Raised Alanine Aminotransferase Levels Research Articles

Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia-Pacific.

Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Indexscore > 1.5, fibrosis-4score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV)antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p < 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00-5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person-years). Those HCV-antibodypositive (hazard ratio [HR]: 5.54, 95% CI: 3.75-8.18, p < 0.001) and had high alcohol consumption (HR: 2.06, 95%CI: 1.23-3.45, p = 0.006) were associated with liver cirrhosis. HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

PNPLA3 polymorphisms are associated with raised alanine aminotransferase levels in hepatitis C virus genotype 3

Background and study aimsHepatitis C virus (HCV) infection is one of the leading causes of end-stage liver diseases. This study aimed to determine the association between polymorphisms in interleukin 28B (IL28B), PNPLA3, toll-like receptor 7 (TLR7), nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and retinoic inducible gene-I (RIG-I) and HCV genotype and clinical presentation in an Indian population. Patients and methodsA total of 500 patients with chronic HCV were enrolled in 19 centres across India. Genomic DNA was extracted from whole blood samples, and single nucleotide polymorphisms (SNPs) for IL28B, PNPLA3, TLR7, NOD2 and RIG-I genes were genotyped by real-time PCR using a TaqManSNP genotyping assay. ResultsThe mean age of the patients was 45 + 13 years, and the most common genotype observed was HCV genotype 3 (54%), followed by genotype 1 (24%). Although the allelic frequencies of TLR7, NOD2 and RIG-I were in significant disequilibrium in HCV patients compared with those in controls, the PNPLA3 polymorphism correlated significantly with higher viral load and alanine aminotransferase (ALT) levels in genotype 3 patients. Patients with PNPLA3 CG/GG genotypes, along with IL28B genotype CC, had higher levels of ALT than those with other genotypes. ConclusionThese results indicate that PNPLA3 polymorphisms are associated with higher ALT levels in HCV genotype 3 patients in India and can help in identifying people who are at greater risk of developing HCV-associated liver diseases.

Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial

REP 2139 clears circulating hepatitis B virus (HBV) surface antigen (HBsAg), enhancing the restoration of functional control of HBV infection by immunotherapy. We assessed the safety and efficacy of REP 2139 and pegylated interferon alfa-2a in patients with chronic HBV and hepatitis D virus (HDV) co-infection. In this open-label, non-randomised, phase 2 trial, patients aged 18-55 years, who were treatment naive, hepatitis B e antigen [HBeAg] negative, anti-hepatitis D antigen [HDAg] positive, and HDV RNA positive, with serum HBsAg concentrations of more than 1000 IU/mL, and a history of HDV infection for 6 months or more before treatment, were recruited at Toma Ciorbă Hospital of Infectious Diseases in Chișinău, Moldova. Patients were excluded if they had HDV superinfection, liver infections other than HBV and HDV, or liver cirrhosis. Patients received 500 mg intravenous REP 2139 once per week for 15 weeks, followed by combined therapy with 250 mg intravenous REP 2139 and 180 μg subcutaneous pegylated interferon alfa-2a once per week for 15 weeks, then monotherapy with 180 μg pegylated interferon alfa-2a once per week for 33 weeks. The primary endpoints assessed at the end of treatment were the safety and tolerability of the treatment regimen, analysed in the intention-to-treat population. Secondary outcomes included the proportion of patients with serum HBsAg less than 50 IU/mL, the proportion of patients with suppressed HBV DNA, and the proportion of patients who maintained these responses through follow-up. The REP 301 trial is registered with ClinicalTrials.gov, number NCT02233075. We also did an additional follow-up at 1 year after the end of treatment, as an interim analysis of the REP 301-LTF trial (planned duration 3 years), registered with ClinicalTrials.gov, number NCT02876419, which is ongoing but not recruiting patients. Between Sept 8, 2014, and Jan 27, 2015, we enrolled 12 patients into the REP 301 study. All 12 patients experienced at least one adverse event during treatment: two (17%) patients experienced anaemia, eight (67%) neutropenia, and ten (83%) thrombocytopenia. Five (42%) patients had raised alanine aminotransferase levels, four (33%) had raised aspartate aminotransferase levels, and two (17%) had increased bilirubin concentrations. Four (33%) patients had a serious adverse event, and 12 (100%) patients had treatment-emergent lab abnormalities. Six patients had HBsAg levels less than 50 IU/mL by the end of treatment (all <0·05 IU/mL); five maintained this level of suppression at the end of 1 year follow-up. Six patients had hepatitis B surface antibody (anti-HBs) titres above 10 mIU/mL at the end of treatment (five had maximum anti-HBs concentrations of 7681-86 532 mIU/mL during treatment), which were maintained at the end of 1 year follow-up in these five patients. Elevated alanine and aspartate aminotransferase concentrations and profound elevations of anti-HBs titres were restricted to patients who had HBsAg levels of less than <1 IU/mL before the introduction of pegylated interferon alfa-2a. Nine patients had suppressed HBV DNA (<10 IU/mL]) at the end of treatment, which was maintained by seven patients and newly established in an eighth patient at the end of 1 year follow-up. 11 patients became HDV RNA negative during treatment, with nine remaining HDV RNA negative at the end of treatment; seven of these patients remained HDV RNA negative by the end of 1 year follow-up. By the end of 1 year follow-up, normalisation of serum aminotransferases occurred in nine of 12 patients. Combined REP 2139 and pegylated interferon alfa-2a therapy is safe, well tolerated, and establishes functional control of HBV and HDV co-infection and normalisation of serum aminotransferases in a high proportion of patients 1 year after therapy. This combination therapy approach might provide a new treatment option for patients with HBV and HDV co-infection. Replicor.

Detection of newly discovered KIs virus in India

KIs virus (KIs-V) is a putative new hepatitis virus recently identified from Japan. Prevalence of this virus was found to be significantly higher in individuals with past exposure to hepatitis E virus and having moderately raised alanine aminotransferase levels. The present work was undertaken to see the circulation of this virus in India. Blood samples (n=648) collected during hepatitis E outbreaks from different states (1990–2014) were screened by PCR. One anti- HEV IgM positive serum was found to be positive for two closely related viruses, one with 100% and other with 94.4% homology with the KIs-V sequence reported from Japan. This is the first evidence of KIs-V occurrence in India. Significance of association between KIs-V and hepatitis E virus still remains unanswered. Further studies are needed for understanding pathogenesis of KIs-V in humans.

Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial

Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC). In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions. We randomly assigned participants (1:1) to receive oral dacomitinib 45 mg/day (in 28-day cycles) or oral gefitinib 250 mg/day (in 28-day cycles) until disease progression or another discontinuation criterion was met. Randomisation, stratified by race and EGFR mutation type, was done with a computer-generated random code assigned by a central interactive web response system. The primary endpoint was progression-free survival assessed by masked independent review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01774721, and is ongoing but no longer recruiting patients. Between May 9, 2013, and March 20, 2015, 452 eligible patients were randomly assigned to receive dacomitinib (n=227) or gefitinib (n=225). Median duration of follow-up for progression-free survival was 22·1 months (95% CI 20·3-23·9). Median progression-free survival according to masked independent review was 14·7 months (95% CI 11·1-16·6) in the dacomitinib group and 9·2 months (9·1-11·0) in the gefitinib group (hazard ratio 0·59, 95% CI 0·47-0·74; p<0·0001). The most common grade 3-4 adverse events were dermatitis acneiform (31 [14%] of 227 patients given dacomitinib vs none of 224 patients given gefitinib), diarrhoea (19 [8%] vs two [1%]), and raised alanine aminotransferase levels (two [1%] vs 19 [8%]). Treatment-related serious adverse events were reported in 21 (9%) patients given dacomitinib and in ten (4%) patients given gefitinib. Two treatment-related deaths occurred in the dacomitinib group (one related to untreated diarrhoea and one to untreated cholelithases/liver disease) and one in the gefitinib group (related to sigmoid colon diverticulitis/rupture complicated by pneumonia). Dacomitinib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population. SFJ Pharmaceuticals Group and Pfizer.

Significantly raised alanine aminotransferase level following single dose of intravenous paracetamol in a healthy patient

A 12-year-old ASA I female patient underwent correction of posterior scoliosis of dorsolumbar spine under total intravenous anesthesia using a combination of remifentanil and propofol. Induced hypotension was maintained between 55 and 65 mmHg. Intraoperatively, patient received a single injection of 1.0 g paracetamol. Surgery lasted 6 h and 40 min and was essentially uneventful. A follow-up investigation in the intensive care unit 6 h after the surgery revealed alanine transaminase levels of 547 I/U. This increased to 924 I/U on the 2 nd postoperative day after the patient received 500 mg per-rectal paracetamol. Stopping administration of paracetamol restored alanine transaminase level to normal without needing N-acetylcysteine.

Non-alcoholic fatty liver disease among visitors to a hepatitis awareness programme.

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. The present study aimed to evaluate the prevalence of NAFLD among the visitors screened on World Hepatitis Day 2010 and 2011. Attendees of the hepatitis awareness programme (n = 928) were offered screening to rule out liver ailments. The participants were evaluated on history, body mass index (BMI) measurement, blood tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), alanine aminotransferase (ALT) levels and abdominal ultrasound (US). On ultrasonography, fatty liver was present in 142 of 806 subjects who were found negative for viral serology and had no history of regular alcohol intake. This accounted for 15.3% of all the visitors. Comparing them with the rest of the serology-negative alcohol-negative subjects, there were more housewives (p = 0.005) with fatty liver. They were older with mean age 43.3 +/- 12.1 years compared to 33.1 +/- 16.1 years (p = 0.000) in patients without fatty liver and had a higher BMI 28.6 +/- 6.0 kg/m2 vs. 22.2 +/- 5.3 kg/m2 (p = 0.000). Regression analysis suggested BMI as the only significant independent risk factor (p = 0.000). However, 32 subjects with fatty liver had BMI < 25 kg/m2 and 6 of them had diabetes mellitus. Thirty-one subjects (21.8%) with fatty liver had raised ALT level (p = 0.000) and possible non-alcoholic steatohepatitis (NASH) which accounts for 3.34% (31/928) of the total visitors. This analysis reveals that our general population is at risk of having NAFLD and NASH and these should be looked into even in non-obese persons.

Characteristics and outcome of dengue infection; clinical perspective from a secondary care hospital of Karachi.

Objective: To determine the frequency and characteristics of dengue fever (DF) in patients of acute febrile illness presenting at a secondary care hospital. Methodology: The observational cross sectional study was carried out from May to October 2010 in Remedial Centre Karachi and included patients above the age of 12 years who presented with acute febrile illness. The WHO classification and case definitions were used to classify the disease as Dengue Fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Clinical, hematological and biochemical findings were recorded serially until discharge. Results: During the study period, 90 (34.75%) presented with typical features of DF, 28 (31.11%) were dengue proven, seven (7.7%) proved to be of malaria in which malarial parasites were found positive in the peripheral blood, while the remaining 55 (61.11%) patients were dengue probable. Age of the patients ranged from 13 to 76 years. Fever was the most common clinical presentation (100%) followed by vomiting 50 (55.56%), body ache 31 (34.44%) abdominal pain 17 (18.89%) and headache 9 (10%). Maculopapular rash was seen in 4(4.44%) patients. Laboratory findings included thrombocytopenia, leucopenia and raised alanine aminotransferase levels. Eighty one patients (90%) improved clinically and hematologically and were discharged in stable condition. Conclusion: Fever and thrombocytopenia were the most common presentation of dengue fever (DF). The overall mortality of DF is low, if treated appropriately. Awareness of health care professionals and public regarding preventive strategies is essential to fight against this disease.

Management of Chronic Hepatitis B e Antigen-Negative Disease: Another Step Forward

Chronic hepatitis B (CHB) infection is a global health problem affecting more than 2 billion people worldwide. Among them, more than 75% reside in AsiaPacific countries. Although only a minority (15%–40%) of infected individuals go on to develop cirrhosis, liver failure, and hepatocellular carcinoma (HCC), which account for an estimated 0.5–1.2 million deaths per year, CHB is ranked as the 10th leading cause of death worldwide [ 1 ]. In Asia, most patients acquire hepatitis B virus (HBV) infection either during the perinatal period or in early childhood. In general, the natural course of chronic HBV infection consists of 4 phases, although not all patients go through all phases [ 2 ]. The initial immune-tolerant phase is characterized by the presence of hepatitis B e antigen (HBeAg), high serum HBV DNA levels, and persistently normal levels of alanine aminotransferase (ALT). Most patients in the immune tolerant phase have minimal liver injury, and prognosis is favorable during follow-up of up to 10 years. There is usually no, or only minimal, disease progression while serum ALT concentrations remain normal [ 3 , 4 ]. This is followed by an immune clearance phase when the HBeAg-positive patients have raised ALT levels. During this phase, spontaneous HBeAg seroconversion occurs at a rate of 10%–20% per year. HBeAg seroconversion is frequently, but not always, accompanied by a sudden increase in ALT levels [ 5 ]. Patients who undergo spontaneous HBeAg seroconversion before the age of 40 have a good prognosis [ 6 ]. They then enter an inactive (carrier) phase, which is characterized by the absence of HBeAg, the presence of HBe antibody (anti-HBe), persistently normal ALT levels, and low or undetectable levels of serum HBV DNA. Patients in this phase have a favorable prognosis [ 7 ]. Recently, because of aging populations and increased availability of molecular technology, more patients in Asia are being noted to enter the 4th reactivation phase. This phase, also termed HBeAg-negative CHB, is characterized by the absence of HBeAg, the presence of anti-HBe, intermittently or persistently elevated serum HBV DNA and ALT levels, and active inflammation in the liver. The annual rates of reactivation of hepatitis B are 1.5%–3.3%, and these individuals usually have more advanced liver disease than patients in the other phases of the disease. Indeed, it is estimated that subjects with HBeAg-negative hepatitis developed cirrhosis, with or without HCC, at a rate of 3%–4% per year. Currently, 7 treatments are approved for CHB e antigen–negative patients, including 2 formulations of interferon (IFN; conventional IFN and PEG-IFN) and 5 nucleoside/nucleotide analogs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil). The use of these therapeutic agents results in varying success. Viral relapse occurs in almost all patients when nucleoside/nucleotide analogs are discontinued, and a 1-year course of PEGIFN resulted in undetectable serum HBV DNA and normalization of ALT levels in fewer than one-third of patients. Learning from chronic hepatitis C virus infection,

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

BackgroundLiver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease.MethodsThis study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis.ResultsOf the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection.ConclusionsBased on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population.

Occult Hepatitis B Virus infection in ART-Naive HIV-Infected Patients seen at a Tertiary Care Centre in North India

BackgroundCo-infections of hepatitis B and C viruses are frequent with HIV due to shared routes of transmission. In most of the tertiary care health settings, HIV reactive patients are routinely tested for HBsAg and anti-HCV antibodies to rule out these co-infections. However, using the routine serological markers one can only detect active HBV infection while the occult HBV infection may be missed. There is insufficient data from India on HIV-HBV co-infection and even scarce on occult HBV infection in this group.MethodsWe estimated the burden of HBV infection in patients who were tested positive for HIV at a tertiary care centre in north India. We also attempted to determine the prevalence and clinical characteristics of occult HBV infection among these treatment-naïve patients and compare their demographic features with other HIV patients. During a period of 6 years between January 2002 to December 2007, 837 HIV positive patients (631 males and 206 females (M: F :: 3.06:1) were tested for serological markers of HBV (HBsAg) and HCV (anti-HCV antibodies) infections in our laboratory. For comparison 1000 apparently healthy, HIV-negative organ donors were also included in the study. Data on demographics, sexual behaviour, medical history, laboratory tests including the serum ALT and CD4 count of these patients were recorded. A sub-group of 53 HBsAg negative samples from HIV positive patients were assessed for anti-HBs, anti-HBc total (IgG+IgM) and HBV-DNA using a highly sensitive qualitative PCR and analysed retrospectively.ResultsOverall, 7.28% of HIV positive patients showed presence of HBsAg as compared to 1.4% in the HIV negative control group. The prevalence of HBsAg was higher (8.55%) in males than females (3.39%). The study revealed that occult HBV infection with detectable HBV-DNA was prevalent in 24.5% of patients positive for anti-HBc antibodies; being 45.5% in HBsAg negative patients. Most importantly the occult infection was seen in 20.7% patients who were positive for anti-HBs antibodies. However, in none of the seronegative patient HBV-DNA was detected. Five of the nine HBV-DNA positive (55.6%) patients showed raised alanine aminotransferase levels and 66.7% had CD4+ T cell counts below 200 cells/cumm.ConclusionsHigh prevalence of HIV-HBV co-infection was found in our patients. A sizeable number of co-infected patients remain undiagnosed, if only conventional serological markers are used. Presence of anti-HBs antibodies was not a reliable surrogate marker to rule out occult HBV infection. The most reliable method to diagnose occult HBV co-infection in HIV seropositive patients is the detection of HBV-DNA.

Assessment and proposal of a new combination of screening criteria for hepatitis C in France

The current French hepatitis C virus infection screening programme is not yet reaching all populations at risk. In order to better identify individuals that would benefit from a screening test, we investigated an expanded combination of personal characteristics as potential screening criteria for this infection. We constructed two multiple-regression models predicting hepatitis C antibody seropositivity using the population sample from the 2004 French national hepatitis C antibody seroprevalence survey (SPS) (n = 14 416): one representing current screening guidelines and another constructed from personal characteristics collected for the SPS. Performance of the two predictive models was statistically compared and we internally validated the better performing model. The expanded screening criteria model better discriminated seropositive and seronegative individuals [area under the ROC curve (AUC) 0.869 (95% CI 0.861-0.873)] than the current screening guidelines model [AUC 0.821 (95% CI 0.810-0.824)]. This performance difference was statistically significant (P < 0.00001). The expanded criteria model contains the variables age, sex, pre-1992 blood transfusion, intra-venous drug use, receipt of medical welfare for precarious individuals, previous surgeries, illicit nasal drug use, previous hepatitis C screening, tattoo, raised alanine aminotransferase level and birth in a hepatitis C high/moderate-prevalence country. Results indicate that an expanded combination of screening criteria better predicted hepatitis C antibody status and thus individuals needing screening than the current French-screening guidelines. The proposed combination of screening criteria could more effectively target hepatitis C risk-populations in France and could serve as the basis for a decision-making screening tool for the general population.

Clinical Features of Human Influenza A (H5N1) Infection in Vietnam: 2004–2006

The first cases of avian influenza A (H5N1) in humans in Vietnam were detected in early 2004, and Vietnam has reported the second highest number of cases globally. We obtained retrospective clinical data through review of medical records for laboratory confirmed cases of influenza A (H5N1) infection diagnosed in Vietnam from January 2004 through December 2006. Standard data was abstracted regarding clinical and laboratory features, treatment, and outcome. Data were obtained for 67 (72%) of 93 cases diagnosed in Vietnam over the study period. Patients presented to the hospital after a median duration of illness of 6 days with fever (75%), cough (89%), and dyspnea (81%). Diarrhea and mucosal bleeding at presentation were more common in fatal than in nonfatal cases. Common findings were bilateral pulmonary infiltrates on chest radiograph (72%), lymphopenia (73%), and increased serum transaminase levels (aspartate aminotransferase, 69%; alanine aminotransferase, 61%). Twenty-six patients died (case fatality rate, 39%; 95% confidence interval, 27%-51%) and the most reliable predictor of a fatal outcome was the presence of both neutropenia and raised alanine aminotransferase level at admission, which correctly predicted 91% of deaths and 82% of survivals. The risk of death was higher among persons aged < or =16 years, compared with older persons (P < .001), and the risk of death was higher among patients who did not receive oseltamivir treatment (P = .048). The benefit of oseltamivir treatment remained after controlling for potential confounding by 1 measure of severity (odds ratio, 0.15; 95% confidence interval, 0.026-0.893; P = .034). In cases of infection with Influenza A (H5N1), the presence of both neutropenia and raised serum transaminase levels predicts a poor outcome. Oseltamivir treatment shows benefit, but treatment with corticosteroids is associated with an increased risk of death.

Immunogenicity and protective efficacy in rhesus monkeys of a recombinant ORF2 protein from hepatitis E virus genotype 4

Several antigens derived from hepatitis E virus (HEV) genotype 1 strains have shown immunogenicity and efficacy against hepatitis E in primates and humans. However, the protective effect of a vaccine derived from HEV genotype 4 has not been studied. This study aimed to evaluate the immunogenicity and protective efficacy of the T1-ORF2 (56 kDa) capsid protein derived from HEV strain T1 (genotype 4) in rhesus monkeys. Two doses (40 microg) of alum-absorbed T1-ORF2 capsid protein were administered 4 weeks apart. Seroconversion occurred in all immunized monkeys 1-2 weeks after the first dose. The peak levels of anti-HEV IgG appeared at 2-3 weeks after the second dose and ranged from 5.7 to 196.0 U/ml. All monkeys showed an anamnestic antibody response to the second dose. Control monkeys immunized with saline remained negative for HEV antibodies throughout the pre-challenge period. The immunized monkeys were challenged intravenously with HEV genotypes 1 and 4. Monkeys immunized with T1-ORF2 were protected from infection and hepatitis after challenge with 5 x 10(4) genome equivalents of HEV, regardless of the genotype. After challenge with 5 x 10(5) genome equivalents of HEV genotype 4, the monkeys immunized with T1-ORF2 had a shorter period of raised alanine aminotransferase levels and a shorter duration of fecal shedding compared to control monkeys immunized with saline. In conclusion, these results suggest that, in rhesus monkeys, the T1-ORF2 capsid protein of HEV genotype 4 has similar cross-protective effects to other candidate vaccines derived from HEV genotype 1.

Freqüência de alterações hepáticas em pacientes com esclerodermia

INTRODUCTION: to determine the frequency of hepatic disease in patients with scleroderma and, secondarily, to investigate the frequency of hepatitis B and C virus infection and determine the frequency of autoantibodies in this disease. MATERIAL AND METHODS: patients with scleroderma followed at Hospital Santa Izabel were included in the study and patients with acne vulgaris served as a comparison group. RESULTS: considering the 65 scleroderma patients, 35% had elevated gamma-glutamyltranspeptidase (gamma-GT), 30% had elevated alkaline phosphatase and 17.1% had alanine aminotransferase (ALT) higher than the reference range. Raised ALT levels were more common in the scleroderma patients than in the control group. Nineteen percent (19%) of the patients tested positive for anti-smooth muscle antibodies and only one patient had anti-mitocondria antibodies. There was no statistical difference between the two groups regarding antibody testing. Anti-HCV antibodies were observed in one patient and HBsAg was detected in another scleroderma patient. There was no patient with clinically significant hepatic disease. CONCLUSIONS: the present study showed that clinical hepatic disease did not occur in our scleroderma patients, despite the relatively increased frequency of liver enzymes abnormalities.

Direct Thrombin Inhibition and Stroke Prevention in Elderly Patients With Atrial Fibrillation

Warfarin prevents stroke in atrial fibrillation (AF); however, concerns regarding international normalized ratio control and hemorrhage limit its use in the elderly. The oral direct thrombin inhibitors (DTIs) are potential alternatives to warfarin, offering fixed dosing without drug and dietary interactions and the need for international normalized ratio monitoring. Although ximelagatran, a DTI studied in the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation trials, has been withdrawn, development of other DTIs continues. We report our experience in elderly high-risk AF patients on ximelagatran compared with warfarin therapy. Data from patients with AF and stroke risk factors randomized in Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III and V trials to ximelagatran or warfarin were analyzed for stroke/systemic emboli, bleeding, and raised alanine aminotransferase levels in those >or=75 (n=2804) and <75 (n=4525) years. Ximelagatran was as effective as warfarin in reducing stroke/systemic emboli in the elderly (2.23%/y with ximelagatran vs 2.27%/y with warfarin) as in younger patients (1.25%/y vs 1.28%/y). Total bleeds were significantly lower with ximelagatran compared with warfarin in elderly (40% vs 45%, P=0.01) and younger (27% vs 35%, P<0.001) patients. Raised alanine aminotransferase values (>3-fold elevation) among ximelagatran patients were more common in older (7.5% old vs 5.3% young) patients, particularly women (9.5% elderly women vs 6.1% elderly men). In high-risk elderly AF patients, ximelagatran is as effective as warfarin with less bleeding, but alanine aminotransferase elevations are common, particularly in elderly women. Oral DTIs for stroke prevention show promise in elderly patients.

Asian Pacific Association for the Study of the Liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection

Asian Pacific Association for the Study of the Liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection

Antihepatitis C virus status in hepatocellular carcinoma and the influence on clinicopathological findings and operative results.

Antihepatitis C virus (HCV) status was investigated in 100 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between 1980 and 1989. The clinicopathological findings and operative results, in patients with or without HCV marker, were compared retrospectively. The positivity rate of anti-HCV was 51 per cent. In this group there was a higher mean age, fewer symptoms, raised alanine aminotransferase level, higher 15-min indocyanine green clearance rate and earlier tumour stage compared with the anti-HCV negative group. Positive tumour margins and vascular invasion were seen less frequently in the anti-HCV positive group. HCC with HCV marker showed characteristic features of chronic non-A non-B hepatitis and of HCC originating from liver cirrhosis. There was a better cumulative 1-year survival rate for anti-HCV positive patients, but 3- and 5-year survival rates after hepatectomy were similar in both groups. Although HCV-related HCC had typical features of chronic non-A non-B hepatitis and a relatively early stage of tumour, biological features and operative results were similar with or without the HCV marker.

Hepatitis E virus immunoglobulin G antibodies in different populations in Campinas, Brazil.

The seroprevalence of anti-hepatitis E virus (HEV) antibodies was investigated by enzyme immunoassay in 205 volunteer blood donors, 214 women who attended a center for anonymous testing for human immunodeficiency virus (HIV) infection, and 170 hospital employees in Campinas, a city in southeastern Brazil. The prevalence of anti-HEV antibodies ranged from 2.6% (3 of 117) in health care professionals to 17.7% (38 of 214) in women who considered themselves at risk for HIV. The prevalence of anti-HEV antibodies in health care professionals was not significantly different from that in healthy blood donors (3.0%, 5 of 165) and blood donors with raised alanine aminotransferase levels (7.5%, 3 of 40). The prevalence of anti-HEV antibodies (13.2%, 7 of 53) in cleaning service workers at a University hospital was similar to that among women at risk for HIV infection. These results suggest that HEV is circulating in southeastern Brazil and that low socioeconomic status is an important risk factor for HEV infection in this region.

Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase

BACKGROUNDIn the UK approximately 1 in 140 people are homozygous for the C282Y mutation of the HFE gene and are at risk from iron overload caused by genetic haemochromatosis (GH)....