Increased Liver Enzyme Levels Research Articles

#2672 Cryoglobulin-Induced membranoproliferative glomerulonephritis in a HEV-infected kidney transplant recipient: outcomes post ribavirin failure

Abstract Background and Aims Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. It is the most prevalent hepatitis virus worldwide. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced in immunocompromised patients such as transplant recipients. CHE can induce extra-hepatic manifestations, such as immune-mediated thrombocytopenia, neurological symptoms, and kidney injuries. Few cases of glomerulonephritis (GN) and cryoglobulinemia in transplant patients have been related with CHE, with a good progression thanks to viral control with ribavirin introduction. There have been no reported cases in the literature of good progress in renal function in renal transplant patients despite failure of treatment with Ribavirin. Method We report here what is to our knowledge, the first documented case of HEV-induced de novo cryoglobulinemic membranoproliferative glomerulonephritis in a renal transplant patient with a ten-year history of CHE infection unsuccessfully treated with ribavirin. Results A 69-year-old man underwent a kidney transplant for diabetes type 1. 7 years after transplantation, he was diagnosed with a chronic genotype 3.1H-HEV infection. He was treated by Ribavirin, but it did not allow to eradicate HEV but a biochemical response. At 18 years post transplant, he presented with asthenia, abdominal pains and increased liver enzyme levels: liver tests were disrupted with cytolysis and cholestasis. He presented also a nephritic syndrome with high blood pressure, oedemas, increased serum creatinine level, proteinuria with hypoalbuminemia and de novo microscopic hematuria. Biological analysis revealed presence of type 2 cryoglobulinemia with monoclonal IgM Kappa (2285 mg/L), and polyclonal immunoglobulins association. Rheumatoid factor was increased (573 UI/ml) and C4 level was reduced (0.04 g/L). The concentration of HEV RNA in the serum was 750 000 UI/mL. Viral serologies were performed for HBV, HCV, HAV, HIV, EBV, CMV. Hematologic diseases were ruled out by analyzing a bone marrow biopsy specimen. Histologic analysis of a kidney biopsy specimen revealed diffuse endocapillary proliferation, diffuse mesangial proliferation and focal glomerular basal membrane duplication. One arteriolar section showed a focal lesion of vasculitis (Fig. 1). There was no argument for allograft rejection. Immunofluorescence microscopy revealed mesangial and capillary wall deposits of IgM, IgG, C3 and C1q, polytypic for k and l light chains. We suspected cryoglobulinemic membranoproliferative glomerulonephritis induced by VHE. The initial treatment plan involved 10 sessions of plasmapheresis and steroid pulses (500 mg/d for 3 days), alongside a course of rituximab (1 g/week for 4 weeks). However, the patient experienced intolerance to rituximab, prompting a switch to Obinutuzumab. Subsequently, the anti-HEV therapy was modified, and the patient was placed on a course of Sofosbuvir. Consequently, three months after treatment kidney function kidney improved with return to baseline and cryoglobulinemia became undetectable. However, proteinuria remained impaired and VHE RNA was still present. Conclusion Cryoglobulinemia is rarely associated with glomerular disease in HEV infection, and cases currently reported in the literature showed a favorable outcome with ribavirin. This case is the first to display a chronic HEV infection with cryoglobulin-induced glomerulonephritis with global improvement despite unsuccessful treatment with ribavirin. Although the difficulty of managing immunity in the treatment of cryoglobulinemia by immunodepleting treatment, with the risk of increased viral replication in the absence of an effective antiviral, it seems interesting to offer a first-line treatment of cryoglobulinemia that appears to improve renal function despite continued viral replication. These results need to be confirmed in further studies.

Nonseizure- and seizure-related benefits of cannabidiol treatment in the real world: plain language summary of the results from a caregiver survey

What is this summary about? Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are rare forms of epilepsy that start in childhood and cause life-long disability. People with LGS and DS experience many seizure types and nonseizure-related problems with cognition (ability to think and understand), learning, behaviour and communication. People with LGS and DS depend on caregivers to assist with daily activities. Although many medications are available to treat seizures associated with LGS and DS, the effect on nonseizure outcomes is unclear. A highly purified (defined as a substance that has undergone a special process to remove impurities) oral (by mouth) solution of cannabidiol (CBD; Epidiolex®) from plants is approved by the United States (US) Food and Drug Administration (FDA) for the treatment of seizures associated with LGS, DS and tuberous sclerosis complex in people who are at least 1 year old. In clinical studies, treatment with CBD reduced the number of seizures. Common side effects (secondary, typically unintended effects of the medication) were increased liver enzyme levels, sleepiness, decreased appetite, diarrhea, fever, vomiting, tiredness, rash, problems with sleep and infections. CBD may also improve nonseizure outcomes, such as cognition, behavior and quality of life. The BEhavior, COgnition and More with Epidiolex® (BECOME) survey was designed to find out whether caregivers of people with LGS or DS taking CBD noticed changes in nonseizure and seizure outcomes. What are the key takeaways? Caregivers of people with LGS or DS taking CBD noticed improvements in cognition, language and communication, emotional and social functioning, physical functioning, sleep and ability to do daily activities, as well as a reduction in the number and severity of seizures. People with reduction in seizures were more likely to experience nonseizure benefits, but some people without seizure reduction also experienced improvements in nonseizure outcomes. Caregivers reported that both seizure and nonseizure effects were important when thinking about treatment options. What were the main conclusions reported by the researchers? The BECOME survey provides a unique caregiver perspective on nonseizure outcomes that may be affected by CBD. These results support further study of CBD for nonseizure outcomes in people with LGS or DS.

Potential therapeutic effect of Thymoquinone on Cisplatin-induced hepatotoxicity in rats

Aim: Cisplatin (CIS), an antineoplastic agent, shows serious side effects such as hepatotoxicity. Thymoquinone (ThQ) is a powerful anti-oxidant with many beneficial effects such as anti-inflammatory, anti-tumoral. The aim of this study was to investigate whether ThQ treatment has hepatoprotective effect in CIS-induced hepatotoxicity model in rats and also to determine how CIS and/or ThQ treatments affect OTULIN levels, one of the deubiquitinases, in liver tissue. Materials and Methods: The 28 rats used in the study control (application not done), CIS (7 mg/kg CIS, first day of experiment, intraperitoneal), CIS+ThQ (7 mg/kg CIS, first day of experiment, intraperitoneal + 10 mg/kg/day ThQ, oral gavage) and ThQ (10 mg/kg/day ThQ, oral gavage) were divided into four equal groups (n=7). The experiment was terminated upon completion of all applications (day 15). The effects of CIS and\or ThQ apps on liver tissues were examined biochemically, histopathologically and immunohistochemically. Results: CIS application increased liver enzyme levels, histopathological changes, inflammation, oxidative stress and apoptosis in liver tissue and caused a decrease in OTULIN level. However, ThQ administration showed a positive regulatory effect on CIS-induced changes in liver tissue. Conclusion: ThQ supplementation has a hepatoprotective effect against CIS-induced liver tissue damage.

Entecavir: A Review and Considerations for Its Application in Oncology.

Entecavir (ETV) is a drug used as a first-line treatment for chronic hepatitis B (CHB) virus infection because it is a guanosine nucleoside analogue with activity against the hepatitis B virus polymerase. The ETV dosage can range from 0.5 mg to 1 mg once a day and the most common side effects include headache, insomnia, fatigue, dizziness, somnolence, vomiting, diarrhea, nausea, dyspepsia, and increased liver enzyme levels. In addition to its conventional use, ETV acts as an inhibitor of lysine-specific demethylase 5B (KDM5B), an enzyme that is overexpressed in breast, lung, skin, liver, and prostate tumors and is involved in the hormonal response, stem cell regeneration, genomic stability, cell proliferation, and differentiation. The KDM5B enzyme acts as a transcriptional repressor in tumor suppressor genes, silencing them, and its overexpression leads to drug resistance in certain tumor types. Furthermore, the literature suggests that KDM5B activates the PI3K/AKT signaling pathway, while reducing KDM5B expression decreases AKT signaling, resulting in decreased tumor cell proliferation. In silico studies have demonstrated that ETV can inhibit tumor cell proliferation and induce apoptosis by reducing KDM5B expression. ETV also appears to inhibit PARP-1, has a high genetic barrier, reducing the chance of resistance development, and can also prevent the reactivation of the hepatitis B virus in cancer patients, which have proven to be significant advantages regarding its use as a repurposed drug in oncology. Therefore, ETV holds promise beyond its original therapeutic indication.

Glomerular lipidosis as a feature of renal-limited macrophage activation syndrome in a transplanted kidney: a case report

BackgroundGlomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS.Case presentationA 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68+ foam cells (histiocytes) intermingled with many CD3+ T-cells (predominantly CD8+ cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8+ cells (CD8+, HLA-DR+ cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient’s extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar.ConclusionTo our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8+ T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.

Clinical and genetic spectrum of GSD type 6 in Korea

BackgroundGlycogen storage disease type VI (GSD VI) is a rare disease in which liver glycogen metabolism is impaired by mutations in the glycogen phosphorylase L (PYGL). This study aimed to examine the clinical features, genetic analyses, and long-term outcomes of patients with GSD VI in Korea.MethodsFrom January 2002 to November 2022, we retrospectively reviewed patients diagnosed with GSD VI using a gene panel at Seoul National University Hospital. We investigated the clinical profile, liver histology, molecular diagnosis, and long-term outcomes of patients with GSD VI.ResultsFive patients were included in the study. The age at onset was 18–30 months (median, 21 months), and current age was 3.7–17 years (median, 11 years). All patients showed hepatomegaly, elevated liver transaminase activity, and hypertriglyceridaemia. Hypercholesterolaemia and fasting hypoglycaemia occurred in 60% and 40% of patients, respectively. Ten variants of PYGL were identified, of which six were novel: five missense (p.[Gly607Val], p.[Leu445Pro], p.[Gly695Glu], p.[Val828Gly], p.[Tyr158His]), and one frameshift (p.[Arg67AlafsTer34]). All patients were treated with a high-protein diet, and four also received corn starch. All patients showed improved liver function tests, hypertriglyceridaemia, hepatomegaly, and height z score.ConclusionsThe GSD gene panel is a useful diagnostic tool for confirming the presence of GSD VI. Genetic heterogeneity was observed in all patients with GSD VI. Increased liver enzyme levels, hypertriglyceridaemia, and height z score in patients with GSD VI improved during long-term follow-up.

Association between Type 2 Diabetes and Elevaton of Liver Enzymes

Millions of people throughout the world are impacted by T2DM, often known as type 2 diabetes mellitus. This study looked at the relationship between elevated liver enzyme levels and the prevalence of T2DM in certain Iraqis. Only a small amount of research has been done on the connection between liver enzymes and T2DM. Methods: In all, 80 people (40 with diabetes and 40 without) participated in the study. Blood serum was examined to determine the activity of alanine and aspartate aminotransferases (ALT, AST), -Glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP). Fasting blood glucose (FBG) of less than 126 mg/dL or self-reported recent usage of insulin or anti-diabetic drugs were used to define T2DM. Results: When compared to the non-diabetes group, the diabetic group's AST and ALP levels were considerably (P0.05) higher. In contrast, there was no difference in ALT (P>0.05). However, AST and ALT data based on gender revealed no statistically significant difference (P>0.05) between any of the groups for either enzyme. However, as compared to the non-diabetes male and female groups, the ALP enzyme findings showed that there was a significant increase (p0.05) in the diabetes male group. Conclusions: T2DM patients frequently have increased liver enzyme levels.

Sumc (Rhus coriaria L.) fruit ameliorates paracetamol-induced hepatotoxicity

Sumac [Rhus coriaria L. (Anacardiaceae)] is a widely used spice in the Middle East. In this study, the hepatoprotective effects of sumac fruit were evaluated using a rat model of paracetamol-induced liver injury. The experimental design relies on the pretreatment of rats with intraperitoneal sumac extract followed by a toxic dose of paracetamol. Tissue alterations, serum levels of oxidative stress markers, as well as gene expression of immunomarkers were evaluated. Rats pre-treated with sumac displayed attenuated signs of toxicity. Upon paracetamol intoxication, sumac-pretreated animals showed a minimal increase in liver enzyme levels. In parallel, serum albumin and total protein levels were close to normal. Moreover, pretreated sumac animals had preserved hepatocyte morphology, whereas unprotected animals had necrotic deformations. Importantly, these effects were dose-dependent and comparable to the silymarin-treated positive control group. In conclusion, sumac extract offers a potential hepatoprotective regimen against xenobiotic-induced hepatotoxicity and for oxidative stress management.

The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats.

Cadmium (CD) causes widespread and severe toxic effects on various tissues. Studies have shown that apoptosis, inflammation, and endoplasmic reticulum stress play a role in organ damage caused by CD. Phenolic compounds with strong antioxidant effects are found in various fruits and vegetables. One of these compounds is Gallic acid (GA), which is found both free and hydrolyzable in grapes, pomegranate, tea, hops, and oak bark. Result of various studies show that GA has active antioxidant, anti-inflammatory, and anti-apoptotic properties. In our study, we investigated the mechanism of the protective effect of GA on CD-induced hepatotoxicity in rats. In this study, 50 adult male Sprague Dawley rats weighing approximately 200-250 g were used and the rats were divided into 5 groups: Control, CD, GA50+CD, GA100+CD, and GA100. The rats were treated with GA (50 and 100 mg/kg body weight), and Cd (6.5 mg/kg) was administrated to the rats for 5 consecutive days. The liver enzymes, TB levels in serum samples, oxidative stress, inflammation, ER stresses, apoptosis marker, histopathology, 8-OHDG, and caspase-3 positivity were analyzed. CD administration significantly increased liver enzyme levels (AST, ALT, ALP, and LDH), MDA, IL-1-β, IFN-γ, TNF-α, IL-10, IL-6, GRP78, CHOP, ATF6, p -IRE1, sXBP, Bax mRNA expression, Caspase 3, and 8-OHdG expression (P<0.05). These values were found to be significantly lower in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). CD administration significantly decreased the expression levels of TB, IL-4, SOD, GSH, CAT, GPX, and Bcl-2 mRNA (P<0.05). These values were found to be significantly higher in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). The results of the present study indicated that GA prevented Cd-induced hepatic oxidative stress, inflammation, ER stress, apoptosis, and tissue damage in rats.

Дефіцит орнітин-транскарбамілази - мало відоме орфанне захворювання в дитячій гепатології (клінічний випадок)

The article reviews literature and demonstrates personal observation of a preschool patient with ornithine transcarbamylase deficiency. This disease is characterized by an excessive accumulation of ammonia in the body, which leads to damage of the nervous system, gastrointestinal tract, and impaired liver function. It has a genetically determined mechanism of development associated with mutations in the OTC gene. Purpose - to study specific aspects of manifestation, clinical picture, course and diagnosis of ornithine transcarbamylase deficiency. Clinical case. Girl U. was admitted to the pediatric hepatology department with complaints of abdominal pain, periodic vomiting, accompanied by high ketones in urine test, irritability, tearfulness, emotional lability, and increased liver enzyme levels. Physical exam revealed hepatosplenomegaly. Bloodwork series showed transaminase levels 4-20 times ULN, hyperammonemia, and increased orotic acid in urine. A molecular genetic study was performed, and identified a variant of uncertain significance in the OTC gene associated with X-linked ornithine transcarbamylase deficiency. Metabolic therapy and protein-restricted nutrition were prescribed to prevent hyperammonemia. Conclusions. Transcarbamylase deficiency is a rare genetic disease characterized by excessive accumulation of ammonia in the body with typical clinical and laboratory symptoms. Detection of ammonia concentration and molecular genetic testing are crucial diagnostic components in children with liver diseases associated with other organs and systems damage. Untimely diagnosis and treatment correlates with the severity of the disease, the development of irreversible changes, disability and possible death in young age. The study was performed according to the principles of the Declaration of Helsinki. The informed consent of the child's parents was obtained for the conducted research. The authors declare no conflict of interest.

Hepatic involvement in children with acute bronchiolitis.

Respiratory syncytial virus (RSV) is a prevalent cause of lower respiratory tract infections. It may be associated with hepatocellular involvement, as indicated by increased liver enzymes aspartate aminotransferase and alanine transaminase (ALT). To evaluate the rate of increased liver enzyme levels in children with acute bronchiolitis and correlate them with clinical, laboratory, and radiological variables. The study was a retrospective review of the medical records of children who presented with acute bronchiolitis when admitted to the Pediatric Department, Salmaniya Medical Complex, the Kingdom of Bahrain, between 2019 and 2020. We collected the demographic data, the clinical presentation, the laboratory and radiological findings, and the clinical outcomes. We compared the patients with elevated liver enzymes to those with normal levels at the time of presentation and at follow-up. We included 166 (57.8%) of 287 patients with acute bronchiolitis who fulfilled the inclusion criteria. Ninety-three (56%) patients were males. The median age at presentation was 3.4 (interquartile range 1.1 to 12.4) mo. Fifty-four (28%) patients tested positive for RSV, which was confirmed in 15 of them (28%) by PCR. Laboratory findings of 161 patients tested at presentation showed high ALT levels in 14 (8.7%) patients and normal ALT in 147 (91.3%). Coagulation profiles were measured in 46 (27.7%) of 166 patients. High prothrombin time was present in 15 (32.6%), a high international normalized ratio was present in 13 (28.3%), and high activated partial thromboplastin time was present in three (6.5%). Thrombin time was elevated in nine (27.3%) of 33 patients. Five (21.7%) of 23 patients with available radiological data had hepatomegaly; one of them had findings suggestive of fatty infiltration. High ALT had a significant association with lengthy hospital stays (P < 0.05) and positive urine culture (P < 0.05). Seventy (42.2%) patients had documented follow-up with liver function tests over a median follow-up period of 10.2 (IQR, 2.4-23.3) mo. Total serum protein and serum globulin levels were normalized at the follow-up time, with a significant P value of < 0.05. This study showed a low prevalence of liver function involvement in patients with acute bronchiolitis with a benign course. However, there was a rising trend in ALT during follow-up. Prolonged hospital stay and positive urine cultures were associated with elevated liver enzymes.

Exposure to ambient air pollution and indicators of maternal liver function during pregnancy: Findings from a birth cohort study in Foshan City, Southern China

Evidence concerning the associations between gestational air pollution exposure and maternal liver function is scarce. We explored this topic by analyzing data from a birth cohort study conducted in Foshan city, Southern China. Between 2015 and 2019, we recruited a total of 49,568 pregnant women from 16 hospitals in Foshan city. Basic socio-demographical information and lifestyle factors was collected from the hospital medical records. Daily PM2.5, PM10, SO2, NO2, and O3 exposure of each participant during study period was assessed by inverse-distance weighted method. Then, we assigned the average air pollutant levels during trimester 1, trimester 2, and the first two trimesters to each participant. Liver function indicators (liver enzymes, serum protein, and serum bilirubin) of each participant were measured during their third trimester prenatal visit. Mixed-effects linear and logistic regression models were used to evaluate the associations of gestational air pollution exposure and maternal liver function indicators. Our findings suggested that maternal exposure to air pollution during pregnancy, especially trimester 2, was associated with increased liver enzyme levels and decreased serum protein levels.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease.

BACKGROUNDRecently, nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic-associated fatty liver disease (MAFLD). Based on the definition for MAFLD, a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature. AIMTo analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD.METHODSEighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups. The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction. The histologic features were compared according to different metabolic disorders and liver enzyme levels.RESULTSMAFLD individuals had a higher NAFLD activity score (P = 0.002) and higher severity of hepatic steatosis (42.6% Grade 1, 42.6% Grade 2, and 14.8% Grade 3 in MAFLD; 81.8% Grade 1, 13.6% Grade 2, and 4.5% Grade 3 in non-MAFLD; P = 0.007) than the non-MAFLD group. Lobular and portal inflammation, hepatic ballooning, fibrosis grade, and the presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis were comparable between the two groups. The higher the liver enzyme levels, the more severe the grades of hepatic steatosis (75.0% Grade 1 and 25.0% Grade 2 in normal liver function; 56.6% Grade 1, 39.6% Grade 2, and 3.8% Grade 3 in increased liver enzyme levels; 27.8% Grade 1, 27.8% Grade 2, and 44.4% Grade 3 in liver injury; P < 0.001). Patients with liver injury (alanine aminotransferase > 3 × upper limit of normal) presented a higher severity of hepatocellular ballooning (P = 0.021). Moreover, the grade of steatosis correlated significantly with hepatocellular ballooning degree (r = 0.338, P = 0.002) and the presence of NASH (r = 0.466, P < 0.001).CONCLUSIONMetabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD. Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

Telemedicine management of systemic therapy with isotretinoin of patients with moderate-to-severe acne during the COVID-19 pandemic: A longitudinal prospective feasibility study

Telemedicine management of systemic therapy with isotretinoin of patients with moderate-to-severe acne during the COVID-19 pandemic: A longitudinal prospective feasibility study

Influence of Nonalcoholic Fatty Liver Disease With Increased Liver Enzyme Levels on the Risk of Cirrhosis and Hepatocellular Carcinoma

The influence of nonalcoholic fatty liver disease (NAFLD) on the long-term risk of cirrhosis and hepatocellular carcinoma (HCC) in Asian populations has not been widely investigated. We enrolled 129,374 adults aged 30 years and older, all of whom participated in a health screening program from 2008 through 2013, were seronegative for hepatitis B surface antigen and anti-hepatitis C virus antibodies, and had limited daily alcohol consumption (<20 g/d for men and <10 g/d for women). Abdominal ultrasonography was performed to determine the presence of NAFLD. The participants were divided into the following groups: NAFLD with increased or normal liver enzyme levels, and non-NAFLD with normal liver enzyme levels. The incidences of cirrhosis and HCC were determined through computerized data linkage with nationwide registries. Cox proportional hazard models were used to estimate the hazard ratios of NAFLD on the risks of cirrhosis and HCC. The incidence rates of cirrhosis and HCC increased as follows: non-NAFLD with normal liver enzyme levels (n= 66,801; 51%), NAFLD with normal liver enzyme levels (n= 41,461; 32%), and NAFLD with increased liver enzyme levels (n= 21,112; 16%). In the NAFLD group with increased liver enzyme levels and the NAFLD group with normal liver enzyme levels, the corresponding multivariate-adjusted hazard ratios for cirrhosis were 3.51 (95% confidence interval [CI]: 2.36-5.22) and 0.73 (95% CI: 0.46-1.16), and for HCC were 1.91 (95% CI: 1.08-3.38) and 0.57 (95% CI: 0.31-1.04), respectively, compared with the non-NAFLD group (P for trend < .001). The findings were consistent after restricting the analysis to nonobese individuals (body mass index, <25 kg/m2) and nonobese individuals without diabetes (P < .05). Individuals with NAFLD and increased liver enzyme levels showed significantly higher risks for cirrhosis and HCC and should be monitored.

Abstract 12379: Distal Waveform Patterns in the Fontan Circulation Are Related to Pulmonary, Liver and Cardiac Function

Introduction: The lack of a sub-pulmonary ventricle in patients with a Fontan circulation leads to irreversible circulatory decline. Our group has determined that single-site waveform analysis correlates to clinical features of Fontan patients. The goal of this study was to determine if multi-site waveform analysis contributes to detecting early cardiovascular decline. Methods: Patients with a Fontan circulation that underwent cardiac MRI were included in this retrospective study. Hemodynamic flow curves were measured in the ascending aorta (AAo N=94), superior vena cava (SVC N=82), inferior vena cava (IVC N=91) and left pulmonary artery (LPA N=85). Flow curves were interpolated to equal temporal phases and were used to create three data matrices of proximal and distal waveforms. Principal component analysis (PCA), a data transformation method used to obtain a wieldy number of ranked components (the PCs) representing the variance of the input data, was performed on each matrix. PCs were correlated to clinical measures of current patient status. Results: PCs that accounted for more than 20% of the variance in a data matrix are reported (Pearson’s r, p ) in Table 1. Conclusions: These results indicate that increased liver enzyme levels, with a possible link to Fontan associated liver disease, are related to increased diastolic SVC flow and increased volume in the SVC and IVC throughout the cardiac cycle. An increased diastolic SVC flow profile relates to worsening pulmonary function and oxygen consumption during exercise. A decreased ventricular-vascular coupling ratio is related to increased IVC volume and low oxygen saturations may be indicative of increased LPA volume. Little variations were apparent in the AAo waveforms, suggesting cardiovascular decline may appear distally prior to proximal presentation. We have, for the first time, evaluated multi-site flow patterns and correlated them to functional status in one of the largest Fontan patient cohorts to date.

Ameliorative Effect of Annona m uricata Leaf Extract on Fipronil Induced Liver Biochemical Alterations in Oreochromis m ossambicus

The diverse array of pharmacological properties present in the natural compounds of Annona muricata and its wide use in traditional medicine have all been prime area of research focus. The present study was undertaken to focus on the hepatoprotective role of Annona muricata leaf extract in Oreochromis mossambicus exposed to fipronil toxicity for 15 and 30 days. The study of fipronil toxicity in antioxidant/detoxification enzymes in liver such as Catalase (CAT), Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP), Acid phosphatase (ACP) and Lactate dehydrogenase (LDH) is an attempt to provide a clear concept of hepatic toxicity of fipronil. Fishes were exposed to 3 sublethal concentrations (1/5, 1/10, 1/15) of fipronil for 15 and 30 days fed with normal and plant extract supplement feed. The antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) showed decreased activity on exposure to fipronil for 15 days and 30 days. The A.muricata supplemented group also showed decreased activity significant and dose-dependent but this decrease in activity was less when compared to fipronil exposed groups fed with normal feed. This indicates the stressed condition of O.mossambicus on exposure to fipronil that was reduced in A.muricata extract supplemented groups indicating the ameliorative effect of leaf extract. The liver enzymes AST, ALT, ALP, ACP and LDH showed increased activity for all concentrations for 15 and 30 days of fipronil exposure. A. muricata supplemented groups also showed increased liver enzyme levels but this increase was less when compared with fishes fed with normal feed. The increase in activity was significant and dose-dependent. This reveals liver damage alteration in liver activity when exposed to fipronil whereas fipronil exposed groups fed with plant extract supplement showed a recovery of chronic toxicity as evidenced by the liver enzyme activity.

Prevalence of hepatitis B and C viral infections in hospitalized patients with increased liver enzyme levels and with no known history of hepatic disease

Introduction and objectivesIdentification of asymptomatic hepatitis B virus (HBV) and hepatitis C virus (HCV) carriers is fundamental to reach the World Health Organization objective to eradicate viral hepatitis. The aim of this study was to evaluate the HBV and HCV prevalence among patients hospitalized for a non-liver-related disease but showing increased liver enzyme values. Patients and methodsAll consecutive patients without history of hepatic disease but showing increased amino-transferase and/or gamma-glutamil-transpeptidase levels at admission to the Internal Medicine and Surgery divisions of the Messina University Hospital from 1st January to 31st December 2019 (“study group”) were tested for HBV surface antigen (HBsAg) and anti-HCV antibody. Analogously, HBsAg and anti-HCV were tested for in all the individuals with normal liver enzyme values consecutively admitted from October 1st to December 31st, 2019 (“control group”). ResultsOf the 332 “study group” patients, 13 (3.9%) were anti-HCV positive versus 5/306 (1.6%) patients of the “control group” (p=0.008). HCV RNA was detected in 11/13 and in 0/5 anti-HCV patients of the “study group” and “control group”, respectively (p=0.001). HBsAg was detected in 5 (1.5%) “study group” patients and in none of the “control group” (p=0.03). Prevalence of diabetes, arterial hypertension, and dyslipidaemia was comparable between the two groups, whereas 75/332 (22.3%) patients of the “study group” and 34/306 (11.1%) patients of the “control group” drank > 2 alcohol units/day (p < 0.001). ConclusionTesting HBsAg and anti-HCV in subjects showing increased liver enzyme values may represent an efficacious tool to identify asymptomatic carriers of hepatitis virus infections.

Impact of COVID-19 on liver.

The incidence of liver injury after coronavirus disease 2019 (COVID-19) infection ranged from 15%-53%. The mechanism includes direct viral cytopathic effect, cytokinesis, and treatment drug-induced liver injury. The symptoms include nausea, vomiting, diarrhea, and loss of appetite. The laboratory results include increased liver enzyme levels, decreased monocyte count, and longer prothrombin time. The most common imaging findings are hepatomegaly on ultrasound, ground-glass opacity on chest computed tomography (CT), and liver hypodensity and pericholecystic fat stranding on abdominal CT. Patients may also have different presentations and poor outcomes of different liver diseases concomitant with COVID-19 infection. Liver function test (LFT) results should be monitored, and all factors known to cause or predispose liver injury should be investigated while managing the patients. The risks of transfer to an intensive care unit, need for mechanical ventilator support, and acute kidney injury is higher in COVID-19 patients with than without abnormal LFTs. Increased mortality and length of hospital stay are both observed.

Ruxolitinib treatment permits lower cumulative glucocorticoid dosing in children with secondary hemophagocytic lymphohistiocytosis

BackgroundThis study aimed to analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH).MethodsEleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) during the same period were also analyzed.ResultsIn group R, three patients who did not respond to methylprednisolone (MP) pulse and intravenous immunoglobulin (IVIG) therapies were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment (dexamethasone and etoposide, with or without cyclosporine A), but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperatures of eleven patients decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The glucocorticoid dosage in group R was significantly lower than that in group C. Both groups were followed-up for 2–2.5 years. No obvious adverse drug reactions to ruxolitinib were observed during treatment and follow-up.ConclusionRuxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for glucocorticoid therapy for HLH treatment in children, thereby reducing or avoiding glucocorticoid-related adverse reactions.