Rise In Transaminases Research Articles

Starvation in Mice Induces Liver Damage Associated with Autophagy.

Anorexia nervosa (AN) induces organ dysfunction caused by malnutrition, including liver damage leading to a rise in transaminases due to hepatocyte damage. The underlying pathophysiology of starvation-induced liver damage is poorly understood. We investigate the effect of a 25% body weight reduction on murine livers in a mouse model and examine possible underlying mechanisms of starvation-induced liver damage. Female mice received a restricted amount of food with access to running wheels until a 25% weight reduction was achieved. This weight reduction was maintained for two weeks to mimic chronic starvation. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured spectrophotometrically. Liver fat content was analyzed using an Oil Red O stain, and liver glycogen was determined using a Periodic acid-Schiff (PAS) stain. Immunohistochemical stains were used to investigate macrophages, proliferation, apoptosis, and autophagy. Starvation led to an elevation of AST and ALT values, a decreased amount of liver fat, and reduced glycogen deposits. The density of F4/80+ macrophage numbers as well as proliferating KI67+ cells were decreased by starvation, while apoptosis was not altered. This was paralleled by an increase in autophagy-related protein staining. Increased transaminase values suggest the presence of liver damage in the examined livers of starved mice. The observed starvation-induced liver damage may be attributed to increased autophagy. Whether other mechanisms play an additional role in starvation-induced liver damage remains to be investigated.

Predictive correlation of adverse clinical outcomes with thrombocytopenia in dengue fever

Background: Dengue fever is the most widely distributed viral infection in the world with more than 100 million people affected. In this study we attempt to study the co-relation between the nadir of the plateletcount and the onset of warning signs (persistent pain abdomen and vomiting, mucocutaneous bleed or clinical fluid accumulations). A positive co-relation in between these two elements could help predict onset of shock and third spacing and facilitate prognostication and early intervention. Methods: We studied 82 patients with a diagnosis of dengue fever, the basis of which was clinical signs and symptoms with a positive NS1 antigen test. The nadir of thrombocytopenia and rise in transaminases were studied along with onset of various warning signs. Results: The nadir of thrombocytopenia correlates with onset of warning signs such as clinical fluid accumulation (two tailed P value <0.002) and mucosal bleed (two tailed P value <0.001). However, the rising value of transaminases does not co-relate statistically with onset of warning signs in Dengue fever. Conclusions: The age of patients ranged from 18 to 60 with 23 out of 83 (27.7%) being in the 30-40 years age group.

P146 Hepatitis E infection in rheumatic disease: no evidence of chronicity

Abstract Background/Aims Hepatitis E virus [HEV] is the most common cause of acute hepatitis in developing countries but rare in the industrialised world. In the vast majority it causes an acute self-limiting infection which is often asymptomatic. It is usually detected due to raised transaminases in liver function tests [LFTs] which are checked as part of DMARD monitoring. There is increasing literature that immunocompromised patients with human immunodeficiency virus or transplant recipients are at risk of developing chronic HEV infection, which can progress to liver failure. It is unclear that immunosuppressed patients who have a rheumatological conditions have similar issues, which we have looked into locally. Chronic infection is defined as having detectable RNA for over 3 months. Methods Retrospective review of patients attending rheumatology outpatient clinic for blood monitoring, who had positive Hepatitis E serology between 2010 and 2021. Results We identified nine patients attending the rheumatology clinic in Sheffield, confirmed as having acute infection with HEV as Hep E IgM antibody was positive. They were all on immunosuppression and hence having regular monitoring bloods and were receiving either prednisolone, DMARDS or biologics or in combination. There were five males and four females, with an age range of 38 to 71 years. Eight patients had acutely abnormal LFTs with a peak ALT [normal <41 IU/L] ranging from 59 to 1651 while in one the LFTs remained normal. Eight out of nine patient's LFTs recovered to baseline over a period ranging from 3 to 6 weeks (one moved out of area). Five patients had HEV RNA tested after the positive IgM. Two patients had HEV RNA detected initially, the rest had undetectable RNAs. Repeat RNA testing 2 months later was undetectable in both patients, suggesting no chronic HEV infection in all patients. No patients were given HEV antiviral treatment. Almost all patients had their immunosuppressant treatment paused, which was recommenced once their LFTs normalised. In all patients LFTs have remained normal even after 5 years with no evidence of reactivation in spite of ongoing immunosuppression. We plan to check HEV RNA if the LFTs were to become abnormal. Conclusion Our case series raises awareness that rheumatologists should consider HEV as a differential in patients with a marked unexpected rise in transaminases. We observed that all our patients cleared HEV infection and there was no evidence of chronicity even with ongoing immunosuppression, which is different from Hepatitis B & C. We recommend that immunosuppressant treatment should be stopped initially following HEV infection and reintroduced once LFTs have normalised and HEV RNA is undetectable. Disclosure C.A. Zollinger-Read: None. M. Raza: None. M.F. Kazmi: None.

PREDICTIVE CORRELATION OF ADVERSE CLINICAL OUTCOMES WITH THROMBOCYTOPENIA IN DENGUE FEVER: A SINGLE CENTER EXPERIENCE

Background: Dengue fever is the most widely distributed viral infection in the world with more than 100 million people affected. In this study we attempt to study the co-relation between the nadir of the platelet count and the onset of warning signs (persistent pain abdomen and vomiting, mucocutaneous bleed or clinical uid accumulations). A positive co-relation in between these two elements could help predict onset of shock and third spacing and facilitate prognostication and early intervention. Methods: We studied 82 patients with a diagnosis of dengue fever, the basis of which was clinical signs and symptoms with a positive NS1 antigen test. The nadir of thrombocytopenia and rise in transaminases were studied along with onset of various warning signs. Results:The nadir of thrombocytopenia correlates with onset of warning signs such as clinical uid accumulation (two tailed P value <0.002) and mucosal bleed (two tailed P value <0.001). However, the rising value of transaminases does not co-relate statistically with onset of warning signs in Dengue fever. Conclusions: The age of patients ranged from 18 to 60 with 23 out of 83 (27.7%) being in the 30-40 years age group. Clinical uid accumulation was seen in 54 (64.7%) patients, mucosal bleed in 61 patients (74.3%) and liver was palpable more than 2 cm in 28 patients (33.7%). The importance of serial monitoring of platelets is important not only for the prediction of severe dengue, but also with the onset of other warning signs such as clinical uid accumulation. This nuanced fact re-enforces the critical importance of platelet count predict other warning signs which contribute to morbidity and mortality in dengue fever.

552 NON-ALCOHOLIC FATTY LIVER DISEASE AND THE HEPATIC RESPONSE TO SURGERY AMONG PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA

Abstract Visceral obesity, metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) represent risk factors for esophageal adenocarcinoma (EAC). The prevalence of NAFLD, and its impact on the hepatic response to esophageal cancer surgery, has never been systematically evaluated, and was the focus of this study. Methods Consecutive patients (n = 547) treated with curative intent for esophageal cancer from 2007–2017 were studied. In an unselected subgroup (n = 138), liver biopsies were collected intraoperatively and assessed for NAFLD, defined as ≥5% macrovesicular steatosis. Postoperative complications were recorded prospectively, including Clavien-Dindo grade (CD) and comprehensive complications index (CCI). Liver function tests were monitored in the first postoperative week, with hepatocellular dysfunction defined as a transaminase rise ≥3-times the upper limit of normal. Multivariable logistic and Cox proportional hazards regression were utilised to determine independent predictors of operative and oncologic outcome. The study was registered on clinicaltrials.gov (NCT04152044). Results NAFLD was evident in 62 patients (47.7%) who had biopsies, with a mean (SD) score of 10.1(9.3)%. NAFLD was associated with metabolic syndrome (41.9 vs 25%, P = 0.04), obesity (44.1 vs 11.9%, P < 0.001) and visceral adiposity (172.8 vs 136.5 cm2, P = 0.008), but not clinical or pathologic disease stage. Postoperative hepatocellular dysfunction was observed in 287 (54.8%) patients, associated with NAFLD (P = 0.006), but not visceral obesity (P = 0.396), and normalized in a median (range) of 9 (1–76) days. NAFLD did not impact oncologic outcome, but postoperative hepatocellular dysfunction was independently associated with reduced overall survival (HR 1.87 (1.16–2.29), P = 0.002) on multivariable analysis. Conclusion A marker of metabolic dysregulation in obesity-associated carcinogenesis, NAFLD is prevalent among patients with esophageal cancer. Liver dysfunction post esophagectomy is common, and although temporary, is associated with worse oncologic outcomes. Baseline NAFLD did not incur an adverse long-term oncologic outcome.

Association of early recurrence within one year of liver transplant for hepatocellular carcinoma with poor survival.

296 Background: Treatment of hepatocellular carcinoma (HCC) recurrences following liver transplant is challenging. All the clinical trials of systemic therapies for advanced HCC excluded patients with any history of organ transplant. Here we review outcome, and the safety and efficacy of the application of systemic medical therapies in this clinical setting. Methods: This is a retrospective cross-sectional study of consecutive adult patients with recurrence of HCC following liver transplant for the indication of treatment of HCC in Queen Mary Hospital from January 2005 to January 2018. Results: Forty-three consecutive patients with a recurrence of HCC following liver transplant were identified from 2005 to 2018. Median survival from diagnosis of recurrence was 17 months (CI 11.3, 22.7). Early recurrence within 12 months of transplant was associated with a significantly worse median survival of 10 months CI 8.5, 11.4) compared to 26 months (CI 18.8, 33.2) when recurrences occurred after 12 months from transplant (p< 0.001) after adjustment with peritumoural vascular invasion, first line therapy with sorafenib, any second line therapy and use of mTOR inhibitors as immunosuppressants, with a hazard ratio of 0.104 (log-rank test, p<0.001). 41 patients who received medical systemic therapies, 34 (79.1% ) received sorafenib as the first line systemic therapy. 47.1% (N= 16) received subsequent lines of systemic therapies (ranging from 1 to 4 lines). Hand-foot syndrome was most common among the adverse events and it was observed in 34.7% patients treated with sorafenib. It led to dose interruptions in 8.8 % of patients who were given sorafenib. 26.7% had grade 1 diarrhoea. 14.3% had grade 1 transaminase rise. Conclusions: Early recurrence within one year from transplant was the most significant risk factor. Treatment efficacy and adverse events and tolerability of sorafenib were comparable with those in the setting of advanced HCC without transplant.

EP03 Parechovirus in a pathologist

Case report - IntroductionA 42-year-old pathologist presented with a 1-week history of muscle pain and subjective weakness. CK level on 2 occasions was >3000.The patient was systemically well with no past medical history, medication, or foreign travel. He had 1-day history of shivering with no recorded pyrexia. He reported pain in his proximal muscles and neck and subjective muscle weakness and lack of finger dexterity with no objective findings. Case report - Case descriptionAutoantibody panel and inflammatory markers were performed which were normal. Full blood count with differential white cell count including eosinophils was normal. There was a modest rise in transaminases. Myositis panel was negative. Full viral screen was positive for parechovirus with titre of 30 on several samples. MRI proximal musculature showed increased fluid signal in the perifascial region of both thighs primarily involving the hamstrings, not definitive for myositis but suggestive of fasciitis.Case report - DiscussionParechovirus is a picornavirus, often causing mild gastrointestinal or respiratory illness but has been associated with epidemic myalgia and myositis during outbreaks of parechovirus in a Japanese population.The patient improved spontaneously with CK reduced to 187 and improved symptoms after 1 week. We expect a good outcome and will review on patient's request if necessary.Case report - Key learning pointsParechovirus can cause myofasciitis which is usually mild and self-limiting. It can be associated with elevated CK, transaminases and MRI findings and can be confirmed on respiratory viral swab.

Idiopathic nonhistaminergic acquired angioedema in a patient with coronavirus disease 2019

Idiopathic nonhistaminergic acquired angioedema in a patient with coronavirus disease 2019

M200. CLOZAPINE-INDUCED HEPATOTOXICITY: TWO CASE REPORTS

BackgroundLiver function tests (LFT) abnormalities secondary to antipsychotics (AP) are common, early, and often mild and transient. Up to 60% of patients on clozapine experience an increase in LFT, at medium-range doses (200–400mg), and usually dose-dependent, with spontaneous resolution in half the cases, no dose reduction needed. Fatal outcomes are extremally rare, with an incidence around 0.001%. The hepatotoxic effects of clozapine have received considerable less attention than its cardiometabolic and hematologic counterparts. Consequently, there are few independents guidelines on how to handle such cases. Our objective is to report 2 cases of mild clozapine-induced liver injury and discuss possible protocols of early detection and management.MethodsWe described 2 cases of clozapine induced hepatitotoxicity in patients with schizophrenia.ResultsCASE 1: 33 y/o, male, caucasian, 5y of illness. Had previously used risperidone and paliperidone, and was currently taking olanzapine, without good response. Clozapine 25mg/d was introduced – in addition to olanzapine 15mg/d – with a 25mg increase every 2d. On D12 of clozapine (150mg/day), he reported nausea, diarrhea and dizziness, worsening the next few days, with confusion and choluria. Blood tests detected increases of ALT (242U/L), serum bilirubin (total 1.59mg/dL; direct 1.29g/dL; indirect 0.3mg/dL) and ESR (60mm/1sth). He was admitted and AP were interrupted. After 48h, presented full clinical recovery. Leukocyte blood count and ESR were still high in the first week, but LFT and bilirubins progressively decreased. All exams normalized in 1m. After 2w, olanzapine was reintroduced, with no LFT changes.CASE 248 y/o, female, caucasian, 15y of illness. Partial response to risperidone and olanzapine. 20d after clozapine was introduced (75mg/d), she reported nausea, vomiting, choluria, abdominal pain and headache. Presented elevated AST (88U/L), ALT (77U/L), CK (732U/L), GGT (141U/L) and ALP (161U/L), decreased Hb (9.6g/dL), mild leukocytosis (10,800/mm3), mild leukocyturia and hematuria, though bilirubin and platelet levels were normal. Clozapine was immediately suspended and olanzapine 10mg/d reintroduced progressively, maintaining partial remission of positive symptoms. Blood counts and LFT were normalized within 1m and no hospitalization was required.DiscussionBoth cases illustrate different presentations of hepatotoxicity by clozapine. Case 1 had no LFT dosage before the introduction and no indicative hepatic risk. With a regular dose evaluation, developed a severe hepatic injury. Case 2 had a history of side effects to previous antipsychotics. She started with normal LFT levels and evolved with mild hepatic injury due to the slow dose increase.In both cases LFT weren’t requested periodically until clinical symptoms emerged. At this point, it was fundamental to instruct the patient to report any warning clinical signs.A serialized LFT protocol wouldn’t show benefits to prevent hepatotoxicity in the outcome of our cases. However, some authors recommend monitoring them 4–6m after starting AP, specially the first 4–5w, since it could predict a bad outcome of severe hepatitis. Previous studies point ALT>3ULN or ALP>2ULN or any rise of transaminases with CK or bilirrubin altered as sensitive markers for liver damage. In such cases, the AP should be suspended.There is no consistent data regarding the indication of clozapine rechallenge after hepatotoxicity. Yet, the early onset of drug injury (1–6w) and the rapid rise in ALT on rechallenge may be a contraindication of a new try or continuous use of the drug.Considering guidelines on clozapine induced hepatotoxicity are not clear, we suggest the topic to be revisited and better established.

Acute Liver Failure in Postpartum Period—A Rare Complication of Dengue Infection: A Case Report

ABSTRACTAimSuccessful management of acute liver failure in a case of dengue infection in postpartum patient by a multidisciplinary approach.BackgroundDengue fever is a viral infection transmitted by the bite ofAedes aegyptimosquito. It is a major public health problem in developing countries like India. Symptomatology of dengue ranges from mild self-limiting illness to fulminant liver failure. Hepatic dysfunction is a known complication in dengue fever that ranges from mild to moderate elevation of serum transaminases to catastrophic fulminant liver failure. Acute liver failure is a rare complication of dengue infection with high mortality rate.Case descriptionWe report here a case of 19-year-old female who was referred to our center for management of primary postpartum hemorrhage with acute febrile illness. Laboratory investigations revealed anemia, thrombocytopenia, and positive dengue NS1 antigen test. The patient was managed in the critical care unit for pulmonary edema, acute kidney injury, and deranged coagulation profile secondary to hepatic dysfunction. Postpartum hemorrhage was another challenge tackled conservatively. The spectrum of liver involvement varied from a modest rise in transaminases in the early phase and culminating finally in acute hepatic failure by the end of 2 weeks. Multiple blood and blood products were transfused during her 1 month stay in intensive care. There was no perinatal transmission. A multidisciplinary approach involving obstetricians, intensivists, and gastroenterologists resulted in successful recovery of the patient from acute liver failure.ConclusionClinicians should have a high index of suspicion for dengue fever in endemic areas in a case of acute febrile illness with/without the classical signs and symptoms of dengue fever. Pregnancy poses a special challenge for the obstetrician as delivery during this period can have devastating complications. A multidisciplinary approach with cautious fluid management is advisable in patients with severe dengue infection. Postpartum hemorrhage can be one of the life-threatening complications due to thrombocytopenia and deranged coagulation profile. Acute liver failure is a rare complication but can develop in patients with severe hepatitis.Clinical significanceDengue infection in pregnancy can mimic other causes of thrombocytopenia like HELLP syndrome, megaloblastic anemia, and gestational thrombocytopenia; hence, a detailed evaluation is warranted in pregnant women presenting with acute febrile illness with thrombocytopenia. Liver involvement in dengue infection can have devastating consequences leading to severe hepatitis and acute liver failure.How to cite this articleSapre S, Upadhyay H, Parikh C. Acute Liver Failure in Postpartum Period—A Rare Complication of Dengue Infection: A Case Report. J South Asian Feder Obst Gynae 2020;12(5):317–319.

2383 Amiodarone-Induced Acute Liver Injury

INTRODUCTION: Amiodarone is a lipophilic structure with a half-life of 25-100 days. Long term oral amiodarone is associated with photosensitivity, thyroid dysfunction, pulmonary, and hepatic toxicity. Hepatic toxicity varies from an asymptomatic and transient rise of serum aminotransferases that resolves after dose reduction or withdrawal, to severe liver disease. Acute hepatotoxicity is a rare but lethal complication of amiodarone use. CASE DESCRIPTION/METHODS: A 60-year-old male with a past medical history of hypertension and atrial fibrillation admitted for shortness of breath. He was taking Lopressor 25 mg twice a day and apixaban 5 mg twice a day at home. On exam, blood pressure was 130/70 mmHg, saturation 92% on room air, respiratory rate 13, and heart rate 145, which was irregular. ECG showed atrial fibrillation with a rapid ventricular rate. He was treated with diltiazem bolus and infusion but became hypotensive, so diltiazem infusion was discontinued. Amiodarone 150 mg bolus was given, followed by continuous amiodarone infusion of 900 mg over 24 hours. Blood work performed 24 hours later showed a sudden rise in aminotransferases (aspartate aminotransferase 3254 U/L, alanine aminotransferase 1643 U/L), and direct bilirubin (5.12 mg/dL). International normalized ratio, Gamma-GT, and alkaline phosphatase were normal. Extensive workup like abdominal ultrasonography, viral hepatitis serologies (hepatitis B and C, cytomegalovirus, Epstein-Barr, HIV and herpes zoster viruses) and autoimmune markers (antinuclear antibody, anti-smooth muscle antibody, anti-liver/kidney microsomal antibody type 1) were unremarkable. Amiodarone was discontinued about 50 hours after its beginning and his liver enzymes improved with normalization in 7 days. He was started on oral Lopressor and diltiazem, and his heart rate was well controlled. DISCUSSION: Acute intravenous amiodarone-induced hepatotoxicity is a rare but potentially lethal side effect so physicians should be aware of it and check for its occurrence by performing serial liver tests. The exact mechanism for intravenous amiodarone-induced acute liver failure is not well defined, but the hypotensive effect attributable to polysorbate 80 present in intravenous amiodarone is a compelling hypothesis. Treatment is mainly supportive. A recent study favored the use of N-acetylcysteine in acute liver injury beyond acetaminophen intoxication. Liver injury does not recur upon reintroduction of amiodarone by the oral route.

Heart and liver are infected in fatal cases of dengue: three PCR based case studies

BackgroundDengue is a global problem mainly in the tropics. Meticulous clinical management of cases has reduced the death rate significantly, but large numbers of people still succumb to severe complications of the infection. Presence of myocarditis is often overlooked leading to a poor outcome. Clinical management guidelines of dengue do not stress the importance of myocarditis as a manifestation in dengue infection. Severe hepatic dysfunction also needs emphasis.Case presentationWe present three patients who had come to hospital on the 3rd day of fever. Two of them (case 1 and 3) were in shock on admission and case 2, who was stable on the3rd day, went into the critical phase and developed shock while in the hospital on the 4thday. All three had tachycardia on admission that got worse with time. The clinical course was unstable with fluctuations in urine output and deterioration of organ function. Despite frequent monitoring and life support they survived only 2–3 days in hospital. All three patients had myocarditis during the critical phase. In the first case, myocarditis was confirmed by troponin estimation and echocardiogram. In the second and third cases, histopathology confirmed myocarditis. Haemorrhagic necrosis of the liver was found in case 2 and 3 with exponential rise of transaminases. In all three cases, viral RNA was detected in both heart and liver tissues by PCR amplification.ConclusionsWe stress that detection of myocarditis and liver involvement in any dengue patient is important from the onset of the illness where treatment should be tailored to prevent development of hypotension. Our findings are novel as PCR and histology are rarely done on tissues of deceased dengue patients in the world. Studies are needed to find therapeutic interventions to reverse cardiac and hepatic dysfunction in dengue infection.

A Rare Case of Perimpullary Duodenal Diverticulitis Diagnosed by ERCP Causing Obstructive Jaundice (Lemmelʼs Syndrome)

Background Periampullary duodenal diverticulum (PAD) is a common finding in ERCP. Duodenal diverticulitis is rare and can result in pancreatico-biliary complications. Lemmel's syndrome is a rare complication of periampullary diverticulum that results in obstructive jaundice in absence of stones or malignancy. In our case, duodenal diverticulitis lead to biliary obstruction, and was diagnosed at the time of ERCP. Case report The patient is a 66-year-old woman with a history of migraine, osteoarthritis, rheumatoid arthritis and prior cholecystectomy 17 years ago who presented with epigastric and right upper quadrant abdominal pain radiating to the back with associated nausea, vomiting and diarrhea after she had an undercooked meal. Initial work up revealed leukocytosis of 16,000 with no fever. Transaminases and bilirubin were normal initially. CT abdomen showed non-obstructive bowel gas pattern, post operative cholecystectomy with secondary CBD dilation and a 3.6x4.5 cm periampullary diverticulum without signs of inflammation. Two days later she developed fever, acute rise in transaminases and bilirubin (AST 524 IU/L, ALT 767 IU/L, T. bilirubin 6 mg/dl). She was started on IV Zosyn with fluid resuscitation. MRI/MRCP showed mild to moderate intra and extrahepatic dilation with tapering of distal CBD (13 mm) without stones or signs of diverticulitis. She subsequently underwent ERCP that showed duodenal diverticulitis causing obstruction of the adjacent ampulla and distal bile duct. Pancreatic and CBD stents were inserted. Repeat review of the prior MRI/MRCP confirmed duodenal diverticular inflammation that was not initially appreciated. The patient's fever and symptoms resolved after the ERCP and with antibiotics. Follow up ERCP after 6 weeks showed scarring down of the PAD opening and resolution of bile duct stricture. Discussion Periampullary duodenal diverticulum are located within 3 cm from the ampulla of Vater and found in 10-20% of patients undergoing ERCP. PAD may be associated with CBD stones, acute pancreatitis and can lead to difficult cannulation during ERCP. Lemmel's syndrome is a rare complication from PAD in which obstructive jaundice occurs secondary to compression from the PAD. Duodenal diverticulitis is very rare and usually diagnosed with CT scan in most of cases. In our case, it was diagnosed at the time of ERCP.1380_A.tif Figure 1: Pancreatic duct stent with diverticulum1380_B.tif Figure 2: Duodenal diverticulitis1380_C.tif Figure 3: Follow up ERCP

Hepatic Complications of Anorexia Nervosa.

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric illnesses due to the widespread organ dysfunction caused by the underlying severe malnutrition. Starvation causes hepatocyte injury and death leading to a rise in aminotransferases. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases. Acute liver failure associated with coagulopathy and encephalopathy can rarely occur. Liver enzymes may also less commonly increase as part of the refeeding process due to hepatic steatosis and can be distinguished from starvation hepatitis by the finding of a fatty liver on ultrasonography. Individuals with AN and starvation-induced hepatitis are at increased risk of hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis. Gastroenterology and hepatology consultations are often requested when patients with AN and signs of hepatitis are hospitalized. It should be noted that additional laboratory testing, imaging, or liver biopsy all have low diagnostic yield, are costly, and potentially invasive, therefore, not generally recommended for diagnostic purposes. While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.

Norethisterone Related Drug Induced Liver Injury: A Series of 3 Cases

Drug induced liver injury (DILI) is uncommon and severe forms are associated with significant morbidity and mortality. Female sex hormones (estrogens and progestogens) related DILI generally occur with estrogen component. Progesterone component related DILI are infrequently reported. Norethisterone is commonly used drug in gynecologic practice to prevent excess per vaginal bleeding. We report 3 cases of Norethisterone related DILI manifesting as significant rise of transaminases. All of these patients took Norethisterone for prolonged periods and improved completely after withdrawal of drug.

Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial

SummaryBackgroundHot flushes affect 70% of menopausal women and often severely impact physical, psychosocial, sexual, and overall wellbeing. Hormone replacement therapy is effective but is not without risk. Neurokinin B signalling is increased in menopausal women, and has been implicated as an important mediator of hot flushes.MethodsThis phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes. Eligible participants were healthy women aged 40–62 years, having seven or more hot flushes in every 24 h of which some were reported as being severe or bothersome, who had not had a menstrual period for at least 12 months, and who had not been taking any medication shown to improve menopausal flushes in the preceding 8 weeks. Participants received 4 weeks of MLE4901 (40 mg, orally, twice daily) and placebo (orally, twice daily) in random order separated by a 2 week washout period. Randomisation was completed by a central computer, and participants were allocated to treatment number in numerical order. The primary outcome was the total number of hot flushes during the final week of both treatment periods. Analyses were by intention to treat and per protocol using generalised linear mixed models and standard crossover analysis. All analyses were prespecified in the study protocol. The trial is registered at ClinicalTrials.gov, number NCT02668185.Findings68 women were screened between Feb 3 and Oct 10, 2016, of which 37 were randomly assigned and included in an intention-to-treat analysis. 28 participants completed the trial and were included in a per-protocol analysis. MLE4901 significantly reduced the total weekly number of hot flushes by 45 percentage points (95% CI 22–67) compared with the placebo (intention-to-treat adjusted means: placebo 49·01 [95% CI 40·81–58·56] vs MLE4901 19·35 [15·99–23·42]; adjusted estimate of difference 29·66 [17·39–42·87], p<0·0001). Treatment was well tolerated. Three participants developed a transaminase rise (alanine aminotransferase 4·5–5·9 times the upper limit of normal) with a normal bilirubin 28 days after starting MLE4901, which normalised within 90 days.InterpretationTreatment with a neurokinin 3 receptor antagonist (MLE4901) could be practice changing as it safely and effectively relieves hot flush symptoms without the need for oestrogen exposure. Larger scale studies of longer duration are now indicated.FundingUK Medical Research Council and National Institute for Health Research.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study

Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department.Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia.Results. We analyzed 273 patients – 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values.Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

Antitubercular therapy induced liver function tests abnormalities in human immunodeficiency virus infected individuals

BackgroundBoth antitubercular therapy (ATT) and antiretroviral therapy (ART) can cause drug induced liver injury (DILI) in tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection. The aim of this research was to study ATT-induced liver function test (LFT) abnormalities in HIV-infected patients. MethodsHIV-infected patients diagnosed with TB were evaluated with baseline LFT and CD4 counts. ATT regimen was modified if baseline LFT was significantly abnormal. Patients on protease inhibitors were given rifabutin instead of rifampicin. In patients on nevirapine-based ART, efavirenz was substituted for nevirapine. In ART-naive patients, the timing of introduction of ART was according to CD4 cell counts. LFT were repeated fortnightly or as clinically indicated for 10 weeks. ResultsWe studied 100 patients with HIV ([M – 67, F – 23], mean age: 40.05±10.75 years, mean CD4 cell count: 239.157±228.49cells/dL). Sixty-one patients were on ART prior to diagnosis of TB. Baseline LFT abnormalities (n=40) were similar in ART and non-ART group (28/61 vs 12/39, p=0.13). After starting ATT, derangement of LFT was observed in majority of patients (99/100). However, liver sparing ATT was required only in 15 patients. Bilirubin >2.5mg/dL was seen only in 9 patients. Significant rise in transaminases was commoner in patients on concurrent ART and ATT (p=0.044) and with baseline LFT abnormalities (p=0.00016). There was no case of acute liver failure or mortality. ConclusionMild LFT abnormalities are common in HIV-infected individuals on ATT. Concomitant use of ATT and ART and baseline LFT abnormalities increase the risk of significant DILI. However, with closer follow-up, serious liver injury can be prevented.

A METHOD OF INTEGRATED ASSESSMENT OF LIVER FIBROSIS DEGREE: A COMPARISON OF THE OPTICAL METHOD FOR THE STUDY OF RED BLOOD CELLS AND INDIRECT ELASTOGRAPHY OF THE LIVER

The presented method of integrated assessment of liver fibrosis degree based on the comparison of the data obtained in the study of electric and viscoelastic parameters of erythrocytes by the dielectrophoresis method using the electro-optical system of the detection cells and method for indirect elastometry. A high degree of comparability of the results of the above-described methods was established when the degree of fibrosis F 2-4 in the absence of marked cytolysis, cholestasis, inflammatory syndrome, metal overload. It is shown that parallel using the methods of dielectrophoresis and indirect elastography is needed in the presence of a rise of transaminases, gammaglutamyltranspeptidase more than 5 norms, expressed dysproteinemia, syndromes of iron overload, copper to increase the accuracy in determining the degree of liver fibrosis. The evaluation of dynamics of changes of the degree of fibrosis during antiviral therapy is more accurate by the method of indirect elastometry, and the method of dielectrophoresis is preferable in the treatment of nonalcoholic fatty liver disease. In cases of restrictions on the use of the method for indirect elastography (marked obesity, ascites, cholelithiasis, pregnancy, presence of pacemaker, prosthesis) to determine the degree of fibrosis the method of dielectrophoresis of red blood cells can be used. Simultaneous use of both methods (using the identified discriminatory values) allows to reduce or to neutralize their disadvantages, dependence on associated syndromes, to expand the possibilities of their application, to improve the diagnostic accuracy in determining each of the degrees of liver fibrosis. Integrated application of both methods — indirect elastography and dielectrophoresis of red blood cells — for determining the degree of liver fibrosis allows to achieve high levels of sensitivity (88.9 percent) and specificity (100 percent) compared to the “gold standard” — biopsy of the liver.

The Magnitude of Hepatic Transaminase Rise and Its Correlation with the Severity of Dengue Fever

Background and Objective: Biochemical evidence of hepatic enzyme rise is very common in dengue fever. This study was designed to see the levels of elevated hepatic enzymes and their correlation with severity of dengue fever (DF).\Materials and Methods: It was an observational study conducted in the Department of Internal Medicine of BIRDEM Hospital, Dhaka, over a period of six months (July to December, 2010). Fifty serologically confirmed (IgM/IgM and IgG) dengue fever patients were included in the study.Results: Of the 50 patients, 32 (64%) were male and 18 (36%) were female. The mean age was 44.2 (21-54) years. Out of 50 cases, 23 (46%) cases had classical dengue fever, 20 (40%) had dengue haemorrhagic fever (DHF) Grade I, 6 (12%) had DHF Grade II and 1 (2%) had DHF Grade III. Hepatic enzymes were raised in 47 (94%) cases. Mean aspartate aminotransferase (AST) was 98.77 U/L, mean alanine aminotransferase (ALT) was 88.09 U/L. In 46 (92%) cases AST was more than ALT. Enzyme rise was more in DHF (Grade III- mean AST 298 U/L, mean ALT 232 U/L, Grade II- mean AST 212.6 U/L, mean ALT 198.7 U/L, Grade I- mean AST 97.3 U/ L, mean ALT 86.2 U/L) than classical dengue fever (mean AST 61.7 U/L, mean ALT 54.9 U/L). Mean bilirubin was 1.82 mg/dl. No difference was observed between classical dengue fever and DHF regarding serum bilirubin level.Conclusion: The above results suggest that hepatic involvement in dengue fever is common and the amplitude of transaminase rise indicates the severity of the disease.Birdem Med J 2015; 5(2): 74-77