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Reliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4., (© 2021. The Author(s).)

Background: Interleukin (IL)-35 is a newly indentified cytokine and induces immunotolerance via suppression of CD8 + T cell activity in chronic viral hepatitis., Aims: To investigate the modulatory function of IL-35 to CD8 + T cells in viral hepatitis-induced acute-on-chronic liver failure (ACLF)., Methods: Fifty-five ACLF patients and 21 healthy controls were enrolled. Serum IL-35 concentration was measured by ELISA. Absolute accounts for T cells, immune checkpoint molecules, and cytotoxic molecules in CD8 + T cells were measured by flow cytometry and real-time PCR, respectively. Direct and indirect contact co-culture systems between CD8 + T cells and HepG2 cells were set up. The regulatory function of IL-35 to CD8 + T cells was assessed by measuring lactate dehydrogenase expression and cytokine production., Results: Serum IL-35 concentration was elevated in ACLF patients and positively correlated with total bilirubin, but negatively correlated with prothrombin time activity. Peripheral CD8 + T cells showed exhausted phenotype in ACLF patients, which manifested as up-regulation of programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and lymphocyte activation gene-3 (LAG-3) but down-regulation of perforin, granzyme B, and FasL. Recombinant IL-35 stimulation dampened cytotoxicity and interferon-γ production in both direct and indirect contact co-culture systems. This process was accompanied by elevation of PD-1, CTLA-4, and LAG3, as well as reduction of perforin, granzyme B, and FasL in CD8 + T cells., Conclusion: Elevated IL-35 suppressed both cytolytic and non-cytolytic activity of CD8 + T cells in ACLF patients.

Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Hepatitis E Virus (HEV) are highly endemic in several African countries including Nigeria with adverse effects on pregnancy outcomes resulting in fatality. This study aimed to determine the viral hepatitis in pregnant women attending antenatal clinic, AMTHI. Informed consent questionnaire was administered before blood collection via venipuncture. a total of 904 pregnant women plasma samples were tested for HBV, HCV, and HEV using ELISA kit. Data was analyzed using packages within SPSS software and P ≤ 0.05 was considered significant. Out of 904 samples analyzed, the overall prevalence of hepatitis infections among pregnant women attending antenatal clinic in AMTHI was 66(7.3%). High prevalence of the hepatitis infections was found among young women within the age group 21-30 which might be associated with active sex, intravenous drug use, sharing of sharp objects and alcoholism. Blood group O Positive had the highest prevalence of hepatitis. There was statistical significance between blood group and HBsAg infection ( P < .05). Genotype AA women had highest prevalence of hepatitis. This study showed significant association between HBsAg, HCV, and HEV positive status with blood group O positive and Genotype AA pregnant women.

Liver fibrosis is one of the risk factors for hepatocellular carcinoma (HCC) development. The staging of liver fibrosis can be evaluated only via a liver biopsy, which is an invasive procedure. Noninvasive methods for the diagnosis of liver fibrosis can be divided into morphological tests such as elastography and serum biochemical tests. Transient elastography is reported to have excellent performance in the diagnosis of liver fibrosis and has been accepted as a useful tool for the prediction of HCC development and other clinical outcomes. Two-dimensional shear wave elastography is a new technique and provides a real-time stiffness image. Serum fibrosis markers have been studied based on the mechanism of fibrogenesis and fibrolysis. In the healthy liver, homeostasis of the extracellular matrix is maintained directly by enzymes called matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). MMPs and TIMPs could be useful serum biomarkers for liver fibrosis and promising candidates for the treatment of liver fibrosis. Further studies are required to establish liver fibrosis-specific markers based on further clinical and molecular research. In this review, we summarize noninvasive fibrosis tests and molecular mechanism of liver fibrosis in current daily clinical practice.

Background: The capacity to integrate platforms across vendors and disciplines has become an essential feature in the design of total laboratory automation (TLA) due space and test menu constraints. However, data on its performance are lacking. We aim to evaluate an integrated third-party immunoassay platform to the TLA system for the performance of hepatitis testing using turnaround time (TAT)., Methods: We use the Beckman Power Express (PE) system with linked 2 Beckman AU5800, 2 Beckman DxI 800, 2 Abbott Architect i2000, and other accessory components. The PE system is managed and interfaced to the laboratory information system (LIS) through Beckman Remisol (middleware) and Cennexus (track software). The hepatitis tests are performed on the Abbott Architect i2000 using Abbott Instrument Manager (middleware) for test results and this is interfaced with LIS and Cennexus. Using Viewics and Microsoft Excel, the test volumes and TAT of hepatitis results were analyzed before (February 2017 to January 2018) and after (February 2018 to January 2019) integration., Results: The TAT for each hepatitis test has decreased significantly, ranging from 13 to 81-minute reductions (P value <0.0001 for all tests) after instrument integration. The standard deviations of the TAT also decreased for each test. In addition, savings in labor expenditure of around 2 hours per day were observed. There were no laboratory space savings identified. Instead, 47.6 square foot more of space was utilized by the track connection lines., Conclusions: Our findings show significant improvement of TAT of hepatitis testing with the integration of the third-party Abbott Architect i2000 to Beckman PE system. In addition, the synchronization of multiple middleware for specimen management and result reporting allow the laboratory to achieve new efficiencies handling reflex tests and managing human resources., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown., Methods: This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n = 79) and severe group(n = 26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined., Results: 56.2% (59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% (96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P <  0.05). The percentage of the patients with elevated both ALT and AST was 12.7% (10/79) in mild cases vs. 46.2% (12/26) in severe cases (P = 0.001). 34.6% (9/26) severe group patients started to have abnormal ALT after admission, and 73.3% (77/105) of all patients had normal ALT before discharge., Conclusions: Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN, but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.

During the progression from hepatitis to fibrosis, cirrhosis, and liver failure, the accumulation of stressed/damaged hepatocyte elements associated with liver inflammation is critical. The causes of hepatocyte injuries include viral hepatitis infections, alcoholic hepatitis, and non-alcoholic fatty liver disease. Hepatocyte-derived extracellular vesicles (Hep-EVs) released from stressed/damaged hepatocytes are partly responsible for liver disease progression and liver damage because they activate non-parenchymal cells and infiltrate inflammatory cells within the liver, which are in turn are an important source of EVs. This cell-to-cell signaling is prevalent during inflammation in many liver diseases. Accordingly, special emphasis should be placed on liquid biopsy methods for the long-term monitoring of chronic liver diseases. In the present review, we have highlighted various aspects of current liquid biopsy research into chronic liver diseases. We have also reviewed recent progress on liquid biopsies that focus on cell-free DNA (cfDNA), long non-coding RNA (lncRNA), and the proteins in EVs as potential diagnostic tools and novel therapeutic targets in patients with viral hepatitis, fatty liver steatosis, and alcoholic liver diseases.

The review presents the data accumulated for more than 20 years of research of torque teno virus (TTV). Its molecular genetic structure, immunobiology, epidemiology, diagnostic methods, possible replication sites, and pathogenicity factors are described. TTV is a virus that is frequently detectable in patients with different viral hepatitides, in cases of hepatitis without an obvious viral agent, as well as in a healthy population. There is evidence suggesting that biochemical and histological changes occur in liver tissue and bile duct epithelium in TTV monoinfection. There are sufficient histological signs of liver damage, which confirm that the virus can undergo a replicative cycle in hepatocytes. Along with this, cytological hybridization in TTV-infected cells has shown no substantial cytopathic (cell-damaging) effects that are characteristic of pathogenic hepatotropic viruses. Studying TTV has led to the evolution of views on its role in the development of human pathology. The first ideas about the hepatotropism of the virus were gradually reformed as new data became available on the prevalence of the virus and its co-infection with other viruses, including the viruses of the known types of hepatitides. The high prevalence of TTV in the human population indicates its persistence in the body as a virome and a non-pathogenic virus. It has recently been proposed that the level of TTV DNA in the blood of patients undergoing organ transplantation should be used as an endogenous marker of the body's immune status. The available data show the polytropism of the virus and deny the fact that TTV can be assigned exclusively to hepatitis viruses. Fortunately, the rare detection of the damaging effect of TTV on hepatic and bile duct epithelial cells may be indirect evidence of its conditionally pathogenic properties. The ubiquity of the virus and the variability of its existence in humans cannot put an end to its study., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and O bjectives : Cirrhotic cardiomyopathy is a chronic cardiac dysfunction associated with liver cirrhosis, in patients without previous heart disease, irrespective of the etiology of cirrhosis. Electrocardiography (ECG) is an important way to evaluate patients with cirrhosis and may reveal significant changes associated with liver disease. Our study aimed to evaluate ECG changes in patients with diagnosed liver cirrhosis and compare them to patients with chronic hepatitis. Materials and Methods : We evaluated laboratory findings and ECG tracings in 63 patients with cirrhosis and 54 patients with chronic hepatitis of viral etiology. The end points of the study were prolonged QT interval, QRS hypovoltage and T-peak-to-T-end decrease. We confirmed the diagnosis of cirrhotic cardiomyopathy using echocardiography data. Results : Advanced liver disease was associated with prolonged QT intervals. Also, QRS amplitude was lower in patients with decompensated cirrhosis than in patients with compensated liver disease. We found an accentuated deceleration of the T wave in patients with cirrhosis. These findings correlated to serum levels of albumin, cholesterol and ammonia. Conclusions : ECG changes in liver cirrhosis are frequently encountered and are important noninvasive markers for the presence of cirrhotic cardiomyopathy., Competing Interests: The authors declare no conflict of interest.

There is an increasing concern about the co-infection of visceral leishmaniosis (VL) with human immunodeficiency virus (HIV) and/or viral hepatitis B/C. The aim of this study was to determine the prevalence of HIV and viral hepatitis co-infections among VL patients in a hyperendemic area in Eastern Sudan and to assess antibody levels in co-infected patients. This is a retrospective study where the sera of confirmed VL cases and non-VL individuals were analysed. The sera were screened for co-infections using immunochromatographic tests and ELISA for anti-HIV 1+2 antibodies, hepatitis B surface antigen (HBsAg), and anti-hepatitis C virus (HCV). Anti-Leishmania donovani antibodies in the sera of VL alone were assessed and compared to the sera of co-infected patients. Of the 100 screened VL sera, 6 (6%), 0 (0%), and 1 (1%) were positive for HBsAg, anti-HCV, and anti-HIV, respectively. These values were 5 (5%), 0 (0%), and 1 (1%) in the control group. Of note, the HCV screening test (Biorex, UK) showed positive reactivity in 32 (32%) and 17 (17%) sera of VL and control groups, respectively. All reactive sera tested negative in HCV ELISA. Of the 93 VL sera, 75 (80.6%) had strong DAT titers (1:˃102400), 2 (2.1%) demonstrated the lowest DAT titers (1:≤800), and 5 (5.4%) had marginal DAT titers (1:1600). Interestingly, the VL/HIV co-infected serum had a negative antibody titer (1:1600). Of the 6 VL/HBV co-infected sera, 1 (16.7%) and 5 (83.3%) demonstrated moderate (1:12800–1:51600) and strong (1:≥102400) DAT titers, respectively. The strong DAT titers observed in the VL/HBV co-infected sera were comparable to the DAT titers of the VL sera. The VL co-infection with HIV and hepatitis B/C is low in endemic areas in Eastern Sudan but may create a diagnostic difficulty. VL/HIV co-infected patients can have low Leishmania antibodies, thus alternative methodologies (e.g., antigen tests) may help the diagnosis.

Background: A serum alanine aminotransferase (ALT) test is currently demanded for blood donation in China. One of the major reasons to include such a test is possible etiology of known or unknown hepatotropic viruses. However, this hypothesis has never been examined convincingly., Study Design and Methods: The study recruited 90 Chinese blood donors that were divided into three groups based on their ALT values. Serum virome from these donors was explored using a metagenomics approach with enhanced sensitivity resolved at single sequencing reads., Results: Anellovirus and pegivirus C (GBV-C) were detected among these donors. None of them were found solely in donors with abnormal liver enzyme. Anellovirus was highly prevalent (93.3%) and the co-infection with multiple genera (alpha, beta, and gammatorquevirus) were more common in the donors with normal ALT values in comparison to those with elevated ALT (single/double/triple Anellovirus genera, 1/3/24 vs. 7/7/14 or 6/7/13, p = 0.009). For unmapped reads that accounted for 15 ± 14.9% of the data, similarity-based (BLASTN, BLASTP, and HMMER3) and similarity-independent (k-mer frequency) analysis identified several circular rep encoding ssDNA (CRESS-DNA) genomes. Direct PCR testing indicated these genomes were likely reagent contaminants., Conclusion: Viral etiology is not responsible for elevated ALT levels in Chinese blood donors. The ALT test, if not abandoned, should be adjusted for its cutoff in response to donor shortage in China., (© 2019 AABB.)

Infections due to hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV) and hepatitis E (HEV) viruses are the major causes of hepatitis and are associated with significant morbidity and mortality in developing countries like Bangladesh. The aim of this study was to assess the distribution pattern of serological markers in patients of acute viral hepatitis. This was a hospital based observational cross sectional study among purposively selected 107 patients admitted with acute viral hepatitis in the Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from April 2017 to September 2017. Data were collected by face-to-face interview of the patients, clinical assessment and investigations of biochemical and serological parameters using a structured questionnaire. Descriptive analysis was done using the analytic software SPSS version 21.0. The mean age of the patients was 33.35±12.97 years. Majority was male (68.2%), Muslim (87.9%), married (72.9%) and came from urban area (63.6%) with different level of educational qualifications. The prevalence of viral hepatitis is higher in male (68.22%) than female (31.78%). The common clinical presentations were dark coloured urine (100.0%), yellow colouration of the sclera (100.0%), anorexia (90.6%), nausea/vomiting (79.4%) and abdominal pain (68.2%). Of the 107 patients, 51.40% (n=55) had acute viral E hepatitis, 36.40% (n=39) had acute viral B hepatitis, 12.15% (n=13) had acute viral A hepatitis. Mixed infection with both hepatitis E and A viruses was 1.87% (n=2). HEV and HBV are common in relatively older age while HAV is common in relatively younger age to cause acute viral hepatitis. The study revealed a high prevalence of HEV followed by HBV and HAV in the Bangladeshi population suspected of having suffered from acute viral hepatitis.

Introduction: Hepatitis G virus (HGV) infection appears to be common in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to investigate the prevalence of HCV/HGV in patients with chronic hepatitis C (CHC) in Pakistan and to look for possible associations with various clinical and histopathological changes in HCV/HGV coinfection and HCV infection., Patients and Methods: The present study included 136 patients. Clinical, biochemical, virological and histological findings were compared between patients coinfected with HCV/HGV and patients with HCV alone., Results: Of the 136 patients with CHC, 16 (11.76%) were coinfected with HCV/HGV. The mean age of coinfected patients was lower than in patients with HCV alone. HCV/HGV coinfected patients did not show significant differences in sex, clinical presentation, biochemical markers, and liver fibrosis as compared to those with HCV infection. Only the mean values of platelets count, mean corpuscular hemoglobin (MCH), and MCH concentration markers were significantly different in HCV/HGV coinfected patients as compare to patients with HCV alone., Conclusion: It was found that 11.76% of patients with CHC in Pakistan were associated with HCV/HGV coinfection. No significant differences were observed in clinical and histological features except for platelets count, MCH, and MCH concentration markers between HCV and HGV coinfected patients in comparison with HCV-infected patients.

Cytochrome p4502E1 (CYP2E1) autoantibodies are biomarkers for drug-induced hepatitis and chronic hepatitis C. However, major histocompatibility-restricted CYP2E1 epitopes associated with these diseases have not been identified. We hypothesized that CYP2E1 epitopes associated with different types of hepatitis may be shared and may impact immune responses and metabolism. SYFPEITHI epitope prediction identified CYP2E1 candidate epitopes that would be recognized by MHC II haplotypes. Candidate epitopes were tested for induction of hepatitis and CYP2E1 autoantibodies in mice and recognition by sera from patients with anesthetic drug-induced and viral hepatitis. Human liver cells treated with epitope hybridoma serum were analyzed for mitochondrial stress. CYP2E1 activity was measured in human microsomes similarly treated. Epitope antibodies in viral hepatitis sera were analyzed using linear regression to uncover associations with liver pathology. A P value of <0.05 was considered significant. One epitope (Gly 113 -Leu 135 ) induced hepatitis and CYP2E1 autoantibodies in mice after modification of Lys 123 ( P <  0.05). Gly 113 -Leu 135 antiserum recognized mitochondria and endoplasmic reticula ( P <  0.05), upregulated HSP27 ( P  < 0.01) and mitochondrial oxidative stress via complex 1 inhibition ( P  < 0.001), and inhibited CYP2E1 activity. Gly 113 -Leu 135 IgG4 detected in viral hepatitis sera was associated with severe hepatic fibrosis ( P  = 0.0142). We found a novel CYP2E1 epitope that was detected in anesthetic and viral hepatitis and that triggered hepatitis in mice. Our findings may improve understanding of hepatic immune responses triggered by metabolism or viruses. IMPORTANCE Drug-induced hepatitis is the leading reason that an approved drug is removed from the commercial market. Halogenated anesthetics can induce hepatitis in susceptible persons, and cytochrome p4502E1 (CYP2E1) enzymes responsible for their metabolism induce antibodies in addition to hepatitis. CYP2E1 antibodies detected in anesthetic hepatitis patients have been detected in patients with viral hepatitis, suggesting that these different forms of hepatitis could develop immune reactions to a common segment or epitope of CYP2E1. We have found a common MHC-restricted CYP2E1 epitope in anesthetic and viral hepatitis that is a dominant epitope in anesthetic hepatitis and is significantly associated with fibrosis in patients with viral hepatitis. Along with conformational epitopes, our identification of MHC-restricted CYP2E1 epitopes can be used to develop specific diagnostic tests for drug-induced or viral hepatitis or associated fibrosis or to predict individuals at risk for developing these diseases or their sequelae., (Copyright © 2018 McCarthy et al.)

Background/aims: Fibroblast growth factor (FGF) 21 is associated with hepatic inflammation and fibrosis. However, little is known regarding the effects of inflammation and fibrosis on the β-Klotho and FGF21 pathway in the liver., Methods: Enrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and β-Klotho levels were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Furthermore, we explored the underlying mechanisms for this process by evaluating nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathway involvement in Huh-7 cells., Results: We observed that the FGF19 and FGF21 serum and mRNA levels in the biopsied liver tissue gradually increased and were correlated with fibrosis stage. Inflammatory markers (interleukin 1β [IL-1β], IL-6, and tumor necrosis factor-α) were positively correlated, while β-Klotho expression was negatively correlated with the degree of fibrosis. In Huh-7 cells, IL-1β increased FGF21 levels and decreased β-Klotho levels. NF-κB and JNK inhibitors abolished the effect of IL-1β on both FGF21 and β-Klotho expression. FGF21 protected IL-1β-induced growth retardation in Huh-7 cells., Conclusions: These results indicate that the inflammatory response during fibrogenesis increases FGF21 levels and suppresses β-Klotho via the NF-κB and JNK pathway. In addition, FGF21 likely protects hepatocytes from hepatic inflammation and fibrosis.

The purpose of this essay is to recall the actions taken globally to improve the viral safety of coagulation factor concentrates, mainly in the years 1985-1990, at a time of confusing and often contradictory information on bloodborne viral infections in multitransfused patients with hemophilia (PWHs). I shall first recall the problem of the transmission and control of the hepatitis viruses, and then that of HIV: not only for temporal reasons, but also because understanding the progress of knowledge on hepatitis and the poor success of the early measures taken to tackle this problem in PWHs is essential to understand how the problem of HIV transmission was ultimately dealt with successfully., (© 2018 International Society on Thrombosis and Haemostasis.)

Background and Aim: Viral hepatitis is a global health issue and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Guidelines for viral hepatitis screening in the transgender population do not exist. Transgender patients may be at higher risk for contracting viral hepatitis due to socioeconomic and behavioral factors. The aim of this study was to measure the quality of screening, prevalence, and susceptibility of viral hepatitis, and to identify barriers to screening in transgender patients undergoing gender identity hormonal therapy., Methods: LGBTQ-friendly clinic visits from transgender patients older than 18 years in New York City from 2012 to 2015 were reviewed., Results: Approximately 13% of patients were screened for any viral hepatitis on initial consultation. Screening rates for hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis A virus (HAV) at any point were 27, 22, and 20%. HAV screening was performed in 28% of the female to male (FtM) patients and 16% of male to female (MtF) (P<0.05) patients. HBV screening was performed in 30% of FtM patients and 18% of MtF patients (P<0.05). Thirty-one percent of FtM, 24% of MtF, and 17% of genderqueer patients were tested for HCV (P>0.05). Prevalence of HCV, HBV, and HIV in FtM was 0, 0, and 0.44% and that in MtF was 1.78, 0.89, and 1.78%, respectively. Percentage of patients immune to hepatitis A in FtM and MtF subgroups were 55 and 47% (P>0.05). Percentage of patients immune to HBV in FtM and MtF subgroups were 54 and 48% (P>0.05)., Conclusion: This study indicates a significant lack of hepatitis screening in the transgender population and a concerning proportion of patients susceptible to disease.

Hepatitis is a general term meaning inflammation of the liver, which can be caused by a variety of viruses. However, a substantial number of cases remain with unknown aetiology. We analysed the serum of patients with clinical signs of hepatitis using a metagenomics approach to characterize their viral species composition. Four pools of patients with hepatitis without identified aetiological agents were evaluated. Additionally, one pool of patients with hepatitis E (HEV) and pools of healthy volunteers were included as controls. A high diversity of anelloviruses, including novel sequences, was found in pools from patients with hepatitis of unknown aetiology. Moreover, viruses recently associated with gastroenteritis as sapovirus GV.2 and astrovirus VA3 were also detected only in those pools. Besides, most of the HEV genome was recovered from the HEV pool. Finally, GB virus C and human endogenous retrovirus were found in the HEV and healthy pools. Our study provides an overview of the virome in serum from hepatitis patients suggesting a potential role of these viruses not previously described in cases of hepatitis. However, further epidemiologic studies are necessary to confirm their contribution to the development of hepatitis.

Of the 40 million donations screened with Nucleic acid testing (NAT) between July 2001 and December 2015 in France, 20 HIV-positive, 13 HCV-positive and 17 HBV (HBV-NAT was initiated in 2005 and extended to the whole country in 2010) donations were discarded thanks to NAT. The main benefit in terms of discarded donations is related to HBV with a yield of 0.88 per million donations, which is 12.5 and 1.8 times higher than for HCV and HIV respectively. The main risk factor found in these donors during the post donation interview was having sex with men for males (n=11, all repeat blood donors), having a partner HCV positive (n=6) or at-risk partner (originated from endemic area or HBV positive) for HBV (n=8) for HIV, HCV and HBV, respectively. Although the mean viral load was high for HIV (5.6 log copies/mL) and HCV (7 log IU/mL), HBV cases show low level of DNA (1.8 log IU/mL) demonstrating the need of a highly sensitive NAT assay. Overall, the clinical benefit for recipients remains those related to the prevention of HIV contaminations since HCV avoided transmissions are extremely rare (only one case in the last 5 years thanks to NAT) and the potential infectivity of HBV-NAT only positive cases is questionable due to the low level of HBV DNA and the presence of anti-HBs in more than a half of DNA positive/HBsAg and anti-HBc negative donors., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Migration because of miscellaneous political crises in countries in the Middle East and Africa is a global challenge for whole Europe from an economic, social, and public health view. There is an urgent need to generate comprehensive, evidence-based data to expedite further screening and vaccination strategies., Methods: A total of 604 individuals ranging in age from 2 to 68 years who enrolled at a single reception center were tested for the prevalence of serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV), respectively., Results: Anti-HAV antibody prevalence was 91.2 and 70.3% in children younger than 18 years of age. The prevalence of anti-HEV antibodies was 20.1% among the individuals. 3.0% were positive for hepatitis B surface antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated against hepatitis B and had a protective anti-hepatitis B surface level of at least 10 mIU/ml. Significant differences in vaccination status were found between the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence interval=12.7-19.3%) versus African Region with 1/55 (1.8%; 95% confidence interval=0-5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7% HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals were HCV coinfected (n=3)., Conclusion: The prevalence of refugees with previous exposure to hepatitis viruses was higher than that in the general German population, but lower than in other migrant populations in Germany. The vaccination status against hepatitis B was poor.

Clinicians are required to assess abnormal liver chemistries on a daily basis. The most common liver chemistries ordered are serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin. These tests should be termed liver chemistries or liver tests. Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels. Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels. The majority of bilirubin circulates as unconjugated bilirubin and an elevated conjugated bilirubin implies hepatocellular disease or cholestasis. Multiple studies have demonstrated that the presence of an elevated ALT has been associated with increased liver-related mortality. A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females and levels above this should be assessed. The degree of elevation of ALT and or AST in the clinical setting helps guide the evaluation. The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency. In addition, a history of prescribed and over-the-counter medicines should be sought. For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken. Total bilirubin elevation can occur in either cholestatic or hepatocellular diseases. Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible.

The viral hepatitis abnormalities in the female reproductive system are due to hepatic and extrahepatic damage. On the background of HBV- and HCV-infections, menstrual disorders prevail in the structure of reproductive system pathology; disorders of reproductive function in the form of pregnancy loss and infertility are detected in each second case. Depression of T-cell immunity in the immune status is observed in the patients with intact reproductive function. When miscarriage was in past medical history then divergent changes subpopulations of lymphocytes are found. When patients have infertility, signify depression of T-cell immunity is observed with a decrease in total T-cells, T-helper cells and active lymphocytes.

Background: Previous studies have indicated that the prevalence of human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) virus infections among trauma patients seems to be higher compared to the general population., Objective: This study investigated the seroprevalence of blood-borne pathogens among patients with suspected severe multiple trauma in a German university hospital (level I trauma center)., Methods: Routine blood samples taken from trauma patients at the university hospital Frankfurt were tested for HBV, HCV and HIV (from 1 February 2014 to 31 January 2015)., Results: Overall, 275 patients with a median injury severity score (ISS) of 9 points (range 0-54) were included in the study representing 84.4 % of all trauma room admissions during this time period. Altogether 3.3 % (n = 9) of the patients were infected with blood-borne pathogens, where 7 patients were infected with HCV and 2 patients had an active HBV infection. None of the patients were tested HIV positive and only one initial diagnosis for HCV was made. A further six samples (five HCV and one HIV) showed a weak reaction in the screening assay that could not be verified by the confirmatory assay., Conclusion: To the best of our knowledge this study is the first report on the prevalence of blood-borne infections among trauma patients at a level I trauma center in an urban area in Germany. Compared to the general population the prevalence of blood-borne infections was higher but considerably lower than indicated in previous international studies. Considering the broad implications of occupationally transmitted blood-borne infections occupational safety is of paramount importance.

We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The present review describes the current status of multiplex quantitative real time polymerase chain reaction (qPCR) assays developed and used globally for detection and subtyping of hepatitis viruses in body fluids. Several studies have reported the use of multiplex qPCR for the detection of hepatitis viruses, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). In addition, multiplex qPCR has also been developed for genotyping HBV, HCV, and HEV subtypes. Although a single step multiplex qPCR assay for all six hepatitis viruses, i.e., A to G viruses, is not yet reported, it may be available in the near future as the technologies continue to advance. All studies use a conserved region of the viral genome as the basis of amplification and hydrolysis probes as the preferred chemistries for improved detection. Based on a standard plot prepared using varying concentrations of template and the observed threshold cycle value, it is possible to determine the linear dynamic range and to calculate an exact copy number of virus in the specimen. Advantages of multiplex qPCR assay over singleplex or other molecular techniques in samples from patients with co-infection include fast results, low cost, and a single step investigation process.

The chronic viral hepatitis is characterized by progressing course. In connection with this fact, there is a risk of development of fibrosis of liver. The diagnostic of this disease biopsy is applied as main technique. However, this invasive procedure is not always safe for patient. Therefore, it is applied only in specialized institutions, requires special training of medical personnel and has a number of contraindications. In recent years, in the capacity of noninvasive diagnostic of different stages of fibrosis of liver a number of serum markers are considered. Among them, the most number of studies concerns hyaluronic acid, collagen type IV, matrix metalloproteinase and their tissue inhibitors, transforming growth factor β. The review presents actual information concerning possibilities of application of these serological indices in practical medicine in patients with chronic viral hepatitis.

Objective: Extreme elevations of serum aminotransferases (EESAT), defined as alanine transaminase (ALT) or aspartate transaminase (AST) level of above 3000 U/L, reflect severe liver injury and poor outcomes of the patients. This study aimed to evaluate the prevalence, etiology and clinical outcomes of EESAT in Asian patients and to identify the predictors of early mortality., Methods: Medical records of patients with EESAT over a 1-year period were retrospectively analyzed for disease prevalence, etiology and clinical outcome. The primary outcome was 28-day mortality (defined as death occurring within 28 days of the onset of EESAT). A logistic regression was performed to identify independent predictors of mortality., Results: A total of 101 patients with a mean age of 57.4 ± 18.0 years met the criteria for EESAT, resulted in a prevalence of 1.4 per 1000 admissions. Altogether 63.4% of the patients were men. The etiologies of EESAT were hypoxic hepatitis (74.2%), viral hepatitis (20.8%), rhabdomyolysis (3.0%), drug-induced hepatitis (1.0%) and choledocholithiasis (1%). The 28-day mortality of EESAT was 53.5%. EESAT due to hypoxic hepatitis was associated with high mortality (70.7%) whereas the mortality risk was low in EESAT from viral hepatitis (9.5%). Serum albumin <28 g/L (HR 5.78, 95% CI 1.41-23.62) and age >55 years (HR 4.81, 95% CI 1.29-17.90) were independent predictors of mortality., Conclusions: The main etiology of EESAT is hypoxic hepatitis, which carries a high mortality. EESAT due to viral hepatitis is common in Asians and has a good outcome. Low serum albumin and elder age are independent predictors of early mortality in EESAT patients., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: The great significance for the metabolism of lipoproteins is the composition of carbohydrate chain of apolipoproteins, where sialic acid (SA) is located. In VILDL and LDL sialic acid is attached to apolipoprotein B. The sialylation of serum proteins including apolipoprotein B can be affected in the course of liver diseases. Therefore, the aim of this study was to assess the effect of liver diseases on the concentration and content of SA in ApoB-containing lipoproteins., Methods: The tested group consisted of 165 patients (118 males, 47 females) with liver diseases: alcoholic cirrhosis, non-alcoholic cirrhosis, chronic hepatitis, toxic hepatitis, chronic viral hepatitis, and liver cancer. ApoB-containing lipoproteins were isolated by a turbidimetric procedure and SA concentration was measured according to an enzymatic method., Results: There was a significant increase in the serum concentration of SA in ApoB-containing lipoproteins in viral hepatitis. Although the serum concentration of ApoB was not significantly different between specific liver diseases, the serum levels of SA in ApoB-containing lipoproteins appeared to be different. There is an association between SA concentration and triglycerides in alcoholic cirrhosis and viral hepatitis. Also, in viral hepatitis SA concentration correlated negatively with HDL-cholesterol. The content of SA in ApoB-containing lipoproteins in alcoholic cirrhosis and viral hepatitis was significantly higher than that in the control group, but did not differ between diseases., Conclusions: This study may explain the variations in serum lipids and lipoproteins in liver diseases. It seems that the reason for these abnormalities is the changes in the concentration of sialic acid in ApoB-containing lipoproteins.

We here report the case of a 52-year old man who presented hepatitis with hemophagocytic syndrome triggered by herpes simplex 1 (HSV-1) primary infection. A high-level viremia was observed, and HSV-1 DNA remained detectable in blood for a long time after patient's recovery., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Antibodies (Abs) to disease-causing viruses in human blood are important indicators of infection status. While ELISA has been widely used to detect these Abs, a multiplex assay system for simultaneous detection of multiple Abs is still a desirable alternative method for a more efficient screening process because of the lack of multiplexing ability in ELISA. However, as all antibodies are based on immunoglobulin and recognized commonly by the same secondary antibody, it is impossible to multiplex the conventional indirect ELISA in a 96-microwell plate-based platform. To overcome this hurdle, we designed an assay consisting of two steps: capturing target Abs by specific antigens on DNA-encoded gold nanoparticles; and quantifying the target Abs by producing RNase H-mediated detection signals based on the DNA and additional RNA probes. With this newly designed method, we could simultaneously analyze three infectious disease-related Abs, anti-HIV Ab, anti-HCV Ab, and anti-HBV Ab, on the microwell-based platform. The assay performance was evaluated by comparison with ELISA. Furthermore, the accuracy and precision of the assay in a practical application was also estimated by determining the amount of target Abs in human serum solutions.

Background: Evidence suggests that estrogen plays a preventive role in primary liver cancer development, and it might be thought that isoflavones, which are structurally similar to estrogens and bind to estrogen receptors, are associated with the risk of liver cancer. We investigated this suspected association by measuring plasma concentrations of isoflavones in a nested case-control study of a population-based prospective cohort in Japan., Methods: From 18,628 target participants ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or hepatitis C virus infection at baseline (n = 1,544). Among these, 90 (28 women and 62 men) were newly diagnosed with primary liver cancer from 1993 through 2006; they were matched with 175 controls (54 women and 121 men). Plasma concentrations of isoflavones (genistein, daidzein, glycitein, and equol) were measured using triple quadrupole tandem liquid chromatography-mass spectrometry. The ORs of liver cancer development based on plasma concentrations were estimated with a conditional logistic regression model., Results: Basically, distributions of plasma isoflavone concentrations did not differ between the cases and controls. No statistically significant associations of genistein, daidzein, glycitein, and equol with primary liver cancer risk were found in either women or men., Conclusions: In middle-aged Japanese women and men with hepatitis virus infection, plasma isoflavones were unassociated with the occurrence of primary liver cancer., Impact: The role of isoflavones in liver carcinogenesis merits further study using both biomarkers and data on dietary intake of isoflavones. Cancer Epidemiol Biomarkers Prev; 24(3); 532-7. ©2014 AACR., (©2014 American Association for Cancer Research.)

From blood donor collection to transfusion of the recipient, there are several layers of protection of the blood supply. These measures combined with huge progresses over the three past decades in pathogen discovery and blood testing for specific pathogens (human immunodeficiency virus (HIV), hepatitis B (HBV) and C (HCV) viruses, Human T-cell leukemia virus (HTLV)), provide the greatest safety. With the implementation of serological and molecular testing, at least in high-income countries, transfusion-transmitted infections have become extremely rare. However, for pathogen agents, which are not tested and especially those which are responsible for emerging infectious disease, it became apparent that full control of infectious disease had not been achieved. In addition, the immune status of the recipient has also an impact in the outcome of infectious diseases transmitted by transfusion. Blood safety is based on several measures: education and deferral of donors with risk factors for transmissible disease, blood testing, pathogen reduction interventions, and patient blood management. This paper proposes a review of the residual risk of transmission of infectious diseases by transfusion and of the additional interventions able to further reduce it., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Unlabelled: Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 × ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA-34a correlated positively with illicit drug use and ethanol consumption., Conclusion: Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients., (© 2014 by the American Association for the Study of Liver Diseases.)

An efficient, innovative preconcentration method, dual-cloud point extraction (d-CPE) has been developed for the extraction and preconcentration of copper (Cu(2+)) in serum samples of different viral hepatitis patients prior to couple with flame atomic absorption spectrometry (FAAS). The d-CPE procedure was based on forming complexes of elemental ions with complexing reagent 1-(2-pyridylazo)-2-naphthol (PAN), and subsequent entrapping the complexes in nonionic surfactant (Triton X-114). Then the surfactant rich phase containing the metal complexes was treated with aqueous nitric acid solution, and metal ions were back extracted into the aqueous phase, as second cloud point extraction stage, and finally determined by flame atomic absorption spectrometry using conventional nebulization. The multivariate strategy was applied to estimate the optimum values of experimental variables for the recovery of Cu(2+) using d-CPE. In optimum experimental conditions, the limit of detection and the enrichment factor were 0.046μgL(-1) and 78, respectively. The validity and accuracy of proposed method were checked by analysis of Cu(2+) in certified sample of serum (CRM) by d-CPE and conventional CPE procedure on same CRM. The proposed method was successfully applied to the determination of Cu(2+) in serum samples of different viral hepatitis patients and healthy controls., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To observe the therapeutic effect of Chishaodanpi decoction (CSDPD) on chronic viral cholestatic hepatitis., Methods: A total of 107 subjects with chronic viral cholestatic hepatitis were enrolled in our hospital from March 2007 to November 2012. Patients were randomly divided into treatment (54 cases) and control groups (53 cases). The control group was treated with potassium magnesium aspartate, diammonium glycyrrhizinate, glucurolactone, vitamin C, and lamivudine, once a day. The treatment group was treated with modified CSDPD, 100 mL a time, twice a day, in addition to the treatment given to the control group. The patients in both groups were treated for 8 weeks. The main symptoms and signs were recorded every day throughout the clinical trial. Before and after the trial, changes in liver function including total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), and the activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (γ-GT), were all detected. Adverse reactions were also recorded., Results: There were no differences in gender, age, disease duration, symptoms, signs, or laboratory findings between the two groups (P > 0.05). After an 8-week treatment, improvements in jaundice, weakness, poor appetite, abdominal distention, and skin itching were significantly better in the treatment group than in the control group (P < 0.05). In the treatment group, 43 patients had a significant response to the treatment, seven patients had a response, and four patients had no response, with 21, 12, and 20 patients in the control group, respectively. The total effective rate was 92.6% in the treatment group and 62.3% in the control group, which was a significant difference (P < 0.05). The levels of TBil, DBil, TBA, ALP, ALT, AST, and γ-GT in both groups were significantly lower after treatment, and were significantly different between the two groups (P < 0.05). A few patients in the treatment group had mild adverse effects such as increased bowel movement frequency and mild stomach-ache. No other adverse reactions were observed in either group.

Unlabelled: Portal vein thrombosis is an unusual condition and its association with an acute cytomegalovirus (CMV) infection is known but rarely reported. We present here the case of a 24-year-old woman suffering from a symptomatic portal vein thrombosis, confirmed by CT angiography, and acute CMV-related hepatitis. Besides a second generation oral contraceptive with estrogen and progesterone, not associated with smoking, the acute CMV infection was the only cause found to have provoked the venous thrombosis; a myeloproliferative disorder or biological thrombophilia were ruled out. The patient rapidly recovered with vitamin K antagonists (VKA) anticoagulant treatment. Eighteen cases of splanchnic vein thrombosis complicating acute CMV infection were found in the literature. All patients had acute hepatitis. The outcome was usually favorable with warfarin therapy for a period lasting 3 to 7 months. Antiviral treatment (anti-CMV) was used in three cases of severe infection. The antiviral therapy was given only in immunosuppressed patients. For immunocompetent patients, CMV infection is usually asymptomatic and clinical signs are often non-specific and mild, not requiring treatment., Conclusion: This case report and the review of the literature recall the need to search for acute CMV infection in patients with portal thrombosis so a possible transient trigger for venous thromboembolism can be identified, avoiding extended anticoagulation., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Seroprevalence data on viral hepatitis in the general population vary widely. The aim of this study was to determine the prevalence of hepatitis A (HAV), hepatitis B (HBV) and hepatitis C (HCV) viruses in the general Croatian adult population undergoing routine check-ups. The seroprevalence of anti-HAV, anti-HBc and anti-HCV was 40.5%, 7.0% and 0.9%, respectively. HBsAg was found in 0.7% and anti-HBs antibodies in 24.4% of participants. Gender was not associated with HAV, HBV or HCV seropositivity. HAV and HBV seropositivity increased progressively with age (HAV from 11.7% to 90.4%, p < 0.001; HBV from 1.7% to 15.8%, p < 0.001). Participants from rural areas showed a significantly higher HBV seroprevalence rate than those from urban areas (10.7% vs. 6.1%, p = 0.007). Results of univariate and multiple logistic regression showed that older age was a significant predictor for both HAV and HBV seropositivity while rural place of residence was a significant predictor for HBV seropositivity.

Unlabelled: PRÉREQUIS: Viral hepatitis is a public health problem in many parts of the globe. In Tunisia, the respective responsibility of five viruses (HAV, HDV, HBV, HCV and HEV) in the genesis of acute hepatitis in adults is only roughly indicated in the absence of suitable serological studies, given as important to plan appropriate preventive strategies., Objectives: To approach the role of viral hepatitis in all adult with acute hepatitis, identify the current share of each virus A, B, C and E in the genesis of hepatitis and to study the epidemiological and evolution of these diseases., Methods: We conducted a prospective study over two years including patients aged from 15 to 65 years old, with clinical and / or biological acute hepatitis. Data were collected through a standard questionnaire wich covered sociodemographic charactereristics and risk factors. Blood samples were collected and were tested for IgM anti-HAV, IgM anti-HEV, HBsAg, IgM anti-HBc, anti-HCV antibodies .When serological tests were negatives, further explorations including immunological test, search for HCV RNA and a pharmacovigilance survey was conducted. Statistical analysis was performed by SPSS version 10.0 RESULTS: 105 patients were included. Acute viral hepatitis was diagnosis in 70 patients (67%). The proportion of patients with acute viral hepatitis A, B, C and E was 51.5% , 38.5%, 4.3% and 5.7% respectively. The risk factors of viral hepatitis A was drinking of untreated water and poor socioeconomic status. In the HBV group, the notion of sexual contact risk was found in 30% of cases. The small numbers of acute hepatitis E and C does not permit us to draw conclusions., Conclusion: Our study confirms the shift in age of onset of hepatitis A to the age of adolescence and young adulthood. The respective responsibilities of the different viruses studied in the genesis of acute hepatitis in adults in our area brings us closer of western populations where HAV infection predominates followed by HBV.

Introduction: Chronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore., Materials and Methods: This was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed., Results: Among the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm³. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006)., Conclusion: This study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health.

Background: Seronegative hepatitis is a recognized cause of liver failure requiring transplantation. The aetiology is unknown, but might relate to an unidentified virus or immune dysregulation. There are few data on seronegative hepatitis presenting to nontransplant centres., Objectives: To describe the clinical/laboratory features and natural history of seronegative hepatitis and compare these with viral/autoimmune hepatitis., Methods: Cases of seronegative, viral and autoimmune hepatitis were identified from 2080 consecutive patients attending a rapid-access jaundice clinic over a 14-year period., Results: Of 881 patients with hepatocellular jaundice, 27 (3%) had seronegative hepatitis, 44 (5%) autoimmune and 62 (7%) viral hepatitis (acute hepatitis A, B, C and E viruses). Fifteen out of 27 (56%) patients with seronegative hepatitis were male, median age 60 years (range 14-74). Peak bilirubin was 63 μmol/l (range 9-363), alanine aminotransferase 932 IU/l (range 503-3807). Duration of illness was 7 weeks (range 4-12). No patients developed liver failure or had further bouts of hepatitis. One patient developed acute lymphoblastic leukaemia shortly after presentation.There was no difference in age/sex of patients with seronegative hepatitis and those with viral hepatitis. Compared with autoimmune hepatitis (age 65 years, range 15-91), patients with seronegative hepatitis were younger (P=0.002) and more likely to be male (P=0.004). Patients with autoimmune hepatitis were more likely (P<0.0001) to have an albumin less than 35 g/l, international normalized ratio greater than 1.2, raised IgG and positive antinuclear/smooth muscle antibody, compared with patients with seronegative hepatitis., Conclusion: Seronegative hepatitis presenting to a nontransplant centre is generally a self-limiting illness. The aetiology is more likely to be viral than autoimmune.

We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.

In chronic viral hepatitis the liver biopsy helps the clinician to decide when to start treatment and plan follow-up. However, the execution of a liver biopsy is associated with discomfort, and sampling error can lead to misinterpretation. Serum markers and transient elastography (TE) are being considered as surrogates to the liver biopsy. The noninvasive tests are considered equal in identifying significant fibrosis, but TE is superior in identifying cirrhosis.

Background: Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study., Methods: Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0-75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls)., Results: During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2-62.6) and 221.6 ng/mL (74.9-611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75-250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86-9.26, p<0.0007) and 28.22 (95% CI 14.95-46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR -5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001)., Conclusions: An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.

The main objectives of the design of GB virus C (GBV-C) peptide microarrays are the miniaturisation of antigen-antibody interaction assays, the simultaneous analysis of several peptide sequences and the reduction in the volume of serum required from patients since this always represents a limiting factor in studies to develop new systems for diagnosing human diseases. We herein report the design of a microarray immunoassay based on synthetic peptides derived from the GBV-C E2 protein to evaluate their diagnostic value in detecting anti-E2 antibodies in HIV-1 patients. To this end, peptide microarrays were initially prepared to identify the most relevant epitopes in the GBV-C E2 protein. Thus, 124 peptides composed of 18 amino acids covering the whole E2-protein sequence, with 15 residue overlaps, were spotted in triplicate onto γ-aminopropyl silane-functionalised adsorbent binding slides. The procedure to select the E2 protein epitopes was carried out using serum samples from HIV-1-infected patients. The samples had previously been tested for the presence or absence of GBV-C anti-E2 antibodies by means of the Abbott test. Thus, 11 specific epitopes in the GBV-C E2 protein were identified. Subsequently, peptide antigen microarrays were constructed using the E2 epitopes identified to detect GBV-C anti-E2 antibodies in the serum of HIV-1-infected patients with no known GBV-C co-infection. The 11 peptides selected identified anti-E2 GBV-C antibodies among HIV-1-infected patients, and a reactivity of 47 % was established. The potential antigenic peptides selected could be considered a useful tool for designing a new diagnostic system based on peptide microarrays to determine anti-GBV-C E2 antibodies in the serum of HIV-1-infected patients.