Serological Markers Of Viral Hepatitis Research Articles

VIRAL CO-INFECTIONS IN PATIENTS WITH HIV-INFECTION

The paper presents the results of a study of the detection frequency of co-infectionserological markers of viral origin in persons suffering from HIV infection who are onantiretroviral therapy (ART). The relationship between the number of CD4 lymphocytesand the presence of markers of pathogens’ active replication of co-infections, caused byherpesviruses (cytomegalovirus – CMV, herpes simplex viruses of types 1 and 2 – HSV½,Epstein- Barr virus – EBV), and hepatitis B, C viruses in the plasma of HIV-infectedpatients, was considered.The purpose of the study – to determine the spectrum of viral co-infections in patientswith HIV infection and to find out the impact of these infections on the developmentof immunodeficiency based on the number of CD4 lymphocytes. Materials and methods. 146 patients with HIV infection, who were under outpatientobservation during 2020-2022 in the regional center of prevention and fight against AIDS inChernivtsi, were examined. When establishing the diagnosis, clinical and epidemiologicaldata and the results of laboratory tests, in particular: serological and immunological, weretaken into account. The level of CD4+ T-lymphocytes was examined after the disappearanceof the symptoms of the accompanying acute infectious disease (at least after 4 weeks).The results. The significance of the clinical manifestations and the nature of the course ofherpes simplex and shingles against a background of HIV infection depended on the degree ofreduction in the number of CD4+ lymphocytes. In most of the examined (57.0 %), the numberof CD4+ lymphocytes was less than 500 cells in 1 mm3 of blood, which contributed to theactivation of herpes simplex and shingles. A careful analysis of the frequency of detection ofserological markers of viral co-infections, depending on the route of HIV infection, showedthat hepatitis B virus markers were significantly more often detected in persons with a sexualroute of infection, and hepatitis C and mixed hepatitis virus markers – in those personsinfected with HIV, most likely, due to parenteral administration of narcotic substances.Conclusions. 1. Analysis of the spectrum of co-infections of viral genesis in HIV-infectedpersons demonstrated a wide distribution of parenteral viral hepatitis and a high levelof activation of chronic infections caused by HSV½, CMV and EBV. Markers of viralhepatitis B and C were detected in 56.8 % of patients with HIV infection. Activationof chronic infections, caused by CMV, HSV½ and EBV, was observed in 32.2 % of thesubjects. 2. Serological markers of viral hepatitis C and mixed hepatitis (HS + HBV)are most often detected in persons with parenteral HIV infection, and markers of viralhepatitis B – mostly in persons with sexual infection of HIV. 3. Antiretroviral therapyeffectively suppresses the replicative activity of the hepatitis B virus (HBV). 4. Theaverage values of the number of CD4-lymphocytes in HIV-infected persons who hadmarkers of co-infections of viral genesis, almost did not differ from the values of the levelof CD4-lymphocytes of those patients in whom these markers were not observed. Thistestifies to the effectiveness of antiretroviral therapy used in patients with HIV infection.

Sero-epidemiological characteristics of the hepatitis D virus infection among hepatitis B virus infected-patients at a single center in Xinjiang region

Objective: To investigate the sero-epidemiological characteristics of the hepatitis D virus (HDV) infection among hepatitis B virus (HBV)-infected patients in Xinjiang region. Methods: A single-center cross-sectional analysis method was used to select 264 cases of hepatitis B virus infection who were hospitalized in the Center for Infectious Diseases and Liver Diseases of the First Affiliated Hospital of Xinjiang Medical University from August 2021 to January 2022. All patients were tested for HDV Ag, HDV IgM, HDV IgG, and HDV RNA. The infection status of hepatitis D virus was analyzed by grouping according to their clinical type, HBV viral load, and HBsAg level. A paired t-test was used for data with measurement data conforming to normal distribution. A paired rank sum test was used for data that did not conform to normal distribution before and after treatment. Results: A total of 36 cases (13.64%) and 26 cases (9.85%) were positive for HDV serological markers and HDV RNA. According to clinical type grouping, the positive rates of HDV serum markers in patients with chronic hepatitis B, hepatitis B-related cirrhosis, liver cancer, and liver failure were 13.46%, 12.43%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=0.86, P=0.649). The positive rates of HDV RNA were 11.54%, 8.11%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=4.015, P=0.134). According to HBV viral load grouping, the positive rates of HDV serum markers among patients with viral loads <20, 20-2 000, and >2 000 IU/ml were 17.15%, 7.81%, and 6.67%, respectively, and the difference was not statistically significant among the three groups (χ2=4.846, P=0.089). The positive rates of HDV RNA were 9.47%, 10.94%, and 10%, respectively, and the difference was not statistically significant among the three groups (χ2=0.113, P=0.945). According to HBsAg level grouping, the positive rates of HDV serum markers in HBsAg<0.05, 0.05~250, and >250 IU/ml were 14.29%, 16.67%, and 10.85%, respectively, and there was no statistically significance between the three groups (χ2=1.745, P=0.418). The positive rates of HDV RNA were 4.76%, 8.77%, and 11.63%, respectively, and there was no statistically significant difference among the three groups (χ2=1.221, P=0.543). Clinical outcome, disease course, HBV DNA, serological markers of viral hepatitis, routine blood test, biochemical indicators, coagulation function, and other laboratory indicators were compared between HDV serum marker and/or nucleic acid positive and negative patients, and there was no statistically significant difference (P>0.05). Conclusion: The positive rate of HDV serological markers and HDV RNA is 13.64% and 9.85%, respectively, at a single center in the Xinjiang region, and there is still a high HDV infection rate among the HBV-infected patients with low levels of viral load and HBsAg.

Ураження печінки у хворих на неспецифічний виразковий коліт

Актуальність. Стаття присвячена темі хронічних запальних захворювань кишечника, зокрема, приділяється увага неспецифічному виразковому коліту (НВК). НВК перебігає з розвитком низки позакишкових уражень, серед яких особливе місце відводиться змінам печінки і жовчовивідних шляхів. У зв’язку з цим було проведено дослідження, метою якого була оцінка поширеності, характеру і клінічних особливостей уражень печінки у хворих на НВК. Матеріали та методи. Під наглядом перебувало 180 пацієнтів із НВК, підтвердженим ендоскопічно і морфологічно. Усім пацієнтам проводили мультимодальне ультразвукове дослідження печінки, досліджували біохімічні ознаки цитолізу і/або холестазу при негативних серологічних маркерах вірусного гепатиту В, С, D і аутоімунного гепатиту. Також проводили біохімічне дослідження ліпідного спектра крові, а пацієнтам із підозрою на аутоімунні ураження печінки — аналіз спектру відповідних антитіл. Результати. Зі 180 хворих на НВК ураження печінки виявлені у 58 (32,2 %). Паренхіматозні ураження печінки виявлені у 40 (22,2 %) хворих на НВК, а зміни з боку жовчовивідних шляхів — у 18 (10,0 %) пацієнтів із НВК. Неалкогольний стеатогепатит (НАСГ), аутоімунний гепатит (АГ) і первинний біліарний цироз (ПБЦ) печінки виявлені у 40 (69,0 %) пацієнтів з НВК, а ураження поза- і жовчних проток і жовчного міхура — у 18 (31,0 %). Серед паренхіматозних уражень печінки домінував НАСГ (53,5 %). АГ діагностовано у 8,6 % пацієнтів, ПБЦ — у 5,2 % хворих на НВК. Усі хворі на НВК з НАСГ крім базисної терапії приймали препарат есенціальних фосфоліпідіву добовій дозі 1800 мг (по 2 капсули 3 рази на день) протягом трьох місяців. Після закінчення лікування тільки у 2 (6,5 %) пацієнтів зберігалися незначні скарги. До лікування у всіх обстежених хворих було виявлене достовірне підвищення АСТ і АЛТ в 2,3 і 2,2 раза відповідно, у поєднанні з підвищенням ГГТ в 3,7 раза порівняно з нормою, що може свідчити про помірно виражений синдром цитолізу. Після лікування у хворих відзначена тенденція до нормалізації ферментативного статусу, хоча показники залишалися підвищеними порівняно з нормою. Висновки. Ураження печінки виявлені у 32,2 % хворих, переважно при поширених формах, середньотяжкому і тяжкому перебігу і високій активності НВК. Для лікування НАСГ у хворих на НВК доцільне використання есенціальних фосфоліпідів.

Improved ascertainment of modes of HIV transmission in Ukraine indicates importance of drug injecting and homosexual risk

BackgroundIt is important to understand how HIV infection is transmitted in the population in order to guide prevention activities and properly allocate limited resources. In Ukraine and other countries where injecting drug use and homosexuality are stigmatized, the information about mode of transmission in case registration systems is often biased.MethodsWe conducted a cross-sectional survey in a random sample of patients registered at HIV clinics in seven regions of Ukraine in 2013–2015. The survey assessed behavioral risk factors and serological markers of viral hepatitis B and C. We analyzed the discrepancies between the registered mode of transmission and the survey data, and evaluated trends over 3 years.ResultsOf 2285 participants, 1032 (45.2%) were females. The proportion of new HIV cases likely caused by injecting drug use based on the survey data was 59.7% compared to 33.2% in official reporting, and proportion of cases likely acquired through homosexual transmission was 3.8% compared to 2.8%. We found a significant decrease from 63.2 to 57.5% in the proportion of injecting drug use-related cases and a steep increase from 2.5 to 5.2% in homosexual transmission over 3 years.ConclusionsThe study confirmed the significant degree of misclassification of HIV mode of transmission among registered cases. The role of injecting drug use in HIV transmission is gradually decreasing, but remains high. The proportion of cases related to homosexual transmission is relatively modest, but is rapidly increasing, especially in younger men. Improvements in ascertaining the risk factor information are essential to monitor the epidemic and to guide programmatic response.

Fulminant hepatitis with negative viral serological markers: A possible case of occult hepatitis B virus infection

Infection with hepatitis B virus (HBV) shows variable clinical manifestations ranging from asymptomatic carrier state, acute, chronic, fulminant, and occult HBV infection (OBI). OBI is defined as the presence of HBV viral DNA in the liver (with or without detectable HBV DNA in serum) of hepatitis B surface antigen-negative individuals tested with the currently available assays. A cutoff of HBV DNA if present is expected to be <200 IU/ml. As high as 20% of individuals with OBI carriage evidenced by HBV DNA detection could be nonreactive for anti-hepatitis B core or any other serological evidence of exposure to HBV. With a reported prevalence of 5.4% among blood donors in Ile Ife, Nigeria, OBI is a risk factor for chronic liver disease and hepatocellular carcinoma. Given the sensitivity of our diagnostic tools in this environment, it is likely that most cases of OBI are going undiagnosed among many blood donors. We present a case of fulminant hepatitis with negative serological markers for viral hepatitis in a 25-year-old male.

ANALYSIS OF FACTORS ASSOCIATED WITH PUBLIC CONFIDENCE IN VACCINATION AGAINST VIRAL HEPATITIS B IN ARKHANGELSK REGION

To reveal factors associated with negative attitude to vaccination against viral hepatitis B we performed two crosssectional studies including 1243 adults aged 18–39 years, recruited by a public opinion agency applying a quota sampling method to achieve a data set with similar age- and sex-distribution as the population in Arkhangelsk, and 2896 parents, visiting child’s health-care facilities of Arkhangelsk region. Binary logistic regression was used to analyze factors associated with negative attitude to vaccination. Among 1243 adult respondents 3,5% expressed a negative attitude to vaccination against viral hepatitis B. According to serological testing 15,9% of participants who demonstrated negative attitude to vaccination had serological markers of viral hepatitis B infection (HBsAg, antiHBc-antibodies, sometimes in combination with antiHBs-antibodies). Respondents younger than 30 years and people who had standard risk factors of infection (injecting drug use, blood transfusion, surgery, induced abortions, tattoo, 5 and more sexual partners in a year), more often demonstrated positive attitude to vaccination against viral hepatitis B in comparison with others. Among 2896 parents 1,6% expressed a negative attitude to vaccination of their children against viral hepatitis B. Factors associated with negative attitude to vaccination were age younger than 25 years, high education, concerns and misinformation about vaccines, distrust in physicians. Thus, young adult people, who had standard risk factors of infection, had positive attitude to vaccination against viral hepatitis B. Young parents underestimated the risk of infection in children and importance of timely vaccination. The major reasons for negative public attitude to vaccination against viral hepatitis B were lack of information about vaccination and, as a consequence, unawareness of the need of immunization.

Serological markers of viral hepatitis B and C in children with sickle cell disease monitored in the Pediatrics Department at the University Hospital of Bobo-Dioulasso (Burkina Faso)

Viral hepatitis B and C are universal public health problems. Burkina Faso is a high endemic area for hepatitis B. Patients with sickle cell disease are at risk. The aim of this study was to investigate and quantify the serological markers of viral hepatitis B and C among pediatric patients with sickle cell disease. This was a descriptive cross-sectional study, which took place from July to November 2014 at the Department of Pediatrics, University Hospital of Bobo- Dioulasso. The study included 44 SS and 26 SC sickle cell patients. General data (age, gender) and medical information (vaccinations, medical history including transfusion) were collected. Blood samples were taken for research and titration of serological markers of hepatitis viruses B and C with a commercial Elisa test on the ARCHITECT i1000® automat of Abbott Laboratories. The mean age of the patients was 7.98 years. Seventeen patients (13 SS and SC 4) had already been transfused at least once. The transfusion rate was significantly higher among the SS patients than among SC (29.5% and 15.3% respectively) patients. No patient with HBs Ag was been found. In two patients, the anti-HBc Ab was found alone. In 33% of cases, no markers of hepatitis B were found. Less than 20% of children fully vaccinated (N = 45) had a protective level of anti-HBs Ab (greater than 10 IU/l). The prevalence of anti-VHC Ab was 2.8%. No case of HBV-HCV co-infection was found. The prevention of infection is an important part of the management of sickle cell patients. Immunization against hepatitis B should be systematic. The results of this study assume that blood safety was good.

The prevalence of serological markers of viral hepatitis among labor migrants arriving in the Russian Federation

Aim. To determine of the prevalence of viral hepatitis A, E, B, C and D markers in migrant workers. Materials and methods. Blood serum samples from 1,333 migrant workers recently arrived in Russia from Uzbekistan (n = 464), Tajikistan (n = 415), Ukraine (n = 308) and Moldova (n = 146) were analyzed. Anti-HAV IgG, anti-HEV IgM and IgG, HBsAg, anti-HBV and anti-HCV were tested using commercial ELISA tests. Results. The frequency of HBsAg detection was significantly higher among migrants from Tajikistan and Uzbekistan (5,3% and 5,2%, respectively) compared to migrants from Ukraine (1,0%) and Moldova (3,4%). No anti-HDV was detected in any positive HBsAg sample. The rate of anti-HCV detection was high regardless of the country of origin: 4,5% (Uzbekistan), 4.8% (Tajikistan), 3,9% (Ukraine), 4,8% (Moldova). Anti-HEV IgG was significantly higher in migrants from Uzbekistan and Tajikistan compared to those from Ukraine and Moldova (25,4% and 43,1%, vs. 7,8% and 12,3%, respectively, p &lt;0,05). Anti-HEV IgM, indicative of current or recent infection, was detected in migrants from Uzbekistan, Tajikistan, Ukraine and Moldova with similar frequency – 3,9%, 7,8%, 5,8% and 6,8%, respectively. AntiHAV IgG positivity rate was significantly lower in migrants from Ukraine compared to those from Moldova, Uzbekistan and Tajikistan (70,1% versus 91,8%, 98,7%, 99,8%, respectively, p &lt;0,05). Conclusion. The high prevalence of hepatitis B and C serologic markers in labor migrants, as well as anti-HEV IgM, suggests a high probability of the importation of HCV, HBV and HEV in the Russian Federation. Thus, inclusion of hepatitis B, C and E testing into routine screening of labor migrants might be beneficial.

Prevalence of occult hepatitis B virus infection in hemodialysis patients in Isfahan, Iran.

Background:The absence of a detectable hepatitis B surface antigen (HBsAg) with or without hepatitis B core antibody (anti-HBc) or hepatitis B surface antibody (anti-HBs) in the presence of hepatitis B virus-DNA (HBV-DNA) is defined as occult HBV infection. This study was aimed to evaluate the prevalence of occult HBV infection in patients receiving hemodialysis (HD) in Isfahan, Iran.Materials and Methods:This cross sectional study was done on 400 patients without acute or chronic HBV infection with end-stage renal disease undergoing regular HD. Blood samples were collected prior to the HD session, and serological markers of viral hepatitis B included HBsAg, anti-HBs and anti-HBc were measured using standard third generation commercially available enzyme immunoassays kit, then samples of positive anti-HBc and negative anti-HBs were tested for HBV DNA using quantitative real-time polymerase chain reaction techniques. Data were analyzed by SPSS using t-test and Chi-square test.Results:The mean age of patients was 51.6 ± 11.2 years. Anti-HBc positive was observed in 32 (8%) of 400 studied patients with negative HBsAg. Of 32 patients with anti-HBc positive, 15 were males and 17 were females with mean age of 49.7 ± 12.6 years. Among 32 patients with anti-HBc positive, 10 patients were negative for anti-HBs. All of 10 patients were negative for HBV DNA. The prevalence of occult HBV infection was 0%.Conclusions:The prevalence of occult HBV infection in HBsAg negative patients undergoing HD was 0% and look to be among the lowest worldwide. So, occult HBV infection is not a significant health problem in HD patients in this region.

Resistin and Insulin Resistance: A Link Between Inflammation and Hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA >4 being 1.6 times more likely to have HCC. HOMA and serum resistin allow for early identification of patients with cirrhosis who are at substantially increased risk of HCC. HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC.

Severe Aplastic Anemia and Seronegative Autoimmune Hepatitis: A Concurrence or Consequence?

Hepatitis-associated aplastic anemia (HAAA) is a variant of bone marrow failure that usually follows an acute attack of hepatitis. It usually affects children and young adolescents and is uncommon in adults. The causative factor in the majority of cases remains unknown. The efficacy of immunosuppressive regimens suggests autoimmunity as a key mechanism of HAAA. Although rare, seronegative autoimmune hepatitis can be a cause of bone marrow failure.A 43-year-old Caucasian male patient with a past medical history of hypertension was admitted due to abdominal pain of two-week duration and progressive jaundice. He denied alcohol, smoking, illicit drug use, foreign travel, recent bites, scrapes, or injuries. His medications included hydrochlorothiazide, lisinopril and hydrocodone/acetaminophen. On physical exam, there was right upper-quadrant tenderness and notable jaundice but no hepato-splenomegaly. Admission laboratory data showed transaminitis and pancytopenia without neutropenia. The white blood cell count was 3.7×103/µl, hemoglobin 13.6 mg/dl, platelets 69×103/µl, ALT 2451 IU/l, AST 1573 IU/l, total bilirubin 7.7 mg/dl, alkaline phosphatase 185 IU/l and lipase 172. Further investigations included serological markers of viral hepatitis which were negative. Urine histoplasma and Cryptococcus antigens were negative. Anti-nuclear, anti-smooth muscle, anti-LKM and anti-mitochondrial antibodies were negative. Serum immunoglobulins, ceruloplasmin, acetaminophen level, DIC panel and anti-tissue transglutaminase (anti-tTG) IgA were normal. Liver ultrasound, endoscopic ultrasound, and MRI of the liver did not show any acute process. A liver biopsy showed autoimmune hepatitis (AIH). Four weeks later, pancytopenia worsened with severe neutropenia, but showed significant improvement in transaminases. Laboratory data showed white blood cell count of 1.1×103/µl, absolute neutrophil count 418, hemoglobin 10.7 mg/dl, platelets 19×103/µl, ALT 164 IU/l, and AST 50 IU/l. Peripheral blood workup for pancytopenia was unremarkable. Bone marrow biopsy showed aplastic anemia. The patient was started on steroids, cyclosporine, and anti-thymocyte globulin (ATG). His counts improved after staring immunosuppressive therapy and his liver function returned to normal. Cyclosporine was stopped because patient developed microangiopathic hemolytic anemia. Three months after initiation of therapy, his counts were stable and immunosuppressive therapy was stopped. He required no further therapy or transfusion.Aplastic anemia (AA) may develop in as many as 1 in 3 cases of seronegative clinically identifiable hepatitis. In most cases, the hepatitis is self-limiting, but the liver disease may be prolonged or recurrent. AA is characterized by diminished number or total lack of hematopoietic precursors in the bone marrow. In most cases, stem-cell failure is acquired as a consequence to exposure to ionizing radiation, environmental chemicals, drugs, or viruses. However, in some patients AA seems to be immune mediated, with active destruction of blood-forming cells. Up to 13% of patients are diagnosed with autoimmune hepatitis and have no typical antibodies or hypergammaglobulinemia at presentation. Our patient was seronegative for known hepatotoxic viruses. Although he had negative autoantibody markers, liver biopsy showed autoimmune hepatitis, thus confirming the diagnosis of seronegative autoimmune hepatitis (SAIH). Clinically, the disease presented as a protracted hepatitis with episodes of jaundice and very high transaminases. Usually bone marrow failure follows SAIH, but in our case the patient had mild bone marrow failure on admission and severe hepatitis. It is unknown whether the immune mediated mechanism targets the liver and bone marrow simultaneously or aplastic anemia is a consequence of SAIH. The hepatitis and aplastic anemia responded well to immunosuppressive therapy which confirmed autoimmunity as the etiology of aplastic anemia and hepatitis in our patient.The major pathogenic mechanisms leading to the liver injury and bone marrow destruction in SAIH patients seem to have an immune nature. Patients with SAIH should be monitored carefully, and in the presence of cytopenia directed to hematologist. Early treatment of SAIH with corticosteroids could prevent development of end stage liver disease and aplastic anemia. DisclosuresNo relevant conflicts of interest to declare.

GW24-e3161 Non alcoholic fatty liver disease in a high risk cardiovascular disease : a case report

ObjectivesNon alcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymesin developed countries. This condition is characterised by insulin resistance,hepatic steatosis, and frequently diabetes mellitus type...

Role of fibrogenic markers in chronic hepatitis C and associated hepatocellular carcinoma

Detection and follow up of fibrogenesis in chronic hepatitis C (CHC) is mandatory for early treatment and risk stratification. The current study included 120 patients with CHC, of whom 30 had liver cirrhosis (LC) and 30 had hepatocellular carcinoma (HCC). 15 wedge liver biopsies, taken during laparoscopic cholecystectomy, were included as normal controls. Cases were subjected to laboratory investigations, serologic markers for viral hepatitis and assessment of circulating levels of hyaluronic acid (HA) and platelet-derived growth factor (PDGF). Immunohistochemical expression of connective tissue growth factor (CTGF), PDGF and transforming growth factor-β1 (TGF-β1) was also carried out. A significant increase (p < 0.01) in serum HA was noticed in CHC, LC and HCC compared to controls. Although, a significant decrease in serum PDGF was detected in CHC and LC compared to controls, HCC values were comparable. A significant up-regulation of CTGF was detected in CHC, LC and HCC (p < 0.01) in contrast to its limited mild expression in normal livers. Intense PDGF positive staining was noticed in CHC, LC and HCC compared to scattered faint expression in controls. The significant expression and marked intensity of PDGF staining matched the progress to tumorigenesis. A positive TGF-β1 immunostaining was also noticed in CHC, LC and HCC. An intense and extensive cytoplasmic expression of TGF-β1 was encountered in patients with LC revealing that CTGF, PDGF and TGF-β1 act synergistically in LC. Data revealed that HA and CTGF may be implicated as important diagnostic parameters for assessment of hepatic fibrosis and PDGF for monitoring malignant transformation in CHC.

Early Detection of Hepatocellular Carcinoma on top of Liver Cirrhosis: The Fas Receptor and Ligand System

Hepatocyte aberrations, accumulation of chromosomal damage and possibly initiation of hepatic carcinogenesis is thought to be caused by the continued viral replication and the persistent attempt by a less than optimal immune response to eliminate hepatitis C virus (HCV) infected cells. The identification of the “death factors including Fas and its Ligand (Fas-L) as a major regulator of both apoptosis and immune function has provided insight into an attractive mechanism of tumor escape from immune clearance. Aim: To assess the hepatic expression of Fas/Fas-L, the Fas receptor (Fas-R) expression on lymphocyte, and serum soluble Fas (sFas) in an attempt to analyze the role of Fas receptor/ligand system in the multistep process of fibrosis/carcinogenesis and the possible use of the serum marker as possible candidate biomarkers for an early detection of hepatocellular carcinoma (HCC). Material and Method: The current study included 100 samples from cases at Theodor Bilharz Research Institute and Kasr Al Aini Hospital in Egypt. There were 90 cases of chronic hepatitis C (CHC) infection (and negative hepatitis B virus infection). There were 30 cases without liver cirrhosis, 30 cases with liver cirrhosis and 30 cases with HCC. 10 liver biopsies were taken from healthy livers as normal controls. Histopathologic study and immunohistochemistry for detection of hepatic Fas and Fas-L expression were determined for all cases. Electron microscopy (EM) and immunoelectron microscopy (IEM) examination for detection of Fas-R expression on lymphocytes were also done. sFas, liver function tests, serologic markers for viral hepatitis, and serum alpha-fetoprotein level (alpha-FP) were done. Results: The sFas in both HCC and CHC with cirrhosis patients were significantly higher than those of normal controls and CHC without cirrhosis (P<0.01), but there was no significant difference between the cirrhosis and HCC patients. Positive hepatic expression of both Fas and Fas-L were significantly increased in the diseased groups (p<0. 01) compared to the control specimens. A progressive Fas and FasL increase from CHC without cirrhosis to CHC with cirrhosis followed by a decline from the latter to HCC. Apoptotic Fas and Fas-L proteins expression was significantly increased with the necroinflammatory activity and the advancement of fibrosis. There was a non-significant negative correlation between sFas and hepatic Fas. In addition a significant over expression of Fas-R on separated lymphocytes was associated with a higher frequency of apoptotic cell death as detected by EM examination. Conclusion: The Fas receptor/ligand system was significantly involved in the process of liver cirrhosis converting into HCC. Down-regulation of Fas expression, up-regulation of Fas-L expression in hepatocytes and elevation of serum sFas level were important in tumor evasion from immune surveillance and in hepatic carcinogenesis.

Seroprevalencia de hepatitis viral B en estudiantes universitarios en Abancay, Perú

To determine the prevalence of serological markers of viral hepatitis B in university students of the city of Abancay, we performed a cross-sectional study on 240 students from three universities, from January to October 2010. Informed consent was requested to every student, an epidemiological record was filled, and a venous blood sample was drawn to determine the presence of HBsAg, total anti - HBcAg, anti - HBe, HBeAg and IgM Anti - HBc by ELISA. A prevalence of 2.5% (six positive samples) was found for HBsAg and of 28.3% (68 positive samples) for anti – HbcAg antibodies. The male sex was associated with the presence of anti - HBcAg (OR = 2.0, 95% CI, 1.2 to 3.6). We did not found HBeAg or IgM anti – HBc, however, the 6 HBsAg carriers were anti - HBe positive. In conclusion hepatitis B infection is still a public health problem in Abancay, with a significant prevalence in university students.

Seroprevalencia de hepatitis viral B en estudiantes universitarios en Abancay, Perú

To determine the prevalence of serological markers of viral hepatitis B in university students of the city of Abancay, we performed a cross-sectional study on 240 students from three universities, from January to October 2010. Informed consent was requested to every student, an epidemiological record was filled, and a venous blood sample was drawn to determine the presence of HBsAg, total anti - HBcAg, anti - HBe, HBeAg and IgM Anti - HBc by ELISA. A prevalence of 2.5% (six positive samples) was found for HBsAg and of 28.3% (68 positive samples) for anti - HbcAg antibodies. The male sex was associated with the presence of anti - HBcAg (OR = 2.0, 95% CI, 1.2 to 3.6). We did not found HBeAg or IgM anti - HBc, however, the 6 HBsAg carriers were anti - HBe positive. In conclusion hepatitis B infection is still a public health problem in Abancay, with a significant prevalence in university students.

330 ACOUSTIC RADIATION FORCE IMPULSE-IMAGING FOR NON-INVASIVE ASSESSMENT OF LIVER FIBROSIS: A POOLED META-ANALYSIS

ageand sex-matched healthy subjects served as controls. Urine and stool analysis, liver function tests, prothrombin time, serological markers for viral hepatitis and ultra-sonography were conducted. Flow cytometric analysis of circulating leucocytes was carried out using primary antibodies against CD34, CD45 and CXCR4. Results: Increased expression of CD34, CD45 and CXRC4 on circulating leucocytes was detected in patients with CHC (p < 0.01) compared to controls. Patients with advanced stages of fibrosis had more pronounced expression of these markers (p < 0.01) than patients with early stages of fibrosis. Conclusion: The increased expression of CD34, CD45 and CXCR4 on circulating leucocytes implies a central role of fibrocytes in the expansion of myo-fibroblast pool in HCV-mediated liver fibrosis. Those markers can be used as effective parameters for early prediction of outcome of the clinical course of HCV infection.

Differential expression of cell cycle regulators in HCVinfection and related hepatocellular carcinoma

To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. Subjects of the current study included 50 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis (LC), and 30 cases of hepatitis C-related hepatocellular carcinoma (HCC) admitted to the Department of Hepato-Gastroenterology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. Fifteen wedge liver biopsies, taken during laparoscopic cholecystectomy, were also included as normal controls. Laboratory investigations including urine and stool analysis, liver function tests and prothrombin concentration; serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1, Cyclin E, p21, p27 and Rb/p105 proteins. Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1, p21 and p27. Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC (P < 0.01) to HCC (P < 0.001) cases; meanwhile, Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity. The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well- and poorly-differentiated tumors. p21 showed only a nuclear pattern of staining, while, p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases. Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases (P < 0.001), between Cyclin D1 and Cyclin E in HCCs (P < 0.01); however, an inverse relationship was detected between Cyclin D1 and p21 or p27 (P < 0.001) and between p21 and Rb/p105 (P < 0.05) in HCCs. Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC; while, Cyclin E may be a useful marker formonitoring tumor behavior. p21 and p27 can be used as predictive markers for HCC. Furthermore, higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.

Shift work aggravates metabolic syndrome developmentamong early-middle-aged males with elevated ALT

To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle-aged males with elevated alanine aminotransferase (e-ALT). A retrospective, observational follow-up study on MetS development at a 5-year interval was conducted using health examination data. Nine hundred and ninety six male employees not fulfilling MetS criteria at screening were enrolled. Age, MetS-components, liver enzymes, serological markers for viral hepatitis, abdominal ultrasound, insulin resistance status, lifestyles, and workplace factors were analyzed. The prevalence of elevated serum ALT (> 40 U/L, e-ALT) at baseline was 19.1%. There were 381 (38.3%) workers with long-term exposures to day-night rotating shift work (RSW). 14.2% of subjects developed MetS during follow-up. After 5 years, the workers with e-ALT had significantly unfavorable changes in MetS-components, and higher rates of MetS development, vs subjects with normal baseline ALT levels. Workers with both baseline e-ALT and 5-year persistent RSW (pRSW) exposure had the highest rate of MetS development. Also, e-ALT-plus-pRSW workers had a significant increase in MetS-components at follow-up, compared with the other subgroups. After controlling for potential confounders, e-ALT-plus-pRSW workers posed a significant risk for MetS development (odds ratio, 2.7; 95% confidence interval, 1.4-5.3, vs workers without baseline e-ALT nor pRSW). We suggest that all early middle-aged male employees with e-ALT should be evaluated and managed for MetS. Particularly in terms of job arrangements, impacts of long-term RSW on MetS development should be assessed for all male employees having baseline e-ALT.

Non-alcoholic fatty liver disease in obese persons with diabetes

Obesity, diabetes and different lipid metabolic disorders are the most frequent risk factors for nonalcoholic fatty liver disease, presented with a high variability in clinical and histological findings. We presented a case of 37-year-old male, suffering from type 2 diabetes mellitus, grade III obesity (BMI 45 kg/m2) and multiple metabolic disorders. Abdominal ultrasound revealed hepatomegaly during the last six months. Laboratory diagnostics showed increased serum transaminase levels. Serologic markers for viral hepatitis B and C were negative. The patient denied significant alcohol consumption. Liver biopsy and pathohistologic finding revealed macro- (III grade) and microvesicular (I grade) fatty degeneration, as well as mixed-cell portal infiltration with moderate liver fibrosis, corresponding to the typical presentation of NASH (Non Alcoholic Steatohepatitis). NASH treatment options include the reduction of body mass and an adequate antidiabetic and dislipidemia treatment. The aim of all therapeutic measures was to stop the progression of the disease, to prevent the progression of fibrosis and the development of cirrhosis.