Cause Of Abnormal Liver Function Research Articles

New Insights Into the Role of Autophagy in Liver Surgery in the Setting of Metabolic Syndrome and Related Diseases

Visceral obesity is an important component of metabolic syndrome, a cluster of diseases that also includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function, which manifests as non-alcoholic fatty liver disease (NAFLD). NAFLD is a common cause of abnormal liver function, and numerous studies have established the enormously deleterious role of hepatic steatosis in ischemia-reperfusion (I/R) injury that inevitably occurs in both liver resection and transplantation. Thus, steatotic livers exhibit a higher frequency of post-surgical complications after hepatectomy, and using liver grafts from donors with NAFLD is associated with an increased risk of post-surgical morbidity and mortality in the recipient. Diabetes, another MetS-related metabolic disorder, also worsens hepatic I/R injury, and similar to NAFLD, diabetes is associated with a poor prognosis after liver surgery. Due to the large increase in the prevalence of MetS, NAFLD, and diabetes, their association is frequent in the population and therefore, in patients requiring liver resection and in potential liver graft donors. This scenario requires advancement in therapies to improve postoperative results in patients suffering from metabolic diseases and undergoing liver surgery; and in this sense, the bases for designing therapeutic strategies are in-depth knowledge about the molecular signaling pathways underlying the effects of MetS-related diseases and I/R injury on liver tissue. A common denominator in all these diseases is autophagy. In fact, in the context of obesity, autophagy is profoundly diminished in hepatocytes and alters mitochondrial functions in the liver. In insulin resistance conditions, there is a suppression of autophagy in the liver, which is associated with the accumulation of lipids, being this is a risk factor for NAFLD. Also, oxidative stress occurring in hepatic I/R injury promotes autophagy. The present review aims to shed some light on the role of autophagy in livers undergoing surgery and also suffering from metabolic diseases, which may lead to the discovery of effective therapeutic targets that could be translated from laboratory to clinical practice, to improve postoperative results of liver surgeries when performed in the presence of one or more metabolic diseases.

Novel ABCB4 mutation in a Chinese female patient with progressive familial intrahepatic cholestasis type 3: a case report

BackgroundProgressive familial intrahepatic cholestasis (PFIC) is a rare group of autosomal recessive hereditary hepatic diseases. There are three types of PFIC, classified according to the mutated gene. For example, PFIC type 3 (PFIC3) is due to mutations in the ABCB4 gene (encoding multidrug-resistant protein 3 [MDR3]).Case presentationWe present a 19-year-old Chinese female patient who had a 2-year history of recurrent liver dysfunction, with mainly elevated alkaline phosphatase and γ-glutamyl transpeptidase(γ-GT) levels. After excluding other causes of abnormal liver function and cholestasis, the final diagnosis of PFIC3 was confirmed by histopathological examination and gene detection. The immunohistochemical results showed no MDR3 protein expression in the bile duct membrane. Genetic sequencing analysis revealed a novel heterozygous 2137G > A; p. V713M mutation (Exon 17) and a synonymous 504C > T; p. N168N mutation (Exon 6) in ABCB4.ConclusionsOur patient with long-term liver dysfunction demonstrated that elevated alkaline phosphatase and γ-GT levels should be associated with the diagnosis of PFIC3, and gene detection is the key to diagnosis. From our in silico analysis, the novel mutation p. V713M in Exon 17 was predicted to affect protein function, with a SIFT (Sorting Intolerant from Tolerant) score of 0.02, indicating a deleterious effect. Further studies are necessary to investigate the impact of the novel heterozygous 2137G > A; p. V713M mutation (Exon 17) on functional defects of MDR3 and PFIC3.

Implications of abnormal liver function in pregnancy and non-alcoholic fatty liver disease.

Elevated liver enzyme levels can sometimes be encountered in asymptomatic pregnant women. Similar to non-pregnant subjects, women with elevated gamma glutamyltransferase or alanine aminotransferase in early pregnancy have increased risk of subsequent complications, especially gestational diabetes mellitus. In non-pregnant subjects, the commonest cause of abnormal liver function currently is non-alcoholic fatty liver disease. Risk factors include obesity, diabetes, and the metabolic syndrome. It can progress to hepatocellular carcinoma through the development of steatohepatitis, and has become the leading cause for liver transplantation in women. Found in as many as 16-18% of pregnant women, it is associated with an increased risk of pregnancy complications and abnormal foetal growth, which predisposes the offspring to the same problem subsequently. This condition probably explains the majority of the cases of "idiopathic" abnormal liver function in pregnancy, and should be looked out for in high-risk women owing to its implications on their long-term health outcome.

2280 Propafenone-Induced Hepatocellular and Cholestatic Injury

INTRODUCTION: Propafenone, an antiarrhythmic medication, decreases cardiac automaticity and increases refractory periods slowing cardiac conduction. Propafenone-induced hepatic injury is rare with only eight reported cases in the literature. We report a case of propafenone-induced hepatic injury in a patient presenting with painless jaundice. CASE DESCRIPTION/METHODS: A 60-year-old woman presented with sudden onset jaundice and a one week history of 10-pound weight loss, right upper quadrant abdominal pain, nausea and vomiting. Two months prior to presentation, she was diagnosed with atrial fibrillation and was begun on Propafenone 325 mg oral twice daily. She had no history of alcohol, drugs, or herbal medication use. Physical exam was significant only for generalized jaundice. On admission, laboratory studies were significant for AST 304 IU/L, ALT 601 IU/L, ALP 334 IU/L, total bilirubin 7.9 mg/dL, and direct bilirubin 5.4 mg/dL.Abdominal ultrasound revealed fatty liver without biliary obstruction. CT abdomen was unremarkable for hepatic or biliary pathology. Viral serologic markers and acetaminophen levels were negative as well as workup for Autoimmune hepatitis, and Primary biliary cholangitis. Liver biopsy revealed steatohepatitis with superimposed ductular and centrilobular cholestasis suggestive of drug-induced injury.The patient was begun on N-Acetylcysteine and Propafenone was discontinued. Several days after withdrawal of Propafenone, liver function tests began to improve slowly. The patient was discharged home and one month later, transaminases returned to normal and jaundice had resolved. DISCUSSION: Propafenone is a Class 1C antiarrhythmic indicated for symptomatic atrial fibrillation without structural abnormalities. The mechanism for hepatic injury is unknown. Like in our patient, the injury is self-limited and has not been linked to acute liver failure, chronic liver injury, or vanishing bile duct syndrome. Once identified as the cause, the medication should be immediately stopped and never prescribed because re-exposure is associated with recurrence of symptoms. As in other reports, our patient’s liver injury occurred within a 2-6-week period after exposure and, resolved 3-5 weeks after cessation of the offending medication. Propafenone-induced hepatic injury should be suspected in a patient presenting with hepatocellular and cholestatic injury, especially in a patient recently begun on that medication after exclusion of other causes of abnormal liver function.

Research progress on abnormal liver function in pregnancy

Abnormal liver function in pregnancy is a common clinical problem in the department of obstetrics and liver disease, but its severity can cause danger to the life of the mother and fetus. Therefore, the different cause of abnormal liver function in pregnancy should be assessed accurately in order to take early intervention measures. Moreover, it is necessary to comprehensively evaluate the situation of both mother and fetus to obtain the optimal treatment effect for abnormal liver function caused by different types of pregnancy-related liver diseases.

Deranged liver enzyme status in thalassemicpaediatric patients- is it hepatitis or iron overload?

INTRODUCTION: The susceptibility to infections in thalassemia arises from a large spectrum of immunological abnormalities and from the exposure to infectious agents by allogenic blood transfusions. Increased hepatic iron may potentiate progression towards liver fibrosis in chronic HCV infection and may contribute to poor response to therapy OBJECTIVE: (1) To determine the prevalence of hepatitis B and hepatitis C in thalassemic paediatric patients. (2) To determine the relationship between elevated liver enzymes with serum ferritin and viral hepatitis in thalassemia. METHOD: Sera was obtained from 100 thalassemia children and was processed for anti-HCV and HBsAg, serum ferritin,ALT/SGPT & AST/SGOT RESULTS: 100 subjects were evaluated. Eight subjects (8%) were HBsAg positive and six (75%)received more than 100 blood transfusions.Out of these eight subjects with, seven had raised SGOT, & six had raised SGPT. Four subjects were positive for hepatitis C & all of them (100%) received more than hundred blood transfusions.All four HCV subjects had raised SGOT & SGPT (p=0.037).SGOT was raised in 68% subjects and 47 (69%) had more than 100 blood transfusions (p=0.002). SGPT was raised in 49% subjects and 37 (75.5%) had more than 100 blood transfusions. 86% subjects had serum ferritin in range of 1000-2000ng/ml & 14% had serum ferritin <1000 ng/ml.Serum ferritin showed strong correlation with SGOT & SGPT (p=0.036 & p=0.002). CONCLUSIONS: Prevalence of hepatitis B in Thalassemic’s in our study was 8% while hepatitis B in general population is 4.35%. Hepatitis C was 4% in our study while that in children in general population is 0.31%. Serum ferritin showed significant correlation with SGOT & SGPT. This finding suggests that iron overload is one of the major causes of abnormal liver function in subjects with thalassemia.So the treatment of hepatitis as well as iron overload should be done to prevent progression to liver disease. DOI:10.21276/APALM.1616

Effects of high isoflavone soy diet vs casein or arginine‐supplemented casein diet on liver steatosis

Non‐alcoholic fatty liver disease (NAFLD), the major cause of abnormal liver function, is often associated with obesity. Arginine (Arg) plays a role in reducing body fat, but there is limited data as to the role that Arg may play in soy protein's ability to protect from fatty liver. The objective of this study was to find the role of native Arg in soy to protect from fatty liver in male obese Zucker rats (N=49; 6 weeks old). Rats had ad libitum access to water and were randomly assigned to one of 3 diets for 8 or 16 weeks: Casein (CAS) diet as control (0.6% Arg) or a casein diet supplemented to contain 1.3% Arg (ARG) or a soy protein isolate diet with high isoflavones (SPI) (1.3% Arg). SPI and ARG rats gained more weight (P&lt;0.05) than CAS rats after 16 weeks only. The SPI rats had lower liver steatosis after 8 and 16 weeks (P&lt;0.05 and P&lt;0.001, respectively) compared to CAS &amp; ARG rats. SPI rats had lower serum alanine amino transferase (ALT) &amp; aminotransferase (AST) levels (P&lt;0.05) compared to CAS after 16 weeks and AST was lower (P&lt;0.05) compared to ARG rats. After 16 weeks the SPI rats had lower (P&lt;0.05) serum ALT and AST levels than SPI rats at 8 weeks. Our results suggest that longer period of SPI feeding results in lower liver steatosis and serum ALT and AST levels while ARG diet had no effect on steatosis or ALT and AST levels. The protective effect of soy protein to reduce fatty liver does not appear to be due to its arginine content. Supported by ABI to RH

Non-Alcoholic Steatohepatitis: What Can We Learn from Animal Models?

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver function and correlates with central adiposity, obesity, insulin resistance, the metabolic syndrome and type 2 diabetes mellitus. The pathological spectrum of NAFLD ranges from fatty liver to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and even hepatocellular carcinoma. Though NAFLD and NASH are becoming a major public health problem, ethical constraints on obtaining human liver tissue limit the interpretability of the data and the ability to delineate cause and effect from complex, interactive disease pathogenic pathways. Animal models of NASH can provide critical information leading to identify potential drug targets and to understand their molecular mechanisms, and are platforms for compound screening in drug development and for the assessment of novel therapeutic strategies. This review is aimed to offer an updated overview of the nutritional, genetic and pharmacologic animal models of NASH. Though the information derived from these models has clear relevance for the comprehension of the molecular basis of human disease, most of them fail to reproduce the full spectrum of liver pathology and the metabolic context that characterizes human NASH. Consequently, it is necessary to establish animal models that can best mimic the actual etiology, progression, and pathogenesis of the disease, and prove effectiveness for examining and selecting compounds with potential therapeutic benefit in NASH.

Liver fatty acid composition in mice with or without nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver function. Because fatty acids can damage biological membranes, fatty acid accumulation in the liver may be partially responsible for the functional and morphological changes that are observed in nonalcoholic liver disease. The aim of this study was to use gas chromatography-mass spectrometry to evaluate the fatty acid composition of an experimental mouse model of NAFLD induced by high-fat feed and CCl4 and to assess the association between liver fatty acid accumulation and NAFLD. C57BL/6J mice were given high-fat feed for six consecutive weeks to develop experimental NAFLD. Meanwhile, these mice were given subcutaneous injections of a 40% CCl4-vegetable oil mixture twice per week.ResultsA pathological examination found that NAFLD had developed in the C57BL/6J mice. High-fat feed and CCl4 led to significant increases in C14:0, C16:0, C18:0 and C20:3 (P < 0.01), and decreases in C15:0, C18:1, C18:2 and C18:3 (P < 0.01) in the mouse liver. The treatment also led to an increase in SFA and decreases in other fatty acids (UFA, PUFA and MUFA). An increase in the ratio of product/precursor n-6 (C20:4/C18:2) and n-3 ([C20:5+C22:6]/C18:3) and a decrease in the ratio of n-6/n-3 (C20:4/[C20:5+C22:6]) were also observed.ConclusionThese data are consistent with the hypothesis that fatty acids are deranged in mice with non-alcoholic fatty liver injury induced by high-fat feed and CCl4, which may be involved in its pathogenesis and/or progression via an unclear mechanism.

Evaluation of Liver Functions in Beta-thalassemic Patients in Ismailia

Background and objective: Regular packed RBCs transfusion puts Beta-thalassemia major patients at a high risk of developing hepatic iron overload and hepatitis C viral infection. Aim: The aim of this study was to evaluate liver functions in thalassemic patients in Ismailia. A descriptive cross sectional study was carried out in the outpatient pediatric hematological clinic of Suez Canal University hospital. Material and Methods: A sample of 25 Egyptian transfusion dependant β-thalassemia major children was studied. Individual patients underwent full history undertaking, clinical examination and a panel of laboratory tests including hemoglobin level, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum ferritin, hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (HCV Ab). Results: Both ALT and AST means were elevated being 62.32 IU/L and 70.76 IU/L respectively. 32% of the studied patients were HCV Ab positive while no one was HBs Ag positive. A highly significant correlation between ALT and AST was found. There was a statistically significant relationship between serum ferritin and HCV Ab status. Conclusion: These findings suggest that both HCV and iron overload are the main causes of abnormal liver function in patients with thalassemia. The treatment of both problems if coexisting in patients with thalassemia is required to prevent progression to chronic liver diseases.

An unusual cause of abnormal liver function in a patient with rheumatoid arthritis

An unusual cause of abnormal liver function in a patient with rheumatoid arthritis

A Chat on Fat in the Liver

A Chat on Fat in the Liver

Prevalence and clinical significance of hepatitis C virus infection in Thai patients with thalassemia.

Hepatitis C virus (HCV) infection is a common cause of liver disease in thalassemia major patients in Western, especially Mediterranean, countries. Its significance in thalassemic patients from Southeast Asia has not been critically evaluated. In this report, we describe our study of the prevalence of HCV infection among Thai patients with thalassemia. The relationships of the infection to blood transfusion and the infection's effects on liver function have also been determined. Of the 104 patients studied, 21 (20.2%) tested positively by enzyme immunoassay for anti-HCV antibody, whereas only 2 patients (2%) had the hepatitis B surface antigen. There was no significant relationship between the presence of anti-HCV antibodies and the number and frequency of blood transfusions. In fact, 2 patients (10%) who tested positive for anti-HCV antibodies had never received transfusions. Patients with anti-HCV antibodies had significantly abnormal liver functions, such as higher levels of serum aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) and lower levels of serum albumin, compared with patients without anti-HCV antibodies (P = .021, .017, and .004, respectively). However, there were also significant correlations between iron status as indicated by transferrin saturation or serum ferritin levels and SGOT, SGPT, and gamma-glutamyltransferase (GGT) levels. Moreover, abnormal liver function as represented by elevated levels of SGOT, SGPT, GGT, and serum alkaline phosphatase was observed more frequently in patients with iron overload than in patients with a lower degree of iron burden. The presence of HCV did not alter the effects of iron overload on liver function. The findings suggest that both HCV and iron overload are the main causes of abnormal liver function in Thai patients with thalassemia. The treatment of both problems, if coexisting in patients with thalassemia, is required to prevent progression to chronic liver disease.

Liver disease complicating bone marrow transplantation: A clinical audit

Hepatic dysfunction following bone marrow transplantation (BMT) may present complex management issues. The incidence and aetiology of abnormal liver function following allogeneic and autologous BMT was reviewed over a 2 year period in Royal Perth Hospital and these findings were related to management decisions and patient outcome. Abnormal serum liver biochemistry during the first 12 post-transplant months occurred in all allogeneic (n = 31) and 14 of 23 (61%) autologous transplant patients; 13 (41%) allogeneic and three (13%) autologous patients developed severe hepatic dysfunction. In allogeneic transplants, the most common causes of liver disease were graft-versus-host disease (33%), drug hepatotoxicity (19%) and posttransplant viral hepatitis (15%); in autologous patients, disease recurrence (28%) and sepsis (17%) were the most frequent identifiable cause of abnormal liver function. The aetiology of abnormal liver biochemistry was not determined in 13 instances, but this did not adversely affect patient outcome. Percutaneous liver biopsy or endoscopic cholangiography were only required in three patients. Liver disease contributed to death in two allogeneic patients with multiple causes for liver dysfunction, and in one patient with refractory severe hepatic graft-versus-host disease. It was concluded that hepatic dysfunction is common after BMT, the cause of which can be determined in many cases with simple non-invasive tests used in conjunction with the clinical setting. Specific treatment, where necessary, is then able to be commenced in a majority of patients without the need for invasive investigation.