Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis

AIM:To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis(AIH)and primary biliary cirrhosis(PBC)with AIH features.METHODS:Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined.The activity of periportal and lobular inflammation was scored0(none or minimal activity)to 4(severe),and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3.The infiltration of mononuclear cells positive for CD20,CD38,CD3,CD4,and CD8 and positive for immunoglobulins(IgG,IgM,and IgA)at the periportal areas(interface hepatitis)and in the hepatic lobules(lobular hepatitis)were semiquantitatively scored in immunostained liver sections(score 0-6).Serum aspartate aminotransferase(AST),immunoglobulins,and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions.RESULTS:Lobular hepatitis,hepatitic rosette formation,and emperipolesis were more extensive and frequent in AIH than in PBC.CD3+,CD4+,and CD8+cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC.The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC,but to a lesser degree in AIH.CD20+cells were mainly found in the portal tracts and,occasionally,at the interface in both diseases.Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration,specifically CD38+cells in PBC.No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH.While most AIH cases were IgG-predominant at the interface,PBC cases were divided into IgM-predominant,IgM/IgGequal,and IgG-predominant types,with the latter sharing several features with AIH.CONCLUSION:These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.     

Latent hepatitis B is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C

AIM:To study the potential association between hepatocellular carcinoma(HCC)in patients with chronic hepatitis C(CHC),cirrhosis and latent hepatitis B(LHB)infection,defined as the absence of detectable serum hepatitis B surface antigen(HBsAg)and the presence of hepatitis B core antibody(HBcAb).METHODS:This retrospective analysis is comprised of 185 cirrhotic patients with HCC who were hepatitis C virus antibody(HCV Ab)(+)and HBsAg(-)at Wayne State University between 1999 and 2008.From these,108 patients had HCV polymerase chain reaction confirmation of viremia while the remaining(77)were considered to have CHC on the basis of a positive HCV Ab and the absence of any other cause of liver disease.Controls were drawn from our institutional database from the same time period and consisted of 356 HBsAg(-)age,race and gender matched patients with HCV RNA-confirmed CHC and without evidence of HCC.A subgroup of controls included 118matched patients with liver cirrhosis.χ2test and t test were used for data analysis.RESULTS:Seventy-seven percent of patients in all3 groups were African Americans.Patients with HCC had a significantly higher body mass index(P=0.03),a higher rate of co-infection with human immunodeficiency virus(HIV)(P=0.05)and a higher prevalence of alcohol abuse(P=0.03)than the controls.More patients with HCC had LHB than controls(78%vs39%,P=0.01).Sixty three percent of patients with HCC were both hepatitis B surface antigen(HBsAb)(-)and HBcAb(+)compared to 23%of controls(P<0.01).When compared to cirrhotic controls,the frequency of HBcAb(+)remained higher in patients with HCC(78%vs 45%,P=0.02).Patients with HCC were more likely to be both HBsAb(-)and HBcAb(+)than the cirrhotic controls(63%vs 28%,P=0.01).Although not statistically significant,100%of CHC and HIV coinfected patients with HCC(n=11)were HBcAb(+)when compared to controls(44%;n=9).CONCLUSION:These data suggest that LHB occurs at a significantly increased frequency in patients with CHC and HCC than in patients with CHC without HCC.     

Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis: a comparative study

AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV p...     

Chronic hepatitis C genotype 1 virus: Who should wait for treatment?

Elucidation of the natural history of chronic hepatitis C(CHC)and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment(triple therapy)in favour of waiting for new drug availability for patients who are at low risk of progression to significant liver disease.Newer generation drugs are currently under development,and are expected to feature improved efficacy and safety profiles,as well as less complex and shorter duration delivery regimens,compared to the current standards of care.In addition,patients with cirrhosis and prior null responders have a low rate(around 15%)of achieving sustained virological response(SVR)with triple therapy,and physicians must also consider the decision to wait for new treatments in the future for these patients as well.Naive patients are the most likely to achieve a close to 100%SVR rate;therefore,it may be advisable to recommend that patients with mild to moderate CHC should wait for the newer therapy options.In contrast,patients with advanced fibrosis and cirrhosis will be those with the greatest need for expedited therapeutic intervention.There remains a need,however,for establishing definitive clinical management guidelines to maximize the benefit of waiting for new drugs and minimize risk of side effects and non-response to the current triple therapy.     

Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection

AIM:To evaluate the efficacy and tolerability of lowdose standard or pegylated interferon(PEG-IFN)in hepatitis C virus(HCV)-positive hemodialysis patients.METHODS:In total,19 patients were enrolled in this study,of which 12 received PEG-IFNα-2a 67.5μg 1time/wk(Group 1)and 7 received standard interferonα-2b subcutaneously 1.5×106 U 3 times/wk(Group2).The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3.All patients were prospectively followed after the completion of therapy.The efficacy and tolerability of the treatment were evaluated based on the sustained virological response(SVR)and treatment-related drop-out rate.RESULTS:In Group 1,11 of the 12 patients completed the treatment.Early virological response(EVR)and sustained virological response(SVR)rates were 83.3%and 91.7%,respectively.One patient withdrew from treatment due to an adverse event(leukopenia).The drop-out rate was 8.3%in this group.In Group 2,5 of the 7 patients completed the treatment with an EVR and SVR of 85.7%and 71.4%,respectively.Two patients withdrew due to treatment-related adverse events(nausea and depression).In this group,the drop-out rate was 28.6%.In total,16 of the patients attained EVR,and 15 of them completed the treatment.The SVR rate for the patients who attained EVR was93.7%.Anemia was the most frequent side effect and was observed in 10/19 patients(55.5%),but could be effectively managed with erythropoietin.CONCLUSION:Low-dose interferon monotherapy,either with PEG-IFNα-2a or standard interferonα-2b,is an effective treatment option for hemodialysis patients with chronic hepatitis C.     

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis

AIM:To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis(AIH) with or without centrilobular necrosis(CN).METHODS:Our study comprised 41 patients with biopsy-proven acute presentation(acute exacerbation phase 36,acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009.Elevated serum alanine aminotransferase(ALT)(> 5x upper limit of normal) identified acute presentation of the disease.We compared clinicopathological features of these AIH patients with or without CN.The data used for analysis included patient background(age,sex,type of disease,presence of complications with other autoimmune diseases,human leukocyte antigen,and International Autoimmune Hepatitis Group score),clinical parameters at presentation(ALT,alkaline phosphatase,IgG,anti-nuclear antibodies,and anti-smooth muscle antibodies),histology and therapy.RESULTS:CN was found in 13(31.7%) patients with acute presentation(acute exacerbation phase 10,acute hepatitis phase 3) of AIH.Serum IgG levels of patients with CN were significantly lower than those of patients without CN(mean:2307 mg/dL vs 3126 mg/dL,P < 0.05),while antinuclear antibody-negative rates were significantly higher(30.7%vs 3.5%,P < 0.05).However,other clinical features were similar between the two groups.The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN(F0-2:84.6% vs 35.7%,F3-4:15.4% vs 64.3%,P < 0.05).Other histological features were similar between the two groups.Although there was no significant difference between groups when evaluated using the revised original score(12 vs 14),the simplified AIH score of patients with CN was significantly lower(6 vs 7,P < 0.05).Frequency of DR4 was similar between patients with and without CN.CONCLUSION:CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH,although AIH with CN often shows clinical features of the genuine acute form.     

Influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (X2=6.33, P<0.025, RR=2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (X2=6.71, P<0.05). The positivity of HLA-DRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRBI *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.     

Models for predicting hepatitis B e antigen seroconversion in response to interferon-α in chronic hepatitis B patients

AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag1 log10 S/CO,and anti-HBc11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc11.4 S/CO,and decline in HBe Ag2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.     

Relationship between HBV genotypes and anti-viral therapeutic efficacy of interferon-alpha

BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-α (IFN-α) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-α were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-α in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-α was only observed in genotype B. The response to IFN-α in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patientswith partial or no response to IFN-α. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-α. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.     

Alcoholic hepatitis and concomitant hepatitis C virus infection

Hepatitis C virus(HCV)infection and alcohol abuse are two most important causes of chronic liver disease in the United States.Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality.About 20%of patients presenting with alcoholic hepatitis have concomitant HCV infection.Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage.Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection.The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research.     

Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders

During the course of chronic hepatitis C virus(HCV)infection,various extrahepatic manifestations of autoimmune disorders may occur,including arthralgia/arthritis,sicca complex,purpura,cutaneous ulcer,and thyroid dysfunction.In addition,the prevalence of circulating autoantibodies is high among patients with HCV infection.Commonly detected autoantibodies in HCVinfected patients include rheumatoid factor,antinuclear antibody,anti-SSA/anti-SSB antibody,cryoglobulin,antineutrophil cytoplasmic antibody,anti-smooth muscle antibody,anti-liver and anti-thyroid autoantibodies.These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection.A possible reason for antibody production is overactivation and proliferation of B lymphocytes,via the interaction with the surface protein of HCV.Because immunotherapy can cause HCV flare-up or liver damage,overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided.This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection.     

Prevalence of coeliac disease in patients with autoimmune thyroiditis in a Turkish population

AIM:To investigate the prevalence of coeliac disease in a series of Turkish patients with autoimmune thyroiditis.METHODS:Sera from 136 consecutive patients with newly diagnosed autoimmune thyroiditis and 119 healthy blood donors were tested for IgA tissue transglutaminase antibody with enzyme-linked immunosorbent assay.Endoscopic mucosal biopsy from the second part of duodenum was performed in patients with positive antibody test.RESULTS:Eight patients(5.9%)and one control subject(0.8%)were positive for IgA tissue transglutaminase antibody(OR:7.38,95% CI:0.91-59.85,P = 0.04).Six patients and one control agreed to take biopsies.Histopathological examination revealed changes classified as Marsh Ⅲa in one,Marsh Ⅱ in one,Marsh Ⅰ in two,and Marsh 0 in two patients with autoimmune throiditis,and MarshⅠin one blood donor.CONCLUSION:Turkish patients with autoimmune thyroiditis have an increased risk of coeliac disease and serological screening may be useful for early detection of coeliac disease in these patients.Our findings need to be confirmed in a larger series of patients.     

Role of international criteria in the diagnosis of autoimmune hepatitis

AIM: To study the clinical and laboratory characteristics of autoimmune hepatitis (AIH), and compare them with International Autoimmune Hepatitis Group (IAHG) criteria. METHODS: Sixty consecutive patients with AIH attended the University Clinic at Tabriz University of Medical Sciences, Iran for a 12mo period and were assessed in a case series study. Serological and biochemical evaluations were carried out in all patients. Autoantibodies, such as antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody (ALKM-1) type 1, and perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) were evaluated in these patients. A liver biopsy was performed after diagnosis of the disease. Patients were evaluated in terms of their signs and symptoms, and laboratory results and the degree to which they corresponded with the diagnostic criteria of IAHG. In this study, both a comprehensive diagnostic scoring system and a simplified diagnostic scoring system were employed for AIH.RESULTS: Sixty patients, 2-0 male, 40 female, mean age 39.45 ± 17.50 years, participated in the study. Treatment began immediately after enrolment into the study. The percent distribution of the study population into definite and probable did not change after the treatment. The most common symptoms in descending order were fatigue (100%), icter (66.7%), abdominal discomfort (33.3%), abdominal distension (2-8.3%), dark urine (2-3.3%), edema (2-3.3%), hematemesis (2-0.0%), pruritus (2-0.0%), melena (11.7%) and pale stool (10.0%). At the physical examination, splenomegaly, ascites, hepatomegaly, epigastric tenderness and an abdominal mass were found in 50.0%, 16.7%, 13.3%, 5.0% and 3.3% of patients, respectively. Hypergammaglobulinemia was detected in 95.0% of cases. ALKM-1, P-ANCA, ANA and ASMA were positive in 71.4%, 66.7%, 42-.4% and 19.4% of cases, respectively. Portal hypertensive gastropathy (45.0%), esophageal varices (41.7%) and cirrhosis (40.0%) were the most prevalent complications of AIH, and there was     

Expression of interferon-alpha／beta receptor protein in liver of patients with hepatitis C virus-related chronic liver disease

ABM: To study the expression of interferon-alpha/beta (IFN-α/β) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance. METHODS: A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC). CHC patients were treated with five megaunits of interferon-α1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and non-responsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-α/β receptor (IFN-α/βR) protein in liver of all patients was determined with immunofluorescence. RESULTS: In liver of patients with HCV-related chronic liver disease, the expression of IFN-α/βR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic lobules. The weak positive, positive and strong positive expression of IFN-α/βR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong positive expression. In the non-responsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-α/βR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group. CONCLUSION: Expression of IFN-α/βR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.     

Autoimmune hepatitis,one disease with many faces:Etiopathogenetic,clinico-laboratory and histological characteristics

Autoimmune hepatitis(AIH) is an unresolving progressive liver disease of unknown etiology characterized byhypergammaglobulinemia,autoantibodies detection and interface hepatitis.Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical,laboratory and histological features,AIH diagnosis may be potentially difficult.Therefore,in this in-depth review we summarize the substantial progress on etiopathogenesis,clinical,serological and histological phenotypes of AIH.AIH has a global distribution affecting any age,both sexes and all ethnic groups.Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis.Hypergammaglobulinemia with selective elevation of IgG is found in most cases.Autoimmune attack is perpetuated,possibly via molecular mimicry,and favored by the impaired control of T-regulatory cells.Histology(interface hepatitis,emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic,are still the hallmark for a timely diagnosis.AIH remains a major diagnostic challenge.AIH should be considered in every case in the absence of viral,metabolic,genetic and toxic etiology of chronic or acute hepatitis.Laboratory personnel,hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.     

Autoimmune hepatitis in human immunodeficiency virus-infected patients: A case series and review of the literature

BACKGROUND Abnormal liver chemistry is a common problem in human immunodeficiency virus(HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity,and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals; however, this condition has been increasingly reported over the past few years.CASE SUMMARY We present 13 HIV-infected patients(5 males and 8 females) who developed autoimmune hepatitis(AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 10~6 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were178 and 177 U/m L, respectively. Elevation of immunoglobulin G levels was present in 11(85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11(85%) and 5(38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible withAIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications.CONCLUSION This report underscores the emergence of autoimmune hepatitis in the context of HIV infection.     

Natural YMDD-motif mutants affect clinical course of lamivudine in chronic hepatitis B

AIM:To investigate the prevalence of nature tyrosinemethionine-aspartic acid-aspartic acid motif mutations in chronic hepatitis B(CHB)patients and to evaluate the efficacy of lamivudine.METHODS:A total of 1268 CHB patients were recruited from the outpatient and inpatient departments of six centers.Tyrosine-methionine-aspartic acid-aspartic acid(YMDD)mutations were analyzed using the hepatitis B virus(HBV)drug resistance line probe assay.Forty voluntary patients were selected from those with positive or negative natural YMDD mutations to undergo treatment with lamivudine.RESULTS:YMDD mutations were detected in 288(22.71%)of the 1268 CHB patients.Multivariate analysis revealed that the patients’HBV DNA level(P=0.0282)and hepatitis B e antigen status(P=0.0133)were also associated with natural YMDD mutations.The rates of normalization of alanine aminotransferase levels and HBV DNA nondetection at 6,24,36,and 48 wk were compared between the patients with natural YMDD mutations and those without,and the differences were not significant.However,there was a significant difference in the cumulative emergence rates of virological breakthrough at 48 wk in the patients with natural YMDD mutations and those without(32.5%vs 12.5%,P=0.032).CONCLUSION:Naturally occurring YMDD mutationsare detectable in a large proportion of CHB patients;breakthrough hepatitis tended to occur in patients with natural YMDD mutations.     

Serum concentration of sFas and sFasL in healthy HBsAg carriers,chronic viral hepatitis B and C patients

AIM:To estimate the amount of apoptosis among healthyHBsAg carriers,patients with chronic HBV infection treatedwibh lamivudine and patients with chronic HCV infection treatedwith interferon alpha and ribavirin.Activity of apoptosis wasevaluated by serum sFas/sFasL concentration measurement.Moreover dependence between apoptosis and HBV-DNA orHCV-RNA levels was studied.METHODS:Eighty-six persons were included into study:34healthy HBsAg carders,33 patients with chronic HBV infecl~onand 19 patients with chronic HCV infection.Serum levels ofsFas/sFasL were measured by ELISA assay.HBV-DNA andHCV-RNA were measured by RT-PCR assay.Levels ofsFas/sFasL were determined before and 2 and 12 wk aftertherapy in patients with chronic hepatitis B and C infection.HBV-DNA or HCV-RNA was detected before treatment and 6mo after treatment.RESULTS:Twenty-four (71%) healthy HBsAg carders showedHBV-DNA over 10~5/mL,which was comparable to the patientswith chronic hepatitis B.independently from HBV-DNA levels,the concentration of sFas among healthy HBsAg carders wascomparable to healthy persons.Among patients with chronichepatitis B and C,the concentration of sFas was significantlyhigher in comparison to healthy HBsAg carriers and healthypersons.In chronic hepatitis B patients the concentrationof sFas was decreased during lamivudine treatment.Amongchronic hepatitis C patients the concentration of sFas wasincreased during IFN alpha and ribavirin treatment,sFasLwas not detected in control group.Furbhermore sFasL occurredmore frequently in chronic hepatitis C patients in comparisonto chronic hepatitis B patients.CONCLUSION:There are no correlations between apoptosisand HBV-DNA levels.However ther is an association betweenapoptosis and activity of inflammation in patients with chronicHBV infection.Apoptosis can be increased in patients withchronic hepatitis C by effective treatment which may be aresult of apoptosis stimulation by IFN-α.     

Flow cytometry assay of myeloid dendritic cells （mDCs） in peripheral blood during acute hepatitis C： Possible pathogenetic mechanisms

AIM:To asses the expression of myeloid dendritic cells(CD11c )subset during acute HCV hepatitis and itspossible involvement in natural history of the infection.METHODS:We enrolled 11 patients with acute hepatitisC(AHC)(Group A),10 patients with acute hepatitis A(AHA)(as infective control-Group B)and 10 healthydonors(group C)in this study.All patients underwentselective flow cytometry gating strategies to assess theperipheral number of the myeloid dendritic cells(mDCs)to understand the possible role and differences duringacute hepatitis.RESULTS:Eight of 11 patients with acute HCV hepatitisdid not show any increase of mDCs compared to healthyindividuals,while a significant decrease of mDCs wasfound in absolute cell count(z=-2.37;P<0.05)andpercentage(z=-2.30;P<0.05)as compared with AHA.On the contrary,The remaining three patients of thegroup A had a higher mDCs number and percentage asoccur in group B.Interestingly,after six months,thosepatients did not show any increase of mDCs subset werechronically infected,while the three subjects with anincrease of peripheral mDCs,as in HAV acute infection,resolved the illness.CONCLUSION:The lack of increase of mDCs duringacute hepatitis C might be an important factor involvedin chronicization of the infection.     

Seroprevalence of anti-HAV among patients with chronic viral liver disease

AIM:To investigate the current seroprevalence of hepatitis A virus(HAV) antibodies in patients with chronic viral liver disease in Korea.We also tried to identify the factors affecting the prevalence of HAV antibodies. METHODS:We performed an analysis of the clinical records of 986 patients(mean age:49±9 years,714 males/272 females) with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS:The overall prevale...