Clinical, histological and molecular profiling of different stages of alcohol-related liver disease

ObjectiveAlcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking.DesignTwo large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed.ResultsAge and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism.ConclusionsDespite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

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Clinical and pathologic features of acute bovine liver disease in Australia

Journal of Veterinary Diagnostic Investigation ◽

10.1177/10406387211025829 ◽

2021 ◽

pp. 104063872110258

Author(s):

Eve M. Manthorpe ◽

Ian V. Jerrett ◽

Grant T. Rawlin ◽

Lucy Woolford

Keyword(s):

Liver Disease ◽

Clinical Signs ◽

Bovine Liver ◽

Gamma Glutamyl Transferase ◽

Reticular Pattern ◽

Pathologic Features ◽

Histologic Lesion ◽

Massive Necrosis ◽

Glutamyl Transferase ◽

Lactating Dairy Cattle

Acute bovine liver disease (ABLD) is a sporadic hepatic disease affecting cattle in southern Australia, characterized histologically by striking periportal hepatocellular necrosis. The cause of ABLD is unknown; however, the seasonality and acute presentation of outbreaks suggest mycotoxin involvement. We describe here the clinical and pathologic findings of ABLD in 45 naturally affected cattle from 13 outbreaks occurring from 2010 to 2019 in Victoria, Australia. Outbreaks occurred in herds located along the southern coastal plain of Victoria and were observed most frequently in lactating dairy cattle. Clinical signs commonly included a combination of mild photosensitization, progressive neurologic signs, and hypogalactia, which preceded death by ≤ 48 h. All affected animals had marked elevations in activities of glutamate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transferase. At autopsy, the most common lesions were serosal petechiae and/or gastrointestinal hemorrhage, and hepatomegaly with a pronounced hepatic reticular pattern. The principal histologic lesion was widespread—severe periportal hepatocellular coagulative necrosis and erythrocyte pooling—which often extended to massive necrosis. Lesions in other organs were uncommon. Our study of ABLD suggests involvement of a potent hepatotoxin that is either directly cytopathic or requires bioactivation by periportal-specific enzymes.

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Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study

BMC Infectious Diseases ◽

10.1186/s12879-021-06572-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qing-Lei Zeng ◽

Zu-Jiang Yu ◽

Fanpu Ji ◽

Guang-Ming Li ◽

Guo-Fan Zhang ◽

...

Keyword(s):

Retrospective Study ◽

Liver Disease ◽

Liver Function ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Gamma Glutamyl Transferase ◽

Dynamic Changes ◽

Viral Shedding ◽

Glutamyl Transferase ◽

Multicentre Retrospective Study

Abstract Background Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. Results In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. Conclusions SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

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Pemafibrate Ameliorates Liver Dysfunction and Fatty Liver in Patients with Non-Alcoholic Fatty Liver Disease with Hypertriglyceridemia: A Retrospective Study with the Outcome after a Mid-Term Follow-Up

Diagnostics ◽

10.3390/diagnostics11122316 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2316

Author(s):

Suguru Ikeda ◽

Takaaki Sugihara ◽

Takuya Kihara ◽

Yukako Matsuki ◽

Takakazu Nagahara ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Serum Triglyceride ◽

Gamma Glutamyl Transferase ◽

Alcoholic Fatty Liver ◽

Clinical Criteria ◽

One Year ◽

Glutamyl Transferase ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. No standard pharmacological treatment has yet been established. We retrospectively evaluated the efficacy of pemafibrate in 16 NAFLD patients (11 men and 5 women; median age, 59 years; range, 27–81 years) who had taken pemafibrate for at least one year. They were all diagnosed with fatty liver according to imaging and clinical criteria. They were administered pemafibrate from October 2018 to October 2021 (median, 94 weeks; range, 56–157 weeks). Serum triglyceride was significantly decreased by −41.9% (342.3 ± 54.0 to 198.9 ± 20.4 mg/dL, p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transferase levels significantly decreased by −42.1% (49.6 ± 7.0 to 28.7 ± 3.4 U/L, p < 0.001), −57.1% (65.1 ± 10.8 to 27.9 ± 3.7 U/L, p < 0.001), and −43.2% (68.9 ± 10.9 to 39.1 ± 5.3 U/L, p < 0.05), respectively. The AST to platelet ratio (APRI) (0.8 ± 0.1 to 0.4 ± 0.1, p < 0.001) and fibrosis based on four factors (FIB-4) index (1.8 ± 0.3 to 1.4 ± 0.2, p < 0.05) also significantly decreased. Liver attenuation (39.1 ± 1.2 to 57.8 ± 2.7 HU, p = 0.028) and liver/spleen ratio (0.76 ± 0.04 to 1.18 ± 0.02, p = 0.012) significantly improved in three patients, as assessed by computed tomography. In conclusion, pemafibrate significantly improves serum triglyceride levels, liver function, FIB-4 index, APRI, and fatty liver in NAFLD patients with hypertriglyceridemia.

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Abstract P027: Gamma-Glutamyl Transferase is More Strongly Associated with Diabetes Risk Than Alanine and Aspartate Aminotransferase: Results from the Atherosclerosis Risk in Communities (ARIC) StudyStudy

Circulation ◽

10.1161/circ.125.suppl_10.ap027 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Andrea L Christman ◽

Mariana Lazo ◽

Chiadi E Ndumele ◽

James Pankow ◽

Josef Coresh ◽

...

Keyword(s):

Risk Factors ◽

Liver Disease ◽

Aspartate Aminotransferase ◽

Liver Enzymes ◽

Gamma Glutamyl Transferase ◽

Community Based ◽

Gamma Glutamyl ◽

Spline Models ◽

Glutamyl Transferase ◽

Diagnosed Diabetes

Introduction: Liver disease and diabetes often co-occur and have shared risk factors. We undertook this study to investigate which liver enzyme (alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT)) would be most strongly associated with incident diabetes in a large, community-based population. Hypothesis: We hypothesized that ALT, AST, and GGT would be independently associated with diabetes and that ALT would be most strongly associated with diabetes due to its liver specificity. Methods: We conducted a prospective analysis of 9,524 participants in the ARIC Study without diagnosed diabetes or a history of high alcohol consumption (>14 [women] and >21 [men] drinks/week). Enzymes were measured from stored plasma samples. We examined the association of sex-specific quartiles of liver enzymes with incident diagnosed diabetes using Cox proportional hazards models adjusted for demographic, lifestyle, and behavioral risk factors. Restricted cubic spline models were fit to model the continuous associations. Results: Median ALT, AST, and GGT were 13, 18, and 22 U/L, respectively. During a median follow-up of 11 years, there were 1,905 self-reported cases of diabetes. All three liver enzymes were significantly associated with diabetes, even after adjustment for all covariates (HRs (95% CIs): ALT, 1.63 (1.44, 1.85); AST, 1.23 (1.09, 1.40); GGT, 1.99 (1.71, 2.30) comparing Q4 versus Q1). The restricted cubic spline models show similar patterns (Figure). After simultaneously adjustment for the other liver enzymes, only ALT and GGT remained significantly associated with diabetes. In analyses further restricted to participants who reported never consuming alcohol only GGT remained significant. Conclusion: In this community-based population, GGT was more strongly associated with diabetes risk than ALT and AST. Although ALT and AST are considered to be more specific markers of liver disease, higher levels of GGT may be a more important risk factor for diabetes.

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Quantitative fractionation of alkaline phosphatase isoenzymes according to their thermostability.

Clinical Chemistry ◽

10.1093/clinchem/22.1.42 ◽

1976 ◽

Vol 22 (1) ◽

pp. 42-48 ◽

Cited By ~ 26

Author(s):

C PetitClerc

Keyword(s):

Alkaline Phosphatase ◽

Liver Disease ◽

Phosphatase Activity ◽

Alkaline Phosphatase Activity ◽

Normal Serum ◽

Transferase Activity ◽

Gamma Glutamyl Transferase ◽

Heat Labile ◽

Alkaline Phosphatase Isoenzymes ◽

Glutamyl Transferase

Abstract Continuous monitoring of heat denaturation of a mixture of alkaline phosphatase isoenzymes at 60 degrees C and pH 7.5 permits the simultaneous direct identification and quantitation of three isoenzymes: the placental isoenzyme, the L-phenylalanine-sensitive intestinal isoenzyme, and the liver isoenzyme (hepatocytic). The isoenzyme that is principally of bone origin cannot be identified as such without the help of other diagnostic aids and the patient's medical history. All human tissues contain alkaline phosphatase, many organs more than one of the isoenzymes. Liver alkaline phosphatase, which constitutes 40-50% of normal serum alkaline phosphatase activity, was measured in the serum of persons with various liver diseases. Its activity exceeded normal in all types of liver disease; in 80% of cases this increase was accompanied by increased gamma-glutamyl-transferase activity, but the quantitative correlationship (r = 0.54) was not as good as expected if both enzymes come from the same source and are indices of liver dieases. Liver alkaline phosphatase activity increases in the blood early in liver disease, before most liver tests show abnormalities. The other major isoenzyme of normal serum probably represents a mixture of isoenzymes from bone and reticulo-endothelial and vascular tissues, which all contain the same "very heat-labile" alkaline phosphatase. Cord blood and children's sera contain mostly this very heat-labile isoenzyme.

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Serum Scoring and Quantitative Magnetic Resonance Imaging in Intestinal Failure-Associated Liver Disease: A Feasibility Study

Nutrients ◽

10.3390/nu12072151 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2151

Author(s):

Konstantinos C. Fragkos ◽

María Claudia Picasso Bouroncle ◽

Shankar Kumar ◽

Lucy Caselton ◽

Alex Menys ◽

...

Keyword(s):

Liver Disease ◽

Liver Diseases ◽

Liver Blood Flow ◽

Intestinal Failure ◽

Quantitative Mri ◽

Liver Fat ◽

Gamma Glutamyl Transferase ◽

Small Bowel Motility ◽

Fat Fraction ◽

Glutamyl Transferase

(1) Background: Intestinal failure-associated liver disease (IFALD) in adults is characterized by steatosis with variable progression to fibrosis/cirrhosis. Reference standard liver biopsy is not feasible for all patients, but non-invasive serological and quantitative MRI markers for diagnosis/monitoring have not been previously validated. Here, we examine the potential of serum scores and feasibility of quantitative MRI used in non-IFALD liver diseases for the diagnosis of IFALD steatosis; (2) Methods: Clinical and biochemical parameters were used to calculate serum scores in patients on home parenteral nutrition (HPN) with/without IFALD steatosis. A sub-group underwent multiparameter quantitative MRI measurements of liver fat fraction, iron content, tissue T1, liver blood flow and small bowel motility; (3) Results: Compared to non-IFALD (n = 12), patients with IFALD steatosis (n = 8) demonstrated serum score elevations in Enhanced Liver Fibrosis (p = 0.032), Aspartate transaminase-to-Platelet Ratio Index (p < 0.001), Fibrosis-4 Index (p = 0.010), Forns Index (p = 0.001), Gamma-glutamyl transferase-to-Platelet Ratio Index (p = 0.002) and Fibrosis Index (p = 0.001). Quantitative MRI scanning was feasible in all 10 sub-group patients. Median liver fat fraction was higher in IFALD steatosis patients (10.9% vs 2.1%, p = 0.032); other parameter differences were non-significant; (4) Conclusion: Serum scores used for non-IFALD liver diseases may be useful in IFALD steatosis. Multiparameter MRI is feasible in patients on HPN.

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Serum Adropin Levels Are Reduced in Adult Patients with Nonalcoholic Fatty Liver Disease

Medical Principles and Practice ◽

10.1159/000500106 ◽

2019 ◽

Vol 28 (5) ◽

pp. 463-469 ◽

Cited By ~ 6

Author(s):

Orkide Kutlu ◽

Özgür Altun ◽

Okan Dikker ◽

Şerife Aktaş ◽

Neslihan Özsoy ◽

...

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Adult Patients ◽

Gamma Glutamyl Transferase ◽

Nonalcoholic Fatty Liver ◽

Healthy Control ◽

Glutamyl Transferase

Objectives: Adropin is a novel marker of metabolic syndrome and insulin resistance. The aim of this study was to explore the association of serum adropin levels with hepatosteatosis among adult patients. Materials and Methods: Serum biochemical parameters including liver and renal function tests, insulin levels, and serum adropin levels were compared between adult patients with nonalcoholic fatty liver disease (NAFLD) and healthy control cases. Results: A total of 51 patients with a mean age of 37.9 ± 9.96 years diagnosed with grade 2–3 hepatosteatosis and 30 healthy control cases with a mean age of 34.8 ± 9.5 years were included in the study. Serum adropin levels in the NAFLD group were statistically significantly lower than in the control cases (588.4 ± 261.0 vs. 894.2 ± 301.2, respectively; p < 0.001). The study participants were further subdivided into 2 groups as patients with (n = 35) or without (n = 46) insulin resistance using the serum homeostatic model of assessment-insulin resistance (HOMA-IR). Serum adropin levels were statistically significantly lower in patients with insulin resistance (p < 0.01). There was a negative correlation between adropin levels and serum insulin, HOMA-IR, urea, gamma-glutamyl transferase, total cholesterol, and triglyceride levels. Conclusion: We observed a decrease in serum adropin levels among adult patients with NAFLD. We also found lower levels of serum adropin in patients with insulin resistance, supporting previous data in the literature. Studies investigating the association of adropin levels with other inflammatory parameters are warranted to define its exact role in the pathogenesis of hepatosteatosis.

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Biochemical Scoring System For Diagnosing Nonalcoholic steatohepatitis

Bangladesh Journal of Medicine ◽

10.3329/bjmed.v30i2.41531 ◽

2019 ◽

Vol 30 (2) ◽

pp. 58-62

Author(s):

Sheikh Mohammad Noor E Alam ◽

Shahinul Alam ◽

Dulal Chandra Das ◽

Mamun Al Mahtab

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Scoring System ◽

Fatty Liver Disease ◽

Serum Triglyceride ◽

Gamma Glutamyl Transferase ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Nonalcoholic Fatty Liver ◽

Glutamyl Transferase

Background: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from simple steatosis to steatohepatitis, advanced fibrosis, and end stage liver disease. Despite the high prevalence and severity of hepatic illness, NAFLD remains underdiagnosed, because of few symptoms, lack of accurate laboratory markers. Objective: To evaluate a biochemical score for diagnosing non-alcoholic steatohepatitis. Methods: An observational, cross sectional study was carried out for a period of two years in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. 43 patients of Non-alcoholic fatty liver disease (NAFLD) attending at department of Hepatology were selected and underwent for biochemical investigations and liver biopsy with NAFLD Activity Score (NAS). Results: A biochemical score (TAAG score) assigned 1 point for each parameter (fasting serum triglyceride >ULN, alanine aminotransferase >ULN, AST/ALT ratio (AAR) ≤1 and gamma-glutamyl transferase >ULN) was evaluated. TAAG score ≥3 was present in 32.5% of study population and 40% of NASH patients. It had a sensitivity of 40%, specificity 26% and AUROC 0.54. Conclusion: Biochemical scoring system comprising traditional biomarkers did not significantly predict NASH. Biopsy is the only way to estimate steatohepatitis and/or fibrosis. Bangladesh J Medicine July 2019; 30(2) : 58-62

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Insufficient nocturnal sleep was associated with a higher risk of fibrosis in patients with diabetes with metabolic associated fatty liver disease

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820947550 ◽

2020 ◽

Vol 11 ◽

pp. 204201882094755

Author(s):

Jiaping Zheng ◽

Sijie Chen ◽

Yuqing Cai ◽

Su Lin ◽

Sujie Ke ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Serum Uric Acid Level ◽

Multivariate Regression Analysis ◽

Gamma Glutamyl Transferase ◽

Baseline Characteristic ◽

Nocturnal Sleep ◽

Glutamyl Transferase

Background: Metabolic associated fatty liver disease (MAFLD) refers to metabolic dysfunction associated with fatty liver disease, and liver fibrosis stage is closely connected with liver-related and all-cause mortality. This study aimed to explore the association of sleep duration with liver fibrosis in the diabetic subgroup of the MAFLD population. Methods: This retrospective study analyzed 342 patients with MAFLD. Anthropometric measurements, clinical and biochemical markers, and lifestyle parameters were collected. Fibrosis was defined as fibrosis-4 ⩾1.3. Propensity score matching (PSM) was performed to match cases. Student’s t-test and chi-square tests were applied for group comparisons, and binary regression models were used to explore the independent risk factors of liver fibrosis. Results: Among the 342 subjects, 87 (25.4%) were diagnosed with fibrosis and 255 (74.6%) without. Baseline characteristic comparisons showed differences in age and diabetes duration between the two groups, and adjustment was made by PSM. Ultimately, the fibrosis group and nonfibrosis group each had 87 patients. The fibrosis group had shorter duration of nocturnal sleep (6.77 ± 1.59 h) than the nonfibrosis group (7.77 ± 1.92 h, p < 0.001). More patients in the fibrosis group stayed up late at night (32.2% versus 14.9%, p < 0.01). Visceral adipose tissue (VAT) areas were larger in the fibrosis group than in the nonfibrosis group ( p < 0.001). Glycemic profile, lipid profile, gamma-glutamyl transferase level, and serum uric acid level were not significantly different between the two groups. In the multivariate regression analysis, nocturnal sleep and VAT areas were independently associated with liver fibrosis, with odds ratios of 0.694 [95% confidence interval (CI) 0.551–0.875, p < 0.01] for nocturnal sleep and 1.031 (95% CI 1.014–1.048, p < 0.001) for VAT areas. Conclusion: Insufficient nocturnal sleep was independently related to a higher risk of fibrosis. Sleep modification might be beneficial in promoting the health of patients with MAFLD.

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The Relationship between Liver Function Tests and Alcohol Intake in Patients Admitted to an Alcoholism Unit

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456328402100406 ◽

1984 ◽

Vol 21 (4) ◽

pp. 261-267 ◽

Cited By ~ 5

Author(s):

J R Evans ◽

S Ogston ◽

Anne Guthrie ◽

B Johnston ◽

L McKechnie

Keyword(s):

Alcohol Intake ◽

Reference Group ◽

Reliability And Validity ◽

Liver Function Tests ◽

Gamma Glutamyl Transferase ◽

Dose Response Relationship ◽

Social Drinkers ◽

Heavy Drinkers ◽

Glutamyl Transferase ◽

The Relationship

Values of various blood plasma tests have been determined in heavy drinkers admitted to an Alcoholism Unit and in a reference group of occasional social drinkers. These tests were total protein, albumin, bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), asparate amino transferase (AST) and amylase. The aim of this study was to assess the reliability and validity of GGT and AST as indices of alcohol intake in heavy drinkers entering an Alcoholism Unit. The data indicate that in the patients group intra-personal variance and analytical variances are relatively small compared with the between-person variance. The data also indicate, however, that in the patients group GGT and AST are not valid group indices of alcohol intake since the between-person variation is large and the correlation with alcohol intake is weak due to large differences in the dose-response relationship between individuals. AST and GGT are poor indicators of alcohol intake in admissions to an Alcoholism Unit.

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