Abnormal Liver Function Test Results Research Articles

Leptospirosis in a patient with cardiac manifestation: A case report study and literature review

Key Clinical MessageCommon cardiac arrhythmias seen in patients with leptospirosis are usually atrial fibrillation or first‐degree atrioventricular block, with bradyarrhythmia being rare in this group. It is essential to prioritize the examination of the patient's medical background, clinical symptoms, and comprehensive physical evaluation in order to promptly identify and address the patient's condition.AbstractLeptospirosis, a zoonotic disease that is widespread worldwide, has a significant impact on tropical areas and can affect various organs throughout the infection. During the initial stage, symptoms are typically non‐specific. Although cases of all three cardiac layers being affected have been reported, issues with the conduction system are especially significant in the early phase of the disease. The most frequent discoveries in these patients are atrial fibrillation or first‐degree atrioventricular block, with bradyarrhythmia being rare. We describe a 37‐year‐old male farmer who initially sought medical attention for general symptoms that had been deteriorating despite receiving outpatient treatment for 3 days for a presumed diagnosis of influenza. During his initial assessment, he exhibited sinus bradycardia, anemia, leukocytosis, elevated levels of direct and total bilirubin, and abnormal liver function test results. Through thorough history‐taking, physical examination, and laboratory analyses, a diagnosis of leptospirosis was conclusively established for him. Focusing on the patient's medical history, clinical manifestations, and thorough physical assessment is crucial for promptly diagnosing and treating patients. This becomes particularly significant for individuals who exhibit atypical symptoms, exemplified by our patient presenting with nonspecific indications and cardiac issues manifested as bradycardia.

The Use of Antiepileptic Drug for Postcranioplasty Seizure: A Systematic Review and Meta-analysis

Introduction: Cranioplasty, a common procedure following craniectomy, aims to repair cranial defects resulting from various causes, including trauma and raised intracranial pressure. Despite its routine application, cranioplasty is associated with complications, notably seizures. The incidence of postcranioplasty seizures (PCS) and the role of antiepileptic drug (AED) prophylaxis remain underexplored. This meta-analysis aims to evaluate the impact of AED prophylaxis on both early and late PCS. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic literature search on PubMed, Europe PMC, ClinicalTrials.gov, and EMBASE, yielding 1292 articles. Eligibility criteria included randomized clinical trials (RCTs) in English reporting PCS incidence with or without AED prophylaxis. The risk of bias was assessed using Cochrane’s RoB 2 tool. Statistical analysis employed RevMan 5.4 software. Results: Of the initially identified articles, two RCTs met the inclusion criteria, involving a total of 497 cases. AED prophylaxis significantly reduced the risk of early PCS (risk ratio [RR]: 0.15, confidence interval [CI]: 0.06–0.37, P < 0.0001), with no heterogeneity (I 2 = 0%, P = 0.78). However, there was no significant difference in late PCS incidence between the intervention and control groups (RR: 0.32, CI: 0.06–1.56, P = 0.16). No significant differences in abnormal liver function or blood test results were observed between groups. Conclusion: AED prophylaxis significantly reduces the risk of early PCS following cranioplasty, but its effectiveness in preventing late PCS remains uncertain. Further studies are warranted to determine optimal AED regimens and address the limitations of the current meta-analysis.

Hepatitis E Virus Infection Caused Elevation of Alanine Aminotransferase Levels in a Patient with Chronic Hepatitis B and Choledocholithiasis

Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic strains that are primarily transmitted through the consumption of undercooked pork or game meat. They also cause asymptomatic infections, acute hepatitis, acute-on-chronic liver failure, chronic hepatitis, and extrahepatic manifestations. Here, we report a man in his 80s who had chronic hepatitis B, took entecavir for it, and presented with higher levels of alanine aminotransferase (ALT) and jaundice. An abdominal computed tomography scan revealed choledocholithiasis with cholecystolithiasis. Although endoscopic papillary balloon dilatation was performed for the removal of a common bile duct stone, the abnormal liver function tests, including jaundice, were prolonged. After other viral hepatitis and other causes of the liver injury were ruled out, as his serum was positive for immunoglobulin A anti-HEV and HEV genotype 3b RNA, we diagnosed him as having acute hepatitis E. In this case, with chronic hepatitis B and a common bile duct stone, the prolonged abnormal results for the liver function tests seemed to be caused by HEV infection. In conclusion, in cases with high ALT levels after removing choledocholithiasis, other factors, including HEV infection, should be considered to determine the cause of abnormal liver function test results. The further examination of hepatitis D virus infection and high ALT levels may be needed in HBV-infected individuals.

Prevalence and Molecular Characterization of Hepatitis C in Murree

Background: Hepatitis C infection can result in liver damage ranging from inflammation to cirrhosis and hepatocellular carcinoma. The aim of this study was to determine the prevalence and molecular characterization of hepatitis C virus (HCV) infection in the city of Murree. Methods: A descriptive study was conducted at THQ Hospital Murree, Pakistan from June 2021 to November 2021. The prevalence of hepatitis C was estimated using two major laboratory diagnostic methods: immunochromatographic testing (ICT) and polymerase chain reaction (PCR). A total of 2,163 patients were tested for HCV antibodies by ICT, of whom 446 tested positive for ICT (prevalence 20%). The positive ICT samples were further analyzed using the molecular gold standard method PCR. Of the 446 samples, 381 (85.6%) tested positive by PCR, 38 (8.4%) negative and 27 (6%) had to be re-sampled due to sample inaccuracy. Results: A total of 381 people were included in the study. Of the 2,163 patients screened with ICT, 446 tested positive. All 446 samples underwent PCR, and 381 (85.6%) cases were positive, 38 (8.4%) were negative and 27 (6%) were requested to be re-sampled. The most affected age group was 30- to 39-year-olds (27.4%). Of the subjects with positive HCV results by PCR, 66% had abnormal liver function test results (elevated ALT, ALP, and bilirubin), while 34% had normal liver function test results. The viral load of HCV-positive cases ranged from 1,000,000 to 7,000,000 IU/L in 35.7% of cases and from 100,000 to 999,999 IU/L in 43.8% of cases. Conclusion: The study revealed a high prevalence of hepatitis C (17%) in the population served by Tehsil Headquarters Hospital in Murree, which poses a significant challenge. It is crucial to promote the use of gold standard methods such as PCR in laboratory diagnostics to ensure accurate detection and characterization of HCV infection period.

Post-discharge clinical, laboratory and radiographic features of coronavirus disease 2019 (COVID-19) patients at university hospitals in Japan.

Coronavirus disease 2019 (COVID-19) has affected nearly half million people in Japan. However, information on the prolonged symptoms as well as laboratory and radiographic findings after hospital discharge remains limited. We retrospectively collected the symptoms, laboratory test results, and chest imaging results of COVID-19 patients at the time of the hospital admission and the ambulatory visits after discharge at two university hospitals between July and December 2020. A total of 126 COVID-19 patients, including of 88 with mild to moderate disease and 38 with severe to critical disease, were included. The time between symptom onset and the first outpatient visit was 46 days (Interquartile range, 39 to 55). At the ambulatory visits, 36.5% of patients had at least one symptom. The most frequent symptom was shortness of breath (12.8%), followed by cough (11.1%), and fatigue (8.8%). Of 120 patients with post-discharge laboratory test results, 27 patients (22.5%) had abnormal alanine aminotransferase levels, and 35 patients (29.1%) had lymphocytopenia, including 24 and 27 mild and moderate patients. Of 122 patients with post-discharge chest computed tomography (CT) scans, 105 (83.3%) had abnormal findings. This abnormality was found in both mild to moderate and severe patients. Shortness of breath, abnormal liver function test results and chest CT images often persisted for at least one month after discharge, even when symptoms were mild or moderate during hospitalization.

Association between serum uric acid level and non-alcoholic fatty liver disease in Koreans.

The association between serum uric acid (SUA) levels and non-alcoholic fatty liver disease (NAFLD) is controversial. We compared the association of SUA levels with NAFLD, abnormal alanine transferase (ALT), and the degree of liver fibrosis to clarify the association of SUA levels with NAFLD. We conducted a retrospective cross-sectional study. Adult patients who underwent a health check-up (N = 1,343) were included for analysis. Fatty liver was diagnosed by abdominal ultrasonography. The degree of liver fibrosis was determined using the NAFLD fibrosis score (NFS). Pearson correlation analysis showed a stronger correlation of SUA level with the fatty liver index (r = 0.40, P < 0.001) than the correlation with serum ALT level (r = 0.28, P < 0.001), or NFS (r = 0.018, P = 0.51). SUA levels in patients with NAFLD and an abnormal liver function test (LFT) result were significantly higher than levels in patients without NAFLD and abnormal LFT results. By contrast, there was no significant association of SUA level with NFS grade. When age, male sex, body mass index, the presence of hypertension, diabetic mellitus, and NAFLD, abnormality of ALT level, and SUA level were included in binary logistic regression to evaluate risk factors for elevated NFS grade, hyperuricemia was not significantly associated with NFS grade (OR = 0.94, P = 0.75). Pearson correlation and logistic regression together indicated SUA level is more closely associated with hepatic steatosis than abnormal liver function test or hepatic fibrosis.

Effects of Radiation Dose on Liver After Free-breathing Volumetric Modulated Arc Therapy for Breast Cancer.

To evaluate the early effect of radiation dose on liver function in breast cancer patients undergoing free-breathing volumetric modulated arc therapy (FB-VMAT). Medical records of 125 patients with breast cancer who underwent curative surgery followed by postoperative radiotherapy using FB-VMAT during 2018-2021 were reviewed. Results of the liver function test (LFT), performed within 1-week before and 6-months after radiotherapy, were collected and compared. The LFTs analyzed albumin, total and direct bilirubin, aspartate transaminase, alanine transferase, and alkaline phosphatase levels. The mean dose and relative liver volume receiving at least 10 Gy, 20 Gy, or 30 Gy were calculated. Median follow-up time was 21.4 months. One patient experienced locoregional and distant failures. The mean liver irradiation dose was 325.9 centigray (cGy) for all patients. The liver irradiation dose was higher in patients with right breast cancer than in those with left breast cancer (mean, 434.1 cGy vs. 260.6 cGy, p<0.001). Direct bilirubin and aspartate transaminase levels showed significant differences after FB-VMAT. LFT results outside normal limits were noted in 31 patients at follow-up, but nobody met the criteria of radiation-induced liver disease. Underlying liver disease, breast laterality, systemic treatment, or dose-volume histogram parameters were not associated with abnormal LFT results. FB-VMAT can deliver radiation doses safely without adversely affecting the liver. The mean dose ≤4 Gy could be a useful dose criterium of the liver for FB-VMAT plans.

A rare case of pediatric hepatic fibrinogen storage disease – case report

Hepatic fibrinogen storage disease is a rare autosomal do­mi­nant genetic disorder characterized by the retention of fibrinogen in the hepatocellular endoplasmic reticulum. We describe the case of an asymptomatic 3-year-old boy with abnormal liver function test results and with unexpected hypofibrinogenemia. Liver biopsy showed normal hepatic lobule structure, with microvesicular steatosis, and the im­mu­no­staining results were positive for fibrinogen, changes consistent with the diagnosis of hepatic fibrinogen storage disease. The genetic analysis was not performed.

Association between indocyanine green clearance test and ischemic type biliary lesions within one year after orthotopic liver transplantation

BackgroundIschemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia–reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation. ObjectiveOur aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs. MethodsThis retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis. ResultsITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77–0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI. LimitationsRetrospective, single-center study. ConclusionsThe findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation.

Malignant solitary fibrous tumor of the pancreas: a case report

BackgroundSolitary fibrous tumors (SFTs) are rare tumors, mostly derived from connective tissue mesenchymal cells that arise from the pleura. There are very few reports of primary pancreatic SFT. Preoperative diagnosis is difficult owing to the lack of distinctive radiological findings. We report a case of pancreatic SFT with particularly rare malignant findings.Case presentationA 60-year-old man was referred to the hospital because of a right upper quadrant mass and abnormal liver function test results. Contrast-enhanced computed tomography (CT) showed a well-defined enhanced tumor measuring approximately 8 cm in the pancreatic head. Magnetic resonance imaging (MRI) showed T1WI hypointensity, T2WI hyperintensity, and DWI hyperintensity. The main pancreatic duct and common bile duct were dilated owing to obstruction by the tumor. The following tumor markers were mildly elevated: carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), SPan-1, and DUPAN-2. The histological diagnosis obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was negative for pancreatic ductal carcinoma, malignant lymphoma and neuroendocrine tumor, suggesting the possibility of mesenchymal tumor, but the diagnosis was not confirmed. The patient was judged suitable for surgery and underwent subtotal stomach-preserving pancreatoduodenectomy with D2 lymph node dissection. On histopathological examination of the resected specimen, infiltrating spindle-shaped cells had proliferated, containing numerous mitotic figures, with necrotic findings inside the tumor. Immunostaining was positive for cluster of differentiation-34 (CD34), B cell CLL/lymphoma-2 (Bcl-2), and signal transducer and activator of transcription (STAT6). On the basis of these findings, a diagnosis of malignant pancreatic SFT was made. The patient remains free of recurrent disease after 12 months of follow-up without adjuvant therapy and he is being carefully followed up as an outpatient.ConclusionsWe experienced a case of malignant pancreatic head SFT. Immunohistochemical staining of the extracted specimens was useful for diagnosis.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of Solid-Organ Transplants.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of Solid-Organ Transplants.

Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China. To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management. Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020. Confirmed SARS-CoV-2 infection. Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir. Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results. Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.

Efficacy and safety of levoketoconazole in the treatment of endogenous Cushing's syndrome (SONICS): a phase 3, multicentre, open-label, single-arm trial

Levoketoconazole is a ketoconazole stereoisomer in development for treatment of Cushing's syndrome and has not been assessed previously in a clinical trial in patients with Cushing's syndrome. We aimed to investigate the efficacy and safety of levoketoconazole in patients with endogenous Cushing's syndrome. SONICS is a phase 3, multicentre, open-label, non-randomised, single-arm study in which we recruited adults (≥18 years) with confirmed Cushing's syndrome and a mean 24-h urinary free cortisol (mUFC) of at least 1·5 times the upper limit of normal from 60 hospital and community sites in 19 countries (15 countries in Europe, and Canada, Israel, Turkey, and the USA). Patients were treated with oral levoketoconazole in a 2-21 week incremental dose-titration phase starting at 150 mg twice daily (150 mg increments until mUFC normalisation, maximum 600 mg twice daily) and a 6-month maintenance phase. The primary outcome was the proportion of patients with mUFC normalisation at end of maintenance, without dose increase during the maintenance phase (in the intention-to-treat population). Prespecified adverse events of special interest were potential liver toxicity, corrected QT prolongation, and adrenal insufficiency. This trial is registered with ClinicalTrials.gov, NCT01838551. Between July 30, 2014, and June 30, 2017, 201 individuals were screened and 94 patients were enrolled and received at least one dose of study medication. Of the 94 patients, 80 (85%) had pituitary Cushing's syndrome. Mean mUFC at baseline was 671·4 nmol/24 h (243·3 μg/24 h), which is 4·9 times the upper limit of normal. Of the 77 patients who advanced to the maintenance phase, 62 (81%) had mUFC normalisation by end-of-dose titration. At the end of the 6-month maintenance phase, 29 (31%) of 94 patients were responders; the least-squares mean estimate of the proportion of responders was 0·30 (95% CI 0·21-0·40; p=0·0154 vs null hypothesis of ≤0·20). The most common adverse events in the 94 patients were nausea (30 [32%]) and headache (26 [28%]). Adverse events led to study discontinuation in 12 (13%) of 94 patients. Two patients had a QT interval (Fridericia corrected) of more than 500 ms, and three patients had suspected adrenal insufficiency. Alanine aminotransferase reversibly increased to more than three times the upper limit of normal in ten (11%) patients. Four patients had serious adverse events that were considered probably or definitely related to the study drug: abnormal liver function test results (n=1), prolonged QT interval (n=2), and adrenal insufficiency (n=1). One person died from colon carcinoma unrelated to study medication. Twice-daily oral levoketoconazole treatment led to sustained improvements in urinary free cortisol, with an acceptable safety and tolerability profile. Levoketoconazole might represent a useful therapeutic option for the medical treatment of Cushing's syndrome. Strongbridge Biopharma.

Vascular Anomalies of the Pediatric Liver.

The liver is a unique organ as it receives afferent blood supply from the umbilical vein, portal vein, and hepatic artery in the developing embryo but has only one efferent drainage method, through the hepatic veins. In the postnatal period, about 70% of the afferent blood flow into the liver is from the portal venous system, unique vessels that begin and end in a capillary system. Vascular anomalies of the hepatic artery, hepatic veins, portal vein, and/or umbilical vein can be congenital or acquired secondary to inflammation and/or infection, trauma, systemic disorders, or iatrogenic causes. The vascular anomalies can be incidental findings at imaging, or the infant or child can present with symptoms such as abdominal pain and ascites, be diagnosed with gastrointestinal bleeding, and have abnormal liver function test results. Imaging can demonstrate vascular findings such as shunts, thrombosis, or collaterals; secondary parenchymal findings such as diffuse or focal abnormal enhancement patterns; and parenchymal lesions such as regenerative nodules. This article discusses and illustrates vascular disorders of the liver that may be encountered in the pediatric population. These include (a) normal vascular variants; (b) congenital anomalies (preduodenal portal vein and infradiaphragmatic total anomalous pulmonary venous return); (c) acquired thromboses (extrahepatic portal venous thrombosis); (d) inflammatory vascular conditions, which can result in hepatic artery aneurysms or pseudoaneurysms; (e) hepatic venous outflow disorders (veno-occlusive disease); and shunt lesions. Liver transplantation and associated vascular complications are a large topic and will not be reviewed in this article. Knowledge of the vascular and parenchymal changes seen with these entities can aid imaging diagnosis and guide appropriate management. ©RSNA, 2019.

Concurrent hepatitis B and autoimmune hepatitis a rare presentation of acute liver failure: a case report

Acute liver failure with concurrent Hepatitis b and autoimmune hepatitis is an extremely rare case. We report a 25 year female presenting to our emergency with fatigue and somnolence, distention of abdomen, jaundice, melena and increased hair loss leading to alopecia. Physical examination revealed jaundice, an enlarged liver, ascites and tenderness of upper right abdomen. Laboratory tests revealed an increased level, bilirubin, GGT, increased INR and prothrombin time with elevated IgG levels, and the presence of anti-smooth muscle antibodies, Anti-nuclear antibodies and HBV infection markers. The patient was diagnosed with liver failure resulting from chronic active hepatitis B with an autoimmune component. The treatment consisted of steroids, azathioprine, vitamin K, low-protein diet and lactulose enemas. After undergoing a molecular test (HBV DNA 3.23 × 10 IU/mL and HBeAg reactive), the treatment was modified by adding tenofovir disoproxil fumarate. After one month the patient was discharged in good clinical condition, with the recommendation of continued tenofovir disoproxil fumarate and prednisone. In subsequent follow-ups, no clinical deterioration or abnormal biochemical liver function test results were found.

53P - Impact of chronic hepatitis virus infection on the feasibility and efficacy for Asian patients with hepatocellular carcinoma in phase I clinical trials

Background: In Asia, chronic hepatitis B and C virus infections (CHVI) are major risk factors for liver fibrosis and hepatocellular carcinoma (HCC). Patients with advanced HCC have limited effective therapeutic options and are potential candidates for early phase clinical trials for new anti-cancer agents. The impact of CHVI on the feasibility and efficacy for patients with HCC in Phase I trials (P-Is) has not been reported or elucidated in Western countries. Methods: We retrospectively analyzed the characteristics and outcomes of HCC patients participating in P-Is, with emphasis on CHVI. Patients testing positive for anti-hepatitis C virus (HCV) antibody or hepatitis B virus surface antigen (HBsAg) were diagnosed with CHVI. Results: Eighty-five patients were enrolled in P-Is at our center. There were no significant differences in the clinical and laboratory variables, including the liver function test results, between the 46 (54%) CHVI-positive and 39 (46%) CHVI-negative patients in this study. The median time to treatment failure (TTF) and overall survivals (OS) from enrollment of the P-I were 60 days (95% confidence interval [CI]: 51–85) and 412 days (95% CI: 267–478), respectively. There is no significant difference between positive and negative for hepatitis virus in the best response based on the RECIST. The frequency of abnormal liver function test (LFT) adverse events (grade ≥ 3) was significantly different among CHVI-positive and -negative patients. No patient discontinued P-I treatment secondary to abnormal LFT results or developed reactivation of hepatitis virus, and no treatment-related mortality was observed. Multivariate analysis revealed that the number of prior systemic treatments significantly contributed to poor TTF (≥2; HR: 2.1, 95% CI: 1.3–3.6, P = 0.004) and that poor Eastern Cooperative Oncology Group Performance Status significantly contributed to poor OS (≥1; HR: 1.9, 95% CI: 1.0–3.4, P = 0.04). Conclusions: CHVI did not independently predict TTF and OS. Abnormal LFT adverse events could be related to CHVI but did not lead to discontinuation of P-I treatment. Thus, patients advanced HCC with CHVI can be enrolled in the P-Is. Legal entity responsible for the study: N/A Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.

Interactions between cannabidiol and commonly used antiepileptic drugs.

To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs. In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose. AEDs with interactions seen in initial analysis were plotted for mean change in serum level over time. Subanalyses were performed to determine if the frequency of sedation in participants was related to the mean serum N-desmethylclobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate. Increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p < 0.01) serum levels were seen with increasing CBD dose. Increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) with increasing CBD dose were seen in adults. Except for clobazam and desmethylclobazam, all noted mean level changes were within the accepted therapeutic range. Sedation was more frequent with higher N-desmethylclobazam levels in adults (p = 0.02), and AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01). Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD.

Usefulness of the Direct and/or Total Bilirubin to Predict Adverse Outcomes in Patients With Acute Decompensated Heart Failure

Abnormal liver function test results are often observed in acute decompensated heart failure (ADHF). However, the prognostic value of bilirubin fractionation has not been elucidated. The prognostic value of direct bilirubin (DB), in comparison with total bilirubin (TB), was examined in 556 consecutive patients with ADHF. Patients with elevated DB showed mostly similar patient characteristics including signs of elevated right-sided pressure (frequent hepatomegaly, jugular venous distention, dilated inferior vena cava, and elevated gamma-glutamyltransferase) and decreased cardiac output (cold extremities, decreased pulse pressure, and lower blood pressure) and other parameters of heart failure (HF) severity (increased plasma renin activity, decreased sodium, total cholesterol, and ejection fraction) to elevated TB; however, only patients with elevated DB showed a significant difference in the frequency of HF history and alkaline phosphatase value. Kaplan-Meier analysis showed that patients with elevated DB had a significantly higher rate of the composite end point of all-cause mortality or HF readmission (p= 0.021) compared with those with normal DB, whereas patients with elevated TB did not show a statistically significant difference compared with those with normal TB (NS). A multivariate Cox hazards model showed that DB was an independent predictor of adverse events (adjusted hazard ratio 1.052, 95% confidence interval 1.001 to 1.099, p= 0.034), whereas TB was not (adjusted hazard ratio 1.017, 95% confidence interval 0.985 to 1.046, p= 0.27). Adding DB to existing prognostic variables resulted in higher C-statistics than adding TB (C-statistics: 0.670 to 0.675, 0.670 to 0.674, respectively). In conclusion, elevated DB in ADHF was an independent prognostic predictor that was superior to TB. DB may be useful for further risk stratification in ADHF.

Les soins somatiques en psychiatrie : étude descriptive d’un bilan biologique systématique et implication en termes de prise en charge globale

BackgroundSomatic suffering concerns mental health in many ways, but numerous psychiatrists are still reluctant to take an interest in somatic care due to a supposed lack of expertise and an alteration of the psychotherapeutic link, whilst in parallel numerous fellow physicians are quite apprehensive about treating patients with mental disorders. ObjectivesWe have undertaken a targeted clinical audit regarding the somatic treatment of in-patients in a psychiatric unit to propose the implementation of measures of improvement. Material and methodsOur study focused on the identification and treatment of abnormal liver function tests, a subject that has been overlooked in the literature, yet from clinical experience the results are often abnormal in psychiatric unit in-patients. We analysed retrospectively over a period of two years the medical records of psychiatric unit in-patients with abnormal results for at least one of the following hepatic markers: aspartate-aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP) and bilirubin. ResultsIn total, 188 liver test results were abnormal, with an average of 1.7 per patient. The abnormal test results were in decreasing order: elevation in GGT (80 % of patients), elevation in transaminases (65.5 % for each), elevation in ALP (19.1 %) and elevation in bilirubin (7.27 %). Abnormal transaminase levels were lower than 10N, with a peak between 1N and 3N for ALT and a peak between 1N and 5N for AST. The elevation in GGT was between 1N and 34N, although 71.6 % of these values were below 5N. ALP was below 3N. The medical history was traced in 93.6 % of the records. A somatic clinical examination was only reported in 39 records (35.5 %) and was carried out by a hepato-gastroenterologist (HGE) in 30.8 % of cases, the establishment's emergency physician in 25.7 % of cases and the psychiatrists in 12.9 % of cases. Patients with abnormal liver function test results frequently underwent other biological and morphological examinations. A discharge letter was found in almost all cases. Abnormal liver function test results were indicated in less than 45 % of these discharge letters, whilst over half reported the establishment of a future treatment coordinated by the GP, in close collaboration with the gastroenterologist in at least half the cases. DiscussionOur study was carried out in an open psychiatric unit in the heart of a general hospital that mainly receives patients suffering from thymus and anxiety disorders, addictive disorders, somatoform disorders, personality disorders and psycho-organic disorders. Patients suffering from schizophrenia or schizoaffective disorders comprised less than 10 % of admissions. Our retrospective study of over 750 hospital admissions over a period of two years found only 62.93 % of patients underwent liver function tests, which proved to be pathological in nearly 30 % of cases. Following a well-defined anamnesis, just over a third of patients underwent a physical examination whilst in hospital, more often a while after admission and not in the psychiatric unit. The consultation of fellow hospital physicians was limited even if the gastroenterologist was called upon in 30 % of cases. It was sometimes the treatment pathway or the fortuitous presence of co-morbidities that enabled the anaesthetist or emergency physician to carry out this clinical examination. However, when this physical examination was scheduled, clinical hepatobiliary signs were discovered in 30 % of patients. ConclusionAn accurate, formalised reference database detailing the principles of the somatic treatment of psychiatric unit in-patients should be established. Our results indicate the necessity of a referring physician in each psychiatric department.

Prevalence of Dyslipidemia and Associated Factors in Obese Children and Adolescents.

Objective:Childhood-onset obesity is associated with increased mortality and morbidity related to cardiovascular diseases (CVD) during adulthood. Dyslipidemia has a fundamental role in the pathogenesis of CVD. This study aimed to evaluate the prevalence of dyslipidemia and related factors among obese children and adolescents.Methods:Obese patients aged between 2 and 18 years were included in the study. Serum concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), fasting glucose levels, insulin, thyroid-stimulating hormone (TSH), free thyroxine (fT4), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver ultrasound findings were evaluated retrospectively.Results:Among 823 obese patients, 353 (42.9%) met the dyslipidemia criteria: 21.7% had hypertriglyceridemia, 19.7% had low levels of HDL-C, 18.6% had hypercholesterolemia, and 13.7% had high levels of LDL-C. Older age and/or high body mass index (BMI) were related to increased prevalence of dyslipidemia. Hepatosteatosis was more common among dyslipidemic patients. The frequency of insulin resistance (IR) and of higher levels of ALT and TSH were also detected in dyslipidemic patients. Patients with both dyslipidemia and grade 2-3 hepatosteatosis had higher levels of ALT, AST and TSH and lower levels of fT4.Conclusion:Prevalence of dyslipidemia is high in obese children, and hypertriglyceridemia is in the foreground. Higher levels of IR and more apparent abnormal liver function test results are observed in the context of dyslipidemia and hepatosteatosis coexistence. Metabolic and hormonal alterations related with thyroid functions may also be associated with dyslipidemia and hepatosteatosis in obese patients.