Conventional Liver Function Tests Research Articles

Role of Donor-derived Cell-free DNA In Predicting Short-term Allograft Health In Liver Transplant Recipients

BackgroundPredicting allograft dysfunction prior to clinical or biochemical evidence remains one of the challenges in transplantation, and a preclinical detection and early management of its cause allows for improved post-transplant outcomes. Donor derived cell-free DNA (ddcfDNA) has been proposed as an important biomarker of allograft injury and has shown to predict dysfunction prior to any biochemical derangements. We aimed to investigate the diagnostic performance of ddcfDNA in detecting and differentiating the causes of early pre-biochemical detection of graft injury and in predicting the short-term outcomes of graft health using a patented protocol and proprietary set of single nucleotide polymorphisms. MethodsBlood samples were collected on defined postoperative days (1-, 3-, 7- and at 3-months) and were analysed through relatively economical patented protocol (TrunomeTM). Biopsy, biochemical tests, and clinical criteria were analysed between various subgroups. ResultOf a total 50 patients, percentage ddcfDNA (%ddcfDNA) levels were significantly elevated in the rejection group (n=8) as compared to the non-rejection group (n= 42; median elevation 12.8% vs 4.3% respectively) with a significant correlation (r = 0.92, p<0.0001). AUC-ROC analysis revealed that the %ddcfDNA levels can predict graft health more precisely when compared to the conventional liver function tests (AUC for %ddcfDNA- 0.86; p<0.001; AUC for AST-0.65, p=0.08; AUC for ALT- 0.75, p<0.01). Moreover, %ddcfDNA levels (with a threshold >10.2%) on post-operative day 7 accurately predicted short-term (3-months) health status of the graft with 93.33% sensitivity, 94.44% specificity, 87.50% positive predictive value, 97.14% negative predictive value and 94.12% accuracy. ConclusionA single time point ddcfDNA on postoperative day 7 accurately predicts graft health and improves risk stratification in the short-term.

Liver FoxO1 overexpression is positively associated with the degree of liver injury in cirrhotic patients

Abstract Objectives Chronic liver disease and related complications, cirrhosis and hepatocellular carcinoma, are associated with high mortality. Curative treatments, partial hepatectomy or liver transplantation, have limited applicability in patients with cirrhosis due to the poor liver regenerative capacity. Thus, we need to find new diagnostic and therapeutic alternatives, to block the disease progression and to improve the survival of patients. In this context, preclinical studies have demonstrated the key role of the protein kinase B (Akt) in liver dysfunction, but the status of Akt and its targets in patients with chronic hepatopathy remains unknown. Aims: To determine the activation status of the Akt pathway and their association with liver functionality in cirrhotic patients. Methods This retrospective study includes liver tissue samples from 36 hepatectomized patients with (n=27) and without (n=9) cirrhosis. Multiplex analysis of proteins involved in the Akt/mTOR pathway was performed using a Luminex panel and Western blot. Conventional liver function tests were determined in serum before resection surgery. Results Akt and forkhead box protein O1 (FoxO1) are overexpressed in the liver of cirrhotic patients: (2.1 vs. 1.0 densitometric relative units (DRU); p&lt;0.01, and 9.5 vs. 4.4 DRU; p&lt;0.01, respectively). FoxO1 showed the best correlation with markers of liver injury (aspartate aminotransferase (ASAT): r=0.51, p&lt;0.05; alanine aminotransferase (ALAT): r=0.49, p&lt;0.05), and was the only enzyme in the Akt pathway identified as an independent predictor of ASAT and ALAT levels. Conclusions The intrahepatic expression of FoxO1 could have clinical utility as a potential prognostic marker for patients with advanced liver disease.

Proteomic-based identification of APCS as candidate protein for diagnosis of patients exhibiting anti-tubercular drug induced liver injury

Traditional markers evaluate anti-tubercular drug-induced liver injury (AT-DILI). However, these markers have certain limitations and studies are in progress to characterize AT-DILI at an early stage. In the present study, 40 patients were categorized and equally distributed into healthy controls, newly diagnosed tuberculosis (TB), TB without hepatotoxicity and TB with hepatotoxicity groups based on their conventional liver function tests. Relative protein quantification was performed on depleted pooled serum samples of each representative group by LC–MS/MS, and validation of shortlisted protein was done by ELISA. Levels of all analysed biochemical parameters showed a statistical increment in the hepatotoxicity group compared to the other three groups, representing AT-DILI. Comparative proteomic analysis between TB with hepatotoxicity versus TB without hepatotoxicity groups highlighted 24 significant differentially expressed proteins, including PROS1, KNG1, CFH, LCAT, APCS and ADIPOQ. Identified proteins were involved in complement activation, triglyceride-rich lipoprotein particle remodelling and pathways comprising complement, coagulation cascades and cholesterol metabolism. Based on functional relevance, the serum amyloid P component (APCS) was shortlisted for validation, and it showed a similar trend as observed in the discovery phase with 100% sensitivity and 87% specificity; however, findings need exploration in larger cohorts.

Evaluation of Serum Cholinesterase Level as A diagnostic Marker in Chronic Liver Disease

Background: Liver is the main source of Butyrylcholinesterase (serum cholinesterase). It is a non-specific cholinesterase that is reduced in patients with advanced liver diseases. Measurement of serum Butyrylcholinesterase activity serves as a sensitive indicator of synthetic capacity of the liver. Objective: To evaluate serum cholinesterase levels in chronic liver disease patients. Patients and methods: In this study serum cholinesterase level was evaluated in chronic liver disease patients by a colorimetric kinetic assay method. Thirty cirrhotic subjects and thirty non-cirrhotic hepatic disease subjects were compared to 20 normal individuals. This study was done at Al-Azhar University Hospitals in the period between June 2018 and August 2020. Results: A significant decrease in serum Cholinestrease level was observed in all patients of chronic liver disease as compared to control group. Conclusion: Serum cholinesterase is a better diagnostic and prognostic marker than the conventional liver function test that are raised in other liver disease also.

Supportive Hepatocyte Transplantation after Partial Hepatectomy Enhances Liver Regeneration in a Preclinical Pig Model

Background: Hepatocyte transplantation (HTx) is regarded as a potential treatment modality for various liver diseases including acute liver failure. We developed a preclinical pig model to evaluate if HTx could safely support recovery from liver function impairment after partial hepatectomy. Methods: Pigs underwent partial hepatectomy with reduction of the liver volume by 50% to induce a transient but significant impairment of liver function. Thereafter, 2 protocols for HTx were evaluated and compared to a control group receiving liver resection only (group 1, n = 5). Portal pressure-controlled HTx was performed either immediately after surgery (group 2, n = 6) or 3 days postoperatively (group 3, n = 5). In all cases, liver regeneration was monitored by conventional laboratory tests and the novel noninvasive maximum liver function capacity (LiMAx) test with a follow-up of 4 weeks. Results: Partial hepatectomy significantly impaired liver function according to conventional liver function tests as well as LiMAx in all groups. A mean of 4.10 ± 1.1 × 10⁸ and 3.82 ± 0.7 × 10⁸ hepatocytes were transplanted in groups 2 and 3, respectively. All animals remained stable with respect to vital parameters during and after HTx. The animals in group 2 showed enhanced liver regeneration as observed by mean postoperative LiMAx values (621.5 vs. 331.3 μg/kg/h on postoperative day 7; p < 0.001) whereas HTx in group 3 led to a significant increase in mean liver-specific coagulation factor VII (112.2 vs. 54.0% on postoperative day 7; p = 0.003) compared to controls (group 1), respectively. In both experimental groups, thrombotic material was observed in the portal veins and pulmonary arteries on histology, despite the absence of clinical symptoms. Conclusion: HTx can be performed safely and effectively immediately after a partial (50%) hepatectomy as well as 3 days postoperatively, with comparable results regarding the enhancement of liver function and regeneration.

Evaluation of conventional and non-conventional biomarkers of liver toxicity in greenhouse workers occupationally exposed to pesticides

The liver plays a prominent role in maintenance of homeostasis and is the major organ for xenobiotic metabolism, including pesticides. Conventional liver function tests are widely used to assess hepatocellular and biliary system dysfunction by measuring serum levels of aminotransferases (ALT, AST) and cholestasis enzymes (alkaline phosphatase –ALP– and γ-glutamyl transferase –GGT–), respectively. Although these tests are not entirely specific for liver damage, their specificity increases when measured concurrently, but still have limited usefulness to predict early liver dysfunction. Hence, non-conventional biomarkers may have a better performance for the early detection of biochemical hepatotoxicity with a greater specificity and sensitivity. A cross-sectional study with a follow-up component was conducted on 175 greenhouse workers regularly exposed to pesticides under integrated production system, and 91 controls living in the same geographical area. All individuals were evaluated for conventional (ALT, AST, ALP, GGT) and non-conventional biomarkers of hepatotoxicity (ornithine transcarbamylase (–OTC–), Arginase-1 –ARG1– and glutathione S-transferase alpha –GSTα–) over two periods of the same crop season, one of high pesticide exposure and other of low exposure. A slight increase in AST was observed in greenhouse workers relative to controls, suggestive of subtle hepatocellular toxicity. Although ALP, ARG1 and GST-α levels were decreased in greenhouse workers, this might be related to a potential homeostatic mechanism that regulates their expression. Altogether, these findings do not represent unambiguous evidence of liver dysfunction (e.g., hepatocellular or biliary system impairment) but may be the result of the low-toxicity pesticides used by greenhouse workers.

Metabolomics analysis of plasma reveals voriconazole-induced hepatotoxicity is associated with oxidative stress

Voriconazole is one of the most frequently used antifungal drugs for the initial treatment of invasive aspergillosis, but liver-related adverse events occur frequently and usually lead to drug discontinuation. Moreover, the mechanism of voriconazole-induced hepatotoxicity remains unsettled. A holistic understanding of its mechanism is critical to prevent liver-related adverse events. Metabolomics has been demonstrated to be a helpful strategy for investigating drug-induced toxicity. This study aimed to utilize human plasma samples to investigate the mechanism of voriconazole-induced hepatotoxicity through a metabolomics approach. Patients that were administered voriconazole were classified into a voriconazole-induced hepatotoxicity group and control group (n = 65, 18% hepatotoxicity). Plasma samples were analyzed by targeted metabolomics using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. The obtained peak areas for each metabolite were utilized for correlation analysis, fold change evaluation, and univariate statistical tests to identify metabolites associated with voriconazole-induced hepatotoxicity. This study showed a significantly lower glutamine-to-glutamate ratio (p = .04) and a higher β-N-acetylglucosamine (p = .003) in the voriconazole-induced hepatotoxicity group, implying the presence of oxidative stress. Other significant metabolites also indicated several adaptive responses to oxidative stress in patients with voriconazole-induced toxicity, including cell repair, energy production, and alteration to bile acid hemostasis. Furthermore, a metabolite panel consisting of α-ketoglutarate, glycocholate, and β-N-acetylglucosamine demonstrated better performance for detecting voriconazole-induced hepatotoxicity than conventional liver function tests. These metabolomics findings reveal that voriconazole-induced hepatotoxicity is associated with oxidative stress.

Liver function assessment using indocyanine green plasma disappearance rate in a young male with icteric leptospirosis: a case report

BackgroundLeptospirosis is one of the leading global zoonotic causes of morbidity and mortality. It is induced by a pathogenic spirochete of the genus Leptospira. The icteric form of leptospirosis is characterized by pronounced hyperbilirubinemia and associated with significantly increased mortality. Conventional static liver function tests insufficiently assess hepatic damage and have limited prognostic value. Dynamic tests, such as indocyanine green plasma (ICG) clearance, more adequately reflect hepatic functional status. In this case report we describe the ICG plasma disappearance rates (ICG-PDR) in a patient with leptospirosis and massive hyperbilirubinemia, expanding our knowledge of liver dysfunction in icteric leptospirosis.Case presentationA 21-year-old Caucasian man presented with acute-onset jaundice, myalgia, fever and headaches. Laboratory tests upon admission revealed, most notably, acute kidney failure and hyperbilirubinemia of 17 mg/dl with mild elevation of aminotransferases. In the course of the following 4 days, total serum bilirubin increased to 54 mg/dl. The clinical outcome was favorable with intravenous ceftriaxone and doxycycline. Presumptive diagnosis of leptospirosis was later confirmed by PCR-based amplification of leptospiral DNA in the blood. ICG-PDR values, bilirubin as well as aminotransferases were recorded throughout hospitalization and a 3-month follow-up period. Initially dramatically reduced ICG-PDR (2.0%/min, normal range: 18–25%/min) rapidly normalized within 10 days, while bilirubin remained elevated up to week 7. Mild elevation of serum alanine aminotransferase was at its peak of 124 U/l by day 12 and reached close to normal levels by week 7 upon admission.ConclusionsMarkedly diminished ICG-PDR values presented in this case report suggest severe liver function impairment in the acute phase of icteric leptospirosis. Prolonged elevation of serum bilirubin may not adequately reflect recovery of liver injury in this disease. ICG clearance appears to be a promising marker for the detection of hepatic dysfunction and recovery in icteric leptospirosis in addition to the static tests.

Predictive Markers for Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis C Virus Genotype4a

Background: Egypt has the highest prevalence of hepatitis C virus worldwide. Monitoring hepatitis C-infected patients for hepatocellular carcinoma development is an important clinical issue to diagnose these patients during the potentially curable early-stage of disease. This study aims to evaluate the role of N-terminal procollagen III, matrix metalloproteinase- 2, tissue inhibitor of matrix metalloproteinase-1, alpha-fetoprotein, and conventional liver function tests as predictors of hepatocellular carcinoma development upon long-term followup of non-responding hepatitis C virus patients.Methods: The study included 850 treatment-naive hepatitis C virus genotype 4a adult patients; after treatment, 360 achieved sustained viral response while 490 did not. Nonresponding patients had a 5-year rate for hepatocarcinogenesis of 8.4% and a 10-year rate of 27.5%. N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, alpha-fetoprotein, and conventional liver function tests were evaluated in all patients before and after treatment, and after hepatocellular carcinoma development. The study also included a group of 50 hepatocellular carcinoma patients who were negative for hepatitis C and hepatitis B viruses, and a group of 50 healthy subjects as controls.Results: The non-responders had significantly higher age, stage, grade, viral load, alanine aminotransferase, and aspartate aminotransferase than responders. Also N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, and alphafetoprotein were significantly higher in non-responders; after treatment they decreased in responders. In non-responders they remained higher than the control. The most significant risk factors for hepatocellular carcinoma development in non-responding hepatitis C virus patients were male gender and increased age, stage, grade, aspartate aminotransferase, Nterminal procollagen III, and tissue inhibitor of matrix metalloproteinase-1. Patients with viral-hepatocellular carcinoma were of significantly lower age, higher grade, stage, γ-glutamyltransferase, N-terminal procollagen III, and matrix metalloproteinase-2 than non-viral hepatocellular carcinoma patients. Percent positive N-terminal procollagen III, tissue inhibitor of matrix metalloproteinase-1, and alpha-fetoprotein were significantly higher in viral hepatocellular carcinoma patients.Conclusion: Data suggest that high N-terminal procollagen III and tissue inhibitor of matrix metalloproteinase-1levels after treatment might be particularly important as markers of hepatitis C virus-non-responding patients who are at higher risk of developing hepatocellular carcinoma, especially in older males with high stage and grade liver disease. However, studies of larger scale are needed to verify this suggestion.

Clinical value of the conventional liver function test in liver reserve function assessment for large hepatocellular carcinoma

Objective To study the clinical value of the conventional liver function tests in liver reserve function assessment for large hepatocellular carcinoma. Methods The clinicopathological data of 113 patients with Child-Pugh A hepatocellular carcinoma who underwent radical resection with large hepatocellular carcinoma in the Department of Hepatobiliary Surgery of Fuzhou General Hospital of People′s Liberation Army from January 2014 to December 2016 were retrospectively analyzed. The patients were divided into two groups according to the recovery of postoperative liver function, which 105 patients recovered well and 8 patients had hepatic decompensation among them. The liver function index of two groups were analyzed. Measurement data with approximately normal distribution were represented by and groups were compared using t test; measurement data with skewed or uneven disstribution were represented by M (range)and group werecompared using Man-Whitney U test; count data were compared using Fisher exact test; risk factors for postoperative liver dysfunction were analyzed using Logistic single factor and multivariate and ROC curve were drawn. Results Preoperative prothrombin time, international standardization ratio, platelet, prealbumin, total bilirubin, alkaline phosphatase, γ-glutamyl transpeptidase comparison between the two groups were statistically significant (Z=-1.983, -2.180, -2.608, -2.007, -3.577, -2.228, -2.575, P<0.05). Logistic univariate analysis showed that platelet, total bilirubin and prealbumin were the risk factors for the recovery of liver function of radical resection hepatic decompensation with large hepatocellular carcinoma. Logistic multivariate regression analysis showed that preoperative high total bilirubin and low preabumin were independent risk factors of radical resection hepatic decompensation with large hepatocellular carcinoma. Logistic univariate analysis showed that preoperative high total bilirubin and low prealbumin were not risk factors of radical resection liver failure with large hepatocellular carcinoma. The area under the curve of total bilirubin was 0.880, P=0.000, 95%CI: 0.808-0.953, the sensitivity was 87.5%, specificity was 84.8% and the area under prealbumin curve was 0.769, P=0.011, 95%CI: 0.648-0.891, sensitivity was 75.2%, specificity was 77.5% by the ROC curve. The best threshold of total bilirubin and prealbumin after radical resection with large hepatocellular carcinoma were 17.55 μmol/L and 0.18 g/L respectively by the ROC curve. Conclusion The Child-Pugh A patients in radical resection hepatic decompensation with large hepatocellular carcinoma recover well when the preoperative liver function is as follows: total bilirubin<17.55 μmol/L and prealbumin≥0.18 g/L. Key words: Large hepatocellular carcinoma; Prealbumin; Hepatic reserve; Hepatic decompensation; Liver failure

A Neural Network Approach to Predict Acute Allograft Rejection in Liver Transplant Recipients Using Routine Laboratory Data

Background: Discovery of non-invasive methods for acute rejection in liver transplant patients would contribute to preservation of liver function in the graft. Recently, however, outcome prediction based on biostatistical models like artificial neural networks (ANNs) is increasingly becoming impressive in medicine. Objectives: The aim of this study was to obtain a predictive model based on ANN technique and to figure out the best time for early prediction of acute allograft rejection after transplantation in liver transplant recipients. Methods: Feed-forward, back-propagation neural network was developed to predict acute rejection in liver transplant recipients using clinical and biochemical data from 148 liver transplant recipients over days 3, 7, and 14 post-transplantation. Sensitivity and receiver-operating characteristic (ROC) analysis were done to reveal the importance of input variables and the performance of the neural network. Results: The results were compared with a logistic regression (LR) model using the same data. Our results showed that the data related to day 7 gave the best results in terms of ANN performance; and the most important factors in the predictive model were aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The ANN’s accuracy was 90%, sensitivity was 87%, specificity was 90% in the testing set, and the performance of the ANN was better than that of the LR model. The ANN recognized correctly eight out of ten acute rejection patients and 34 out of 36 non-rejection ones in the testing set. Conclusions: This study suggests that ANN could be a valuable adjunct to conventional liver function tests for monitoring liver transplant recipients in the early postoperative period.

Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: A prospective, observational, multicenter cohort study.

BackgroundGraft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection.Methods and findingsTraditional LFTs were performed and plasma GcfDNA was monitored in 115 adults post-LTx at three German transplant centers as part of a prospective, observational, multicenter cohort trial. GcfDNA percentage (graft cfDNA/total cfDNA) was measured using droplet digital PCR (ddPCR), based on a limited number of predefined single nucleotide polymorphisms, enabling same-day turn-around. The same method was used to quantify blood microchimerism. GcfDNA was increased >50% on day 1 post-LTx, presumably from ischemia/reperfusion damage, but rapidly declined in patients without graft injury within 7 to 10 d to a median <10%, where it remained for the 1-y observation period. Of 115 patients, 107 provided samples that met preestablished criteria. In 31 samples taken from 17 patients during biopsy-proven acute rejection episodes, the percentage of GcfDNA was elevated substantially (median 29.6%, 95% CI 23.6%–41.0%) compared with that in 282 samples from 88 patients during stable periods (median 3.3%, 95% CI 2.9%–3.7%; p < 0.001). Only slightly higher values (median 5.9%, 95% CI 4.4%–10.3%) were found in 68 samples from 17 hepatitis C virus (HCV)–positive, rejection-free patients. LFTs had low overall correlations (r = 0.28–0.62) with GcfDNA and showed greater overlap between patient subgroups, especially between acute rejection and HCV+ patients. Multivariable logistic regression modeling demonstrated that GcfDNA provided additional LFT-independent information on graft integrity. Diagnostic sensitivity and specificity were 90.3% (95% CI 74.2%–98.0%) and 92.9% (95% CI 89.3%–95.6%), respectively, for GcfDNA at a threshold value of 10%. The area under the receiver operator characteristic curve was higher for GcfDNA (97.1%, 95% CI 93.4%–100%) than for same-day conventional LFTs (AST: 95.7%; ALT: 95.2%; γ-GT: 94.5%; bilirubin: 82.6%). An evaluation of microchimerism revealed that the maximum donor DNA in circulating white blood cells was only 0.068%. GcfDNA percentage can be influenced by major changes in host cfDNA (e.g., due to leukopenia or leukocytosis). One limitation of our study is that exact time-matched GcfDNA and LFT samples were not available for all patient visits.ConclusionsIn this study, determination of GcfDNA in plasma by ddPCR allowed for earlier and more sensitive discrimination of acute rejection in LTx patients as compared with conventional LFTs. Potential blood microchimerism was quantitatively low and had no significant influence on GcfDNA value. Further research, which should ideally include protocol biopsies, will be needed to establish the practical value of GcfDNA measurements in the management of LTx patients.

Non-invasive tests and markers for liver fibrosis

Chronic liver disease is characterized by liver fibrosis, which may lead to cirrhosis. Conventional serum-based liver function tests do not give information on either the presence or the rate of progress of liver fibrosis. The reference diagnostic test to detect fibrosis is liver biopsy, a procedure subject to various limitations, including risk of patient injury and sampling error. Serum markers have been evaluated for the determination of fibrosis either singly or combined as a panel of markers, however diagnostic accuracy is greatest in studies using a panel together with an algorithm, which generates a predictive score. Serum marker models, especially those targeted at hepatitis C, have multiplied in spectacular fashion over the last five years, with most models regularly achieving a median area under the receiver operating characteristic curve (ROCC) of 0.80 versus liver biopsy. Five years after publication of the first major serum marker model, the first study to document clinical outcomes reported that applying the model to hepatitis C patients improved prediction of decompensated cirrhosis and survival compared to liver biopsy. An obstacle to widespread adoption of serum marker models has been the lack of uniform performance indicators, such as diagnostic odds ratios and likelihood ratios. This review highlights the most well-established noninvasive biomarkers to-date, with a particular emphasis on serum

Protein C Deficiency in Chronic Hepatitis C: Correlation With Histological Extent of Liver Fibrosis.

There is accumulating evidence that the coagulation system is involved in the process of fibrogenesis in chronic liver disease. Recent studies postulated a possible connection between plasmatic hypercoagulability and progression of fibrosis. The aim of the study was to investigate disorders of the coagulation system in patients with chronic hepatitis C having different extent of hepatic fibrosis well defined by liver histology. A total of 62 patients with chronic hepatitis C were recruited and categorized into 2 groups according to their histological fibrosis stage : mild/moderate fibrosis group (F0-F3 group, n = 30) and extensive fibrosis/cirrhosis group (F4-F6 group, n = 32). The control group consisted of 31 healthy individuals. The following hemostatic assays were evaluated: antithrombin III (AT), protein C (PC) activity, activated partial thromboplastin time, prothrombin time, plasma fibrinogen as well as conventional liver function test. The PC level exhibited a significant reduction in both patient groups when compared to the normal control group (89.25% ± 10.05% and 48.33% ± 15.86% vs 111.86 ± 10.90; P < .001 and P < .001). The PC was found to be the strongest associated factor to histological fibrosis stage (r = -.834; P < .0001). Univariate and multivariate analysis showed that AT (P = .003) and PC (P = .0001) were the most important factors associated with advanced fibrosis. The PC (P = .001) was found to be the only predictor of mild fibrosis. In conclusion, PC deficiency occurs in an early stage of liver fibrosis. The severity of deficiency is proportional to extent of fibrosis. The PC may have a key role in linking hypercoagulability with hepatic fibrogenesis in chronic liver disease.

Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish.

Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellular damages were not reflected in two conventional liver function tests performed, Bilirubin assay and alanine aminotransferase (ALT) assay, probably because the short arsenate exposure was insufficient to induce detectable damage. This study demonstrated that metabolic changes could reflect mild liver impairments induced by arsenic exposure, which underscored their potential in reporting early liver injury.

PTU-121 Monitoring changes in hepatic architecture and haemodynamics with quantitative magnetic resonance imaging (MRI) following directly-acting antiviral therapy in hepatitis C patients with decompensated cirrhosis

Introduction Directly-acting antiviral (DAA) therapy achieves sustained virological response (SVR) in over 90% of those with chronic hepatitis C (CHC), but even in those with SVR, the risk for liver related morbidity and mortality persists albeit at a lower level. It is hypothesised that the residual risk of liver related outcome in those with SVR is related to the progression or non-regression of structural and haemodynamic changes of advanced liver disease at the time of HCV therapy. Here, we investigate the effect of DAAs on the hepatic architecture and splanchnic haemodynamics in patients with decompensated cirrhosis, using quantitative MRI techniques. Method We prospectively recruited patients receiving DAAs for CHC related decompensated cirrhosis from the East Midlands hub of the Early Access Programme commissioned by NHS England. MRI was performed before and at the end of a 12-week treatment with Daclatasvir, Sofosbuvir and Ribavarin. A respiratory-triggered inversion recovery scheme was used to measure the longitudinal (T1) relaxation time of the liver employing a fat suppressed Echo Planar Imaging-acquisition. Phase-contrast (PC)-MRI was used to assess the velocity, area and bulk flow in the splanchnic circulation without any intravenous contrast agents. Results 9 patients have undergone baseline and post-treatment MR scans and end-of-treatment response (EOTR) was achieved in all 9 patients, but one patient has had virologic relapse. There was a significant reduction in the T1 relaxation time in patients with SVR (baseline T1: 765 ± 112 ms; post-treatment 737 ± 118 ms; p = 0.043) (Figure 1). There were no significant changes in the hepatic artery, portal vein, superior mesenteric artery and splenic artery flow. The changes in the Model for End-Stage Liver Disease (MELD) and United Kingdom Model for End-Stage Liver Disease (UKELD) score are shown in Table 1. Conclusion Treatment of decompensated CHC related cirrhosis with DAA is associated with early improvement in the MR markers of liver architecture. These early changes are likely to reflect the reduction in the inflammation associated with EOTR and is evident before any improvement in conventional liver function tests. This novel quantitative MR methodology will allow us to non-invasively monitor HCV related liver disease. Disclosure of interest None Declared.

A study on changes in serum GGT and magnesium level in alcoholic liver disease

Aims: A study on changes in Serum GGT and Magnesium level in Alcoholic Liver Disease. Material and Methods: Serum GGT and Serum Mg++ were estimated with the help of commercially available kit in patients of Alcoholic Liver Disease (n=50) and Normal Individuals (n=50) on fully automated biochemistry analyzer Erba XL-640. Results: Serum GGT level was found significantly higher (P< 0.01) in Alcoholic patients as compared to healthy non-alcoholics. Moreover Serum Mg++ was found significantly lower (P< 0.01) in Alcoholic Liver Disease as compare to normal Individuals. In addition to that there is significant inverse correlation (r= - 0.553) between serum GGT and Mg++ in study group. Conclusions: None of the individual tests of conventional liver function tests are of much importance in diagnosis of liver disease; however when many of the liver function tests are abnormal at the same time, liver disease is the most probable diagnosis. Data of the present study clearly conclude that serum GGT activity along with serum Mg++ status can be useful marker for alcoholic liver disease.

Kinetics of liver function tests after a hepatectomy for colorectal liver metastases predict post‐operative liver failure as defined by the International Study Group for Liver Surgery

BackgroundPost‐hepatectomy liver failure (PHLF) has been defined by the International Study Group for Liver Surgery (ISGLS). The purpose of the present study was to examine the kinetics of conventional liver function tests (LFT) after a major liver resection and is the first to examine their utility in predicting PHLF in groups defined by the ISGLS. MethodsConsecutive patients undergoing a major liver resection for colorectal liver metastases were stratified into ISGLS groups and their LFT up to 1 year after surgery compared. Receiving‐operating characteristic (ROC) analysis of LFT identified optimal thresholds in predicting category C liver failure. ResultsIn total, 32, 22 and 19 patients belonged to ISGLS groups A, B and C, respectively. The median international normalized ratio (INR) and bilirubin values on post‐operative days 1, 3, 5 and 7 were significantly different among the groups (all P‐values <0.05). ROC analysis of day 1 INR (AUC 0.813) and day 5 bilirubin (AUC 0.798) revealed thresholds of 1.35 and 52 μmol/l to have sensitivities of 85% and 81% and specificities of 63% and 73%, respectively, to predict group C liver failure. DiscussionPost‐operative LFT after a major liver resection differs significantly among the three ISGLS groups. Thresholds of bilirubin and INR can be used to identify patients who are at a maximum risk of complications.

Male genital lichen sclerosus and hepatitis C

Funding sources: Skin Treatment and Research Trust (START) and Sir John Fisher Foundation. Conflicts of interest: none declared. Madam, Male genital lichen sclerosus (MGLSc) is an acquired cutaneous disease of uncertain aetiology. It causes acute and chronic balanoposthitis and scarring that can result in significant sexual and urinary dysfunction and has been associated with squamous carcinoma of the penis. The aetiopathogenesis of MGLSc is unknown. Prior postulated pathogenic factors in GLSc include genetic and environmental influences, exposure to the irritant effects of urine and infections such as Borrelia and human papillomavirus. A relationship with hepatitis C virus (HCV) has been suggested by case reports of extragenital and genital LSc.1–3 We have therefore screened for HCV seropositivity in a cohort of patients with MGLSc. This work was approved by the local Research Ethics Committee (REC 09/H0607/58). We studied 61 men attending the Male Genital Dermatoses Clinics at Chelsea and Westminster (CWH) and University College Hospitals (UCH), London. All had clinical and histology findings consistent with the diagnosis of GLSc. None of the patients had extragenital LSc upon complete cutaneous examination. The age range was 22–72 years. Patients had blood samples taken for HCV antibody titre and conventional liver function tests (LFTs).

Value of the conventional liver function tests in the assessment of hepatic reserve

Objective To study the risk factors of post-hepatectomy hepatic decompensation (PHD) in patients with hepatocellular carcinoma.Method We reviewed 562 patients with Child-Pugh A classification,who underwent partial hepatectomy for hepatocellular carcinoma at Zhongshan Hospital,Fudan University between July 1st 2007 to December 31st 2007,to study the risk factors of hepatic decompensation.Results Preoperative high total bilirubin (TB) and low prealbumin (PA) were independent risk factors of PHD by logistic multivariate analysis ROC analysis revealed the cut-offs of preoperative PA predicting PHD were 0.14 g/L (sensitivity 41.4％; specificity 83.1％).The incidence of PHD was 16.0％ when TB≥20.4 μmol/L and PA＜0.14 g/L(OR=7.276,P=0.002).Conclusion The Child-Pugh A patients recovered well when the preoperative liver function was as follows:TB＜20.4 μmol/L and PA≥0.14 g/L. Key words: Prealbumin; Hepatic reserve; Hepatic decompensation; Liver failure