Normal Aspartate Aminotransferase Levels Research Articles

GAMBARAN AKTIVITAS ENZIM Aspartat aminotransferase (AST) PADA PEROKOK AKTIF 10-15 TAHUN DI WILAYAH KECAMATAN KAMPUNG MELAYU KOTA BENGKULU

Problem: Smoking is one of the factors causing liver damage because there are chemicals suchastar,nicotine and carbon monoxide.Exposure to cigarette smoke that enters the body and cause lipid peroxidation which causes damage to the normal cell membrane the liver.The purpose of this study was to determine the description of the results of AST enzyme activity in active smokers 10 15 years in the Kampung Melayu District of Bengkulu City.Research Methods type of research Observational research with kineticexamination method using Ray to1904 Cphotometer.The results of research on AST enzyme activity in active smokers 10-15 years from30 samples there were 22 samples within creased AST levels (73.3%),while normal AST levels were 8 samples(26.7%).The conclusion of the study was that the activity of the enzyme aspartateaminotransferase (AST) was higher in active smokers10-15. Keywords: Cigarette, Smoker, Aspartate aminotransferase (AST)

The correlation between aminotransferase enzyme levels, neutrophil-to-lymphocyte ratio, absolute lymphocyte count and the severity of Covid-19

Background/Aim: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) are indicators that are widely used as a determinant of the prognosis of patients with viral pneumonia. Thus, the study aim was to prove the correlation between AST/ALT, NLR and ALC levels with the severity of COVID-19. Methods: The research method was carried out by collecting medical record data of positive COVID-19 patients who were hospitalised at the Indramayu Hospital in the period September 2020 - January 2021. Results: The results showed normal AST levels in 63 and elevated AST levels in 57 patients. Normal and elevated ALT levels were in 68 and 52 patients, respectively. The normal NLR was in 102 patients and the high NLR was in 18 patients. The low and normal ALC was in 19 and 101 patients, respectively. AST levels correlated with the severity of COVID-19 (p = 0.045). Other parameters were without statistical significance (p > 0.05). Conclusion: AST enzyme levels had a weak positive correlation with the severity of COVID-19. On the other hand, ALT, NLR and ALC had not correlated with the severity of COVID-19.

Aminotransferase Level and the Effects of Dual Antiplatelet in Minor Stroke or Transient Ischemic Attack: A post hoc Analysis of a Randomized Control Trial

Introduction: This study was intended to evaluate whether the safety and efficacy of dual antiplatelet treatment in patients with minor ischemic stroke (MIS) or transient ischemic attack (TIA) could be modified by the aminotransferase level. Also, we sought to assess the interaction between aminotransferase level and CYP2C19 loss-of-function status on the efficacy of dual antiplatelet therapy. Methods: This study is a post hoc analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) study, a double-blinded randomized control trial. We included 5,133 patients with a complete workup of baseline alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The primary outcome is stroke or TIA recurrence within 90 days. Cox proportional hazard models were used in the evaluation of the efficacy of antiplatelet treatment in patients with different aminotransferase levels and subgroups categorized by the aminotransferase level × CYP2C19 loss-of-function status. Results: The median age of all the included patients was 62 years; 66.3% of the patients were male. More recurrent stroke or TIA occurred in patients with elevated ALT and AST levels within 90 days compared to patients with normal ALT and AST levels (14.5 vs. 11.2%, p = 0.029). Dual antiplatelet treatment with aspirin and clopidogrel reduced recurrence compared with aspirin alone in patients with both normal (adjusted hazard ratio [HR], 95% confidence interval [CI]: 0.72 [0.60–0.86], p < 0.001) and elevated (adjusted HR [95% CI]: 0. 57 [0. 35–0. 92], p = 0. 020) ALT and AST levels (p = 0.64 for interaction). No significant difference in treatment efficacy on 90-day all-cause death or bleeding events was found. Conclusions: Dual antiplatelet treatment was safe for minor stroke or high-risk TIA patients with mildly elevated aminotransferase. Mild elevation of ALT or AST did not undermine the protective efficacy of the dual antiplatelet regimen in reducing recurrent stroke or TIA within 90 days after MIS or TIA. The interaction between the CYP2C19 loss-of-function allele carrier status and aminotransferase level on the efficacy of dual antiplatelet treatment was not observed.

S3070 Macro AST: An Uncommon Yet Benign Entity

Introduction: An isolated increase in serum aspartate aminotransferase (AST) can be attributed to many conditions, including alcoholic liver disease, myocardial injury or skeletal muscle injury. Persistent elevations in AST without an obvious source can lead to diagnostic confusion. When evaluating such a patient, one must consider macro-enzyme aspartate aminotransferase (macro-AST). Macro-AST is an uncommon, yet benign condition in which a macro-enzyme is formed from self-polymerization of AST molecules or by the formation of a complex with other serum proteins such as immunoglobulins (Ig). These macro-enzymes circulate in the blood stream and can lead to an accumulation along with decreased clearance from the blood stream. Below, is an example of a woman without suggestive symptoms found to have persistently elevated AST. Case Description/Methods: The patient is a 60-year-old Hispanic female with hypothyroidism, hypertension who presented to the emergency room with complaints of lower back pain. Initial blood work revealed an AST of 404 U/L (normal 8-34 U/L) without other significant laboratory abnormalities. A computed tomography (CT) scan of the abdomen and pelvis with intravenous (IV) contrast showed lumbar spinal stenosis without other abnormalities. A right upper quadrant abdominal ultrasound with Doppler showed a normal appearing liver, biliary tree and patent vasculature. She denied any changes in her medications or use of supplements. She denied any history of liver disease, alcohol use or a family history of liver disease. Acetaminophen, ethanol and urine drug screens were negative. Testing for viral hepatitis, autoimmune hepatitis, ceruloplasmin, alpha-1-antitrypsin, ferritin, creatinine kinase, troponin I, Celiac disease and thyroid function tests were all unremarkable. Her AST level remained persistently elevated throughout hospitalization and after discharge. Given unremarkable workup and chronic AST elevation, macro-AST was the likely diagnosis. Discussion: Macro-AST is a benign cause of persistently elevated AST. Though its prevalence is not well known, some reports suggest that they can be seen across a wide age range and have no genetic basis as relatives of the patients have normal AST levels. Some cases have suggested a means of confirming the diagnosis via polyethylene glycol precipitation or electrophoresis. As these elevations can persist for over ten years, it is important for clinicians to be aware of this entity to avoid unnecessary procedures or testing.

Hepatocellular injury and the mortality risk among patients with COVID-19: A retrospective cohort study.

BACKGROUNDClearly, infection with severe acute respiratory syndrome coronavirus 2 is not limited to the lung but also affects other organs. We need predictive models to determine patients’ prognoses and to improve health care resource allocation during the coronavirus disease 2019 (COVID-19) pandemic. While treating COVID-19, we observed differential outcome prediction weights for markers of hepatocellular injury among hospitalized patients.AIMTo investigate the association between hepatocellular injury and all-cause in-hospital mortality among patients with COVID-19.METHODSThis multicentre study employed a retrospective cohort design. All adult patients admitted to Al-Azhar University Hospital, Assiut, Egypt and Abo Teeg General Hospital, Assiut, Egypt with confirmed COVID-19 from June 1, 2020, to July 30, 2020 were eligible. We categorized our cohort into three groups of (1) patients with COVID-19 presenting normal aminotransferase levels; (2) patients with COVID-19 presenting one-fold higher aminotransferase levels; and (3) patients with COVID-19 presenting two-fold higher aminotransferase levels. We analysed the association between elevated aminotransferase levels and all-cause in-hospital mortality. The survival analysis was performed using the Kaplan–Meier method and tested by log-rank analysis.RESULTSIn total, 376 of 419 patients met the inclusion criteria, while 29 (8%) patients in our cohort died during the hospital stay. The median age was 40 years (range: 28-56 years), and 51% were males (n = 194). At admission, 54% of the study cohort had liver injury. The pattern of liver injury was hepatocellular injury with an aspartate aminotransferase (AST) predominance. Admission AST levels were independently associated with all-cause in-hospital mortality in the logistic regression analysis. A one-fold increase in serum AST levels among patients with COVID-19 led to an eleven-fold increase in in-hospital mortality (P < 0.001). Admission AST levels correlated with C-reactive protein (r = 0.2; P < 0.003) and serum ferritin (r = 0.2; P < 0.0002) levels. Admission alanine aminotransferase levels correlated with serum ferritin levels (r = 0.1; P < 0.04). Serum total bilirubin levels were independently associated with in-hospital mortality in the binary logistic regression analysis after adjusting for age and sex but lost its statistical significance in the fully adjusted model. Serum ferritin levels were significantly associated with in-hospital mortality (P < 0.01). The probability of survival was significantly different between the AST groups and showed the following order: a two-fold increase in AST levels > a one-fold increase in in AST levels > normal AST levels (P < 0.0001).CONCLUSIONLiver injury with an AST-dominant pattern predicts the severity of COVID-19. Elevated serum ferritin levels are associated with fatal outcomes.

Association of Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) with Mortality in Patients with Coronavirus Disease 2019 (COVID-19) in Fatmawati General Hospital: A Preliminary Data

Background : COVID-19, caused by SARS-CoV-2 virus, is a novel disease that has not been previously identified. The disease may result in multiple organ impairment leading to death. Liver is also affected by this viral infection. This study aimed to investigate the association of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with mortality rate in these patients. Method : This is a retrospective cohort study of COVID-19 patients admitted in Fatmawati General Hospital during a period of March-April, 2020. Diagnosis of COVID-19 was established from real time Polymerase chain reaction (RT PCR). Association of AST and ALT levels with mortality was analyzed by using SPSS ® version 16.0. Result s : Forty-two patients were diagnosed as confirmed case of COVID-19, 52.3% of them were male. Mean age was 54.6±12 years. Median (IQR) value of AST and ALT levels were 55(48) U/L and 39(40) U/L, respectively. AST and ALT was elevated in 71.4% and 42.9%, respectively. Increased levels of AST and ALT 2 times above the upper normal limit (UNL), >2 times ULN, and > 5 times ULN were found in 33.3% and 21.4%; 38.1% and 21.4%; 4.8% and 4.8%, respectively. Mortality was recorded in 45.1% of these confirmed cases, 50% occurred within 2 days of hospitalization. Higher mean value of AST is associated with an increased mortality risk (101 ± 147 U/L vs. 82.78 ± 173 U/L; p 0.032). Sub-analysis identified that abnormal AST >2 times above UNL has a higher mortality proportion compared with AST 2 times UNL and normal AST levels (62.5% vs. 50% vs. 16.7%; p 0.05). Mean value of ALT is not associated with mortality (p 0.479). Further sub-analysis found that in patients who succumbed to the disease, abnormal levels of AST and ALT is related to the time of death during hospitalization despite being statistically not significant. Conclusion : Mortality rate of COVID-19 in hospitalized patients remains high. Increased AST levels was significantly associated with higher mortality rate. This finding merit further investigation by incorporating larger sample size to discern the role of these factors’ contribution to mortality in COVID-19.

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;

A Survey on the Fluctuations of Liver Enzymes in Severely Dehydrated Children with Acute Gastroenteritis

Background: Acute gastroenteritis (AGE) is a potential life-threatening condition in young children. Objectives: Our aim was to assess hepatic enzymes levels in children with AGE and severe dehydration (> 10%). Methods: We enrolled 138 children with AGE admitted to the Amir-Al-Momenin Hospital of Zabol city in 2016. Children with severe dehydration (> 10%), according to the Vesikari score, were included. Complete blood count, selected inflammatory markers, and hepatic enzymes were investigated. Results: Males and females comprised 89 (64.5%) and 49 (35.5%) of the cases, respectively. The mean age was 3 ± 2.7 years old. Concomitant aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevation and isolated AST elevation were observed in 22 (15.9%) and 60 (43.5%) of the patients, respectively. Normal AST and ALT levels were observed in 56 (40.6%) of the patients. The AST level significantly correlated with age (r = -0.230, P = 0.007) and platelet count (r = 0.184, P =0.03). Significant correlations were also detected between ALT level and age (r = -0.230, P = 0.007), ESR (r = -0.240, P = 0.03), and K+ level (r = 0.244, P = 0.03). Conclusions: Our results highlighted relatively high frequency of elevated liver enzymes in severely dehydrated children with AGE.

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.

Association between Serum Liver Enzymes and Metabolic Syndrome in Korean Adults.

The purpose of this study was to evaluate the association between alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and metabolic syndrome (MS) in the Korean population. A total of 11,587 adults ≥30 years of age and with complete data were selected from Korea National Health and Nutrition Examination Survey VI conducted from 2013 to 2015. Normal ALT and AST levels were divided into quartiles, and their associations with MS were assessed by logistic regression analysis. Elevated levels of ALT [adjusted odds ratio (aOR) = 7.90, 95% confidence interval (CI) = 6.50–9.60] and AST (aOR = 3.81, 95% CI = 3.10–4.74) were both significantly associated with a higher prevalence of MS. The quartile group containing the highest levels of ALT and AST within the normal range also showed an increased risk of MS and its components. Elevated levels of ALT and AST, even within the normal range, were associated with prevalence of MS.

The Relationships between Respiratory Virus Infection and Aminotransferase in Children.

PurposeWe sought to examine the relationship between the clinical manifestations of nonspecific reactive hepatitis and respiratory virus infection in pediatric patients.MethodsPatients admitted to the pediatric unit of Konyang University Hospital for lower respiratory tract disease between January 1, 2014 and December 31, 2014 and who underwent reverse transcriptase polymerase chain reaction tests were examined. The patients were divided into those with increased levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and those with normal ALT or AST levels. Further, patients with increased ALT and AST levels were individually compared with patients in the normal group, and the blood test results were compared according to the type of respiratory virus.ResultsPatients with increased ALT or AST levels had one more day of hospital stay, on average, compared with patients in the normal group (5.3±3.1 days vs. 4.4±3.0 days, p=0.019). Patients in the increased ALT level group were younger and had a longer mean hospital stay, compared with patients in the normal group (p=0.022 and 0.003, respectively). The incidences of increased ALT or AST were the highest in adenovirus infections (6/24, 25.0%), followed by enterovirus (2/11, 18.2%) and respiratory syncytial virus A (21/131, 16.0%) infections.ConclusionNonspecific reactive hepatitis is more common among patients with adenovirus, enterovirus and respiratory syncytial virus infection, as well as among those infected at a younger age. Compared with AST levels, ALT levels are better indicators of the severity of nonspecific reactive hepatitis.

Detection of hepatitis B activity in HBeAg-negative carriers with normal aminotransferase levels in central Brazil

Background and rationale for the study. Hepatitis B virus (HBV) chronic infection may follow a benign course with low risk of cirrhosis or liver cancer. As differentiation of inactive status from HBeAg-negative chronic hepatitis B is often challenging, monitoring of inactive HBV carriers is important to detect viral relapse or formerly undetected activity. The incidence of hepatitis activity in HBeAg-negative carriers with normal aminotransferases was examined by retrospective analysis of a cohort of carriers who had been followed-up at a hospital in Central Brazil. All patients had remained free of evidence of liver disease and maintained normal aminotransferase levels throughout the first year of follow-up. The incidence density of chronic HBV activity was determined and an incidence curve was constructed using the Kaplan-Meier method. Cox regression models were developed to identify for surrogate markers of activity.Results. Among the 224 patients who comprised the cohort, chronic HBV activity was detected in 30 during follow-up. The incidence density of activity was 11.8 per 100 person-years (95% confidence interval: 8.3-16.9). The results of Cox regression analysis indicated that chronic HBV activity was associated with entrance in the latter years of the period examined (p = 0.001) and initial normal aspartate aminotransferase (AST) levels close to the upper-normal value (p = 0.022).Conclusion. Normal AST levels near the upper-normal value may be an indicator of relapse or previously undetected activity, and should thus be monitored closely in HBeAg-negative HBV carriers, in whom risk of relapse should remain an important managing consideration.

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.

Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians

A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; P(genotype) = 1.2 × 10(-5) ; P(allelic) = 1.6 × 10(-6) ) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; P(genotype) = 0.0085; P(allelic) = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; P(genotype) = 0.040; P(allelic) = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (P(combined) = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians.

Improving the End Point of Corticosteroid Therapy in Type 1 Autoimmune Hepatitis to Reduce the Frequency of Relapse

Relapse of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to corticosteroid withdrawal, and liver tissue examination prior to the termination of therapy may be insufficient to predict subsequent course. Our goal was to refine treatment end point criteria so as to reduce the frequency of relapse after drug withdrawal. One hundred thirty-two patients with definite type 1 autoimmune hepatitis who fulfilled clinical, laboratory, and histological criteria for remission were evaluated. The degree of laboratory improvement at the termination of treatment was correlated with subsequent clinical course in patients who had improved to normal or near-normal histological findings during corticosteroid therapy. Serum aspartate aminotransferase (AST) levels at the end of treatment were higher in patients who subsequently relapsed than in those who sustained remission (32 +/- 2 U/L vs 25 +/- 2 U/L, P= 0.04). Serum gamma-globulin (1.4 +/- 0.1 g/dL vs 1.2 +/- 0.1 g/dL, P=0.03) and immunoglobulin G (IgG) (1,416 +/- 55 mg/dL vs 1,079 +/- 57 mg/dL, P=0.001) levels were also higher in these patients prior to termination of therapy. The frequencies of abnormal serum AST (40%vs 13%, P=0.008), gamma-globulin (25%vs 3%, P=0.009), and IgG levels (36%vs 4%, P=0.001) at treatment withdrawal were also greater in the patients who subsequently relapsed. Patients who are treated to normal serum AST, gamma-globulin, and IgG levels have a lower frequency of relapse than others despite comparable histological findings.

Study of IgG Subclass Profiles of Anti-HBs in Populations With Different HBV Infection Status

To study IgG-specific subclasses of hepatitis B virus (HBV) surface antigen (anti-HBs), in different populations in Taiwan, a comparison was made between 104 chronic carriers (60 male and 44 female) and 439 recovered individuals (247 male and 192 female). Biochemical analyses of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also performed. Among the 104 chronic carriers, 21 patients had abnormal ALT and AST levels (> 25 IU/ml). When comparing the patients with abnormal ALT and AST levels to chronic carriers with normal ALT and AST levels, no statistical difference was observed for anti-HBs levels (p > 0.05). The IgG subclass pattern of the relative anti-HBs IgG subclass titers was IgG1 > IgG3 = IgG4 in both chronic carriers and recovered individuals (p < 0.05). IgG1 is the predominant anti-HBs antibody after HBV infection, in either chronic carriers or in HBV-cured individuals. This finding is partly inconsistent with data reported from other group who suggested in individuals naturally infected, the anti-HBs IgG consists mainly of IgG3 and IgG1. In contrast to that of our previous studies of anti-HBe and anti-HBc, the mean OD values of anti-HBs total IgG, and all IgG subclasses except for IgG2, of either males or females, were significantly higher in recovered individuals than in chronic carriers, while the mean OD values of anti-HBe and anti-HBc were significantly higher in chronic carriers than in recovered individuals (P < 0.05). The IgG subclass profile of anti-HBs in chronic carriers was not changed with liver inflammation and was independent of sex and age, except in individuals with abnormal ALT and AST for whom anti-HBs IgG1 was not significantly higher than IgG3 (p > 0.05), in spite of that whose mean O.D. value is higher.

Safety and Effectiveness of Rosiglitazone in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease

Background/PurposeNonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients and to improve the histologic markers of nonalcoholic steatohepatitis. This study aims to determine the safety and effectiveness of rosiglitazone in inadequately controlled type 2 diabetes patients with NAFLD.MethodsTaiwanese type 2 diabetes patients with inadequate control on insulin secretagogues and metformin, with no history of significant alcohol ingestion, with mildly elevated serum aspartate amino-transferase (AST) and/or alanine aminotransferase (ALT) and a diagnosis of fatty liver determined by ultrasonography were enrolled. Patients were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints were change in AST and ALT levels from baseline and reduction in A1C < 6.5%.ResultsOut of a total of 68 patients, 60 (88.2%) completed the study treatment without serious adverse events. Treatment in two (2.9%) patients was discontinued due to elevated AST or ALT levels to more than three times the upper limit of normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60 patients who completed the study treatment, mean fasting plasma glucose, A1C, fasting plasma insulin, mean ALT and homeostasis model assessment for insulin resistance were all significantly reduced. Normal AST and ALT levels were achieved and maintained for at least three consecutive measurements and through to the end of the study period in 20 (33.3%) patients. Weight increased by a mean of 2.6 ± 2.4 kg (p<0.001).ConclusionRosiglitazone was reasonably well tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One-third of patients showed improved liver function after treatment.

Biological Markers of Alcoholism With Respect to Genotypes of Low‐Km Aldehyde Dehydrogenase (ALDH2) in Japanese Subjects

Although the mutant low-Km acetaldehyde dehydrogenase (ALDH2) allele (ALDH2(2)) with reduced capacity to metabolize acetaldehyde offers biological protection against alcoholism and subsequent alcohol-induced organ damage in many individuals, a significant proportion of individuals with heterozygote of the normal and mutant ALDH2 gene (ALDH2(1)/2(2)) consume excessive amounts of alcohol. Indeed, it has been postulated that habitual drinkers with ALDH2(1)/2(2) may be at a higher risk for alcoholic liver disease than those with ALDH2(1)/2(1). In this study, we determined how representative biological markers of alcoholism (gamma-glutamyltransferase [GGT], carbohydrate-deficient transferrin [CDT], and the mean corpuscular volume of erythrocytes [MCV]) differ with respect to the ALDH2 genotypes in Japanese habitual drinkers. We obtained genomic DNA samples from 227 Japanese men with various drinking habits. ALDH2 genotypes were determined by allele-specific polymerase chain reaction. GGT, CDT, and MCV were determined and compared between ALDH2(1)/2(1) and ALDH2(1)/2(2) habitual drinkers who consumed more than 66 g of alcohol per day for more than 5 years. We measured CDT by anion-exchange chromatography followed by turbidity immunoassay by using a commercially available assay kit (Axis %CDT TIA). CDT levels were comparable between the two groups. GGT activities were significantly greater in ALDH2(1)/2(1) than in ALDH2(1)/2(2) habitual drinkers (81 +/- 85 vs. 53 +/- 40 IU/liters, p < 0.02). MCV values, on the other hand, were significantly larger in ALDH2(1)/2(2) than in ALDH2(1)/2(1) subjects (98.2 +/- 5.8 vs. 95.8 +/- 4.2 fl, p = 0.02). When we used elevation of either CDT or GGT to detect habitual drinking in ALDH2(1)/2(1) and 2(1)/2(2) subjects, the sensitivities were 57% and 46%, respectively. CDT levels were similar between habitual drinkers with normal aspartate aminotransferase levels and those with elevated levels. GGT and MCV, but not CDT, differ with respect to the ALDH2 genotypes in Japanese male habitual drinkers. ALDH2 genotypes should be considered when interpreting data on biological markers of alcoholism.

High Prevalence of Hepatitis G Virus in Bone Marrow Transplant Recipients and Patients Treated for Acute Leukemia

Hepatitis G virus (HGV) is a newly described virus that has been implicated in transfusion-associated hepatitis. The prevalence of HGV in a group of multitransfused patients with hematological malignancy was studied using a reverse transcription polymerase chain reaction technique. Transfusion histories and serum aspartate aminotransferase (AST) levels were recorded. HGV was detected in 29 of 60 (48%) patients. There was no difference in HGV positivity rates between those with normal AST levels and those with raised AST levels. Analysis of patients by treatment type showed that 20 of 33 (61%) patients who received a bone marrow transplantation procedure were HGV positive compared with 9 of 27 (33%) treated with conventional combination chemotherapy (P = .036) despite similar transfusion histories. There was no significant difference in HGV positivity between patients treated before the introduction of United Kingdom blood donor screening for hepatitis C virus antibody:18 of 39 (46%) and those treated after the introduction of screening 11 of 21 (52%). HGV infection appears to be extremely common in these patients; however, the clinical significance of these findings with respect to liver dysfunction is not yet clear.

High Prevalence of Hepatitis G Virus in Bone Marrow Transplant Recipients and Patients Treated for Acute Leukemia

AbstractHepatitis G virus (HGV) is a newly described virus that has been implicated in transfusion-associated hepatitis. The prevalence of HGV in a group of multitransfused patients with hematological malignancy was studied using a reverse transcription polymerase chain reaction technique. Transfusion histories and serum aspartate aminotransferase (AST) levels were recorded. HGV was detected in 29 of 60 (48%) patients. There was no difference in HGV positivity rates between those with normal AST levels and those with raised AST levels. Analysis of patients by treatment type showed that 20 of 33 (61%) patients who received a bone marrow transplantation procedure were HGV positive compared with 9 of 27 (33%) treated with conventional combination chemotherapy (P = .036) despite similar transfusion histories. There was no significant difference in HGV positivity between patients treated before the introduction of United Kingdom blood donor screening for hepatitis C virus antibody:18 of 39 (46%) and those treated after the introduction of screening 11 of 21 (52%). HGV infection appears to be extremely common in these patients; however, the clinical significance of these findings with respect to liver dysfunction is not yet clear.