Damage In Hepatitis Research Articles

Haptoglobin 2-2 Genotype is Related to the Severity of Liver Damage in Hepatitis B Patients with Liver Steatosis.

The Haptoglobin (Hp) genotypes have been linked to immune diseases and play a significant role in metabolic diseases. This study aimed to analyze the correlation between Hp gene polymorphism and the severity of hepatitis B accompanied by liver steatosis. A total of 182 with Hepatitis B and concurrent hepatic steatosis were included in the study. Clinical biochemical indices for each participant were recorded. DNA was extracted from peripheral blood leukocytes for globin genotyping. Of these participants, 128 underwent biopsy from which histological data were collected. Subjects with hepatitis B and hepatic steatosis carrying the Hp 2-2 genotype exhibited elevated alanine transaminase (ALT), c-glutamyl transferase (GGT), and aspartate amino transferase (AST) levels. In contrast, high-density lipoprotein (HDL) levels and the copy number of Hepatitis B Virus (HBV)-DNA were significantly reduced in those with the Hp 2-2 genotype (p < 0.05). Furthermore, individuals processing the Hp 2-2 genotype demonstrated a heightened hepatitis score and advanced fibrosis stage (p < 0.05). Notably, the Hp 2-2 genotype was independently associated with increased inflammation (odds ratio (OR) = 7.059, p < 0.001) and progressive fibrosis (OR = 3.05, p < 0.022). The Hp 2-2 genotype is significantly associated with increased severity in cases of hepatitis B with coexisting hepatic steatosis.

The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

Increased HERV-K(HML-2) Transcript Levels Correlate with Clinical Parameters of Liver Damage in Hepatitis C Patients.

Chronic hepatitis C virus (HCV) infection is closely associated with a plethora of diseases, including cancers and autoimmune disorders. However, the distinct triggers and cellular networks leading to such HCV-derived diseases are poorly understood. Around 8% of the human genome consists of human endogenous retroviruses. They are usually silenced but can be reactivated by environmental conditions, including viral infections. Our current understanding indicates that the activation of one specific family—namely, HERV-K(HML-2)—is linked to distinct pathologies, including cancer and autoimmunity. In this study, we analyzed the transcription levels of HERV-K(HML-2) in 42 HCV-infected patients receiving direct-acting antiviral therapies. Samples from the start of treatment until 12 weeks post-treatment were investigated. Our results show increased HERV-K(HML-2) transcript levels in patients with HCV-derived liver cirrhosis throughout the observation period. Several clinical parameters specifying poor liver function are positively correlated with HERV-K(HML-2) expression. Of note, patients without a sustained viral clearance showed a drastic increase in HERV-K(HML-2) transcript levels. Together, our data suggest that increased HERV-K(HML-2) expression is correlated with reduced liver function as well as therapy success in HCV-infected patients.

Albumin binding function is a novel biomarker for early liver damage and disease progression in non-alcoholic fatty liver disease.

Indicators to assess early liver damage and disease progression in nonalcoholic fatty liver disease (NAFLD) remain unsatisfactory. Albumin binding function has been reported to be an early indicator of liver damage in hepatitis and liver cirrhosis. However, its role in NAFLD patients is unknown. An age/sex-matched, case-control study was performed. Albumin-binding capacity (ABiC) and albumin metal ion binding ability, assessed by ischemia modified albumin (IMA), were measured. Correlation analysis was performed to assess the association of albumin binding function with liver function enzymes and noninvasive liver fibrosis markers. A total of 80 NAFLD patients and 41 healthy controls were included. Albumin binding function was significantly lower in NAFLD (ABiC: 196.00%, p < 0.001; IMA transformed (IMAT): 0.461, p < 0.001; and IMAT/albumin: 0.947 × 10-2, p < 0.001) than controls (ABiC: 211.00%; IMAT: 0.575; and IMAT/albumin: 1.206 × 10-2). Albumin binding function was also found to be significantly different among healthy participants and different severity groups of NAFLD (p < 0.001). Besides, albumin binding function showed positive correlation with BMI (ABiC: r = -0.247, p = 0.011; IMAT: r = -0.243, p = 0.013; IMAT/albumin: r = -0.254, p = 0.009) and FIB-4 index (ABiC: r = 0.230, p = 0.029). The ROC curve suggested that albumin binding function combined with BMI and triglyceride may predict the presence of NAFLD (area under ROC (AUROC) = 0.935, p < 0.001). Our findings suggest albumin binding function is a novel biomarker for early liver damage and disease progression in NAFLD.

Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients.

Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r=0.384, P=0.009) and glutamic-pyruvic transaminase (r=0.293, P=0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.

Microbial translocation is correlated with HIV evolution in HIV-HCV co-infected patients.

Microbial translocation (MT) is characterized by bacterial products passing into the blood through the gut barrier and is a key phenomenon in the pathophysiology of Human Immunodeficiency Virus (HIV) infection. MT is also associated with liver damage in Hepatitis C Virus (HCV) patients. The aim of the study was to assess MT in plasma of HIV-HCV co-infected patients. 16S rDNA (16 S Ribosomal DNA subunit) marker and other markers of MT such as Lipopolysaccharide (LPS)-binding protein (LBP), soluble CD14 (sCD14), intestinal fatty acid binding protein (I-FABP) were used. Clinical, biological and immunological characteristics of the population were studied in order to correlate them with the intensity of the MT. We demonstrate that indirect markers of MT, LBP and CD14s, and a marker of intestinal permeability (I-FABP) are significantly higher in HIV-HCV co-infected patients than in healthy controls (17.0 vs 2.6 μg/mL, p < 0.001; 1901.7 vs 1255.0 ng/mL, p = 0.018); 478.3 vs 248.1 pg/mL, p < 0.001, respectively), while a direct marker of MT (16S rDNA copies) is not different between these two populations. However, plasma 16S rDNA was significantly higher in co-infected patients with long-standing HIV infections (RGM = 1.47 per 10 years, CI95% = [1.04:2.06], p = 0.03). Our findings show that in HIV-HCV co-infected patients, plasma 16S rDNA levels, directly reflecting MT, seem to be linked to the duration of HIV infection, while elevated levels of LBP and sCD14 reflect only a persistence of immune activation. The levels of these markers were not correlated with HCV evolution.

Exploratory Studies of (-)-Epicatechin, a Bioactive Compound of Phyllanthus niruri, on the Antioxidant Enzymes and Oxidative Stress Markers in D-galactosamine-induced Hepatitis in Rats: A Study with Reference to Clinical Prospective.

Background:Hepatitis is a health problem affecting millions of people worldwide and it is the major risk factor for liver cirrhosis. In India, many plants are used to treat hepatitis. But little is known about the effects of (-)-epicatechin a bioactive compound of Phyllanthus niruri (PN) in hepatitis rats.Objective:The present study was designed to explore the antioxidant property of (-)-epicatechin isolated from PN in D-Galactosamine (D-GalN) induced hepatitis rats.Materials and Methods:The rats are divided into five groups as per the experimental design. (-)-Epicatchin pretreatment was given to the hepatitis rats for 21 days and biochemical analysis was carried out. The hepatic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA) and serum markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, and bilirubin are estimated.Results:All the antioxidant enzymes activities and albumin levels are depleted in hepatitic rats. Whereas GST, ALP, AST, ALT activities and MDA, and bilirubin levels are elevated in hepatitis rats, (-)-epicatechin pretreatment increased all the antioxidant enzymes and decreased the GST, ALP, AST, ALT, and MDA levels in hepatitis rats. However, histopatholoigic studies also proves that (-)-epicatechin pretreatment decreased the tissue damage in hepatitis condition. This is the first report on the antioxidant enzymes and hepatoprotective effect of (-)-epicatechin in hepatitis rats.Conclusion:From this study, we conclude that (-)-epicatechin treatment decreased the oxidative damage in hepatitis rats.SUMMARY The present study was carried out to know the impact of (-)-epicatechin on antioxidant enzymes activities in hepatitis rats. From this study, we found that the antioxidant enzymes SOD, CAT, GPx, GR, GSH depleted in hepatitis rats and increased with (-)-epicatechin in hepatitis rats.MDA levels increased in hepatitis rats and decreased with (-)-epicatechin in hepatitis rats. From this study, we concluded that (-)-epicatechin will be useful to treat hepatotoxicity in rats. Abbreviations used: Phyllanthus niruri (PN), D-Galactosamine (D-GalN), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), glutathione s transferase (GST), reduced glutathione (GSH) and malondialdehyde (MDA) aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), World Health Organisation (WHO), Indian Institute of Science (IISc), Nicotinamide adenine dinucleotide phosphate (NADPH), thiobarbituric acid reactive substances (TBARS)

Evaluation of miR-122 level in the plasma of chronically HCV infected patients

MicroRNAs (miRNAs) are small non-coding RNA molecules, which have an important function in regulating RNA stability and gene expression. They also can circulate in a cell-free form in the blood thatmakes them potential disease markers. The liver contains various classes of miRNAs in which miR-122 accounts for about 70% of all miRNAs and it has been proved that its level increases in case of liver damage. Here, we investigated plasma levels of miR-122 as a useful disease parameter in patients with chronic hepatitis C (CHC) infection. Thirty five hemophilia and thalassemia patients with CHC were studied. The total RNA was extracted from plasma samples, and miR-122 levels were measured by qPCR and then compared with the specific liver markers. The plasma levels of alanine transaminase (ALT) and aspartate transaminase(AST) were correlated with plasma miR-122 level in CHC patients, and the level of circulating miR-122 in healthy individual groups were rarely lower than those of patients with CHC. In our study, miR-122 levels correlated well with markers of liver inflammatory activity. Plasma miR-122 can be assumed to be another marker in liver similar to the currently used specific markers such as ALT and AST for evaluation of liver damage in hepatitis C virus (HCV) infected patients. Moreover, the correlation between miR-122 and ALT was shown to be higher than between miR-122 and AST.

T cell-mediated immunopathologic mechanism of liver injury in acute viral hepatitis (HUM8P.336)

Abstract CD8+ T cells play an important role in immune responses against intracellular infection. They recognize and lyse infected cells, and secrete anti-viral cytokines to control infection. However, excessive immune responses may lead to tissue damage during infection. In particular, severe CD8+ T cell-mediated liver injury is known as a primary cause of tissue damage in hepatitis A virus (HAV) infection. In this study, we demonstrate that during acute viral hepatitis, CD8+ T cells specific to HAV-unrelated viruses such as influenza virus, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) became activated even in the absence of those viral reactivations, which means that non-HAV-specific CD8+ T cells are able to be activated even without cognate antigen. Interestingly, the severity of liver injury correlated with the activation of these non-HAV-specific T cells, not with activation of HAV-specific T cells. HAV-infected cells produced IL-15, which induced antigen-nonspecific activation of CD8+ T cells. IL-15-activated CD8+ T cells exerted NK-like cytolytic activity by NKG2D dependent manner, even without T cell receptor engagement. HAV-infected hepatocytes overexpressed NKG2D ligands and, thus, could be cytolytic targets during HAV infection. We report a human viral disease in which host injury is attributed to NK-like cytolytic activity of IL-15-activated CD8+ T cells not specific to the infecting virus.

Autoimmune hepatitis in two psoriasis patients treated with inflixmab

To the Editor: A 37-year-old man was referred to our hospital with a 12-year history of severe plaque-type psoriasis without psoriatic arthritis. He did not drink alcohol. His only medication was omeprazole for a hiatal hernia. Six weeks after the third infusion of infliximab (5 mg/kg at weeks 0, 2, and 6), the patient complained of asthenia, abdominal pain, and arthritis of the wrist. No other drugs or alcohol were taken. Blood tests (Table I) showed a strong elevation in transaminase levels, without evidence of cholestatis, but with positive tests for antinuclear antibodies (ANA), double stranded DNA antibodies, and smooth muscle antibodies. Viral serologies were negative. Computed tomography of the liver was normal. No liver biopsy was performed. Spontaneously, the liver function tests (LFTs) became normal within 2 months, with a disappearance of the clinical symptoms. The hepatologist diagnosed autoimmune hepatitis (AIH). Infliximab was responsible for AIH for three reasons: (1) there was no other explanation for the AIH; (2) the delay of 10 weeks between the last infusion and the hepatitic damage; and (3) the spontaneous and complete recovery after stopping infliximab. Table IResults of blood tests after the third infusion of infliximab Laboratory tests Case 1 Case 2 Reference range ALT (IU L−1) 1126 768 10–45 AST (IU L−1) 424 584 10–65 Gamma glutamyl transferase (IU L−1) 240 425 5–65 Alakaline phosphatase (IU L−1) 181 391 30–130 Total bilirubin (pmol L−1) 13 54 0–20 Antinuclear antibody titer 1/200 1/2560 0–1/80 Anti-dsDNA (IU mL−1) 19.5 22,4 < 4.5 Anticardiolipin antibodies (GPL mL−1) 0 40 < 24 Anti–smooth muscle antibody titer 1/100 0 < 1/50 Antimitochondrial antibody titer 0 1/600 <1/50 Hepatitis A, B, and C serology 0 0 0 EBV and CMV serology 0 0 0 ALT, Alanine aminotransferase; AST, aspartate aminotransferase; CMV, cytomegalovirus; dsDNA, double stranded DN; EBV, Epstein–Barr virus; GPL, IgG phospholipid; IU, international unit. Open table in a new tab ALT, Alanine aminotransferase; AST, aspartate aminotransferase; CMV, cytomegalovirus; dsDNA, double stranded DN; EBV, Epstein–Barr virus; GPL, IgG phospholipid; IU, international unit.

Occupational coke oven emissions exposure and risk of abnormal liver function: modifications of body mass index and hepatitis virus infection

ObjectivesOccupational coke oven emissions (COEs) have been considered an important health issue. However, there are no conclusive data on human hepatic injury due to COE exposure. The association of COE...

Steatosis is a lot more than holes in hepatocytes

Chronic hepatitis C infection remains a common and significant cause of liver disease leading to end-stage cirrhosis and liver failure. It is also a common indication for the necessity of a liver transplant. Histologically, chronic inflammation and fibrosis are characteristic features of this disease. The stage and grade of the disease process is measured by the amount of fibrosis and severity of the inflammation. Focal fatty change is a known histological finding of hepatitis C infection. However, the exact significance of such a finding is not clear. In this issue, Zubair et al.[1] demonstrated that the presence of fat, especially macrovesicular steatosis, is associated with a higher stage of fibrosis. They used a routine histological analysis as well as a morphometric evaluation to demonstrate an association. The authors suggested that such fat may result from mitochondrial oxidative stress. Hence, along with viral infection and inflammation, the presence of fat may also modulate the progression of this disease. Fat accumulation is known to cause fibrosis in alcoholic and non alcoholic fatty liver disease. Such changes may occur due to the release of adipocytokines causing tissue damage.[2–4] In addition, mitochondrial oxidative stress may lead to the activation of proinflammatory and fibrogenic factors.[5–7] It is, however, interesting to note that only macrovesicular steatosis has a pronounced effect on an advanced hepatitis C induced lesion. This point is of significant interest from a pathogenetic point of view. However, although this study was not designed to answer the reasons behind such findings, it suggested a possible relationship. In previous studies, it has been shown that serum HCV RNA levels correlate with histological liver damage and concur with steatosis and a high viral load acts together with steatosis in accelerating the progression of liver injury.[8] In an earlier study, this group had also demonstrated that patients with genotype 3a showed a significantly higher prevalence of steatosis compared with those infected with other genotypes.[9] In another study, although hepatic steatosis was not associated with HCV RNA levels, it was associated with being overweight, hepatic fibrosis, and triglyceride levels in chronic hepatitis C infection.[10] Nevertheless, an inevitable question that may arise is whether an assessment of a change in fat is to be included in a routine pathology report to determine a prognosis. This is not easy to answer. However, larger multi-center studies may be required to address such questions. A large-scale study with a detailed clinico-pathological correlation may provide valuable insight. Furthermore, investigations as to the specific mechanisms by which only macrovesicular fat causes tissue damage are very important. Such analysis may have far reaching implications and may also be of importance in other liver diseases associated with fat accumulation in the hepatocytes. Understanding pathogenetic mechanisms is fascinating but a difficult undertaking. Extensive basic science research is needed to address these questions. We need to have concerted efforts involving hepatologists, pathologists, translational researchers, and basic scientists to identify such pathogenetic mechanisms since only a better understanding of such pathogentic mechanisms will lead to the development of specific treatment for advanced tissue damage in hepatitis.

Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C

Nucleic acid damage by reactive nitrogen and oxygen species may contribute to inflammation-related carcinogenesis. To investigate the extent of nucleic acid damage in hepatitis C virus infection and its change after interferon treatment, we measured 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the liver of patients with chronic hepatitis C (CHC) before and after interferon therapy. Hepatic accumulation of 8-nitroguanine and 8-OHdG was immunohistochemically evaluated in 20 CHC patients and 7 control patients with non-alcoholic fatty liver. Immunoreactivities of 8-nitroguanine and 8-OHdG were strongly detected in the liver from patients with CHC, but not in control livers. 8-Nitroguanine accumulation was found not only in infiltrating inflammatory cells, but also hepatocytes particularly in the periportal area. The accumulation of 8-nitroguanine and 8-OHdG increased with inflammatory grade (8-nitroguanine; P = 0.0019, 8-OHdG; P = 0.0009). In the sustained virological responder group after interferon therapy, 8-nitroguanine and 8-OHdG accumulation were markedly decreased in the liver (8-nitroguanine; P = 0.018, 8-OHdG; P = 0.018). In this study, we demonstrated for the first time that 8-nitroguanine accumulated in the liver of patients with CHC. 8-Nitroguanine is a useful biomarker to evaluate the severity of HCV-induced chronic inflammation in relation to hepatocellular carcinoma.

Acute hepatitis E: A cause of lymphocytic destructive cholangitis

Lymphocytic destructive cholangitis is a histological pattern associating bile duct intraepithelial lymphocytic infiltration and bile duct epithelial damage. Lymphocytic destructive cholangitis is an important diagnostic feature of primary biliary cirrhosis, but it can also be seen in primary sclerosing cholangitis, autoimmune hepatitis, the so-called overlap syndrome, acute or chronic viral hepatitis C, drug-induced hepatitis, and acute rejection or graft-versus-host disease in liver or bone marrow transplantation. In the present paper we report a case of acute hepatitis with lymphocytic destructive cholangitis on liver biopsy. Clinical and biological examinations showed that the patient had hepatitis E with no other cause of liver disease. Therefore, hepatitis E should be considered as a diagnostic possibility when liver biopsy shows acute hepatitis and lymphocytic destructive cholangitis. The mechanism of bile duct damage in hepatitis E remains unknown.

CD28-negative CD8-positive cytotoxic T lymphocytes mediate hepatocellular damage in hepatitis C virus infection.

The pathogenic mechanism for hepatocellular damage in hepatitis C virus (HCV) infection has not been clearly understood. Analysis of costimulatory molecules on lymphocytes may give us insight into the pathogenic mechanism of hepatocellular damage in HCV infection. Peripheral blood mononuclear cells (PBMCs) and liver infiltrating mononuclear cells (LIMCs) isolated from the HCV-infected patients were analyzed with antibodies directed against a variety of costimulatory molecules by flow cytometry. Blocking experiment against HLA-A24-restricted HCV-specific CTLs and immunohistochemical analysis were also performed. PBMCs expressing CD8, CD28, CD80, or CD154 were significantly reduced in HCV-infected patients compared with the healthy controls. CD28(+)CD8(+) PBMCs in the patients inversely correlated with ALT levels. Conversely, levels of CD28(-)CD8(+) LIMCs correlated with ALT levels. HCV-specific CTL activity was blocked by the treatment with anti-CD8 antibody, but not with anti-CD4 or anti-CD28 antibody. Immunohistochemical analysis revealed the accumulation of CD28(+) cells around the portal area in the liver of a patient with chronic active hepatitis C. These results suggest that CD28(+)CD8(+) T cells leave the circulation, move to the livers, and are activated in the portal area in proportion to the extent of liver diseases. CD28(-)CD8(+) T cells may finally function as effector T cells causing the hepatocellular damage in HCV infection.

Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C virus-infected recipients following liver transplantation

1. Hepatitis C virus (HCV) infection in the allograft occurs in the setting of greater viral burdens than in patients pretransplantation. 2. Viral burden is increased by such immunosuppressive therapies as corticosteroids and interleukin-2 receptor antibodies. 3. Cholestatic HCV infection occurs in the setting of very high viral load and is almost certainly induced by overimmunosuppression. It is managed best by rapid reduction in levels of immunosuppression. 4. The more common chronic hepatitic HCV disease seems to behave at the molecular/cellular level in a fashion similar to the nontransplantation setting with activation of T helper subtype 1 inflammatory, profibrotic, and proapoptotic pathways. The role of immunosuppression in the acceleration of this disease is unclear, and rapid reduction in immunosuppressive doses may be detrimental. 5. Changes to definitions of types of HCV disease recurrence, disease severity, and acute allograft rejection in the presence of HCV infection are required to improve understanding of the pathogenesis.

Surprising lack of association of prior alcohol consumption on hepatitis C infection and hepatic histology

Background: Chronic alcoholism is common in patients with chronic hepatitis C (CHC) infection. Alcohol can exacerbate liver damage in hepatitis C infection by causing oxidative stress. Heavy alcohol consumption has been associated with higher levels of viremia and more advanced fibrosis. Studies have also suggested that chronic alcoholism causes more rapid progression to cirrhosis and hepatocellular carcinoma in patients with CHC, however alcohol intake has been poorly quantified in these studies.

A novel cytotoxic T-cell epitope presented by HLA-A24 molecule in hepatitis C virus infection

Background/Aims : It has been suggested that cytotoxic T lymphocytes (CTL) have crucial roles for the hepatocellular damage in hepatitis C virus (HCV) infection. A series of CTL epitopes located in the HCV protein have been identified. However, no CTL epitopes restricted by HLA-A24, a common HLA allele in humans, has been identified. Methods : Peripheral blood and liver infiltrating mononuclear cells from the patients with hepatitis C virus infection and healthy controls were stimulated with a series of peptides containing HLA-A24 binding motifs located in HCV protein. Results : An immunodominant HLA-A24 restricted CTL epitope (A24-4; AYSQQTRGL, amino acids 1031–1039) presented by HLA-A24 molecule was identified using a series of synthetic peptides containing the HLA-A24 binding motifs. The CTL activity against this peptide was induced both in peripheral blood and liver infiltrating mononuclear cells from HLA-A24-positive chronic hepatitis C patients, not from HLA-A24-negative patients and HLA-A24-positive healthy controls. CTL activity was blocked by anti-HLA-A24 and anti-CD8 antibodies, not by anti-CD4 antibody. Furthermore, the A24-4-specific CTL recognized the HCV gene transfected target cells. Conclusions : Because this peptide is presented by a common HLA class I molecule, it might be useful for protection against hepatocellular damage and vaccine development in large population of the HCV-infected patients.

Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Consensus Interferon Study Group.

Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including procollogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients. Patients were anti-HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients (382+/-31 vs 110+/-9 microg/L respectively, P< 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179+/-11 microg/L) compared with patients without fibrosis (62+/-20 microg/L; P< 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R=0.5421, P<0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 microg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively. Serum HA measurement may be clinically useful to non-invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis.

Mutation of nucleotide 1,762 in the core promoter region during hepatitis B e seroconversion and its relation to liver damage in hepatitis B e antigen carriers.

In chronic hepatitis B virus (HBV) infection, mutations develop frequently at nucleotides 1,762/1,764 in the X protein open reading frame, where the core promoter is also located. By using a modified allele-specific polymerase chain reaction method, the longitudinal emergence of the A-->T mutation at nucleotide 1,762 was studied in relation to precore mutations, genotype, and liver damage. First, samples from 38 carriers that were drawn before and after hepatitis B e (HBe) seroconversion were tested. T-1,762 mutant strains increased during HBe seroconversion (P = 0.004). In the HBe antigen-negative (HBeAg-) phase, T-1,762 mutants were found in 71% (12 of 17) of patients without compared with 33% (6 of 18) of patients with a concomitant precore mutation that prevents HBeAg synthesis (P = 0.08). Second, in 55 HBeAg+ patients, the T-1,762 mutant was found to be associated with more liver inflammation (P = 0.04) and fibrosis (P = 0.02), as measured by histology activity index (HAI) scores. The results show that the nucleotide (nt) 1,762 A-->T mutation often develops during HBe seroconversion, particularly in strains without precore mutations that prevent HBeAg production. For unknown reasons, the T-1,762 mutant was rare in genotype B strains. The presence of a T-1,762 mutant in the HBeAg+ phase may be useful for identifying immunoactivation in previously immunotolerant carriers, which could be valuable for selecting patients for interferon therapy.