Incidence Of Chronic Liver Disease Research Articles

A review of the clinical utility of the Enhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease.

The rising incidence of chronic liver disease continues to be an increasing health burden. The morbidity and mortality associated with chronic liver disease typically occur in patients with advanced fibrosis. Hence, early identification of those at-risk is of vital importance to ensure appropriate ongoing management. Currently, tools for appropriate risk stratification remain limited. Increasing awareness of the limitations of liver biopsy has driven research into alternative non-invasive methods of fibrosis assessment including serological markers assessing functional changes. One such biomarker, the Enhanced Liver Fibrosis test, was initially validated in a cohort of 1021 patients with mixed aetiology chronic liver disease and shown to perform well. Since this pathfinder study, it has been independently validated in cohorts of hepatitis C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. In addition to performing well as a diagnostic tool, the Enhanced Liver Fibrosis test has been shown to outperform liver biopsy in prognostic studies and is the only non-invasive marker to do so. However, questions remain regarding the use of this test, particularly regarding the possible effect age and alcohol may have on test scores. This review examines the current literature published in relation to the Enhanced Liver Fibrosis test and its clinical utility and highlights areas requiring further study.

1017 HEP C: Helping Everyone Provide a Cure

INTRODUCTION: The incidence of chronic liver disease in the United States is increasing and leading to a disproportionate number of patients for every gastroenterologist and a growing coverage gap in care. Electronic consultation (eConsult) is an asynchronous, text-based question-response between provider and consultant without consultant-patient contact that may improve access to hepatitis C virus (HCV) treatment. The purpose of this study is to assess treatment and referral patterns of HCV infections among primary care physicians and to further assess the role of eConsults in the treatment of chronic hepatitis C (CHC). METHODS: Primary care physicians (PCPs) associated with a large tertiary teaching hospital with a robust eConsult program were surveyed via an optional online questionnaire. Responses from urban, suburban, and rural resident and attending practitioners were anonymously recorded over a three month time spanning from March 1, 2019 to June 1, 2019 with regard to their current evaluation and management of patients with CHC. RESULTS: Fifty nine responses to the survey were generated. Of those surveyed, 0 providers treated HCV without referral to a specialist. The top three issues identified as barriers to treatment included “not enough information on protocol”, “not enough volume of patients to make it worth learning”, and “administrative hurdles.” 83% of those surveyed would be more open to treating HCV if they were provided administrative assistance and indicated that a centralized eConsult for HCV treatment provided adequate administrative support. 41% of physicians surveyed reported that less than half of their patients referred for treatment are ultimately linked to specialty care. Only 22% of providers felt that patient satisfaction would be negatively impacted without a subspecialty consult to manage HCV treatment. CONCLUSION: Our results indicate that PCPs do not routinely treat CHC infection though the vast majority of them would be interested in doing so given the percentage of their patients left without linkage to specialty care. This study identifies eConsults as a modality for expanding treatment of CHC by task-shifting treatment of the disease to PCPs through a uniform and stream-lined eConsult model, which would ultimately improve access to care, improve healthcare expenditures, and limit the direct burden placed on patients to see multiple providers.

An Accurate Data Preparation Approach for the Prediction of Mortality in ACLF Patients using the CANONIC Dataset.

The incidence of chronic liver disease has increased in Europe and can lead to Acute on Chronic Liver Failure (ACLF) which is associated with high levels of mortality due to multisystem organ failure. The characteristics of the ACLF patients can change very rapidly within a short period of time. Continuous assessment of their recovery status is critical for clinicians to adjust and deliver effective treatment. The aim of this paper is to validate the usefulness of a data preparation approach by combining different criteria to replace missing values, balance target-class variables, select useful patient characteristics and optimise hyperparameters of machine learning models for the prediction of ACLF associated mortality rates. A key step in the data preparation is a feature selection Mutual Information (MI) based multivariate approach to build smaller, and yet equally and in some cases more informative, subsets of patient characteristics than those frequently proposed for the prediction of mortality, from patients with ACLF in the CANONIC dataset. The usefulness of the data preparation approach proposed to predict mortality was evaluated by training the XGBoost and Logistic Regression models with the prepared data. Evaluations of the models trained using a test set provided evidence of an overall high accuracy in the prediction of the mortality rates of patients for days after their diagnosis, and in some cases even higher when reduced and more informative subsets of patient characteristics were found.

Histopathology findings of chronic liver diseases in pediatric age group

Objectives: Early and accurate diagnosis of Chronic liver diseases (CLD) in children is very important as it is associated with major cause of mortality and morbidity. Though, nowadays most advanced and ancillary diagnostic techniques are available, Liver biopsy still plays a very important role in diagnosis of chronic liver diseases in children. The present study is aimed to study the role of liver biopsy in diagnosis of various chronic liver diseases in children and to evaluate the histopathologic findings of various liver and hepatobiliary diseases in children. Materials and Methods: This was a prospective study carried out in a large teaching hospital. Total 55 children in pediatric age group (1-12yrs) who presented with chronic liver disease were subjected to liver biopsy. Relevant investigations were done. The procedure was carried out under all aseptic condition after obtaining a written informed consent of the patient’s parents. The liver biopsy procedure was done through two approaches one percutaneous and second is transjugular approach. The second approach was used in patients with deranged PT/PI, to avoid the risk of internal bleeding. The biopsy piece was collected in formalin and sent to histopathology for analysis. An expert pathologist was identified for the study of these biopsy pieces. The biopsy findings were evaluated. Results: In our study the incidence of CLD was high in 6-12 yr of age group (34.34%) with a male predominance (60%). In our study the most common presenting complaint was jaundice and abdominal distension (38.18%) followed by jaundice alone (34.54%). Liver biopsy demonstrated various histopathological abnormalities like inflammation (80%) followed by ballooning of hepatocytes (74.54%). Other findings included cholestasis /necrosis/fibrosis/glycogenation/special stains positivity/cirrhosis. The incidence of cirrhosis on liver biopsy was41.81%.We diagnosed maximum cases of Wilson’s disease 12 out of which 9 patients had cirrhos

Increased risk of chronic liver disease in patients with major depressive disorder: A population-based study

ObjectiveThis study investigated the prevalence and incidence of chronic liver disease in patients with major depressive disorder (MDD), and aimed to identify associated factors. MethodsData of 766,427 adult subjects aged ≥18 years were randomly selected from the National Health Research Institute database from the year 2005. The study first searched for subjects with at least one primary diagnosis of MDD in 2005, and then for those with a primary or secondary diagnosis of chronic liver disease were also identified. The differences in the prevalence of chronic liver disease and its associated factors between patients with MDD and the general population in 2005 were then analyzed. We also compared the incidence of chronic liver disease in patients with MDD and in the general population from 2006 to 2010. ResultsThe prevalence of chronic liver disease in patients with MDD was 2.27 times as high as that of the general population in 2005 (12.4% vs. 5.8%; odds ratio (OR) = 2.27; 95% confidence interval (CI) = 2.07–2.48). The average annual incidence of chronic liver disease in patients with MDD during 2006–2010 was also higher than that of the general population (2.6% vs. 1.7%; risk ratio (RR) = 1.52; 95% CI = 1.37–1.7). ConclusionsPatients with MDD had a significantly higher prevalence and incidence of chronic liver disease than the general population. Among patients with MDD, an older age, the male sex, diabetes, hyperlipidemia and first-generation antipsychotic use were factors associated with chronic liver disease.

Choosing Wisely Canada-Top Five List in Hepatology: Official Position Statement of the Canadian Association for the Study of the Liver (CASL) and Choosing Wisely Canada (CWC)

Introduction and aim. The prevalence and incidence of chronic liver disease is increasing resulting, in substantial direct and indirect medical costs. Overuse of investigations, treatments and procedures contribute to rising health care costs and can expose patients to unnecessary harm and delay in receiving care. The Choosing Wisely Canada (CWC) campaign has encouraged professional societies to develop statements that are directly actionable by their members in an effort to promote higher-value health care that will lead to downstream effect on how other practitioners make decisions.Material and methods. The Canadian Association for the Study of the Liver (CASL) established its Choosing Wisely top five list of recommendations using the framework put forward by CWC. CASL convened a task force that developed a list of draft recommendations and shared this with CASL membership electronically with eventual ranking of the top five recommendations by consensus at Canadian Digestives Disease Week (CDDW) 2017. Following revisions, the CASL Executive Committee endorsed the final list, which was disseminated online by CWC (July 2017).Results. The top five recommendations physicians and patients should question include: 1) Don’t order serum ammonia to diagnose or manage hepatic encephalopathy (HE). 2) Don’t routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures. 3) Don’t order HFE genotyping based on serum ferritin values alone to diagnose hereditary hemochromatosis. 4) Don’t perform computed tomography (CT) or magnetic resonance imaging (MRI) routinely to monitor benign focal liver lesions. 5) Don’t repeat hepatitis C viral load testing in an individual who has established chronic infection, outside of anti-viral treatment.Conclusion. The Choosing Wisely recommendations will foster patient-physician discussions, reduce unnecessary treatment and testing, avert adverse effects from testing and treatment along with reducing medical expenditure in hepatology.

Choosing Wisely Canada – Top Five List in Hepatology: Official Position Statement of the Canadian Association for the Study of the Liver (CASL) and Choosing Wisely Canada (CWC)

Introduction and aim: The prevalence and incidence of chronic liver disease is increasing resulting in substantial direct and indirect medical costs. Overuse of investigations, treatments and procedures contribute to rising health care costs and can expose patients to unnecessary harm and delay in receiving care. The Choosing Wisely Canada (CWC) campaign has encouraged professional societies to develop statements that are directly actionable by their members in an effort to promote higher-value health care that will lead to downstream effect on how other practitioners make decisions. Methods: The Canadian Association for the Study of the Liver (CASL) established its Choosing Wisely top five list of recommendations using the framework put forward by CWC. CASL convened a task force that developed a list of draft recommendations and shared this with CASL membership electronically with eventual ranking of the top five recommendations by consensus at Canadian Digestives Disease Week (CDDW) 2017. Following revisions, the CASL Executive Committee endorsed the final list, which was disseminated online by CWC (July 2017). Results: The top five recommendations physicians and patients should question include: (1) Don’t order serum ammonia to diagnose or manage hepatic encephalopathy (HE); (2) Don’t routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures; (3) Don’t order HFE genotyping based on serum ferritin values alone to diagnose hereditary hemochromatosis; (4) Don’t perform computed tomography (CT) or magnetic resonance imaging (MRI) routinely to monitor benign focal liver lesions; (5) Don’t repeat hepatitis C viral load testing in an individual who has established chronic infection, outside of antiviral treatment. Conclusion: The Choosing Wisely recommendations will foster patient–physician discussions, reduce unnecessary treatment and testing, adverse effects from testing and treatment, and medical expenditure in hepatology.

Association between skirt size and chronic liver disease in post-menopausal women: a prospective cohort study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS)

BackgroundWe investigated the association between self-reported skirt size (SS) and change in SS, and incidence of chronic liver disease (CLD) in a prospective cohort study of women recruited to the UKCTOCS trial.MethodsWomen recruited to UKCTOCS in England without documented CLD self-reported their current UK SS during trial participation and were asked to recall their SS when aged in 20s (via completion of a questionnaire 3–5 years after recruitment). Participants were followed up via electronic health record linkage and hazard ratios (HR) calculated for incident liver-related events (LRE).ResultsThree hundred twenty-two (0.3%) of 94,124 women experienced a first LRE. Compared to SS ≤ 16, rates of LRE were higher in the SS ≥ 18 groups (both when aged in 20s and at questionnaire completion). Event rates were higher if there was no change in SS or an increase in SS, compared to a decrease in SS.In the models adjusted for potential confounders, HRs for LRE were higher in the groups of women reporting SS ≥ 18 both when aged in 20s (HR = 1.39 (95% CI; 0.87–2.23)) and at questionnaire completion (HR = 1.37 (95% CI; 1.07–1.75)). Compared to a decrease in SS, HRs were higher in the no change (HR = 1.78 (95% CI; 0.95–3.34)) and increase (HR = 1.80 (95% CI; 1.01–3.21)) groups.ConclusionCLD is associated with high SS and an increase in SS over time. These data suggest SS can be used in simple public health messages about communicating the risk of liver disease.Trial RegistrationUKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978. Registered 06/04/2000.

Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus

Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease.

Anaesthesia in patients with liver disease.

The purpose of this review is to summarize the most recent up to date research data and recommendations regarding anaesthetic management of patients with liver disease undergoing surgery. The incidence of chronic liver disease (CLD) continues to rise and perioperative mortality and morbidity remains unacceptably high in this group. Meticulous preoperative assessment and carefully planned anaesthetic management are vital in improving outcomes in patients with liver disease undergoing surgery. The presence of cirrhosis is associated with a significantly increased risk of postoperative morbidity and mortality in patients undergoing elective surgery. The Child--Pugh--Turcotte scale and model for end-stage liver disease (MELD) score remain the most commonly applied scoring systems in preoperative risk assessment, but new MELD-based indices and novel scoring systems might offer better prognostic value. Propofol and new inhalational agents (sevoflurane, desflurane) are recommended hypnotic agents. The titration of opiates in the perioperative period is recommended because of their altered metabolism in patients with liver disease. Perioperative management should include close haemodynamic monitoring and admission to a critical care area should be considered. Patients with liver disease undergoing anaesthesia pose significant challenges and advanced planning and preparation are required in order to improve perioperative outcomes in this group. VIDEO ABSTRACT: http://links.lww.com/COAN/A43.

Phase Ib trial of tepotinib in Asian patients with advanced hepatocellular carcinoma (HCC): Final data including long-term outcomes.

4087 Background: The incidence of hepatocellular carcinoma (HCC), a leading cause of cancer death, is increasing with the increasing incidence of chronic liver disease. Sorafenib, the only approved systemic therapy for advanced HCC, provides modest improvement in overall survival. Preclinical studies suggest c-Met is a valid target in HCC, but non-selective TKIs with c-Met inhibitory activity have not shown efficacy in trials, possibly due to lack of c-Met inhibition. Tepotinib (MSC2156119J) is a highly selective c-Met inhibitor that has favorable safety and promising activity, particularly against c-Met+ solid tumors. We report the final results of a phase Ib trial of tepotinib in patients (pts) with advanced HCC. Methods: Pts were Asian adults with confirmed HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG PS 0–2. Pts received tepotinib 300, 500 (the RP2D) or 1,000 mg/day on a 21-day cycle. c-Met expression status was retrospectively determined by IHC. Results: 27 pts were enrolled (median age 57 [38-69]; male 23; ECOG PS 0/1 11/16); 7 received tepotinib 300 mg/day, 14 500 mg/day, and 6 1,000 mg/day (3 with dose reduction). No DLTs were observed. 22 pts experienced treatment-related treatment-emergent adverse events (TRTEAEs), most commonly diarrhea (n = 10), nausea (8), elevated AST (7), and elevated ALT (6). 9 pts had grade ≥3 TRTEAEs, including elevated AST (3) and elevated ALT (3). Best overall response (BOR) was partial response (PR) in 2 pts, one of whom received tepotinib 500 mg (response duration 16.1 months) and one 1,000 mg (4.4 months); both had c-Met+ tumors. A further 8 pts had a BOR of stable disease (SD), 1 pt non-complete response (CR)/non-progressive disease (PD), and 14 pts had PD (2 pts not evaluable). Five pts had progression free survival > 8 months. PK were as expected from previous studies. Conclusions: Tepotinib at doses of up to 1,000 mg/day was well tolerated by Asian pts with advanced HCC and a maximum tolerated dose was not reached. Antitumor activity was observed, particularly in pts with c-Met+ tumors. The ongoing phase II part of this study is comparing the efficacy and safety of first-line tepotinib and sorafenib in pts with c-Met+ HCC. Clinical trial information: NCT01988493.

Multiple Beneficial effects Associated with Coffee Consumption on Human Liver

Coffee is widely consumed beverage in the world. Incidence of chronic liver disease decreases with intake of coffee.The main objective of this study is to elucidate the hepatoprotective as well as chemo protective effect of coffee consumption in relation to previous published data. Prospective cohort studies based on relationship between coffee intake and ultimate effects on liver cancer have drawn various conclusions. Coffee’s beneficial effects in various disease states have been demonstrated in variety of studies. Studies have provided data regarding effects of coffee in hot as well as in cold state. Level of blood cholesterol, following filtration, is affected by the coffee components. Among the components of coffee, caffeine played the significant role in reducing the level of ALT in coffee consumers as compared with non-coffee consumers. Coffee intake is associated with cardiovascular events and hypertension risks. However, intake of coffee has been found to be inversely related to the level of serum enzymes like gamma-glutamyltransferase, and alanine aminotransferase when studies relating to coffee effect on liver were performed in different countries. Moreover, the data based on epidemiological analysis, clearly suggested that liver cirrhosis had inverse relationship with coffee consumption; however, the results obtained were not sufficient to demonstrate that coffee may have hepatoprotective effect in liver injury. There is emerging evidence revealing that consumption of coffee has been associated with reduction of risks of various types of cancers. The emerging data on coffee consumption has revealed that it has beneficial effects in colorectal, pancreatic, and pharyngeal as well as in liver cancer. A systematic review was performed regarding association of coffee consumption and effect of coffee intake on liver diseases like hepatocellular carcinoma (HCC), viral hepatitis, cirrhosis and nonalcoholic fatty liver disease (NAFLD). Coffee consumption, in dose dependent manner, was found to improve the level of serum gamma-glutamyltransferase, alanine aminotransferase and aspartate aminotransferase in individuals which were found to be at risk of liver diseases. Anticancer effect of coffee on liver is achieved by induction as well as inhibition of specific enzymes. The patients with history of chronic liver disease who consume coffee, were reported to be at a reduced risk of liver to be cirrhotic, and a decreased mortality rate was observed in cirrhosis patients, as well as a decreased rate of development of Hepatocellular carcinoma was observed. In individuals with history of chronic hepatitis C, coffee intake was found to be associated with enhanced virologic reaction to antiviral drug therapy. Furthermore, coffee intake was reported to be inversely associated with the severeness of steatohepatitis in individuals with non-alcoholic fatty liver disorder. Therefore, in patients with chronic liver disease, coffee consumption on daily basis should be persuaded.

Development and cost–benefit analysis of a nurse-led paracentesis and infusion service

The rising incidence of chronic liver disease has resulted in many patients needing recurrent paracentesis for abdominal ascites, which requires hospital admission. A novel nurse-led and delivered day-case paracentesis and intravenous infusion service was developed, and a cost-benefit analysis was undertaken to examine the impact of this service. Data for patients admitted for ascitic paracentesis and intravenous infusions between April and January 2016 were collected, and procedure-related costs and income were calculated. Savings delivered by the service were calculated by determining the cost of bed-days saved by the day-case service. A qualitative analysis of the efficacy of the service was conducted by a patient feedback survey. Over the 10-month period, 559 patients were treated by the day-case service—144 ascitic paracenteses (26%), 87 iron infusions (16%), 307 infliximab infusions (55%) and 21 magnesium infusions (3%). Net income over 10-months was £256 876, with an expenditure of £128 570, yielding a profit of £128 306. Cost-modelling exercises indicated that this would yield an additional cost saving of £153 216 due to inpatient bed-days saved, yielding a total financial benefit of £281 522 (over 10-months). A day-case, nurse-led gastroenterology service provides an innovative, profitable and cost-efficient model of service delivery.

Increased risk of chronic liver disease in patients with bipolar disorder: A population-based study.

This study aimed to investigate the prevalence and incidence of chronic liver disease in patients with bipolar disorder. We used a random sample of 766,427 subjects aged ≥18 years from the National Health Research Institute database in the year 2005. Subjects with at least one primary diagnosis of bipolar disorder in 2005 were identified. Patients with a primary or secondary diagnosis of chronic liver disease were also defined. We compared the prevalence and associated factors of chronic liver disease between patients with bipolar disorder and the general population in 2005. We also compared the incidence of chronic liver disease in patients with bipolar disorder and the general population from 2006 to 2010. The prevalence of chronic liver disease in patients with bipolar disorder (13.9%) was 2.68 times higher than that of the general population (5.8%) in 2005. The average annual incidence of chronic liver disease in patients with bipolar disorder from 2006 to 2010 was also higher than that of the general population (2.95% vs. 1.73%; risk ratio: 1.71; 95% confidence interval: 1.46-2.01). Patients with bipolar disorder had a significantly higher prevalence and incidence of chronic liver disease than those in the general population, and younger patients with bipolar disorder have a much higher prevalence and incidence than those in the general population. Male sex, second-generation antipsychotic or antidepressant use, and hyperlipidemia were associated factors for chronic liver disease in patients with bipolar disorder.

ER stress induces NLRP3 inflammasome activation and hepatocyte death.

The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1α and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1β secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1β secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases.

Assessment of renal functions in patients of chronic liver disease

Aims and objectives: Renal involvement in patients of chronic liver disease (CLD) is one of the dreaded complications associated with a steep rise in mortality and morbidity. Derangements in various homeostatic mechanisms in CLD leading to direct renal injury or circulatory compromise have been associated with renal impairment. Method: Consecutive cirrhotic patients (n = 100) were included in the study. Structural and functional renal failure was identified and patients were classified into various renal syndromes pre renal, intra-renal and hepatorenal syndrome (HRS). Results: At the time of presentation, 37 patients had renal dysfunction. Thirty patients had pre-renal type of renal failure, six patients had intrinsic renal disease and one patient had structural renal disease. Patients with pre-renal type were further classified into volume responsive pre-renal failure and volume non responsive HRS. Five patients had features suggestive of HRS. Patients with decompensation such as portal hypertension (PHTN), jaundice, upper gastro-intestinal bleed and hepatic encephalopathy had significantly higher incidence of renal derangements as compared to their counterparts. Infection in the form of SBP and/or sepsis predisposed patients to develop renal dysfunction. Conclusion: Renal impairment in patients with advanced liver disease is not an uncommon phenomenon and is more commonly associated with a more advanced disease. Presence of PHTN and various signs of decompensation increase the chances of renal derangements in these patients. In view of rising incidence of CLD and higher survival (due to better treatment options available), one should be vigilant for the renal derangements in these patients.

Sa1681 Mitochondria-Targeting Antioxidant Attenuates Cholestasis-Induced Liver Fibrosis in Mice

BACKGROUND: Hepatic fibrosis is seen in patients with chronic liver injury. It occurs when damaged regions of the liver undergo unregulated production and degradation of the extracellular matrix. Hepatic fibrosis pathology is frequently reported in 5 stages (0,1,2,3,4): stage 0 representing no fibrosis and stage 4 representing advanced bridging fibrosis with cirrhosis. The gold standard for establishing the stage of fibrosis has been a liver biopsy. It is a preconceived notion that transaminase markers remain normal across the stages of fibrosis, however there has been limited published data to support this claim. We set out to prove: (a) serum markers remain normal amongst stages of hepatic fibrosis and (b) lack of correlation between lab values and progressive stages of fibrosis. METHODS: A retrospective observational study was conducted evaluating liver biopsies from 2010 to 2014. Serum markers (AST, ALT, INR, BUN) were extracted within 90 days before and after liver biopsy. Acute decompensated liver failure patients were also excluded. Mean and 95% confidence intervals (95%CI) were used to describe the distributions of serum markers in different fibrosis stages. A logistic regression model was used to estimate the relative risk of elevated serum markers (over normal value) in the fibrosis stages 1-4 compared to in the stage 0. P-values and 95 percent confidence intervals were calculated using the logistic regression model. All analyses were done in SAS 9.4 (SAS Institute Inc., Cary, NC, USA). P<0.05 was considered as statistically significant. RESULTS: A total of 771 liver biopsies were screened, after exclusion criteria were applied, roughly 600 samples were analyzed. AST 95% confidence interval for fibrosis stage 0 overlapped with all stages of fibrosis including stage 4. ALT 95% confidence interval of fibrosis stage 0, 1, and 4 overlapped. BUN 95% confidence interval for fibrosis stage 0 overlapped with all stages of fibrosis including stage 4. INR 95% confidence interval for fibrosis stage 0 overlapped with all stages of fibrosis, except stage 4. Conclusion: Lab values (AST, ALT) are poor predictors of chronic liver disease. Specifically, these lab values may remain statistically the same throughout the spectrum of chronic liver disease ranging from (stage 0) to cirrhosis (stage 4). One statistically significant value was represented by INR in stage 4 fibrosis, consistent with diminished synthetic function amongst these patients. With the rapidly rising incidence of chronic liver disease largely in part due to NAFLD, it is imperative for clinicians to keep in mind: normal serum markers don't convey a disease free liver.

Interim 18F-FDG PET in Diffuse Large B-Cell Lymphoma: Emerging Worldwide?

655 Objectives As the incidence of chronic liver disease increases worldwide, the accompanying pathological process of liver fibrosis is attracting more research attention. A noninvasive approach for liver fibrosis stage measurement is urgently needed to facilitate early diagnosis as an alternative to the widely used invasive method of liver biopsy. Methods An integrin αvβ3-targeting radiotracer, 99mTc-3PRGD2, was prepared and longitudinal single-photon emission computed tomography (SPECT)/CT imaging was performed to monitor the progression and recovery of liver fibrosis induced in a rat model via thioacetamide (TAA) administration. Results Accumulation of 99mTc-3PRGD2 in the liver was increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control (saline) group as early as week 4 (liver/background ratio: 32.30 ± 3.39 vs. 19.01 ± 3.31; P Conclusions 99mTc-3PRGD2 SPECT was successfully used to monitor the progression and recovery of liver fibrosis in the rat model, and it would be a feasible alternative to the more invasive approach of liver biopsy commonly used for diagnosis and prognosis of liver fibrosis in patients.

Etiological study of acute on chronic liver failure among patients admitted in medicine ward in Chittagong Medical College Hospital

Introduction: Acute on chronic liver failure (ACLF) is defined as acute hepatic insult manifesting as jaundice and coagulopathy complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease. It has various etiology and manifestations, as well as high mortality. These etiologies vary depending on geographical region - from east to west. For example, infectious etiologies predominate in the east whereas alcohol and drugs constitute the majority of acute insults in west. In Asian region, reactivation of hepatitis B virus and superinfection with hepatitis E virus are more common among the infectious etiologies. Objective: As the incidence of chronic liver disease is increasing day by day and the etiology of acute decompensation of underlying chronic liver disease varies depending on geographical location, so it may be different in Bangladesh from other Asian countries. A very few studies have been published so far showing etiological prevalence of Acute on Chronic Liver Failure (ACLF) in Bangladesh. This study has been conducted to address the etiology of ACLF in our perspective. Methods: A cross sectional longitudinal study carried out in the department of Medicine, Chittagong Medical College Hospital. Thirty patients admitted with ACLF as defined by Asia Pacific Association for Study of Liver Disease (APASL) were consecutively included. Detailed history, complete physical examination and laboratory investigations were done for each patient. 77 JAFMC Bangladesh. Vol 9, No 2 (December) 2013 Results: From January 2009 to December 2009, among thirty patients 6 cases (20%) of ACLF was caused by HEV super infection followed by Sepsis (16.67%), variceal bleeding (13.33%) and hepatotoxic drugs (3.33%) respectively. Multiple factors were found in (16.67%) cases while no cause could be identified in (30%) cases. In our study common causes of chronic liver diseases were hepatitis B (50%), hepatitis C (26.67%) and alcohol (16.67%). Among thirty patients five died within forty eight hours of hospital admission. In hospital mortality was 16.67%. Conclusion: Acute on Chronic Liver Failure (ACLF) is one of the commonest causes of mortality, morbidity and socio-economic burden particularly in Bangladesh. Early detection and proper management of acute events that lead to ACLF would alleviate mortality and morbidity. However due to high treatment cost, proper management of chronic liver diseases as well as ACLF cannot be afforded by most people in our country. DOI: http://dx.doi.org/10.3329/jafmc.v9i2.21837 Journal of Armed Forces Medical College Bangladesh Vol.9(2) 2013

Chronic Liver Diseases in Children: Clinical Profile and Histology.

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage liver disease and fulminant hepatic failure and the only way to prevent and treat these patients is by liver transplantation.