Raised Gamma Glutamyl Transferase Research Articles

MO004PRIMARY BILIARY CHOLANGITIS PRESENTING WITH RENAL FANCONI SYNDROME: A FORGOTTEN PHENOTYPE

Abstract Background and Aims Primary biliary cholangitits (PBC) is an autoimmune liver disease, leading to liver fibrosis and cirrhosis. It is a rare disease affecting 1 in 3-4000 people and is more common in females. Symptoms may go unnoticed and include itch and fatigue. Most patients have anti-mitochondrial antibodies (AMA) as well as raised gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels. First line treatment for PBC is ursodeoxycholic acid and is usually continued lifelong. It improves liver biochemistry, histological progression of liver disease and liver transplant-free survival. Renal complications of PBC include distal renal tubular acidosis (RTA), tubule-interstitial nephritis (TIN) and renal Fanconi syndrome. Method We reviewed a case of PBC presenting with renal Fanconi syndrome. Results A 48-year-old female was referred to the renal clinic due to progressive decline in renal function since she was diagnosed with type 2 diabetes in 2007. She was also known to have AMA (>1:640) and previously had transient transaminitis. She was clinically well with no major symptoms but reported that she had had a few episodes of urinary tract infection in the previous year. Her diabetes was managed with lifestyle modifications in the past until a few months ago when Metformin was introduced. However, her HbA1c level had never been greater than 55 mmol/mol. Urine dipstick in the clinic showed pH of 6, blood+, glucose+++, protein+++ and ketone trace. The severity of glycosuria was inconsistent with her glycaemic control. There was a disparity between her urine albumin/creatinine ration (ACR) of 18.8g/mol and protein/creatinine ratio (PCR) of 124mg/mmol. Myeloma screen was negative and further urine analysis showed generalised aminoaciduria. She also had hypouricaemia, intermittent hypophosphataemia and non-anion gap metabolic acidosis. These results are in keeping with renal Fanconi syndrome. Her eGFR was 48 ml/min/1.72m2 in 2007 and was 21 ml/min/1.72m at the time of review. A renal biopsy was undertaken, and the appearances were suggestive of mild tubulo-interstitial nephritis; the glomeruli were unremarkable; there was mild chronic tubulo-interstitial damage. She was started on oral steroid, sodium bicarbonate and ursodeoxycholic acid. The course of steroid had a slight transitory beneficial effect on the renal function. Conclusion Distal RTA is the usual renal feature of PBC, occurring in 1/3 of cases with advanced disease. In contrast, proximal RTA associating with renal Fanconi syndrome occurs rarely. Like our case, the cases that have been previously reported show that Fanconi syndrome occurred during the early phase of PBC in the absence of marked hepatic abnormalities, and were associated with CKD. Fanconi syndrome and TIN are renal features of mitochondrial cytopathies and are perhaps a forgotten association of PBC. Antimitochondrial antibodies may play a role in the onset of tubulo-interstitial nephritis and Fanconi syndrome.

Trajectories of Alcohol Use Disorders and Their Differential Impact: A Population-Based Cohort Study in Goa, India.

AimsThe aim of this study was to examine trajectories of Alcohol Use Disorders (AUD) over a 6 year period and compare the bio-psycho-social correlates between these trajectories.MethodsCommunity-based cohort of 1899 adult men were interviewed in 2006–2008 and 2012–2014. AUD were assessed using the Alcohol Use Disorder Identification Test, and potential correlates including psycho-social problems, morbidity and physiological parameters were measured at follow-up. Logistic regression was conducted to estimate odds ratios (ORs) for the association of persistent and incident AUD, respectively, with the potential correlates. Analyses were weighted to account for sampling design, number of adults aged 18–49 years in the household and non-response.ResultsCompared with men who had recovered from AUD, there was strong evidence (P < 0.001) that men with persistent AUD were more likely to have marital problems, tobacco use, and raised Gamma Glutamyl Transferase (GGT) and strong evidence (0.001 < P < 0.01) that they were more likely to have workplace problems, social problems, increased healthcare contact and raised Mean Corpuscular Volume (MCV). Compared with men who did not have AUD at baseline and follow-up, there was strong evidence (P < 0.001) that men with incident AUD were more likely to have workplace problems, social problems, marital problems, tobacco use, and raised GGT and strong evidence (0.001 < P < 0.01) that they were more likely to have hypertension, accident and injuries and Common Mental Disorders (CMD).ConclusionThis community-based longitudinal study of AUD, the first from a low and middle income country, clearly demonstrates significant health and social consequences of AUD in men and highlights the need for interventions for their treatment and prevention.Short SummaryCompared to persistent AUD, recovery from AUD has several benefits in health and social domains. Compared to developing new AUD, not having AUD has several benefits in health and social domains. Sustaining the state of not having AUD or recovery can lead to accumulation of health and social capital over time.

1260P - Safety of necitumumab and pembrolizumab combination therapy in patients with stage IV non-small cell lung cancer (NSCLC): a phase 1b expansion cohort study

Safety of anti-EGFR necitumumab (neci) was evaluated in combination with anti-PD1 pembrolizumab (pembro) in pre-treated Stage IV NSCLC patients (pts). Single-arm, multicenter Phase 1b study with expansion cohort to investigate the safety and effectiveness of neci combined with pembro in pts with Stage IV NSCLC. Part A: escalating doses of neci (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembro (200 mg IV) on Day 1 Q3W. Part B: expansion cohort with neci at dose identified in Part A administered with pembro. Major eligibility criteria included progression after 1 platinum-based chemotherapy and ECOG PS 0-1. Tumor tissue was collected for analysis of biomarkers. Treatment continued until disease progression or unacceptable toxicity. We present data from an interim safety analysis conducted after the first 15 pts who received the recommended neci 800mg dose completed ≥2 cycles of treatment or discontinued early. All pts in Part A were included. Part A completed without dose-limiting toxicity. As of 11 Feb 2016, 18 pts (neci 600 mg n = 3, 800 mg n = 15) were eligible for inclusion. Patients were female 44.4%, had median age 66.5 years [range 48-76], and adenocarcinoma histology 77.8%. All pts experienced ≥1 treatment-emergent adverse event (AE) with ≥1 related to study treatment. Four serious AEs occurred in 3 (16.7%) pts (all respiratory and mediastinal); none were treatment-related. No discontinuations or deaths were attributable to AEs. AEs occurring with >15% frequency are listed (table). Four (22.2%) pts experienced 8 grade >2 AEs: acute respiratory failure, hypokalaemia, hypophosphataemia, infusion-related reaction, pulmonary embolism, raised gamma-glutamyl transferase (1 pt each), and dyspnoea (2 pts).Tabled 1Treatment-emergent AEs of frequency >15%, n (%)MedDRA preferred termInterim safety population (N = 18)Dermatitis acneiform16 (88.9)Dry skin8 (44.4)Asthenia7 (38.9)Appetite decreased4 (22.2)Constipation4 (22.2)Headache4 (22.2)Hypoalbuminaemia4 (22.2)Hypophosphataemia4 (22.2)Pruritus4 (22.2)Anaemia3 (16.7)Diarrhoea3 (16.7)Dyspnoea3 (16.7)Fatigue3 (16.7)Hypokalaemia3 (16.7)Respiratory tract infection3 (16.7)Stomatitis3 (16.7) Open table in a new tab The combination neci and pembro appears tolerable. The safety profile corresponds to individual profiles for both drugs, with no additive toxicities.

An interesting case of antenatal hiccups – a clue aiding a prompt diagnosis of non-ketotic hyperglycinaemia

A term baby returned for a routine neonatal discharge check on her second day of life. On examination was found to be apnoeic and hypotonic. She then had a generalised seizure, terminated by phenobarbitone. Over the course of the next 24 hours she was invasively ventilated having become completely apnoeic. She received treatment for possible sepsis including anti viral treatment. The only positive results yielded from blood testing and imaging were small ventricles on cranial ultrasound and a raised gamma glutamyl transferase. It was noted that the patient was hiccupping and on revisiting the antenatal history her mother commented she had thought her daughter had hiccupped consistently (multiple times every day) from twenty weeks gestation. With this history and her clinical presentation a neurological opinion was sought. Many plasma, urine and cerebrospinal fluid (CSF) investigations were requested. The paired plasma and CSF glycine levels were in a ratio of 0.4 (normal up to 0.06). This confirmed the clinical suspicion of non-ketotic hyperglycinaemia. This baby was referred to a tertiary intensive care unit, for neurological opinion and withdrawal of life support. This case illustrates the importance of a thorough antenatal history when reviewing babies ready for discharge as well as the danger of babies being discharged home prior to being reviewing a formal neonatal check. With the postnatal wards needing beds there is significant pressure to review the babies within the first day of life, many are being discharged before paediatric review. The case also revealed the importance of beginning discussions of possible outcomes including withdrawal of life support and palliation, at a local level before transfer to another centre. The outcome for this baby would not have been different. However, there are babies who potentially have serious pathology that would require prompt investigation, diagnosis and life saving treatment. The practice of babies being discharged before neonatal discharge check needs review. Trainees are often the doctors best positioned to begin breaking bad news but sometimes we can be afraid we are doing it inadequately and shy away from doing so.

A rare case of intra-cardiac metastasis from an appendiceal carcinoid tumour without liver metastases

Metastatic tumours to the heart are more common than primary cardiac neoplasms and can occur in as many as 1.5% of patients with malignancies. The most common primary tumours that metastasise to the heart are breast, lung and malignant melanoma. The cardiac tissue most frequently affected is the myocardium, followed by the pericardium and then the endocardium. Metastatic tumours extending into the heart chambers and conducting system are less common. The most common route of metastasis is through lymphatic spread, followed by haematogenous dissemination. Carcinoid metastases to the heart are extremely rare, and only 19 cases have been described in the literature over the past 30 years. These invariably occur in the presence of liver metastases. We present a unique case of a patient who, at post-mortem, was found to have intra-cardiac carcinoid metastases involving a sensitive cardiac structure, in the absence of liver or any other metastases. A 51-year-old white woman presented with a 3-month history of central abdominal pain, nausea, lethargy and malaise. She had previously undergone lapararoscopic cholecystectomy and was prescribed hormone replacement therapy and anti-depressant medication. She denied a history of alcohol misuse, previous blood transfusions or risk factors for hepatitis. Clinical examination was unremarkable; liver function tests were shown to be abnormal (raised gamma-glutamyl transferase and alkaline phosphatase). Abdominal ultrasound showed an echogenic pattern suggestive of metastatic disease, with cirrhosis a less likely possibility. Abdominal and chest computed tomography scan revealed a small (<5 mm) lesion in the left lobe of the liver possibly representative of metastatic disease. Retro-peritoneal lymphadenopathy was also noted, with enlarged lymph nodes seen in the porta hepatis and para-aortic regions. A small right pleural effusion was also seen. No obvious primary lesion was identified. Upper and lower gastro-intestinal endoscopy were inconclusive for a primary neoplastic lesion. Her symptoms worsened with increased abdominal distension, shortness of breath and clinical ascites. Radiological biopsy of the paraaortic lesions was not feasible, and she proceeded to a diagnostic laparoscopy and biopsy. At laparoscopy, a mass lesion involving the appendix and terminal ileum with omental caking and peritoneal deposits was found. The procedure was converted to a laparotomy: An appendicectomy and palliative bypass were performed. A liver biopsy was also carried out. Histology revealed a carcinoid tumour in the appendix with infiltration into mesoappendiceal fat and evidence of perineural invasion. The liver wedge biopsy showed diffuse granulomatous inflammatory change but no evidence of malignancy. Two weeks after surgery, the patient suffered a sudden cardiac arrest. Cardiopulmonary resuscitation was performed, with restoration of pulse at 55 bpm but no blood pressure. An electrocardiogram showed left bundle branch block. The family declined any life-sustaining measures, and the patient passed away shortly afterwards. A post-mortem was carried out, which revealed the presence of Hodgkin’s lymphoma in both the liver and retroperitoneal nodes. No evidence of carcinoid involveInt J Colorectal Dis DOI 10.1007/s00384-009-0709-z

Pregnancy outcome in hyperemesis gravidarum and the effect of laboratory clinical indicators of hyperemesis severity

To determine pregnancy outcome in hyperemesis gravidarum and the effect of metabolic, biochemical, hematological and clinical indicators of disease severity on outcome. A retrospective study based on 166 women hospitalized for confirmed hyperemesis gravidarum from January 2004 to January 2005. For each woman, three controls matched for age, parity and ethnicity were obtained from our 2004 birth register. The effects of laboratory indicators of hyperemesis severity were separately analyzed within the hyperemesis gravidarum study group. Outcome measures include stillbirths, Apgar score, mode of delivery, low birthweight, preterm delivery, labor induction, pregnancy induced hypertension and gestational diabetes. Analysis was by t-test, Fisher's exact test and multivariable logistic regression analysis. Women with hyperemesis had similar pregnancy outcome compared to controls. In the analysis of laboratory indicators of hyperemesis severity and pregnancy outcomes, hypokalemia (adjusted odds ratio [AOR] 2.7: 95% confidence interval [CI] 1.0-6.8) was associated with emergency operative delivery, high creatinine (odds ratio 4.4: 95% CI 1.3-15) with labor induction and raised gamma glutamyltransferase (AOR 7.5: 95% CI 1.2-46) with the development of gestational diabetes. Hyperemesis gravidarum per se was not associated adverse pregnancy outcome. Hypokalemia, high creatinine and raised gamma glutamyltransferase in women with hyperemesis gravidarum were associated with adverse pregnancy outcome.

Early intervention in patients with excessive consumption of alcohol: A controlled study

From a population of 2,114 patients attending somatic outpatient clinics, 78 patients were selected who had either an excessive consumption of alcohol according to questionnaires or a raised gamma glutamyltransferase (GGT) value (above 0.6 μkat/l) due to alcohol. They had not undergone treatment for problem drinking previously, and had no serious alcohol dependence. They were thereby classified as excessive consumers of alcohol, and randomly allocated to an intervention (n=36) or to a control group (n=42). Those in the intervention group were followed up by a nurse once a month and by a doctor every third month for a total of 12 months. Laboratory tests were taken monthly. Consumption of alcohol, GGT and triglyceride levels, and sickness allowance days were decreased in the intervention group compared to the time before intervention. In contrast, the number of sickness allowance days in the control group increased. There was also a tendency towards a positive effect of intervention on the number of consultations made with a statistically not significant decrease of consultations after intervention. The study thus indicates that an early and relatively simple intervention programme for problem drinkers may be effective and can be carried out at a low cost and with a positive response from the patients.

Gamma glutamyl transferase activity in rat colon during experimental colonic carcinogenesis.

Colonic gamma glutamyl transferase activity is raised in colonic malignancy. This study was undertaken to determine how early and how extensively this raised activity occurs during carcinogenesis. Sixty rats were given weekly injections of dimethylhydrazine for 16 weeks, and 20 rats acted as controls. Groups of treated and control rats were sacrificed at regular intervals during the pre-cancerous phase of carcinogenesis, and gamma glutamyl transferase activity was measured at several sites in the colon. Gamma glutamyl transferase activity was raised as early as 4 weeks after the first injection of dimethylhydrazine (p less than 0.05), and the elevation persisted until the development of overt tumours. The raised gamma glutamyl transferase activity was observed throughout both the proximal and distal colon long before the appearance of macroscopic tumours. We conclude that an early and widespread elevation of colonic gamma glutamyl transferase activity occurs during carcinogenesis. This may have useful applications in the early detection of colonic malignancy.