnamomi Ramulus treatment( 60 mg·kg~(-1)·d~(-1)) group,and Cinnamomi Ramulus treatment( 20 mg·kg~(-1)·d~(-1)) group,with 8 rats in each group. Except for the normal control group,the other groups were intragastrically administered with the corresponding concentrations of continuous aqueous solution( 0. 005 m L·g~(-1)),once a day,for 7 days.Except for the normal group,the other groups were treated with ANIT( 100 mg·kg~(-1)),once a day,for 3 days. Blood was taken from the abdominal aorta 24 hours after the last administration,and serum alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBi L),and total bile acid( TBA) were measured. 1. 5-2 cm of rat liver tissue was taken. After fixation with10% formaldehyde,paraffin-embedded sections were taken,HE staining was performed,and immunohistochemistry( IHC) was used to analyze the expression of FXR. RNA and protein were extracted from rat liver tissue to detect FXR mRNA expression,as well as bile acid synthesis and detoxification,transport related SHP,UGT2 B4,BSEP protein expressions at downstream of FXR. Compared with the normal group,serum ALT,AST,TBi L,and TBA levels were elevated in the model group( P<0. 01),liver damage was severe,FXR protein's optical density decreased,FXR mRNA expression decreased,and SHP,UGT2 B4,BSEP protein expressions were decreased( P<0. 05,P<0. 01). Compared with the model group,the drug group could reduce serum ALT,AST,TB,TBA levels to different degrees( P<0. 05,P<0. 01),alleviate liver tissue damage,increase the optical density of FXR protein,and promote the expressions of FXR mRNA and FXR,SHP,BSEP and UGT2 B4 proteins( P<0. 05,P<0. 01). Cinnamomi Ramulus can alleviate ANIT-induced intrahepatic cholestasis,and reduce hepatocyte injury and serum ALT,AST,TBi L and TBA levels. The mechanism may be through FXR-SHP,FXR-UGT2 B4,FXR-BSEP signaling pathways. Therefore,in the pathogenesis of intrahepatic cholestasis,we can try to further explore in alleviating intrahepatic cholestasis with Cinnamomi Ramulus,so as to provide effective drugs for clinical treatment of intrahepatic cholestasis.

Determination of the predictive factors for significant liver fibrosis assessed through transient elastography

Several studies have reported the accuracy of transient elastography (TE), a noninvasive, reproducible, and reliable method for predicting liver fibrosis. This study evaluated the predictive factors associated with significant liver fibrosis assessed through TE. This study enrolled 1799 consecutive patients who underwent TE at Taipei Medical University Hospital between February 2014 and June 2015, including 810 patients with normal serum alanine aminotransferase (ALT) levels (&lt;40 U/L). We evaluated the risk factors for significant liver fibrosis (liver stiffness measurement [LSM] &gt; 7 kPa) assessed through TE and compared the results with those of the aspartate aminotransferase (AST)/platelet ratio index (APRI), a validated serum marker of liver fibrosis, in 672 patients with detailed laboratory data. Significant liver fibrosis was defined as an APRI score of &gt;0.7. Significant liver fibrosis was detected through TE in 103 (12.7%) of 810 patients with normal serum ALT levels and in 91 (19.4%), 17 (18.7%), and 13 (5.8%) patients with chronic hepatitis B, chronic hepatitis C, and nonalcoholic fatty liver disease, respectively. Univariate analysis of patients with detailed biochemical test data showed that compared with without significant fibrosis, patients with significant fibrosis in the LSM &gt; 7 kPa group were older; had higher body mass index (BMI) values; had higher fasting glucose, ALT, AST, total bilirubin, gamma‐glutamyltransferase, and ferritin levels; had higher APRI and fibrosis index based on four factors scores; had lower serum albumin levels and platelet counts; and higher rates of hypertension, diabetes, hepatitis C virus (HCV) positivity, splenomegaly, and hepatocellular carcinoma than those without significant fibrosis. Multivariate analysis disclosed that high BMI (P &lt; 0.001), high AST levels (P = 0.006), low platelet counts (P &lt; 0.001), and low albumin levels (P = 0.008) were the independent factors associated with significant liver fibrosis. In patients with normal serum ALT levels, the factors determining significant liver fibrosis were high BMI (P &lt; 0.001), high AST levels (P &lt; 0.001), low platelet counts (P = 0.001), and anti‐HCV positive (P = 0.006). LSM exhibited a moderate correlation with APRI scores (R2 = 0.325, P &lt; 0.001). Among patients with normal serum ALT levels, the percentage of significant liver fibrosis defined as LSM &gt; 7 kPa (11.2%) was higher than that of significant liver fibrosis defined as APRI &gt; 0.7 (2.6%) (P &lt; 0.001). Significant liver fibrosis is not uncommon in patients with chronic hepatitis and normal serum ALT levels. TE is a reliable method for assessing the degree of liver fibrosis. High BMI values, high AST levels, low platelet counts, and low albumin levels are correlated with the diagnosis of significant liver fibrosis through TE.

Correlation between normal range of serum alanine aminotransferase level and metabolic syndrome: A community-based study.

Serum alanine aminotransferase (ALT) is a biomarker of hepatocyte damage. However, the relationship between normal range of serum ALT level and metabolic syndrome (MetS) has not been completely understood. This study aimed to investigate the correlation between normal range of serum ALT level and MetS.A total of 2453 participants from the Beijing Community Pre-Diabetes study were enrolled. Multiple linear regression analysis was performed to calculate the regression coefficient. Normal serum ALT levels were divided into quartiles. Logistic regression model was used to compare the relative risk of MetS, and the receiver operating characteristic (ROC) curve to calculate the optimal ALT boundary value for predicting MetS.The frequency of MetS increased with the ALT level within the normal range. Compared with the first group, the risk of MetS was greater in the other quartiles of ALT level in males, the difference was significant for the fourth group. For females, the risk of MetS increased with ALT level within the normal range as well, with all differences showing statistical significance. The optimal ALT boundary value of the ROC curve for males and females was 24.5 and 14.5 U/L, respectively.ALT was related to metabolic factors and used as one of the indicators to assess the morbidity risk of metabolic diseases.

Clinicopathological features of He Shou Wu-induced liver injury: This ancient anti-aging therapy is not liver-friendly.

Polygonum Multiflorum Thumb (PMT), an ancient anti-aging Chinese herb known traditionally as He Shou Wu, has side effects of liver toxicity. To determine the main clinical and pathological characteristics of liver toxicity induced by PMT and the clinical course after its cessation. Data of patients, diagnosed as drug-induced liver injury and hospitalised in Beijing Friendship Hospital from August 2005 to August 2017, were retrospectively reviewed. Clinical, pathological data and outcome after cessation of He Shou Wu were obtained and analysed. Kruskal-Wallis and Chi-square (χ2 ) tests were performed. Twenty-nine patients with He Shou Wu-induced liver injury were enrolled. The median age was 53years (range 15-74) and 75.9% (22/29) were women. The most common symptom was jaundice (79.3%, 23/29). Of nine patients with liver biopsies, six showed acute cholestatic hepatitis, two acute, and one chronic hepatocellular injury pattern. The latency, liver chemistries and outcomes were comparable between pure He Shou Wu (5 patients) and its compounds (24 patients). Twenty-five of 29 patients (86.2%) had normal serum alanine aminotransferase levels after 45days (range: 10-138days) and total bilirubin of 46days (range: 0-551days). One patient was rechallenged with He Shou Wu and two developed autoimmune features. One patient died of liver failure and three had chronic persistent liver injury. The main clinicopathological injury pattern of He Shou Wu-induced liver injury is moderate to severe hepatitis with or without cholestasis. Most patients recover completely; however, chronic disease and death do occur.

Evaluation of some available HCV antibody detection tests (ELISA, Chemiluminescence, Immune Assay) and RT-PCR assay in the diagnosis of Hepatitis C virus infection

Background: The purpose of diagnosis of viral infection is to allow the infected persons to be identified & treated and to prevent blood-transfusion infection. Majority of primary HCV-infected patients are asymptomatic, thus, symptoms could not be used as specific indicators for HCV infection. HCV viremia could still exist despite a normal serum alanine aminotransferase (ALT) level. Therefore, virological methods rather than ALT levels are used to diagnose HCV infection. The diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies by the enzyme immunoassay(EIA) or Chemiluminescence immunoassay (CIA) of serum samples. These anti-HCV assays are used as a screening test, while PCR is essential for detection of screening test falsity. The presence of HCV-RNA in the serum is a reliable marker of viremia. Universal standardization for HCV-RNA titer is important for diagnosis and follow up. Objective: This study aimed to evaluate the commercially available antibody tests for diagnosis of hepatitis c virus infection in comparison to RT-PCR in Egyptian blood donors. Materials and Methods: This study Included 456 serum samples from blood donor at Al-Hussien hospital blood bank (Al-Azhar University, Cairo) from June 2016 to June 2018. Serum samples subjected to routine laboratory tests (CBC, liver and renal function) to exclude organs affection. Also they are subjected to HCV antibody detection by ELISA and Chemiluminescence tests and HCV–RNA detection by RT-PCR assay. Results: We considered PCR as a standard test to evaluate ELISA and Chemiluminescence. The detected percentage of infectivity of donors in this study was 9% by ELISA, 13% by Chemiluminescence and 8 % by PCR. The percentage of false negativity of HCV antibody by ELISA and CIA when compared with PCR assay were 0.96% and 1.5% respectively. The false positivity of HCV –Ab by ELISA and CIA as compared PCR was 14-6% (6 out of 41) and 26.6% (16 out of 60). Conclusion: Generally, ELISA is more sensitive and specific than Chemiluminescence for blood transfusion screening. But, at gray zone results, PCR should be used as confirmatory method. And so it is very important to screen blood donors using RT–PCR to avoid false positive and false negative results.

Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend.

The natural history of chronic hepatitis B (CHB) is complex and may run through different immune phases that may overlap. In particulars, the immune-tolerant phase is the most interesting and not as well understood as we thought. The concept of true immune tolerance have been under challenged from immunology points of view. The major international guidelines have not yet reached a consensus on the definition of the immune-tolerant phase. While positive hepatitis B e antigen (HBeAg), high serum hepatitis B virus (HBV) DNA and normal serum alanine aminotransferase (ALT) levels are the three key features of this phase, some guidelines also put age into consideration. A new nomenclature, Phase 1 or HBeAg-positive chronic HBV infection, is given by the latest European Association for the Study of the Liver (EASL) published in April 2017. While current guidelines advise against starting antiviral treatment for immune-tolerant CHB patients, some new data suggest treating such patients may reduce the risk of liver fibrosis progression and hepatocellular carcinoma.

Effectiveness of Ipragliflozin, a Sodium-Glucose Co-transporter 2 Inhibitor, as a Second-line Treatment for Non-Alcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Who Do Not Respond to Incretin-Based Therapies Including Glucagon-like Peptide-1 Analogs and Dipeptidyl Peptidase-4 Inhibitors.

We previously reported that incretin-based drugs, such as dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) analogs, improved glycemic control and liver inflammation in non-alcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM). However, the effect on alanine aminotransferase (ALT) normalization was still limited. The aim of this study is to elucidate the effectiveness of sodium-glucose co-transporter 2 (SGLT-2) inhibitors as second-line treatments for NAFLD patients with T2DM who do not respond to incretin-based therapy. We retrospectively enrolled 130 consecutive Japanese NAFLD patients with T2DM who were treated with GLP-1 analogs or DPP-4 inhibitors. Among them, 70 patients (53.8%) had normal ALT levels. Of the remaining 60 patients (46.2%) who did not have normal ALT levels, 24 (40.0%) were enrolled in our study and were administered SGLT-2 inhibitors in addition to GLP-1 analogs or DPP-4 inhibitors. We compared changes in laboratory data including ALT levels and body weight at the end of the follow-up. Thirteen patients were administered a combination of SGLT-2 inhibitors with DPP-4 inhibitors, and the remaining 11 patients were administered a combination of SGLT-2 inhibitors with GLP-1 analogs. The median dosing period was 320days. At the end of the follow-up, body weight (from 84.8 to 81.7kg, p<0.01) and glycosylated hemoglobin levels (from 8.4 to 7.6%, p<0.01) decreased significantly. Serum ALT levels also decreased significantly (from 62 to 38IU/L, p<0.01) with an improvement in the FIB-4 index (from 1.75 to 1.39, p=0.04). Finally, 14 patients (58.3%) achieved normalization of serum ALT levels. Administration of SGLT-2 inhibitors led to not only good glycemic control, but also to a reduction in body weight, normalization of ALT levels, and a reduction in the FIB-4 index even in patients who did not respond to incretin-based therapy.

The prognosis and management of inactive HBV carriers.

Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000 IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAg-negative chronic hepatitis. This is why a confirmed diagnosis of IC requires quarterly ALT and HBV DNA measurements for at least 1 year, while a single-point detection of combined HBsAg <1000 IU/ml and HBV DNA <2000 IU/ml has a robust predictive value for the diagnosis of IC. Characteristically, ICs have minimal or no histological lesions of the liver corresponding to liver stiffness values on Fibroscan of <5 kPa. Antiviral treatment is not indicated in ICs since the prognosis for the progression of liver disease is favourable if there are no cofactors of liver damage such as alcohol abuse, excess weight or co-infection with the hepatitis C virus or delta virus. Moreover, spontaneous HBsAg loss frequently occurs (1-1.9% per year) in these patients while the development of hepatocellular carcinoma (HCC) is rare, at least in Caucasian patients. However, an emerging issue reinforcing the need for clinical surveillance of ICs is the risk of HBV reactivation in patients who undergo immunosuppressive therapy without receiving appropriate antiviral prophylaxis. After diagnosis, management of ICs includes monitoring of ALT and HBV DNA every 12 months with periodic measurement of serum HBsAg levels to identify viral clearance.

Treatment of chronic HCV Genotype 1 infection with Boceprevir in German real-life:The impact of SVR on initially elevated and initially normal serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels

Background: Patients (pts) with chronic HCV G1 infection may present with normal or elevated serum ALT or GGT levels. The aim of the present analysis was to investigate the effect of successful treatment of chronic HCV G1 infection with boceprevir (BOC) triple therapy on initially elevated and initially normal ALT and GGT levels.

A Mechanistic Assessment of the Discordance between Normal Serum Alanine Aminotransferase Levels and Altered Liver Histology in Chronic Hepatitis B.

To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort.

Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival

IntroductionHepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.MethodsWe reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher’s exact test and by multivariate analysis using the Cox regression model.ResultsAmong the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients.ConclusionsDLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.

Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial.

We aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. Eight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. After 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 ± 8.05 vs. 6.21 ± 8.96, P < 0.008). A significant decrease in HbA1c was observed in the carnitine-orotate complex group (-0.33 ± 0.82% [-3.6 ± 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. Treatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.