Normal Gamma-glutamyl Transferase Research Articles

Efficacy of Screening and Brief Intervention for Alcohol Misuse in Opioid Agonist Maintenance Treatment: A Randomized Clinical Trial

ABSTRACT Alcohol misuse is common in persons on opioid agonist maintenance treatment (OAMT). We tested the efficacy of screening and brief intervention (SBI) for harmful/hazardous alcohol use in buprenorphine/naloxone (BNX)-assisted OAMT. It was a double-blind, parallel-group, randomized trial, where 150 participants with alcohol misuse (Alcohol Use Disorder Identification Test – AUDIT 8–19) on BNX were allocated equally to receive either a single session SBI or screening and brief advice (control). Participants were followed up at three months. The primary outcome was the change in AUDIT; other outcomes were risk transition, change in the frequency of heavy drinking, days of abstinence from alcohol, Gamma-glutamyl transferase (GGT) levels, non-prescription opioid use, and adherence to BNX. Follow-up data was gathered from 138 participants. SBI participants had a higher reduction in AUDIT scores at the follow-up (F = 129. 173, df = 1, p < .001, ηp 2 =.469). A higher proportion of participants transitioned to a low-risk category in the SBI group. The SBI group showed a higher reduction in heavy drinking and days of alcohol abstinence. Although the proportion of persons with normal serum GGT increased in both groups, the difference was not significant at the follow-up. The SBI group performed better in non-prescription opioid use and BNX adherence.

Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function

Abstract Limited studies assess reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs). 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR} was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females &amp;gt;50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement (Kappa = 0.48, 95% confidence interval: 0.46-0.51) and positive correlation (r = 0.51; p&amp;lt;0.0001) between ALP and GGT was observed. For ALP and GGT, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and &amp;gt;50 years, respectively. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and &amp;gt;50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Manufacturer RIs agreed well with the IRIs for most subsets, but differed for ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females &amp;gt;50 years. Further investigation of the impact of preselecting patient populations on IRIs and a direct RI study on select patient subsets is worth investigation.

A-093 Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function

Abstract Background There are limited published studies assessing reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance across practice settings. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs) from routine clinical data. Methods 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR}, an algorithm for calculating IRIs, was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females &amp;gt;50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Results Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement between ALP and GGT was observed (Kappa = 0.48, 95% confidence interval: 0.46-0.51). A positive correlation between ALP and GGT was observed r = 0.51 (p&amp;lt;0.0001). For ALP, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and &amp;gt;50 years, respectively. For GGT, no significant differences were observed for the lower limits. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and &amp;gt;50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Conclusions For the majority of patient subsets, the manufacturer RI agreed well with the IRIs. However, significant differences in IRIs were observed for the upper limit of ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females &amp;gt;50 years. Further investigation of the impact of preselecting patient populations on IRI estimation and a direct RI study on select patient subsets is worth investigation.

Comparative Analysis of Liver Enzyme Changes Before and After Korean Medicine Treatment in People with Obesity: A Retrospective, Multicenter, Observational Study

This retrospective, multicenter, observational study aimed to evaluate the effects of herbal medicine treatment on liver function in obese patients exhibiting elevated liver enzymes. Conducted from May 2023 to April 2024 at various Korean medicine clinics, the study included 84 patients who underwent herbal treatments for obesity. All participants had at least one liver function test (LFT) showing elevated levels of aspartic amino transferase (AST), alanine amino transferase (ALT), or gamma glutamyl transferase (GGT), and a subsequent LFT performed after a minimum of 90 days. The study excluded patients with potential confounding factors such as hepatitis, antibiotic usage, or recent surgeries.&lt;/br&gt;The study showed significant reductions in AST, ALT, and GGT levels, with AST and ALT improving to within the normal range and GGT approaching normal levels. Patients also experienced statistically significant reductions in weight and BMI, meeting the minimum clinically important difference threshold.&lt;/br&gt;These findings suggest that herbal treatments for obesity are not only safe for patients with obesity-related liver enzyme abnormalities but also effective in improving liver function. This study shows that herbal treatment is effective in the management of obesity-related liver disease and confirms the safety and efficacy of an obesity treatment herbal formula containing ephedra. Larger prospective studies are needed to confirm these findings.

Benign Recurrent Intrahepatic Cholestasis: Where Are We Now?

Benign recurrent intrahepatic cholestasis (BRIC) stands as a rare genetic contributor to cholestasis, aligning itself within the spectrum of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC) and intrahepatic cholestasis of pregnancy. Manifesting in infancy or early adulthood, BRIC is marked by recurrent episodes of jaundice accompanied by intense pruritus, enduring from weeks to years across the lifespan. Normal gamma-glutamyl transferase (GGT) levels are a characteristic laboratory finding. Initially considered unlikely to progress to chronic liver disease or cirrhosis, some reports suggest BRIC may evolve into a continuous and progressive form of cholestasis. Moreover, these recurrent cholestatic episodes significantly impact quality of life, and certain mutations elevate the risk of hepatobiliary malignancy. Between episodes, histological findings of centrilobular cholestasis and abnormal laboratory parameters revert to normal, potentially obviating the need for liver biopsy. This review focuses on the genetic aspects of BRIC, its pathophysiology, clinical presentation, and prognosis. Additionally, it outlines triggering factors and available treatment options.

Successful Use of Bortezomib for Recurrent Progressive Familial Intrahepatic Cholestasis Type II After Liver Transplantation: A Pediatric Case with a 9-Year Follow-Up.

Recurrence of progressive familial intrahepatic cholestasis (PFIC) type II poses challenges during postoperative liver transplant care. Posttransplant patients with PFIC type II risk developing recurrent cholestasis with normal gamma-glutamyl transferase activity, which mimics the original bile salt export pump (BSEP) protein deficiency and is related to a form of immunoglobulin G antibody (anti-BSEP)-mediated rejection. Bortezomib effectively induces apoptosis of actively antibody-producing plasma cells that may have a role in antibody-mediated rejection. In this case, we used bortezomib to treat PFIC type II recurrence after liver transplantation in a child.

Coagulation Abnormalities in Pediatric Patients with β-Thalassemia, An experience at a Tertiary Care Hospital

Life expectancy in thalassemia has markedly improved due to consistent blood transfer and amenability with iron chelation therapy, therefore this improvement is conditioned with various thromboembolic problems of this prolonged disorder including thromboembolic complaints. Objective: To determine coagulation abnormalities in beta (β) thalassemia major patients who have been multi transfused. Methods: This observational study was conducted at Department of Haematology &amp; Transfusion Medicine, Children hospital &amp; University of Child Health Sciences (CH&amp;UCHS), Lahore, from October 2022 to January 2023. The study included 60 β-thalassemic patient, age less than 16 years whose samples were compared with upper and lower normal value as regards to Prothrombin Time (PT), Active Partial Thromboplastin Time (APTT), Protein S, Protein C, liver enzymes (Alanine Transaminase (ALT), Aspartate Transaminase (AST), Gamma-Glutamyl Transferase (GGT). The data were analyzed using IBM SPSS version 23.0. Results: When values were compared, natural clotting inhibitors (Protein S, Protein C) were remarkably reduced in β-thalassemic paeds patients (p&lt;0.001).PT and APTT were prolonged in thalassemic children (p&gt;0.05 and p&lt;0.05 correspondingly). There was substantial increase in concentrations of ALT and AST in β-thalassemic patients (p &lt; 0.001 and p &lt; 0.001 respectively) due to iron over load by multiple transfusions. Conclusions: Marked changes in coagulation inhibition supporting thrombotic tendency was observed in thalassemic children. There were reduced levels of protein C and protein S, independent of slightly prolonged PT and APTT and elevated levels of ALT, AST with normal GGT in thalassemic children.

A 19-year-old Patient with Recurrent Pruritus and Jaundice

Аim: to highlight the importance of broad differential diagnosis and possibility of conversion of benign recurrent intrahepatic cholestasis type 2 into more aggressive clinical phenotype.Key points. A 19-year-old female patient was admitted to the Clinic with skin pruritus, jaundice, dark urine, clay-colored stool, and general fatigue. Past medical history was significant for recurrent aforementioned symptoms since 3 years old, that relapsed every 1–2 years and were usually ameliorated with conservative therapy. During recent years, frequency of relapses and recovery period increased, at the same time effectiveness of medical therapy decreased. Blood chemistry results revealed an elevation of total bilirubin (up to 634 μmol/L), direct bilirubin (up to 354 μmol/L), bile acids (up to 510 μmol/L) and normal gamma glutamyl transferase level. Workup was negative for viral hepatitis, autoimmune liver diseases, obstructive choledochal lesions, storage diseases, although mutation in gene ABCB11 was found. Benign recurrent intrahepatic cholestasis type 2 was diagnosed. Following conservative therapy and plasmapheresis, jaundice and skin pruritus significantly diminished, levels of bilirubin and bile acids normalized. Regular follow up, liver biopsy and measures for relapse prevention given clinical features of aggressive phenotype were recommended.Conclusion. Identification of etiology of cholestatic liver diseases requires broad differential diagnosis. Clinical course of patients with benign recurrent intrahepatic cholestasis may transform into aggressive phenotype, reminiscent of progressive familial intrahepatic cholestasis.

FRI-500 - Fibrosis-4 score less than 2.67 and normal gamma-glutamyl transferase levels are associated with high negative predictive value for high-risk of liver stiffness in patients with primary biliary cholangitis

FRI-500 - Fibrosis-4 score less than 2.67 and normal gamma-glutamyl transferase levels are associated with high negative predictive value for high-risk of liver stiffness in patients with primary biliary cholangitis

Socio-economic issues in the diagnostic approach and decision to treat of a child with familial cholestasis

Objectives. The diagnostic approach in familial cholestasis cases involves using expensive investigations. The need for complex therapeutic resources is predictable. Material and methods. We present the case of a 3 years 5 months old boy diagnosed with cholestasis and liver cirrhosis, admitted in the Pediatrics Department of “Grigore Alexandrescu” Children’s Hospital for evaluation in order to check the criteria for liver transplantation. Outcomes. The patient is known to our clinic since he was 1 year 3 months; he was admitted at that time for green jaundice. He comes from a family with nine children, low socio-economic status and low education. The first four children have a different father, two of them were stillborn. The next five come from a consanguineous union (the father is maternal uncle of the mother): three (the patient included) presented with the same symptoms, two of them died before 3 years of age with liver cirrhosis. In time, infectious causes, autoimmune, neoplastic and metabolic disease were excluded. The liver biopsy describes cholestasis and fibrosis. Alagille syndrome and progressive familial intrahepatic cholestasis are still debated, but the genetic testing necessary for a positive diagnosis are not financially available to the family. The patient presents with failure to thrive, developmental delay, intense jaundice and pruritus, hippocratic fingers, dyspnea, enlarged abdomen with visible collateral circulation, significant hepatosplenomegaly. The lab tests show anemia, thrombocytopenia, liver cytolysis, normal gamma-glutamyl transferase, low prothrombin activity, normal renal function, no inflammatory syndrome, increased ammonia level, very high bile acids level. The upper endoscopy describes first degree esophageal varices and portal hypertensive gastropathy. A PELD (Pediatric End-Stage Liver Disease) score is calculated – 13.6 (76.3% one year survival rate on the transplant list, 90.9% one year survival rate after liver transplantation). The patient is enrolled on the transplant waiting list provided we would expect suboptimal results considering the developmental delay and difficult post-transplant monitoring. Conclusions. The low education level of the family correlated with a postponed positive diagnosis due to financial reasons and the lack of genetic advice already lead to the demise of four brothers. In this setting, the prognosis of the patient is very likely to be poor.

Neonatal cholestasis – A case report on congenital bile acid synthetic defect type 4 and severe anemia

Congenital defects of bile acid synthesis are rare disorders that cause progressive liver dysfunction. We present a case of alpha methylacyl-CoA racemase (AMACR) deficiency with non-spherocytic hemolytic anemia who presented with rapidly progressive severe cholestasis and liver failure with normal gamma-glutamyl transferase levels. After extensive investigation, he was found to have AMACR deficiency with HBB gene mutation associated with non-spherocytic hemolytic anemia possibly explaining the severity of the disease. To the best of our knowledge, a similar association has not been reported so far.

Mild Phenotype of Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome 1 Caused by a Novel VPS33B Variant.

The arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is an autosomal recessive multisystem disease caused by variants in VPS33B or VIPAS39. The classical presentation includes congenital joint contractures, renal tubular dysfunction, cholestasis, and early death. Additional features include ichthyosis, central nervous system malformations, platelet dysfunction, and severe failure to thrive. We studied three patients with cholestasis, increased aminotransferases, normal gamma-glutamyl transferase, and developmental and language delay. Whole exome sequencing analysis identified VPS33B variants in all patients: patients 1 and 2 presented a novel homozygous variant at position c.1148T>A. p.(Ile383Asn), and patient 3 was compound heterozygous for the same c.1148T>A. variant, in addition to the c.940-2A>G. variant. ARCS is compatible with the symptomatology presented by the studied patients. However, most patients that have been described in the literature with ARCS had severe failure to thrive and died in the first 6 months of life. The three patients studied here have a mild ARCS phenotype with prolonged survival. Consequently, we believe that the molecular analysis of the VPS33B and VIPAS39 should be considered in patients with normal gamma-glutamyl transferase cholestasis.

Newer variants of progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of disorders characterized by defects in bile secretion and presentation with intrahepatic cholestasis in infancy or childhood. The most common types include PFIC 1 (deficiency of FIC1 protein, ATP8B1 gene mutation), PFIC 2 (bile salt export pump deficiency, ABCB11 gene mutation), and PFIC 3 (multidrug resistance protein-3 deficiency, ABCB4 gene mutation). Mutational analysis of subjects with normal gamma-glutamyl transferase cholestasis of unknown etiology has led to the identification of newer variants of PFIC, known as PFIC 4, 5, and MYO5B related (sometimes known as PFIC 6). PFIC 4 is caused by the loss of function of tight junction protein 2 (TJP2) and PFIC 5 is due to NR1H4 mutation causing Farnesoid X receptor deficiency. MYO5B gene mutation causes microvillous inclusion disease (MVID) and is also associated with isolated cholestasis. Children with TJP2 related cholestasis (PFIC-4) have a variable spectrum of presentation. Some have a self-limiting disease, while others have progressive liver disease with an increased risk of hepatocellular carcinoma. Hence, frequent surveillance for hepatocellular carcinoma is recommended from infancy. PFIC-5 patients usually have rapidly progressive liver disease with early onset coagulopathy, high alpha-fetoprotein and ultimately require a liver transplant. Subjects with MYO5 B-related disease can present with isolated cholestasis or cholestasis with intractable diarrhea (MVID). These children are at risk of worsening cholestasis post intestinal transplant (IT) for MVID, hence combined intestinal and liver transplant or IT with biliary diversion is preferred. Immunohistochemistry can differentiate most of the variants of PFIC but confirmation requires genetic analysis.

Liver Transplantation in Progressive Familial Intrahepatic Cholestasis with Normal Gamma-Glutamyl Transferase: Evaluation of Post-transplant Steatosis and Steatohepatitis

Background: Progressive familial intrahepatic cholestasis is a disease presenting with severe cholestasis and progressing to the end-stage liver disease later. Liver transplantation is a treatment modality available for progressive familial intrahepatic cholestasis, especially in patients with end-stage liver disease or those who are unsuitable for or have failed biliary diversion. Objectives: To evaluate clinical and pathological characteristics of progressive familial intrahepatic cholestasis patients who had undergone liver transplantation and to determine post-transplant steatosis and steatohepatitis. Methods: We evaluated 111 progressive familial intrahepatic cholestasis patients with normal gamma-glutamyl transferase that performed liver transplantation in Shiraz Transplant Center in Iran between March 2000 and March 2017. Results: The most common clinical manifestations were jaundice and pruritus. Growth retardation and diarrhea were detected in 76.6% and 42.5% of the patients. After transplantation, growth retardation was seen in 31.5% of the patients, and diarrhea in 36.9% of them. Besides, 29.1% of the patients died post-transplant. Post-transplant liver biopsies were taken from 50 patients, and 15 (30%) patients had steatosis or steatohepatitis, five of whom (10%) had macrovesicular steatosis alone, and 10 (20%) had steatohepatitis. Only one patient showed moderate bridging fibrosis (stage III), and none of them showed severe fibrosis. Conclusions: Liver transplantation is the final treatment option for these patients, and it can relieve most clinical manifestations. However, post-transplant mortality rate was relatively high in our center. Diarrhea, growth retardation, and steatosis are unique post-transplant complications in these patients. The rate of post-transplant steatosis and steatohepatitis in patients with liver biopsy in our study was 30%, with a significant difference from previous studies.

Case Report: A Novel Single Variant TJP2 Mutation in a Case of Benign Recurrent Intrahepatic Cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is a disease on the spectrum of familial intrahepatic cholestasis caused by homozygous ABCB11 or ATP8B1 mutations. In recent years, genetic testing has allowed for discovery of a variety of homozygous or compound heterozygous TJP2 mutations associated with progressive familial intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. To our knowledge, no cases of BRIC caused by a single variant mutation of TJP2 have been reported. We describe a 15-year-old female presenting with recurrent episodes of jaundice, vomiting, with intense pruritus, anorexia, and weight loss. Blood work revealed elevated serum conjugated bilirubin and liver enzymes but normal gamma-glutamyl transferase, consistent with BRIC. A genetic panel identified a not previously described single allele mutation in TJP2 of unknown functional significance. This is the first reported case of a clinical entity resembling BRIC with a heterozygous mutation in TJP2, without associated mutations in other cholestasis-related genes.

Which Preoperative Findings Translate to a Positive Intraoperative Cholangiogram?

Background: The most common investigations used in the preoperative diagnosis of choledocholithiasis are ultrasound and liver function tests (LFTs). These modalities have a low sensitivity for detecting common bile duct stones among the intermediate-risk groups. Aim: The aim of the study is to identify preoperative findings which predict choledocholithiasis in intermediate-risk groups. Describe the implications of a positive intraoperative cholangiogram (IOC). Materials and Methods: A retrospective study of all consecutive laparoscopic cholecystectomies with IOC performed. Data were collected over the past 2 years between January 1, 2015, and December 31, 2016. Standard demographic variables, preoperative symptoms, LFTs, IOC findings, abdomen ultrasound, and postoperative symptoms were included in the study. Results: Of 237 laparoscopic cholecystectomies 23 cases were planned for IOC. The median age was 41 years. Seventeen cases were female. Indications were 12 biliary colic, eight gallstone pancreatitis, two cases of acute cholecystitis, and one case was for ascending cholangitis. Four cases had a positive IOC, and in this group, the median age was 44.5 years with one male. The mean common bile duct diameter was 6.5 mm. Two patients had biliary colic, one patient gallstone pancreatitis, and one acute cholecystitis. One patient had a history of jaundice, and all four cases had elevated gamma-glutamyl transferase (GGT) above 40 mmol/l, three cases had alkaline phosphatase (ALP) above 98 mmol/l. Postoperative, out of 23 cases, five cases had an endoscopic retrograde cholangiopancreaticogram, repeated ultrasound in three cases, persistence symptoms in four cases. Conclusions: GGT was the strongest predictor of choledocholithiasis. A normal GGT seems to be quite good at ruling out Cannabidiol stones. ALP was less accurate. Gallstone pancreatitis is not a good predictor, but it is importance to exclude choledocholithiasis before/during cholecystectomy. There is no relation between the IOC and persistent symptoms.

The Mystery of Episodic Recurrent Jaundice in a Young Male: Cholestasis With a Normal Gamma-Glutamyl Transferase

Benign recurrent intrahepatic cholestasis (BRIC) is a very rare autosomal recessive genetic disorder which presents with recurrent jaundice. We report the case of a young male with a history of methamphetamine use who presented with recurrent episodes of right upper quadrant abdominal pain, vomiting, dark urine, and pale stools. These symptoms always resolved within four weeks of presentation. During these episodes, the patient had a cholestatic pattern derangement of liver function tests with a normal gamma-glutamyl transferase (GGT). Workup for abnormal transaminases was unremarkable. A percutaneous liver biopsy obtained on the third visit was notable for a parenchymal lobule that exhibited slight Kupffer cell hyperplasia and subtle evidence of canalicular cholestasis. There was no evidence of cirrhosis, steatosis, hepatitis, or malignancy. Thus, a diagnosis of BRIC was made, and the patient was managed conservatively. Recognition of this rare entity is critical since its benign natural history is reassuring for the patient, and physicians can refrain from repetitive expansive and costly workups.

Peri-operative derangement in liver function tests in older patients with neck of femur fracture.

Neck of femur fracture is a common consequence of falls in the elderly with a large burden of morbidity and mortality. Derangement in liver function tests (LFTs) is frequently seen in elderly people with neck of femur (NOF) fracture in the peri-operative period and can indicate serious and treatable underlying pathology as well as prognosis.On admission, raised alkaline phosphatase (ALP) levels with normal gamma-glutamyl transferase (GGT) suggest underlying bone pathology such as osteomalacia or Paget's disease but do not confirm or exclude osteoporosis. ALP can also be raised by non-bone pathology such as congestive cardiac failure and chronic kidney disease. LFT derangement in cardiac failure is associated with poorer prognosis. Post-operatively, ALP levels rise after the first week with a peak at 3-4weeks and then fall thereafter. The rate at which they fall may help indicate bone healing in trochanteric fractures. Derangement in other LFTs is commonly due to hepatic injury; causes include trauma, alcohol, and viral hepatitis. There are also iatrogenic causes including surgery and commonly prescribed medication such as beta-lactam antibiotics, non-steroidal anti-inflammatories, and paracetamol.The differential diagnosis for deranged LFTs in the elderly peri-operatively is wide; however, most causes can be elicited through careful history and examination with occasional need for further investigations.

Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study

BackgroundNonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels.MethodsWe designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models.ResultsThe change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group.ConclusionsThe incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.

Treatment of rickets and dyslipidemia in twins with progressive familial intrahepatic cholestasis type 2

BackgroundProgressive Familial Intrahepatic Cholestasis Type 2 (PFIC2) is a rare congenital cholestatic liver disease that progresses to end stage liver disease. It is associated with fat soluble vitamin D deficiency rickets and severe dyslipidemia; however, treatment of these secondary effects remains a challenge.Case presentationOne year old twin males born to a mother with intrahepatic cholestasis during pregnancy presented with jaundice, pruritus and failure to thrive. Lab evaluation revealed significant transaminitis, direct hyperbilirubinemia and normal gamma glutamyl transferase (GGT). Genetic studies confirmed PFIC2. Further evaluation for fat soluble vitamin deficiencies revealed severe vitamin D deficiency rickets. High dose vitamin D replacement therapy using Ergocalciferol (Vitamin D2) 50,000 IU three times a week over 10 weeks led to the improvement of Vitamin D, 25-Hydroxy (25-OH) serum levels and resolution of rickets. Dyslipidemia with very low high density lipoprotein-cholesterol (HDL-C) and high triglycerides was more profound in our patients compared to what has been described in the literature thus far. The dyslipidemia improved 2 months after internal biliary diversion.ConclusionsHigher doses of Vitamin D therapy are needed for treatment of rickets secondary to cholestasis. Extremely low HDL-C levels are characteristic of PFIC and improve with treatment of underlying cholestasis. Maternal intrahepatic cholestasis during pregnancy can be an early warning sign.