Investigation of a hepatitis A outbreak in children in an urban slum in Vellore,Tamil Nadu, using geographic information systems

Background & objectives: An outbreak of symptomatic viral hepatitis in children less than 10 yr of age in Vellore, south India, was investigated and the disease pattern studied using serological and epidemiological methods, supplemented by geographic information systems (GIS) mapping. Methods: Three cases of hepatitis A were identified during routine surveillance in a birth cohort House-to-house visits were undertaken to identify other symptomatic cases and samples collected for anti- HAV IgM, ELISA testing. All cases and controls were mapped and geo-referenced using Arc View GIS 3.3. Spatial clustering was investigated using SaTScan 7.0.1 software. Drinking water sources were tested for coliform counts with the most probable number technique. Results: Of the 965 children surveyed, 26 (2.78%) had jaundice between February to July 2006. From the 26 patients, 11 (42.3%) blood samples were obtained and tested for anti-HAV IgM; 10 (90.9%) were found to be positive. Water analysis showed high coliform counts in all samples. No spatial clustering of cases could be detected. Interpretation & conclusions: The outbreak was identified because of the symptomatic presentation of the cases. Our study highlighted the increasing detection of symptomatic children with hepatitis A virus infection. Water sources in the area were contaminated and may have served as the source of infection. The lack of clustering in GIS analysis could be due to the common water source

Volatile organic compounds for the detection of hepatocellular carcinoma : A scoping review

Funding Information: This study is partially funded by the endowment fund NHS Grampian as part of the project (IRAS 250335).Peer reviewe

Liver Injury in Acute Fatty Liver of Pregnancy: Possible Link to Placental Mitochondrial Dysfunction and Oxidative Stress

Acute fatty liver of pregnancy (AFLP) is a rare disorder which is fatal if not recognized and treated early. Delivery of the feto-placental unit results in dramatic improvement in maternal liver function, suggesting a role for the placenta. However, the mechanisms by which defects in the fetus or placenta lead to maternal liver damage are not well understood and form the focus of this study. Placenta and serum were obtained at delivery from patients with AFLP, and placental mitochondria and peroxisomes were isolated. Placental mitochondrial function, oxidative stress, and fatty acid composition as well asserumantioxidants, oxidativeandnitrosative stress markers,andfatty acid analysis were carried out. Hepatocytes in culture were used to evaluate cell death, mitochondrial function, and lipid accumulation on exposure to fatty acids. Oxidative stress was evident in placental mitochondria and peroxisomes of patients with AFLP, accompanied by compromised mitochondrial function. Increased levels of arachidonic acid were also seen inAFLPplacenta when compared to control. Patients with AFLP also had a significant increase in oxidative and nitrosative stress markers in serum, along with decreased antioxidant levels and elevated levels of arachidonic acid. These levels of arachidonic acid were capable of inducing oxidative stress in hepatocyte mitochondria accompanied by induction of apoptosis. Exposure to arachidonic acid also resulted in increased lipid deposition in hepatocytes. Conclusion: Oxidative stress in placental mitochondria and peroxisomes is accompanied by accumulation of toxic mediators such as arachidonic acid, which may play a causative role in maternal liver damage seen in AFLP

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Liver Injury in Acute Fatty Liver of Pregnancy: Possible Link to Placental Mitochondrial Dysfunction and Oxidative Stress

Acute fatty liver of pregnancy (AFLP) is a rare disorder which is fatal if not recognized and treated early. Delivery of the feto-placental unit results in dramatic improvement in maternal liver function, suggesting a role for the placenta. However, the mechanisms by which defects in the fetus or placenta lead to maternal liver damage are not well understood and form the focus of this study. Placenta and serum were obtained at delivery from patients with AFLP, and placental mitochondria and peroxisomes were isolated. Placental mitochondrial function, oxidative stress, and fatty acid composition as well asserumantioxidants, oxidativeandnitrosative stress markers,andfatty acid analysis were carried out. Hepatocytes in culture were used to evaluate cell death, mitochondrial function, and lipid accumulation on exposure to fatty acids. Oxidative stress was evident in placental mitochondria and peroxisomes of patients with AFLP, accompanied by compromised mitochondrial function. Increased levels of arachidonic acid were also seen inAFLPplacenta when compared to control. Patients with AFLP also had a significant increase in oxidative and nitrosative stress markers in serum, along with decreased antioxidant levels and elevated levels of arachidonic acid. These levels of arachidonic acid were capable of inducing oxidative stress in hepatocyte mitochondria accompanied by induction of apoptosis. Exposure to arachidonic acid also resulted in increased lipid deposition in hepatocytes. Conclusion: Oxidative stress in placental mitochondria and peroxisomes is accompanied by accumulation of toxic mediators such as arachidonic acid, which may play a causative role in maternal liver damage seen in AFLP

Spontaneous bacterial peritonitis results in oxidative and nitrosative stress in ascitic fluid

Background and Aim: Spontaneous bacterial peritonitis (SBP) is a major complication of liver cirrhosis and accounts for significant mortality. Although oxygen free radicals and nitric oxide been implicated in the pathophysiology of liver cirrhosis, information on their role during the development of SBP is scarce. This study examined these active species in ascitic fluid from patients with SBP, and in response to treatment. Methods: Forty-nine consecutive patients with cirrhosis and ascitic fluid neutrophil counts less than 250/cumm were studied as controls. Another 21 patients whose ascitic neutrophil count exceeded 250/cumm were treated as cases. Ascitic fluid was collected from these patients at entry and 48 h after treatment with antibiotics. Nitrate and markers of oxidative stress such as malondialdehyde, protein carbonyl content and total and protein thiols were measured. Results: A significant increase in malondialdehyde and protein carbonyl levels was seen in ascites from patients with SBP when compared to controls. This was accompanied by a decrease in total thiols and protein thiols. In addition, there was a significant increase in ascitic fluid nitrate in patients with SBP when compared to control patients. After antibiotic treatment, malondialdehyde, protein carbonyl and nitrate levels dropped back towards control values, and total thiols also recovered. Conclusions: This study demonstrated the presence of oxidative stress in ascitic fluid from patients with SBP, and showed that ascitic fluid nitrate may be a marker for diagnosing SBP and a useful index in determining therapeutic response to antibiotic treatment

Hepatitis E produces severe decompensation in patients with chronic liver disease

Background and Aims: The adverse effect of acute hepatitis A in chronic liver disease is well known. The outcome of acute hepatitis E in chronic liver disease has not been extensively studied. The present study aimed to examine the clinical profile and outcome of patients with chronic liver disease and hepatitis E virus (HEV) superinfection, and the seroprevalence of hepatitis A and E infections in patients with chronic liver disease and controls in India. Methods: A retrospective study of patients with chronic liver disease and acute icteric hepatitis E was performed. Acute hepatitis E was diagnosed by immunoglobulin (Ig)M ELISA. Seroprevalence studies were carried out using IgG ELISA in 100 patients with chronic liver disease and 79 age- and sex-matched controls. Results: From June 2001 to December 2002, nine patients with chronic liver disease were found to have superinfection with HEV. Out of these, six patients died of advanced liver failure. The etiology of liver disease was Wilson's disease in six, hepatitis B virus in one, autoimmune in one and cryptogenic in one case. The seroprevalence of hepatitis A was 99 and 100% and 56 and 21% for HEV in cases and controls, respectively. Conclusions: Acute HEV in patients with chronic liver disease has a grave prognosis. Wilson's disease was the most common cause of chronic liver disease complicated by acute HEV. Seroprevalence studies showed that 44% of patients with chronic liver disease were at risk of developing hepatitis E. Hepatitis E vaccine, when available, is indicated for use in this group

Quality standards for the management of non-alcoholic fatty liver disease (NAFLD): consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group

Summary Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care. A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group produced the recommendations, which cover: management of people with, or at risk of, NAFLD before the gastroenterology or liver clinic; assessment and investigations in secondary care; and management in secondary care. The quality of evidence for each recommendation was evaluated by the Grading of Recommendation Assessment, Development and Evaluation tool. An anonymous modified Delphi voting process was conducted individually by each member of the group to assess the level of agreement with each statement. Statements were included when agreement was 80% or greater. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice. It is hoped that services will review their practice against our recommendations and key performance indicators and institute service development where needed to improve the care of patients with NAFLD