Search

In patients with treatment-resistant epilepsy (TRE), cannabidiol (CBD) produces variable improvement in seizure control. Patients in the University of Alabama at Birmingham CBD Expanded Access Program (EAP) were enrolled in the genomic study and genotyped using the Affymetrix Drug Metabolizing Enzymes and Transporters plus array. Associations between variants and CBD response (≥50% seizure reduction) and tolerability (diarrhea, sedation, and abnormal liver function) was evaluated under dominant and recessive models. Expression quantitative trait loci (eQTL) influencing potential CBD targets was evaluated in the UK Brain Expression Consortium data set (Braineac), and genetic co-expression examined. Of 169 EAP patients, 112 (54.5% pediatric and 50.0% female) were included in the genetic analyses. Patients with AOX1 rs6729738 CC (aldehyde oxidase; odds ratio (OR) 6.69, 95% confidence interval (CI) 2.19-20.41, P = 0.001) or ABP1 rs12539 (diamine oxidase; OR 3.96, 95% CI 1.62-9.73, P = 0.002) were more likely to respond. Conversely, patients with SLC15A1 rs1339067 TT had lower odds of response (OR 0.06, 95% CI 0.01-0.56, P = 0.001). ABCC5 rs3749442 was associated with lower likelihood of response and abnormal liver function tests, and higher likelihood of sedation. The eQTL revealed that rs1339067 decreased GPR18 expression (endocannabinoid receptor) in white matter (P = 5.6 × 10-3 ), and rs3749442 decreased hippocampal HTR3E expression (serotonin 5-HT3E ; P = 8.5 × 10-5 ). Furthermore, 75% of genes associated with lower likelihood of response were co-expressed. Pharmacogenetic variation is associated with CBD response and influences expression of CBD targets in TRE. Implicated pathways, including cholesterol metabolism and glutathione conjugation, demonstrate potential interactions between CBD and common medications (e.g., statins and acetaminophen) that may require closer monitoring. These results highlight the role of pharmacogenes in fundamental biologic processes and potential genetic underpinnings of treatment-resistance.

Background Abnormal liver function tests (LFT) are common in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vary from 15% to 53%. There are scanty data from India on the prevalence of liver injury in corona virus disease 2019 (COVID-19) patients. Methods We did this retrospective study in a tertiary care hospital, Chennai, India. Patients aged >18 years admitted with COVID-19 from May 1, 2020, to May 31, 2020, were included. We noted the demographic details, symptoms at presentation, history of pre-existing illnesses, and laboratory tests. We also recorded the patient’s clinical course and outcome. Results We took 445 patients for final analysis. Aspartate transaminase (AST) was borderline elevated in 47.5%, mildly elevated in 11.2%, moderately elevated in 2% and severely in 0.7%. Alanine transaminase (ALT) was borderline elevated in 28.7%, mildly elevated in 11.4%, and moderately elevated in 1.3%. Bilirubin and alkaline phosphatase were abnormal in only 19 (4.2%) and 15 (3.3%) patients, respectively. Patients with abnormal LFT were more likely to be symptomatic (90.3% vs. 80.6%, p 0.002). Respiratory symptoms (43.5% vs. 29.7%) and loose stools (11.4% vs. 3.4%) were also more common among them. Patients with abnormal LFT were more likely to have severe disease (25.2% vs. 13.6%, p value 0.003) and mortality (8.8% vs. 0.7%). Conclusion Liver test abnormalities were widespread in patients with COVID-19. Most of the patients had borderline or mild transaminase elevation. Despite only mild changes, patients with abnormal LFT were more likely to be symptomatic and had more severe disease and mortality.

Objectives We aimed to assess the value of liver biopsy in the evaluation of abnormal liver tests. Methods We analyzed consecutive liver biopsy specimens performed for evaluation of unexplained abnormal liver tests from 2014 to 2018. Diagnoses were categorized histologically and clinically. We determined whether histologic examination led to a specific diagnosis and whether prebiopsy laboratory variables predicted the underlying etiology. Results Among the 383 liver biopsy specimens included, chronic hepatitis was the most common histologic (25%) and clinical (17%) diagnosis. Liver biopsy led to a clinical diagnosis in 87% of patients. The most likely clinical diagnoses were autoimmune hepatitis, nonalcoholic fatty liver disease, and drug-induced liver injury (38, 33, and 32 patients, respectively). Using sensitivity, specificity, and positive and negative predictive values, we found that liver tests were not predictive of a specific diagnosis. In patients with no history of liver disease or clinical features of portal hypertension, biopsy specimens revealed histologic cirrhosis in 5% of patients. Conclusions Histopathologic diagnoses were made in 85% of patients undergoing liver biopsy for investigation of unexplained liver tests, leading to a clinical diagnosis in 87% of patients. However, neither liver tests themselves nor their patterns were useful in predicting histologic or clinical diagnoses.

Introduction Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease characterised by pruritus and abnormal liver function tests and it has been associated with intrauterine fetal distress and stillbirth. We compared two guidelines of the management of ICP: One mandating induction at 38 weeks of gestation (Rigshospitalet and Hvidovre Hospital before 2012) and another separating ICP into a mild and severe form and only women with severe ICP were recommended induction at 38 weeks (Hvidovre Hospital after 2012). Material and methods We performed a historical cohort study at two Copenhagen Hospitals from 2004 to 2015. We included 62,937 women with singleton deliveries at Rigshospitalet and 71,015 at Hvidovre Hospital of which 971 women (1.5%) and 998 women (1.4%) were diagnosed with ICP at Rigshospitalet and Hvidovre Hospital respectively. Data was retrieved from a local medical database. For the analysis of induction and comparison of obstetrical outcomes we only included pregnancies with an ICP diagnosis and excluded women with other medical conditions that could mandate induction. Main outcome measures were induction and cesarean section rates, asphyxia and stillbirth. Results We found no changes in the rate of spontaneous labor, cesarean section and induction over the years at Rigshospitalet (p = 0.17) and Hvidovre Hospital (p = 0.38). For women with intended vaginal delivery we found no change in the final mode of delivery over the years at Rigshospitalet (p = 0.28) and Hvidovre Hospital (p = 0.57). Conclusions The two approaches to the management of mild ICP regarding the timing of induction are comparable. Women with mild ICP and their clinicians should be encouraged to engage in shared decision making when discussing timing of induction.

The aim of our study is to examine the association between age and A1C levels in nondiabetic subjects and develop the age-adjusted A1C levels for screening and diagnosis of prediabetes and diabetes.Participants from National Health and Nutrition Examination Survey (NHANES) -1999-2014 with age over 12 years were examined. Individuals with previous diagnosed diabetes, baseline anemia, established hemoglobinopathies, known liver or chronic kidney disease, and abnormal liver function tests or creatinine levels were excluded. Total 16949 subjects consisting of 8651 female subjects and 8298 male subjects were included in the analyses. Linear regression and multivariate regression analyses were performed to assess the relationship between A1C levels and age. Age adjusted A1C levels were determined.Significant positive correlation between A1C and age was found in both female and male subjects in the fasting plasma glucose (FPG) interval between 4.4-7mmol/L (80-126mg/dL) (P0.0001). There was a linear correlation between A1C levels and age. Linear regression analysis suggested A1C levels rose by 0.009% (about 0.09mmol/mol) in female and by 0.008% (about 0.08mmol/mol) in male per year in subjects without abnormality in glucose homeostasis (p0.0001).Our study concluded that age is a significant independent factor of A1C levels.

Objective Whether intensive therapy can alleviate subclinical synovitis and reduce flare in rheumatoid arthritis (RA) patients in clinical remission remains unclear. We designed a 1-year open-labelled, randomized controlled clinical trial to elucidate this question. Methods RA patients in clinical remission/low disease activity (defined by DAS28-CRP≤ 3.2), however with subclinical synovitis on ultrasound [power Doppler (PD)≥1 and/or gray scale (GS)≥2] were randomized to receive maintenance or intensive treatment at a ratio of 1:1. The primary outcome was the rate of RA relapse (defined by DAS28-CRP>3.2 and an increase≥0.6). The secondary outcomes were changes of PD and GS scores, and clinical disease activity at each visit from baseline. Results 108 patients with 54 in each group were enrolled. During 1-year follow-up, the relapse rate was significantly higher in maintenance group than in intensive group, regardless of all enrolled patients or those in remission [24.1% (13/54) vs. 9.1% (5/54), p=0.039; 26.2% (11/42) vs. 5.3% (2/38), p=0.026, respectively]. Although GS and PD scores were decreased at 12 months in both groups, the decline was more remarkable in intensive group than in maintenance group. The improvement of clinical disease activity score was only observed in intensive group, not maintenance group. Adverse events were comparable between two groups. Abnormal liver function tests were observed in 24 (22%) patients with 16 from intensive group. Conclusion Intensive therapy can alleviate subclinical synovitis on ultrasound and clinical disease activity, and prevent relapse in RA patients who have achieved clinical remission or low disease activity, with comparable safety profiles to maintenance therapy. Registration number ChiCTR2000029279

Background Non-alcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in Australia and its recent increase mirrors the obesity and type 2 diabetes epidemics. Currently, many patients who present to primary care with abnormal liver function tests or steatosis on liver ultrasound are referred for assessment in secondary care. Due to the large number of patients with NAFLD, this results in long waits for clinical and fibrosis assessment, placing unnecessary burden on the public hospital system. Methods We will conduct a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD. Participants will be randomised to usual care or the LOCal Assessment and Triage Evaluation (LOCATE) model of care and followed for 1 year. We will recruit patients from the non-neighbouring Sunshine Coast and Metro South Hospital and Health Services (HHSs) in Queensland, Australia. Our primary outcome of interest is time to diagnosis of high-risk NAFLD, based on the number of participants in each arm of the study who receive a diagnosis of clinically significant fibrosis. Two hundred and 34 participants will give us a 95% power to detect a 50% reduction in the primary outcome of time to diagnosis of high-risk disease. We will also conduct an economic evaluation, evaluating the cost-effectiveness of the new model of care. We will also evaluate the implementation of the new model of care. Discussion It is anticipated that the results of this study will provide valuable new information regarding the management of NAFLD in the Australian setting. A relatively simple change to care could result in earlier identification of patients with significant liver disease and lower overall costs for the health system. Results will be directly disseminated to key staff for further distribution to consumers, policy- and decision-makers in the form of evidence briefs, plain language summaries and policy recommendations. Trial registration The trial was registered on 30 January, 2020 and can be found via ANZCTR - number ACTRN12620000158965.

Summary Background & Aims Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders. There is a strong association for primary sclerosing cholangitis (PSC). Primary biliary cholangitis (PBC), another autoimmune cholestatic liver disease, is not usually associated with IBD. The aim of this study is to report cases of PBC-associated IBD, their clinical features, response to therapy, and long-term outcome. Methods Retrospective analysis of a prospectively collated database identified patients presenting with PBC-associated IBD from 2006 to 2016. PBC has been diagnosed according to accepted criteria, and staged according to Ludwig classification. A magnetic resonance cholangiopancreatography (MRCP) was performed to rule out PSC. Response to ursodeoxycholic acid (UDCA) therapy has been assessed by using the Paris II criteria. Results A total of six patients (five females) with PBC-associated IBD were identified. Median age at IBD diagnosis was 44.7 years (range 22.5–48.8). Three had Crohn's disease and three ulcerative colitis. PBC was diagnosed in all after IBD had been diagnosed. All patients presented with cholestasis, all were positive for anti-mitochondrial antibodies. MRCP was normal in all. Liver biopsy was consistent with PBC (stage I in one, stage II in five). One year after initiation of UDCA, all patients responded to therapy. Conclusion Herein we describe the largest series reported to date of PBC-associated IBD. Although the coexistence of the two conditions is rare, PBC should be considered during the work-up of abnormal liver function tests in patients with IBD.

A phase I, open-label study (NCT02197234) assessed the effects of osimertinib on simvastatin exposure in patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer and disease progression post-EGFR tyrosine kinase inhibitor treatment. Here, we report on a retrospective analysis of two patients (patients 1 and 2) who had liver metastases and high simvastatin exposure prior to osimertinib treatment, which changed following treatment. Patients received single oral doses of simvastatin 40 mg on day (D) 1 and D31, and osimertinib 80 mg once daily on D3-32. At baseline, both patients had abnormal liver function tests (LFTs; Child-Pugh scores of 6 and 8, respectively), significant liver metastasis, and, after a single simvastatin dose, had higher (~ 10-fold) exposure compared with all other patients. Following 31 days of continuous osimertinib treatment, simvastatin exposures (area under the plasma concentration-time curve from zero to infinity (AUC) and maximum plasma concentration (Cmax )) and LFTs, such as alanine transaminase, aspartate aminotransferase, and bilirubin normalized to population mean values. Additionally, ~ 50% and ~ 80% reductions in liver metastases were observed on computed tomography scans in patients 1 and 2, respectively. High simvastatin exposure on D1 likely resulted from impairment of hepatic first pass metabolism due to liver metastases. Reduction in hepatic disease burden due to osimertinib treatment likely resulted in liver function returning to normal levels.

Background and aims Non-alcoholic fatty liver disease (NAFLD) commonly affects subjects with obesity, yet non-obese NAFLD is increasingly being recognized. We aimed to investigate the clinicopathological and genetic characteristics of non-obese NAFLD patients. Methods The clinical, histological and genetic data of 84 NAFLD patients with biopsy for abnormal liver function test were reviewed. Both NAS-CRN and SAF scoring systems were applied for histopathological evaluation. PNPLA3 and TMS6F2 genotyping were also performed. Results All of the 84 patients were histologically diagnosed with non-alcoholic steatohepatitis (NASH), with 36 of them (42.9%) being non-obese (BMI

Isotretinoin is an efficacious treatment option for severe acne. Although isotretinoin often causes mild liver enzyme elevation, how acne patients should be monitored on isotretinoin therapy is not well characterized.The purpose of this study was to assess the management and clinical outcome of acne patients with abnormal aspartate transaminase (AST) and alanine aminotransferase (ALT) when receiving isotretinoin.A retrospective chart review was conducted in acne subjects with abnormal AST and ALT levels receiving isotretinoin. Abnormal liver enzymes were graded using the Common Terminology Criteria for Adverse Events version 5.Of 108 subjects with abnormal liver enzymes, 79 subjects were on isotretinoin 80 mg and 23 subjects were on isotretinoin 40 mg. Most abnormalities were during Month 1 of therapy (48). Of the 122 abnormal Grade 1 AST elevations, 40 normalized, 38 remained in Grade 1, and 1 increased into Grade 2 when a healthcare provider maintained the isotretinoin dose. Of the 102 abnormal Grade 1 ALT levels managed by maintaining the isotretinoin dose, 31 normalized and 38 remained persistently elevated.Most mild elevations of isotretinoin therapy do not worsen. Acne patients with isotretinoin may not need continued testing when experiencing low-grade liver enzyme abnormalities.

A 39-year-old woman was referred to the digestive and liver specialist after several weeks of her feeling tired, with complaints of abdominal pain, nausea, and vomiting, and with abnormal liver function tests. The patient was in good general health, with a body mass index of 21.2 kg/m2, no relevant medical history, and a normal physical examination. The stigmata of chronic liver disease were absent. The patient reported that she had been consuming 3 to 4 beers/day and was not taking any medication. An abdominal ultrasonography revealed hepatic steatosis. Blood and urine tests showed the following: aspartate transaminase, 95 U/L [reference interval (RI)3, 0–32 U/L]; alanine transaminase, 66 U/L (RI, 0–33 U/L); alkaline phosphatase, 180 U/L (RI, 35–105 U/L); γ-glutamyl transferase, 1005 U/L (RI, 0–40 U/L); albumin, 34 g/L (RI, 35–52 g/L); total bilirubin, 0.8 mg/dL (13.7 mmol/L) [RI, 0.1–1.2 mg/dL (1.7–20.5 mmol/L)]; direct bilirubin, 0.7 mg/dL (12.0 mmol/L) [RI, 0.0–0.3 mg/dL (0.00–5.1 mmol/L)]; total cholesterol, 546 mg/dL (14.1 mmol/L) [upper reference limit (URL), 739 μg/g tissue. Genetic testing for the ATP7B 4 gene was performed, but no mutations were found. ### QUESTIONS TO CONSIDER 1. What are …

Background Autoimmune liver disease (AILD) includes autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). AILD is often associated with other extra-hepatic immune-mediated disorders (EDs), but there are few pediatric studies available to date. In this study we evaluated the association between AILD and EDs in our pediatric series. Methods In this single centre retrospective study 48 patients (39 AIH and 9 ASC children) were evaluated. Thirty-six children were primarily referred to our Centre for liver disease suspicion, while the remaining twelve had a previous diagnosis of EDs. All the patients were screened for various EDs at AILD diagnosis and yearly during the follow-up. Results Mean duration of follow-up was 9 years and 1 month. Twenty-two (46%) patients had a diagnosis of EDs. Ulcerative colitis (UC) was the most frequent EDs (9 patients), followed by autoimmune thyroid disease (5 patients) and celiac disease (5 patients). In 7 out of 9 UC patients, ASC was present. Conclusions Our study showed a high association (46%) between AILD and EDs. In particular, in 8 out of 9 ASC patients UC was diagnosed (p-value 0.007). It is important to look for EDs in AILD children and, conversely, AILD in EDs children with abnormal liver function tests.

Background Nonalcoholic steatohepatitis (NASH) has a risk of progressing to cirrhosis. The prevalence of NASH and its associated risk factors in community populations are relatively unknown. This study aimed to determine the prevalence of NASH and advanced liver fibrosis using magnetic resonance elastography (MRE), and determine those risk factors in health examinees with asymptomatic fatty liver. Methods This study consecutively selected subjects who underwent health checkups at 13 health-promotion centers in 10 Korean cities between 2018 and 2020. Hepatic steatosis and stiffness were assessed using ultrasonography and MRE, respectively. Stages of liver stiffness were estimated using MRE with cutoff values for NASH and advanced liver fibrosis of 2.91 and 3.60 kPa, respectively. Results The overall prevalence of NASH and advanced liver fibrosis in the subjects with fatty liver were 8.35% and 2.04%, respectively. Multivariate logistic regression analysis indicated that central obesity (OR = 5.12, 95% CI = 2.70–9.71), increased triglyceride (OR = 3.29, 95% CI = 1.72–6.29), abnormal liver function test (OR = 3.09, 95% CI = 1.66–5.76) (all PP = 0.003) were associated with NASH. The main risk factor for advanced liver fibrosis was diabetes (OR = 4.46, 95% CI = 1.14–17.48) (P = 0.032). Conclusion NASH or advanced liver fibrosis is found in one-tenth of health examinees with asymptomatic fatty liver. This suggests that early detection of NASH should be considered to allow early interventions such as lifestyle changes to prevent the adverse effects of NASH and its progression in health examinees with asymptomatic fatty liver.

Background Almost all Koreans are covered by mandatory national health insurance and are required to undergo health screening at least once every 2 years. We aimed to develop a machine learning model to predict the risk of developing hepatocellular carcinoma (HCC) based on the screening results and insurance claim data. Methods The National Health Insurance Service-National Health Screening database was used for this study (NHIS-2020-2-146). Our study cohort consisted of 417,346 health screening examinees between 2004 and 2007 without cancer history, which was split into training and test cohorts by the examination date, before or after 2005. Robust predictors were selected using Cox proportional hazard regression with 1000 different bootstrapped datasets. Random forest and extreme gradient boosting algorithms were used to develop a prediction model for the 9-year risk of HCC development after screening. After optimizing a prediction model via cross validation in the training cohort, the model was validated in the test cohort. Results Of the total examinees, 0.5% (1799/331,694) and 0.4% (390/85,652) in the training cohort and the test cohort were diagnosed with HCC, respectively. Of the selected predictors, older age, male sex, obesity, abnormal liver function tests, the family history of chronic liver disease, and underlying chronic liver disease, chronic hepatitis virus or human immunodeficiency virus infection, and diabetes mellitus were associated with increased risk, whereas higher income, elevated total cholesterol, and underlying dyslipidemia or schizophrenic/delusional disorders were associated with decreased risk of HCC development (p C-index, AUC, and Brier skill score were 0.857, 0.873, and 0.078, respectively. Conclusions Machine learning-based model could be used to predict the risk of HCC development based on the health screening examination results and claim data.

ObjectivesThe health burden of chronic liver disease is increasing worldwide. Its main histological consequence is liver fibrosis, and eventually cirrhosis. This process is rarely diagnosed at the pre-cirrhotic stage due to it being asymptomatic. Little is known about the prevalence of liver fibrosis and associated risk factors in the general population. The aims of this study were to determine the prevalence and distribution of liver fibrosis using magnetic resonance elastography (MRE), as well as the risk factors associated with liver fibrosis in the asymptomatic general population.Design, setting and participantsThis cross-sectional retrospective study consecutively selected subjects who underwent health check-ups including MRE at 13 health promotion centres in Korea between 2018 and 2020. Liver fibrosis was estimated using MRE with cut-off values for significant and advanced liver fibrosis of 2.90 and 3.60 kPa, respectively.Primary and secondary outcome measuresThe Χ2 test was used to compare the prevalence of liver fibrosis according to sex and age groups. Multivariable logistic regression analyses were performed to identify the factors for significant and advanced liver fibrosis.ResultsAmong the 8183 subjects, 778 (9.5%) had ≥significant fibrosis (≥2.9 kPa), which included 214 (2.6%) subjects with ≥advanced fibrosis (≥3.6 kPa). Multivariable analysis revealed that liver fibrosis was associated with age (OR=1.34, 95% CI=1.18 to 1.51), male sex (OR=3.18, 95% CI=1.97 to 5.13), diabetes (OR=2.43, 95% CI=1.8 to 3.28), HBsAg positivity (OR=3.49, 95% CI=2.55 to 4.79), abnormal liver function test (OR=1.9, 95% CI=1.49 to 2.42) and obesity (OR=1.77, 95% CI=1.35 to 2.32) (all pConclusionsThe prevalence of significant or more liver fibrosis was high in the Korean general population and much higher among individuals with risk factors. This suggests that screening of liver fibrosis should be considered in general population, especially among high-risk groups.

Coronavirus disease 2019 (COVID-19) leads to elevated liver biochemistries in approximately half of patients on presentation. To date, data are limited regarding the trend of liver biochemistries over the course of illness. We aimed to evaluate the trend, etiology, and outcomes associated with liver biochemistries in COVID-19.A total of 60 patients with COVID-19 were admitted between March 21 and March 28, 2020. The mean age was 57 years, 65% were male, and 28% were Hispanic. At the study conclusion, 6 patients were deceased, 28 were discharged, and 26 remained admitted. Patients who remained admitted were followed for a median of 12 days. Of 60 patients, 41 (69%) had at least one abnormal liver biochemistry on admission. Median aspartate aminotransferase (AST) was higher than alanine aminotransferase (ALT) at admission (46 vs. 30 U/L) and during the hospital course. Aminotransferases rose above normal in 54 (93%) patients, whereas alkaline phosphatase and total bilirubin elevations were rare. Ten (17%) patients developed aminotransferases more than 5 times the upper limit of normal. AST highly correlated with ALT throughout the illness course (r = 0.97; P 0.0001), whereas correlations with markers of muscle injury and inflammation were weak. Statin use was common before (40%) and during admission (80%) at our center, with no difference in peak liver biochemistries between users and nonusers. No demographic or comorbid illness was associated with liver injury. Admission AST (69 vs. 49; P 0.05), peak AST (364 vs. 77; P = 0.003), and peak ALT (220 vs. 52; P = 0.002) were higher in intubated patients.AST-dominant aminotransferase elevation is common in COVID-19, mirrors disease severity, and appears to reflect true hepatic injury.

Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P 

Background Abnormal liver function tests (LFTs) are commonly seen in pediatric patients with acute infectious diseases. Few studies and no definite clinical guidelines for these conditions are available. The present study aimed to elucidate the causes and factors associated with prolongation of liver enzyme elevation. We also investigated actual real-world practices in Korea. Methods A retrospective study was performed on all patients younger than 18 years, who visited six tertiary teaching hospitals around Korea in 2018 for acute infectious diseases and showed alanine aminotransferase (ALT) levels above 60 IU/L without other specific conditions that could cause ALT elevation. We categorized the infections that cause LFT elevation into six groups: respiratory infection, gastrointestinal infection, urinary tract infection, other febrile disease, Epstein-Barr virus infection, and cytomegalovirus infection. We collected data on the medical specialty of the attending physician who followed up the subject, follow-up duration, percentage of follow-up loss, and their investigation. Results A total of 613 patients were enrolled in this study, half of whom (50.7%) were younger than 12 months. The mean initial aspartate aminotransferase and ALT values were 171.2 ± 274.1 and 194.9 ± 316.1 IU/L (range 23–2,881, 60–2,949 IU/L), respectively; however, other LFTs were within the normal range. Respiratory infection was the most common diagnosis (45.0%), and rhinovirus was the most commonly identified pathogen (9.8%). The follow-up rate was higher with pediatric gastroenterologists (90.5%) and non-gastroenterology pediatricians (76.4%) than with pediatric residents and emergency doctors. Older age was related to better ALT recovery (odds ratio [OR] of age for month = 1.003; 95% confidence interval [CI], 1.001–1.004; P = 0.004), while the number of infection episodes (OR = 0.626; 95% CI, 0.505–0.777; P < 0.001) was associated with poor ALT recovery. Abdominal sonography was the most commonly used diagnostic tool (36.9%), followed by the hepatotropic virus workup. The modalities of hepatitis workup were significantly differently applied by physicians based on their specialties and institutions. Conclusion Abnormal liver function test after a systemic infection was common in respiratory infection and under the age of 1 year. Age, number of infections, and initial results of LFTs were related to ALT recovery time. Inter-physician, inter-institution, and inter-specialty variances were observed in real-world practice., Graphical Abstract

BackgroundMany patients with alpha-1 antitrypsin deficiency (A1ATD) receive care in respiratory clinics without access to specialist hepatology expertise. Liver disease can develop asymptomatically, and non-invasive markers of fibrosis may help identify patients who require definitive assessment with liver biopsy. We evaluated the utility of non-invasive markers of liver fibrosis in A1ATD to guide testing in settings without ready access to hepatology expertise.MethodsPatients attending the London A1ATD service undergo assessment using blood tests to calculate the ‘APRI’ and ‘FIB-4’ score, liver ultrasound and Fibroscan. Liver biopsy is offered to patients who have abnormal liver function tests with abnormal liver ultrasound and/or liver stiffness >6 kPa on Fibroscan. Liver biopsies were assessed for the presence of A1AT, steatosis, fibrosis and inflammation.Results75 patients with A1ATD had results for analysis, 56% were female, age 16–82 years. 75% of patients had Fibroscan 8 kPa. There was a significant correlation between FIB-4 and Fibroscan (r=0.244, p=0.035). Fibroscan >6 kPa corresponded to a FIB-4 score of >1.26. However, FIB-4 >1.26 had poor sensitivity (47%), specificity (32%) and positive-predictive value (PPV; 36%) to identify Fibroscan >6 kPa. The negative-predictive value (NPV) was stronger at 81%. APRI data were similar. Twelve patients underwent liver biopsy, with 11 reports available for analysis. Six had FIB-4 scoresConclusionA combination of liver ultrasound and non-invasive fibrosis tests can help identify patients with A1ATD liver injury. However, APRI and FIB-4 scores alone had poor sensitivity and specificity to justify use as an independent tool for liver pathology in A1ATD.

IntroductionThe progression and severity of the coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), varies significantly in the population. While the hallmarks of SARS-CoV-2 and severe COVID-19 within routine laboratory parameters are emerging, little is known about the impact of sex and age on these profiles.MethodsWe performed multidimensional analysis of millions of records of laboratory parameters and diagnostic tests for 178,887 individuals, of which 33,266 tested positive for SARS-CoV-2. These included complete blood cell count, electrolytes, metabolites, arterial blood gases, enzymes, hormones, cancer biomarkers, and others.ResultsCOVID-19 induced similar alterations in the laboratory parameters in males compared to females. Biomarkers of inflammation, such as C-reactive protein (CRP) and ferritin, were increased especially in older men with COVID-19, whereas other markers such as abnormal liver function tests were common across several age groups, except for young women. Low peripheral blood basophils and eosinophils were also more common in the elderly with COVID-19. Both male and female COVID-19 patients admitted to the intensive care unit (ICU) displayed alterations in the coagulation system, and higher levels of neutrophils, CRP, lactate dehydrogenase (LDH), among others.DiscussionOur study uncovers the laboratory profile of a large cohort of COVID-19 patients that underly discrepancies influenced by aging and biological sex. These profiles directly link COVID-19 disease presentation to an intricate interplay between sex, age and the immune response.One Sentence SummaryBig Data analysis of laboratory results from a large number of COVID-19 patients and controls reveals distinct disease profiles influenced by age and sex which may underly occurrence of severe disease.Key messages- What is the key question?Little is known about the impact of sex and age on the routine laboratory parameters measured in COVID-19 patients.- What is the bottom line?Our in-depth analysis unraveled distinct disease profiles influenced by age and sex which may underly occurrence of severe disease.- Why read on?This work will help physicians to interpret the disease presentation in COIVD-19 patients according to their age and sex.

Introduction Intrahepatic cholestasis of pregnancy (ICP) is associated with a distinctive maternal pruritus, abnormal liver function tests, raised serum total bile acids, and increased rates of adverse fetal outcomes, including intrauterine fetal death. Progesterone has been implicated in the pathogenesis of ICP. We aimed to evaluate whether the incidence of ICP is altered in women receiving long-term daily vaginal progesterone, indicated for a short cervical length. Study design A matched 1:3 case-control study of pregnant women between January 2014 and January 2019. Study cases included pregnant women with the diagnosis of ICP. Control cases were women without ICP. The primary outcome was the rate of vaginal progesterone treatment among the groups. Results The use of vaginal progesterone throughout pregnancy was higher in the ICP group compared with the control group (8/174 [4.6 %] versus 6/522 [1.1 %], respectively, P = 0.03, odds ratio 4 [95 % confidence interval 1.4–11.7]). Conclusions Pregnant women treated with long-term vaginal progesterone preparations for the prevention of preterm birth are at increased risk of developing ICP. In the presence of pruritus during pregnancy, we recommend an early consultation and diagnostic test to confirm or rule-out ICP.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID-19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non-critically ill patients with COVID-19. METHODS: In this multicentre, retrospective study, we collected data about 565 inpatients with COVID-19. Data on LFTs were collected at admission and every 7 ± 2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU). RESULTS: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20% vs 8%; P < .001), acute kidney injury (22% vs 13%, P = .009), need for mechanical ventilation (14% vs 6%; P = .005) and mortality (21% vs 11%; P = .004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR = 3.53; P < .001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint. CONCLUSIONS: LFTs abnormality is common at admission in patients with COVID-19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.

Objective To determine the molecular characterization and disease-associated complications of beta-thalassemia intermedia (β-TI) patients in Sulaymaniyah province, northeastern Iraq. Methods A total of 159 β-TI) patients in Sulaymaniyah province, northeastern Iraq. β-TI) patients in Sulaymaniyah province, northeastern Iraq. Results Nineteen different β-globin gene mutations arranged in 37 various genotypes were determined. The most frequent were IVS-II-I (G>A) (47.2%), followed by IVS-I-6 (T>C) (23.3%) and IVS-I-110 (G>A) (5%). Among disease-related morbidities documented, bone disease amounted to 53% (facial deformity and osteoporosis), followed by endocrinopathies 17.6% (growth retardation and subclinical hypothyroidism), cholelithiasis 13.8%, pulmonary hypertension 11.3%, and abnormal liver function test 7.5%, whereas venous thrombosis, extramedullary hemopoiesis, and leg ulcer were less frequently observed. Age ≥ 35 and female sex were risk factors for cholelithiasis, while age was an independent risk for hypothyroidism and female sex was associated with increased risk for osteoporosis. Mean serum ferritin of ≥1000 μg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.β-TI) patients in Sulaymaniyah province, northeastern Iraq. μg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.β-TI) patients in Sulaymaniyah province, northeastern Iraq. β-TI) patients in Sulaymaniyah province, northeastern Iraq.

Background: Patients with nonalcoholic fatty liver disease (NAFLD) and with abnormal liver function tests (LFTs) most commonly present with elevated hepatocellular enzymes (H pattern), but a subset of patients is found to have elevated cholestatic enzymes (C pattern) or a mixed (M) pattern. Aims and Methods: To determine whether the epidemiologic background and comorbidities, as well as the degree of liver fibrosis, differ between NAFLD patients with different patterns of elevated LFTs by retrospectively analyzing data of 106 patients with a biopsy-proven diagnosis of NAFLD. The pattern of elevated LFTs was determined by adopting the “R-Ratio” formula commonly used for drug-induced liver injury. Results: Advanced fibrosis (F > 2) was found in 15 out of 48 (31.3%) patients with a C pattern of elevated LFTs as compared to 2 out of 44 (4.5%) in M patients and 2 out of 11 (18.2%) in H patients (p = 0.004). Group C patients are older and also had a higher prevalence of diabetes, a higher mean hemoglobin A1c, and a higher prevalence of hypertension, as well as a trend for a higher prevalence of hypertriglyceridemia. Conclusions: Using a simple formula incorporating routine LFTs can help to categorize NAFLD patients as low or high risk for advanced fibrosis stage and metabolic-associated comorbidities.

Intrahepatic cholestasis of pregnancy is a diagnosis of exclusion and presents with unexplained pruritus, abnormal liver function tests, and increased serum bile acid levels, particularly in the third trimester of pregnancy. Serum YKL-40 levels are increased in liver diseases and our aim was to investigate YKL-40 levels in pregnant women with ICP. 40 women with intrahepatic cholestasis of pregnancy and 40 healthy pregnant women were included in this cross-sectional study. Serum YKL-40 levels were measured in both groups and correlation analysis were performed between the YKL-40 and other liver function tests. Serum YKL-40 concentrations were higher in the intrahepatic cholestasis of pregnancy group than in the control group (103.46 ± 53.03 vs. 57.60 ± 30.30 ng/ml

The aim of the study was to analyze the clinical presentations, diagnosis, and treatment of patients ages ≤5 years with early onset Wilson disease (WD).Data from 143 pediatric patients with WD treated at our center between January 1996 and November 2015 were retrospectively analyzed.A review of the 143 pediatric patients with WD identified 21 (10 girls, 11 boys) with first symptoms or abnormal liver function test results at age ≤5 years. The diagnosis of WD was confirmed in 8 patients younger than 5 years. At baseline the mean serum alanine aminotransferase level was 222 U/L and the mean serum aspartate aminotransferase level was 130 U/L. The mean serum ceruloplasmin concentration in 16 tested patients was20 mg/dL. Of the 15 patients who underwent urinary copper excretion testing, 8 had levels between 40 and 100 μg/day, with only 4 having levels100 μg/day. Liver copper quantification was250 μg/g dry weight in 16 patients. The most common mutation was p.H1069Q, with compound heterozygosity in 5 patients and homozygosity in 9. Sixteen patients were treated with zinc salts and 5 with D-penicillamine. Both treatments were effective, with no serious side effects observed after 3 to 24 months.WD can present as early as 2 years of age. Because biochemical tests may be less sensitive in very young children, diagnoses may require a combination of tests. If molecular tests are inconclusive, liver copper content should be measured.

Purpose: Isotretinoin is the most effective drug for acne with some side effects. Few studies exist regarding the effects of isotretinoin on haematological parameters with different results. Mostly, baseline values with a single value during or at the end of the treatment were compared. In this study, we aimed to determine the differences in haematological parameters during isotretinoin treatment until reaching the cumulative dose of 120 mg/kg. Materials and methods: The study included 118 patients with moderate-to-severe acne vulgaris. Patients with preexisting liver disease, anaemia, iron deficiency, abnormal liver function tests, thrombocytopenia/thrombocytosis or hyperlipidaemia were excluded. Laboratory monitoring for haematological parameters was performed at baseline and monthly during treatment. Parameters at the baseline, at the first and second months and at the end of the therapy were taken into account. Results: According to general linear model analysis, platelets and plateletcrit increased at the first month of the treatment and then decreased to baseline. White blood cells and neutrophils decreased at the first month, then increased to baseline value at the second month, and were found to be decreased again at the end of the treatment. Mean corpuscle volume was found to be increased at the end of the treatment. Other parameters in CBC did not show statistically significant differences. Conclusions: Although some changes occur in haematological parameters during isotretinoin therapy, all of these changes remain within the normal range. Evaluating the spot values at any time during treatment may cause misinterpretations. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Purpose: The purpose of this study was to estimate how many individuals with severe obesity and NAFLD should be referred to hepatologists according to the EASL–EASD–EASO guidelines and whether the choice of specific indicators of liver fibrosis would significantly impact the number of referrals. Methods: This was a single-center retrospective study of 495 individuals with severe obesity screened at our institution between 2012 and 2018 for a bariatric surgery intervention. The guidelines were applied using the NAFLD Liver Fat Score (NLFS) to assess the presence of steatosis and the NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and Hepamet Fibrosis Score (HFS) to assess the risk of advanced fibrosis. Results: Three hundred and seventy-nine patients (76.6%) had evidence of liver steatosis. The application of the guidelines would lead to referral of 66.3% of patients using NFS, 31.7% using FIB-4 and 34.2% using HFS. When referrals due to abnormal liver function tests were excluded, these percentages dropped to 55.8%, 7.3% and 12.1%, respectively. The strongest inter-biomarker agreement was found between FIB-4 and HFS (κ = 0.86, 95% CI 0.815–0.910). Conclusion: Strict application of the guidelines in individuals with severe obesity would probably lead to over-referral, although a great variability exists among the different scores.

Background It is engrained in medical training that routine blood screening prior to arthroplasty is necessary for optimal patient care. There is little evidence to support their utility and the aggregate cost to the health system. The purpose of this study was to evaluate preoperative blood screening by identifying the frequency of an abnormal result and to examine the influence of age, gender and body mass index on the frequency of abnormal blood pathology. Methods This is a retrospective review of 1000 patients from a single centre who underwent elective primary hip or knee arthroplasty from 2015 to 2017. Abnormal blood results were identified and clinically relevant intervals were created for routine markers. Results A total of 939 patients had available pathology results with 84% identified as having an abnormal result and 47% having a clinically important range. Abnormal liver function tests and ferritin were most common. With increasing age, there was a significant increase in rates of abnormal clinically important range, renal dysfunction, abnormal haemoglobin and erythrocyte sedimentation rate. Males and patients with body mass index >40 had an increased rate of abnormal results, particularly liver function tests. Conclusion The ordering of preoperative investigations prior to lower limb arthroplasty is recommended by the National Institute for Health and Care Excellence guidelines, alleviating concern of post-operative complications and covering medicolegal issues. Our study determined a high frequency of abnormal results, justifying routine blood screening is recommended prior to surgery, particularly for the elderly, males and obese patients.

Fibrosing cholestatic hepatitis (FCH) posttransplantation can lead to graft failure and death. In the era of direct acting antiviral therapy (DAA), several studies have demonstrated the efficacy and safety of transplanting hepatitis C virus (HCV)-positive allografts into HCV-negative recipients. In this case series, we present two cases of HCV-negative recipients who underwent kidney transplantation from viremic donors and developed FCH. Both patients presented after transplant with abnormal liver function tests and HCV viral loads of greater than 100 000 000 IU/mL. FCH was diagnosed by histology and/or clinical data. Both patients were started on DAA therapy within 24 hours of admission with improvement in LFTs. One patient has undetectable HCV 12 weeks after completing treatment and the other patient has undetectable HCV after completing DAA treatment. The introduction of DAAs has changed the landscape of solid organ transplantation with the potential to expand the donor pool and increase access to organs. While HCV viremic organs have tremendous potential to increase access to a scarce resource, FCH is a potentially fatal complication and therefore clinicians must maintain a high index of suspicion for this unique complication.

Introduction: The cancer research community increasingly question the rigidity of eligibility criteria in clinical trials. Common reasons for “screen failure” (RFSF) are well documented; however, their effect on subsequent standard therapy (SST) and outcomes is unclear. Methods: This retrospective study evaluated patients aged ≥18 years with solid malignancy who were listed as ineligible on a screening log between February 2011 and March 2018. Patients screen-failed for biomarker results or incorrect cancer stage/prior treatment profile were excluded. Data were collected from electronic hospital records, including demographics, cancer history, RFSF, subsequent therapy, and outcomes. Results: Overall, 217 patients were eligible. The most common histologies were lung (28%), melanoma, colon, and pancreatic (all 11%); 90% were metastatic. The most common RFSF were rapid disease progression (PD; 16%), performance status (PS) ≥2 (12%), and abnormal liver function tests (aLFT; 12%). After screen failure, 129/217 (59%) had SST; 9 were dose-reduced. Treatment-naïve or phase III trial-ineligible patients were more likely to receive SST than those pre-treated or phase I trial-ineligible (72/104 vs. 52/113, p = 0.0006; 71/109 vs. 15/42, p = 0.00013), respectively. RFSF stabilised/improved in 104/217 (48%); the main RFSF was co-morbidity (19/104). The most common RFSF to deteriorate were rapid PD (27/72), PS ≥2 (20/72), and aLFT with liver metastases (LM; 13/72). Conclusions: RFSF related to organ function rarely deteriorate unless directly involved with underlying malignancy. Most RFSF do not prevent patients from having SST, nor increase dose reductions, especially in treatment-naïve/phase III trial-ineligible patients. Those with RFSF of poor PS, rapid PD, and aLFT from LM are less suitable for SST. Careful broadening of trial eligibility is warranted.

Objective Abnormal liver function tests in children and young people (CYP) predict a greater burden of liver disease in adulthood, especially in the context of obesity. This study aimed to determine whether obesity and metabolic risk factors predict liver function testing and abnormal liver test results in CYP. Methods This was a retrospective cross-sectional population study using electronic health care records from 257,746 CYP aged 10 to 25 years who were registered with 170 contiguous general practices in London, UK. Demographic and clinical data were extracted, including serum alanine aminotransferase (ALT) tests between 2015 and 2017. BMI category thresholds were adjusted according to age group and ethnicity. Results Fourteen percent of CYP had ALT measured, of whom 5.4% had abnormal results; 36.3% had BMI indicating overweight or obesity. Nonalcoholic fatty liver disease was the most common liver diagnosis. Multivariate analyses demonstrated that overweight or obesity was an independent predictor of ALT testing in young people (ages 18-25) but not in children (ages 10-17) and of abnormal test results in all CYP, irrespective of ALT threshold. Conclusions Overweight and obesity are predictors of liver testing (not in children) and abnormal test results, irrespective of ALT threshold. Given the rising prevalence of metabolic dysfunction, a coordinated strategy is needed for liver testing and interpreting results in this young population.

SARS-CoV-2 or Coronavirus disease 2019 (COVID-19) outbreak which caused by the severe acute respiratory syndrome, has rapidly spread over the world. The exact mechanism how this virus will affect the liver remained elusive. The aim of this study was to evaluate the liver function in patients with severe acute respiratory syndrome coronavirus 2 and potential causes of hepatic enzymes disease in these patients. Clinical characteristics and laboratory findings were collected from patients with COVID-19 who were admitted to the corona center in Erbil city/Kurdistan region of Iraq, from March 10 to July 10, 2020. Serum was collected from patients with COVID-19 and liver enzyme tests were measured. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) were analyzed in these patients. Of the 74 patients, 25 (34.7%) had abnormal ALT activity, 28 (40%) had abnormal AST activity, 12 (20.3%) had abnormal ALP activity, and 39 (52.7%) had abnormal total bilirubin P-value

Liver disease in HIV-infected patients has remained unaddressed in India. This study describes the causes of liver disease in HIV-infected patients and short-term outcome in them. Designed as a prospective observational study, it was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research between September 2011 and March 2013. All consecutive HIV patients (13 years) attending the antiretroviral therapy clinic or admitted in the Medicine Department were screened, and patients with liver disease or with either HBsAg or anti-HCV antibody positivity were included in the study. Of the 198 patients screened, 51 (26 %) had either abnormal liver function test or had HBsAg or anti-HCV positivity. The median age of the patients was 40 years and 82 % were males. The median CD4 count was 123 cells/mm(3). Eighteen (35 %) of them had alcoholic liver disease. Six patients had probable hepatic involvement due to tuberculosis. Ten patients had antituberculosis drug-induced hepatotoxicity. One patient had acute hepatitis B and seven patients had chronic hepatitis B. The cause could not be established in 10 patients (20 %). After a median period of 8 months of follow up, 23 patients had improved, 19 patients (37 %) had died, and six patients had been lost to follow up. Of the patients who had died, 11 patients (58 %) had tuberculosis, and 6 patients (30 %) had decompensated alcoholic liver disease. In conclusion, liver disease in HIV-infected patients was associated with high mortality. Alcohol abuse, tuberculosis, and antituberculosis drugs were the major causes.

Patients with cirrhosis are known to develop small bowel mucosal lesions. However, the occurrence of mucosal lesions in patients with abnormal liver function test results in the absence of chronic liver disease has not been fully evaluated. This study aims to examine the association between small bowel endoscopic lesions and liver dysfunction in patients without confirmed chronic liver disease. Two hundred ninety six consecutive patients who met the selection criteria underwent capsule endoscopy. The severity of the small intestinal mucosal lesions was evaluated quantitatively using the Lewis scoring system, and hepatic dysfunction was evaluated using an algorithm-based combination scoring system with 8 individual serological markers. Small bowel lesions were observed in 121 patients (40.88%). Hepatic dysfunction was significantly more prevalent in patients with small bowel lesions than in those without lesions (33.1%; 40/121 and 5.7%; 10/175, respectively; P < .001). The mean serum ALT and AST levels were significantly higher in patients with small bowel lesions than in those without lesions (P = .007 and P = .004, respectively). The mean scores for AST to Platelet Ratio Index, Forns Index, S-Index, Fibrosis-4 Index and BARD were significantly higher in patients with small bowel lesions than those without lesions. The Lewis score significantly and positively correlated with the Forns Index (P = .008) and the FIB-4 Index (P = .006). There is a close correlation between small intestinal mucosal lesions and hepatic dysfunction. The severity of hepatic dysfunction is directly proportional to the severity of the small intestinal mucosal lesions in patients without confirmed chronic liver disease.

Caspofungin has a liver-dependent metabolism. Reduction of the dose is recommended based on Child-Pugh (C-P) score. In critically ill patients, drug pharmacokinetics (PK) may be altered. The aim of this study was to investigate the prevalence of abnormal liver function tests, increased C-P scores, their effects on caspofungin PK, and whether pharmacokinetic-pharmacodynamic (PK/PD) targets were attained in patients with suspected candidiasis. Intensive care unit patients receiving caspofungin were prospectively included. PK parameters were determined on days 2, 5, and 10, and their correlations to the individual liver function tests and the C-P score were analyzed. Forty-six patients were included with C-P class A (n = 5), B (n = 40), and C (n = 1). On day 5 (steady state), the median and interquartile range for area under the curve from 0 to 24 h (AUC(0–24)), clearance (CL), and central volume of distribution (V(1)) were 57.8 (51.6 to 69.8) mg·h/liter, 0.88 (0.78 to 1.04) liters/h, and 11.9 (9.6 to 13.1) liters, respectively. The C-P score did not correlate with AUC(0–24) (r = 0.03; P = 0.84), CL (r = −0.07; P = 0.68), or V(1) (r = 0.19; P = 0.26), but there was a bilirubin-driven negative correlation with the elimination rate constant (r = −0.46; P = 0.004). Hypoalbuminemia correlated with low AUC(0–24) (r = 0.45; P = 0.005) and was associated with higher clearance (r = −0.31; P = 0.062) and somewhat higher V(1) (r = −0.15; P = 0.37), resulting in a negative correlation with the elimination rate constant (r = −0.34; P = 0.042). For Candida strains with minimal inhibitory concentrations of ≥0.064 μg/ml, PK/PD targets were not attained in all patients. The caspofungin dose should not be reduced in critically ill patients in the absence of cirrhosis, and we advise against the use of the C-P score in patients with trauma- or sepsis-induced liver injury.

Objective Abnormal liver function tests (LFTs) are frequent in Turner syndrome (TS). The causes and clinical significance are unclear. Aims To investigate the prevalence of elevated LFTs in adult TS; secondly, to analyse the associations between elevated LFTs, TS‐karyotypes and TS‐related conditions; and thirdly, to evaluate liver stiffness and histological assessment. Methods A total of 125 TS women were retrospectively studied. Karyotypes, clinical and biochemical details and aortic measurements were recorded. Fibroscan and liver biopsy results were noted. Results Elevated LFTs were found in 49.6%: gamma‐glutamyltransferase (GGT) in 88.7%, ALK in 45.2%, ALT in 40.3% and AST in 29%. A FIB‐4 index >1.3 was found in 11.8%. Women with isochromosome of the X long arm, iso[X](q), had a higher prevalence of elevated LFTs. A lower prevalence of abnormal GGT was found in patients with 45,X/46,XX, 45,X/47,XXX or 45,X/46,XX/47,XXX. Subjects with raised GGT were older, shorter and more likely to have higher triglyceride levels. There was no association with HRT duration after adjusting for age. Among patients with elevated aminotransferases, no differences were noted, except for higher HDL‐cholesterol levels. The sinuses and ascending aorta diameter were greater in the elevated LFTs group. Fibroscan was suggestive of significant liver fibrosis in 38.1%. Among 11 biopsies, liver architectural changes were reported in 45.4%, including two with cirrhosis. Conclusions Elevated LFTs in TS are common and important to detect given the possible progression towards severe liver disease. An association between raised LFTs and karyotype iso[X]q was demonstrated. We have also shown a new association between abnormal LFTs and aortic dilatation.

There are no structured studies on liver histology after hematopoietic stem cell transplantation (HSCT). We aimed to prospectively describe the clinicopathologic features of liver disease in the long term after HSCT in an observational, longitudinal study of liver histology in a consecutive cohort of children undergoing allogeneic HSCT. First liver biopsy was performed in presence of abnormal liver function tests and repeated per protocol thereafter. A previously reported semiquantitative score evaluating inflammation, cholestasis, and ductopenia (bile ducts-to-portal tracts ratio ≤ .5) was adopted. Graft-versus-host disease (GVHD) was diagnosed according to standard criteria. We evaluated 131 biopsies taken in 50 HSCTs performed in 47 children (mean age, 9.7 ± 5.2 years). Pre-HSCT chemotherapy was administered in 36 of 50 (72%). GVHD was diagnosed in 17 of 50 (34%). Over time the overall score decreased from a mean of 6 ± 2.7 to 3.25 ± .96 (P.01), inflammation from 1.22 ± 1.19 to 1 ± 0 (not significant), and cholestasis from 3.9 ± 2.08 to 1.5 ± .58 (P.01). Ductopenia, found in 113 of 131 biopsies (93%), worsened from .63 ± .35 to .16 ± .14 (P.01). On multivariate analysis severe ductopenia (ratio ≤ .2) was associated with previous chemotherapy (P = .04), in particular with thiotepa, but not with history of GVHD. Vanishing bile duct syndrome after HSCT may be due to drug-induced liver disease. Longer follow-up will reveal whether these patients are prone to late liver-related morbidity and mortality.

Previous research indicated the association between hepatitis B virus (HBV) infection/vaccination and the onset of demyelinating diseases. However, most of these studies were single case reports, and comprehensive data are still scarce. Here we present a comprehensive analysis of 10 patients with neuromyelitis optica spectrum disorder (NMOSD) combined with chronic hepatitis B (CHB) infection and seropositive for anti-aquaporin-4 antibody (AQP4-Ab). Demographic, clinical, laboratory, neuroimaging, outcome, and follow-up data of the 10 patients were retrospectively analyzed. The median age at the onset of NMOSD was 35 years (range 25-43). Nine patients were female (90%). All patients were positive for HBsAg and had been diagnosed with CHB earlier than with NMOSD. One patient had an autoimmune disease. All patients had normal thyroid function. Paresthesia and visual impairment were the most common clinical symptoms. The cerebrospinal fluid (CSF) parameters (protein and glucose) were normal in 10 cases, whereas slightly higher CSF white blood cell count was detected in 3 patients. The brain and spinal cord magnetic resonance imaging findings were abnormal in 8 patients. All patients were treated with hormone and immunosuppressive therapy, and anti-HBV agents. Patients with detectable serum HBV DNA were more prone to liver damage after receiving high doses of corticosteroids. In 8 patients, the symptoms improved before they were discharged. Two patients with optic neuritis (ON) maintained the symptoms. A month later, 1/8 patient had recurrence of symptoms, and one ON patient progressed to NMO. Overall, the characteristics of NMOSD patients with CHB and seropositive for AQP4-Ab are usually nonspecific. Abnormal liver function test results in NMOSD patients should be a warning of possible CHB infection, and the treatment should be modified accordingly.

Background & AimsSubclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage.MethodsAll liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy.ResultsMedian time since transplantation to liver biopsy was 13 years (10–22). The most frequently observed histological abnormality was portal inflammation with different degrees of fibrosis, present in 45 biopsies (67%). Two modules of 102 and 425 co-expressed genes were significantly correlated with portal inflammation, interface hepatitis and portal fibrosis. These modules were enriched in molecular pathways known to be associated with T cell mediated rejection. Liver allografts showing the highest expression levels for the two modules recapitulated the transcriptional profile of biopsies with clinically apparent rejection and developed progressive damage over time, as assessed by non-invasive markers of fibrosis.ConclusionsA large proportion of adult liver transplant recipients who survive long-term exhibit subclinical histological abnormalities. The transcriptomic profile of these patients’ liver tissue closely resembles that of T cell mediated rejection and may result in progressive allograft damage.Lay summaryA large proportion of adult liver transplant recipients who survive for a long time exhibit subclinical histological abnormalities. The expression profile (a measurement of the activity of genes) of liver tissue from a large fraction of these patients closely resembles the profile of T cell mediated rejection. Liver allografts showing the highest expression levels of rejection-related genes developed progressive damage over time.

Background/aims To develop a clinical score for the prediction of nonalcoholic steatohepatitis (NASH) using routine parameters in patients with nonalcoholic fatty liver disease who had abnormal liver function tests and/or fatty liver detected by ultrasonography. Materials and methods To identify parameters associated with the presence of NASH by evaluating anthropometric characteristics and routine biomarkers of 82 patients with histologically proven NAFLD and to develop a clinical score for predicting NASH according to the area under the curve of receiver operating characteristics (AUC) of parameters. Results Four parameters [alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), C-reactive protein (CRP), and apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) ratio] were significantly linked to NASH. The AUROCs of ALT, GGT, CRP, and ApoB/ApoA1 ratio for the prediction of NASH were 0.829, 0.892, 0.708, and 0.712, respectively. The AUROC of the combined clinical score for the prediction of NASH was 0.904 (95% CI, 0.885-1.002) at a cut-off of 3.8 points with a sensitivity of 90.2%, specificity of 87.0%, positive predictive value of 88.3%, and negative predictive value of 91.5%. Conclusion In the present study, a clinical score was developed for the noninvasive prediction of NASH; the score was based on a combination of routine biochemical parameters and was useful in distinguishing NASH from NAFLD.

Anorexia nervosa (AN) and eating disorders not otherwise specified (EDNOS) are on the rise in Singapore. Abnormal liver function tests have been reported for up to 12.2% of patients with AN. These patients are also known to present with comorbid psychiatric disorders. This study aims to investigate the correlation between body mass index (BMI) and the severity of abnormal liver function tests, and between BMI and the presence of comorbid psychiatric disorders.A retrospective cohort analysis of 373 patients diagnosed with AN or EDNOS at a tertiary hospital was performed. The clinical course of transaminitis and comorbid psychiatric disorders was correlated with the patient's BMI.Patients with a BMI of ≥ 16.6 kg/m(2) at their first consult had a significantly lower risk of having comorbid psychiatric disorders (χ(2) = 32.08, p0.001). These patients were five times less likely to have comorbid psychiatric disorders as compared to patients from the other BMI groups (odds ratio [OR] 0.21). On the other hand, patients with a BMI of14.6 kg/m(2) had a significantly higher risk of having transaminitis (χ(2) = 72.5, p0.001). They were 11.1 times more likely to develop transaminitis as compared to patients with a BMI of ≥ 14.6 kg/m(2) (OR 11.05).Severity of BMI can be used by clinicians as an indicator to assess for secondary psychiatric comorbidities and/or transaminitis during the first consultation. This could help reduce the morbidity and mortality rates in patients with AN or EDNOS.

BACKGROUND Anidulafungin does not undergo hepatic metabolism like the other echinocandins. Therefore, there is a perception that anidulafungin may be less hepatotoxic or less likely to exacerbate existing liver damage. This has not been substantiated in the literature. METHODS We retrospectively reviewed all cancer patients in whom anidulafungin treatment was immediately preceded by treatment with caspofungin and there existed clinical or laboratory evidence of hepatic damage or dysfunction at M. D. Anderson Cancer Center from January 2010 to December 2013. RESULTS Sixty-one patients were included in the study. Most patients had haematological malignancies (58, 95%), and the patients were administered hepatotoxic agents such as chemotherapeutic agents (47, 77%) and other medications (38, 62%) simultaneously. There were significant decreases in AST and ALT (P

Background Rare inherited metabolic diseases with neurological and gastrointestinal manifestations can be misdiagnosed as other diseases or remain as disorders with indeterminate etiologies. This study aims to provide evidence to recommend the utility of whole exome sequencing in clinical diagnosis of a rare inherited metabolic disease. Methods and results A 4-month-old female baby visited an outpatient clinic due to poor weight gain, repeated seizure-like episodes, developmental delay, and unexplained hepatomegaly with abnormal liver function test results. Although liver biopsy revealed moderate fibrosis with a suggested diagnosis of glycogen storage disease (GSD), no mutations were identified either by single gene approach for GSD ( G6PC and GAA ) or by next generation sequencing panels for GSD (including 21 genes). Whole exome sequencing of the patient revealed compound heterozygous mutations of PMM2 : c.580C > T (p.Arg194*) and c.713G > C (p.Arg238Pro) which mutations were associated with congenital disorder of glycosylation Ia (CDG-Ia: PMM2-CDG). Conclusions We successfully applied exome sequencing to diagnose the first reported Korean patient with CDG-Ia, which was misdiagnosed as GSD. Whole exome sequencing may prove to be the preferred strategy for analysis of clinical features that do not readily suggest a specific diagnosis, such as those observed in inherited metabolic diseases, including CDG.

BACKGROUND AND AIM SEN virus (SENV), is a recently discovered single-stranded DNA virus of Annelloviridae family and is believed may play a role in non A-E hepatitis. We conducted this study to identify the prevalence and clinical association of SENV with acute and chronic hepatitis. METHODS 135 liver disease patients were studied. Extent of liver damage was assessed using the Model for End Stage Liver Disease (MELD) score. A-E viruses and HIV were detected by enzyme immunoassay. Nested PCR was performed for detection of SENV and its genotypes D and H. RESULTS 34 cases (25.18%) were positive for SEN virus DNA, a statistically significant finding (p < 0.01) of which 22 (64%) had acute viral hepatitis, 4 (11.76%) had chronic viral hepatitis, 3 (8.82%) fulminant hepatic failure and 5 (14.70%) cirrhosis. Mean AST was 47.85 IU/L, ALT 51.2 IU/L and INR 1.73, mean MELD score was 18.38 (11 to 24). 17.64% had severely deranged MELD score. SENV-D genotype was detected in 13 (38%) and SENV-H in 19 (58%) cases. SENV-H occurred in both acute (53%) and chronic hepatitis (47%). SENV-D was strongly associated with acute hepatitis (85%). Cirrhotic and FHF cases were SENV-H positive. 12 (44.11%) were co-infected with HBV, 5 (14.7%) with TTV, 4(11.76%) with HEV, 2 (5.88%) with HCV and 5 (14.4%) with HIV. CONCLUSION Significant prevalence of SENV in hepatitis patients was observed. On the basis of clinical findings and abnormal liver function tests, we conclude that SENV appears to be not only hepatotropic but also capable of liver damage. Higher prevalence of SENV-H in cirrhotics may point to its possible role in the development of cirrhosis.

Objective Cases of Japanese spotted fever (JSF) are sometimes complicated by disseminated intravascular coagulation (DIC) with an abnormal liver function, resulting in unfavorable outcomes. The aim of the present study was to clarify the correlation between liver function test results and DIC scores. Methods Twenty patients diagnosed with JSF between April 2010 and April 2014 were enrolled. Age, gender, disturbance of consciousness, body temperature, pulse rate, presence of diffuse erythema, eschar and swelling of lymph nodes, laboratory test results at the time of initial presentation such as blood cell count, C-reactive protein, liver function, renal function and blood coagulation and fibrinolysis, maximum Japanese Association for Acute Medicine (JAAM) DIC score during the course of JSF, treatment and the prognosis were retrospectively reviewed. Results The median age of the patients (8 men, 12 women) was 68.3 years. There were significant differences in the alkaline phosphatase (ALP) and rothrombin time international normalized ratio (PT-INR) between the DIC and non-DIC groups using Mann-Whitney's U test. A multiple logistic regression analysis showed that the ALP and blood urea nitrogen (BUN) levels at the time of initial presentation were independent predictors of the occurrence of DIC. Conclusion We should pay special attention to JSF patients showing high levels of ALP at the initial presentation, since such patients may have a higher likelihood of developing DIC over the course of JSF and unfavorable outcomes than those with lower levels.

Primary care clinicians encounter abnormal liver function tests (LFTs) frequently. This study assesses the prevalence of abnormal LFTs and patient follow-up patterns in response.This is a retrospective study from 2007-2016 of adult patients with abnormal LFTs seen in an internal medicine clinic. The proportion of patients with follow-up testing and the time (in days) to repeat LFTs were the primary outcomes measured. Results were evaluated before and after the implementation of the institution's electronic health record (EHR).This study identified a period prevalence for abnormal LFTs of 39%. Of these, 9,545 unique patients met inclusion criteria, with 8,415 patients (88.2%) possessing follow-up LFTs and no significant difference in the proportion of patients receiving follow-up by degree of initial abnormality. Median time to follow-up in mild abnormalities (1-2 times normal) was 138 days, compared to 21 days for severe abnormalities (4 times normal, P0.0001). Reduced time to repeat testing across all spectrums of abnormality was observed following EHR implementation, but proportions of missing follow-up did not improve. A multivariable logistic regression model identified younger age, poverty, living over 50 miles from clinic, recent cohort entry and a lower magnitude of abnormality as predictors for missing repeat LFT testing (area under the curve = 0.838 [95% CI: 0.827-0.849]).Abnormal LFTs were detected in 39% of all patients seen. The degree of LFT abnormality did not influence rates of follow-up testing, but does appear to play a role in the timing of repeat testing, when obtained. Follow-up rates did not improve with EHR implementation.

BackgroundCoeliac disease (CD) is a gluten-sensitive enteropathy diagnosed on the basis of ESPGHAN criteria and clinical response to gluten-free diet (GFD). Histological abnormalities on liver biopsy have been noted in CD but have seldom been described.AimsTo assess the histological spectrum of ‘coeliac hepatitis’ and possibility of reversal of such features after a GFD.MethodsTwenty-five patients with concomitant CD and hepatic derangement were analysed for clinical profile, laboratory investigations and duodenal and liver biopsy. A histological comparison of pre- and post-GFD duodenal and liver biopsies was carried out, wherever possible.ResultsFifteen patients presenting with CD subsequently developed abnormal liver function tests; 10 patients presenting with liver disease were found to have tissue positive transglutaminase in 70% and antigliadin antibodies in 60%. Serological markers for autoimmune liver disease (AILD) were positive in eight patients. Liver histology ranged from mild reactive hepatitis, chronic hepatitis, steatosis to cirrhosis. Liver biopsies after a GFD were available in six cases, of which five showed a decrease in steatosis, portal and lobular inflammation and fibrosis score.ConclusionCoeliac hepatitis could be a distinct entity and the patients may present with either CD or secondary hepatic derangement. Evaluation for the presence of CD is recommended for patients presenting with AILD, unexplained transaminasaemia or anaemia. This is one of the very few studies demonstrating the continuum of liver histological changes in ‘coeliac hepatitis’. Trial of a GFD may result in clinicopathological improvement of ‘coeliac hepatitis’.

Background Recent data have suggested that upfront cholecystectomy should be performed even in the presence of moderately abnormal liver function tests (LFTs). As a consequence, more common bile duct (CBD) stones are discovered on intra-operative cholangiogram. We assessed the presentation and management of such patients to refine their management plan. Methods Adult patients (>16 years) with an acute gallstone-related disease who had undergone same-stay cholecystectomy from January 2013 to January 2015 were retrospectively assessed. We excluded patients with pre-operative endoscopic CBD exploration. Results Among the 612 patients with same-stay cholecystectomy, 399 patients were included in the study, and 213 were excluded because of a pre-operative CBD exploration. Fifty patients (12.5%) presented an image of CBD stone on the intra-operative cholangiogram. Such patients were younger (47 vs. 55 years, P = .01) and less likely to present with fever (1 vs. 11.7%, P = .04) or signs of cholecystitis on ultrasound (66 vs. 83.7%, P = .003). Admission LFTs were higher in patients with an image of a stone. Among the 50 patients with an image on cholangiogram, a stone was confirmed in 26 (52%). Most patients (n = 32) underwent post-operative assessment with endoscopic ultrasound (EUS). LFTs did not predict the presence of a confirmed stone. However, the absence of contrast passage into the duodenum was negatively associated with a confirmed stone (P = .08), and a filling defect was positively associated with one (P = .11). Most confirmed stones were successfully extracted by endoscopic retrograde cholangiopancreatogram (ERCP) (25/26, 96%), except in one patient who needed a per-cutaneous approach because of duodenal diverticuli. Conclusions Same-stay cholecystectomy can (and should) be performed even in the presence of moderately abnormal liver function tests. The cholangiogram suspicion of a CBD stone is confirmed in only half of the patients (more often in the presence of a filling defect, and less often with the absence of contrast passage). All stones can be safely treated after surgery (most by ERCP). Electronic supplementary material The online version of this article (doi:10.1186/s12893-017-0232-z) contains supplementary material, which is available to authorized users.