Various Stages Of Liver Disease Research Articles

Recompensation of Liver Cirrhosis by TIPS Reduces Epithelial Cell Death Markers, Translating Into Improved Clinical Outcome.

Portal hypertension is the main pathophysiological driver of decompensation in patients with liver cirrhosis. Epithelial cell death markers, m30 and m65, correlate with hepatic injury and predict outcomes across various stages of liver disease. We aim (i) to evaluate whether portal hypertension itself contributes to liver outcome-relevant epithelial injury, and (ii) to analyse the capacity of m30/m65 to predict outcome in patients receiving a transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites. Sixty-six patients undergoing TIPS placement for refractory ascites and 20 patients with compensated cirrhosis as controls were prospectively enrolled in this monocentric cohort study. Epithelial cell death markers were analysed pre-TIPS, as well as 1-3 and 6-9 months post-TIPS. The capacity of baseline levels of m30/m65 in predicting six-month transplant-free survival rates was analysed by multivariable Cox proportional hazards regression. Levels of m30 and m65 were higher in patients with decompensated cirrhosis (pre-TIPS) compared with compensated cirrhosis (controls). Following correction of portal hypertension by TIPS and recompensation, both markers decreased over time, reaching levels comparable to patients with compensated cirrhosis. On multivariable analysis, pre-TIPS baseline levels of m30 and m65 were not predictive for six-month survival. Correction of portal hypertension via TIPS reduces levels of epithelial cell death markers, indicating that portal hypertension is a driver of outcome-relevant, hepatic cell death in patients with decompensated cirrhosis. Baseline m30/m65 values do not affect six-month survival rates, which suggests that TIPS placement overcomes the unfavourable spontaneous prognosis otherwise indicated by elevated baseline m30/65 levels.

Hepatitis B Virus-Associated Liver Carcinoma: The Role of Iron Metabolism and Its Modulation.

Hepatitis B virus (HBV) infection is a significant contributor to the development of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Iron, a central co-factor in various metabolic pathways, plays an essential role in liver function, but its dysregulation can lead to severe health consequences. Accumulation of iron within hepatic cells over time is linked to increased liver injury and is strongly associated with sensitive exposure to a range of conditions, including cirrhosis, fibrosis and ultimately, HCC. This review explores the intricate interplay between iron metabolism and HCC within the context of HBV infection. Hepatic iron overload can arise from liver injury and disruptions in iron homeostasis, causing hepatic necrosis, inflammation, and fibrosis, ultimately culminating in carcinogenesis. Moreover, alterations in serum iron components in HBV-related scenarios have been observed to impact the persistence of HBV infection. Notably, the progression of HBV-associated liver damage exhibits distinct characteristics at various stages of liver disease. In addition to elucidating the complex relationship between iron metabolism and HCC in the context of HBV infection, this review also investigates the prognostic implications of systemic iron levels for HCC. Furthermore, it aims to provide a comprehensive understanding of the intricate interplay between iron metabolism and HCC, extending the discussion to the context of hepatitis C virus (HCV) infection. By shedding light on these multifaceted connections, this review aims to contribute to our understanding of the pathogenesis of HBV-associated HCC and potentially identify novel therapeutic avenues for intervention.

Biomarker Discovery in Liver Disease Using Untargeted Metabolomics in Plasma and Saliva.

Chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), continue to be a global health burden with a rise in incidence and mortality, necessitating a need for the discovery of novel biomarkers for HCC detection. This study aimed to identify novel non-invasive biomarkers for these different liver disease states. We performed untargeted metabolomics in plasma (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 34) and saliva samples (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 22) to test for significant metabolite associations with each disease state. Additionally, we identified enriched biochemical pathways and analyzed correlations of metabolites between, and within, the two biofluids. We identified two salivary metabolites and 28 plasma metabolites significantly associated with at least one liver disease state. No metabolites were significantly correlated between biofluids, but we did identify numerous metabolites correlated within saliva and plasma, respectively. Pathway analysis revealed significant pathways enriched within plasma metabolites for several disease states. Our work provides a detailed analysis of the altered metabolome at various stages of liver disease while providing some context to altered pathways and relationships between metabolites.

B-113 Diagnostic Value of Autoantibodies against D-3-phosphoglycerate Dehydrogenase (PGDH) among Patients with Liver Diseases

Abstract Background We determined serum autoantibodies against D-3-phosphoglycerate dehydrogenase (anti-PGDH) in patients with liver diseases using a well-validated line immunoblot assay, and analysed their diagnostic significance. Methods The studied panel comprised serum samples from 383 patients with the following liver diseases: 87 autoimmune hepatitis (AIH), 88 primary biliary cholangitis (PBC), 76 chronic hepatitis B, 79 hepatitis C, 53 drug-induced liver injury as well as sera from 69 patients with autoimmune diseases (systemic lupus erythematosus or rheumatoid arthritis) and 30 healthy blood donors. The line immunoblot EUROLINE Autoimmune Liver Diseases 14 Ag (EUROIMMUN) was used to test for anti-PGDH. The intensities of the bands were automatically evaluated using the EUROLineScan software (EUROIMMUN). Indirect immunofluorescence was used to detect other autoantibodies, including anti-nuclear autoantibodies (ANA) and anti-smooth muscle antibodies (ASMA). Results The prevalence of anti-PGDH was 18.3% across all patients with liver diseases (36.8% in AIH; 10.2% in PBC), 1.5% in patients with autoimmune diseases, and 3.3% in blood donors. ANA but not ASMA were detectable in all anti-PGDH positive patients with liver diseases. Patients with anti-PGDH displayed no significant differences in age, liver function, IgG serum level and ANA patterns compared to those without anti-PGDH. Anti-PGDH positivity was observed at various stages of liver disease, including acute and chronic liver injury, liver cirrhosis, and liver cancer. Conclusion The anti-PGDH prevalence in AIH patients was highest among patients with liver or autoimmune diseases. Presence of anti-PGDH seems to be a specific marker for AIH and may support the diagnosis of AIH.

Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma.

HCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encompassing various stages of liver disease, identifying 972 differentially expressed genes in HCC. A refined analysis yielded 59 genes specifically differentially expressed in early HCC, including ITGA6. Subsequent validation in multiple datasets confirmed the consistent upregulation of ITGA6 in HCC. In addition, when analyzing progression-free survival (PFS) within the entire patient cohort and overall survival (OS) specifically among patients classified as tumor grade G1, the group of patients characterized by high expression levels of ITGA6 displayed an elevated risk ratio in relation to prognosis. Further analyses demonstrated the predominant expression of ITGA6 in TECs and its enrichment in angiogenesis-related pathways. Additionally, positive correlations were found between ITGA6 expression and pro-tumorigenic immune cells, but not with anti-tumorigenic immune cells. Our study elucidates the potential of ITGA6 as a blood-based marker for HCC early detection and diagnosis and its complex interplay with the tumor microenvironment. Further research may lead to novel strategies for HCC management and patient care.

Usefulness of Mac-2 binding protein glycosylation isomer in non-invasive probing liver disease in the Vietnamese population.

Early diagnosis is critical for successful intervention before liver disease progresses to cirrhosis and hepatocellular carcinoma. To examine a novel biomarker for probing early liver disease quickly using an automated immunology system. This was a cross-sectional study. 140 patients at various stages of liver disease were randomly selected. The cohort consisted of patients who were treatment naïve and currently undergoing therapy. We included patients with diverse liver disease etiologies. Mac-2 binding protein glycosylation isomer (M2BPGi) levels in addition to different clinical parameters, co-morbidities and transient elastography results were collected and compared. M2BPGi levels were significantly correlated with transient elastography for liver fibrosis staging across all disease etiologies. Statistically significant differences were observed in patients with F0-1; F2 and > F3 liver fibrosis. Further examination showed that M2BPGi levels were two-fold higher in F4 than F3 hepatitis C (HCV) patients. M2BPGi was observed to be etiology-specific and HCV patients had higher mean M2BPGi levels. We also observed significant correlations with aspartate aminotransferase to platelet ratio index and fibrosis-4 index as well as HBV DNA levels. Mean M2BPGi levels for HBV patients with a viral load lower than 2000 IU/mL was 1.75-fold lower than those with a viral load greater than 2000 IU/mL. M2BPGi was observed to be a good indicator of early liver disease in patients with different etiologies. Our results provide reference cut-offs for different causes of liver disease and demonstrated the utility of this marker for early disease monitoring. This is useful for remote regions in developing countries.

Association of IL-12 B Gene Polymorphism with Staging of Liver Disease in Chronic HCV Patients.

Cell-mediated immunity plays a critical role in viral clearance and disease progression during Hepatitis C virus (HCV) infection. Interleukin (IL)-12 is a cytokine that has been shown to be a potent antiviral cytokine. The aim of this work is to investigate the association of IL-12 B gene polymorphism with staging of liver disease in chronic HCV patients. This cross sectional study was carried out in tropical medicine department, Tanta university hospital, Egypt, on 120 chronic HCV patients with various stages of liver disease and 30 healthy subjects served as control. All the participants were tested for IL- 12 B (p40) gene polymorphism. the frequency of AA genotype was higher in HCV patients with decompensated cirrhosis and in HCV patients with Hepatocellular carcinoma (HCC). However, the CC genotype was less detected in all groups, with the lowest percentage (6.6%) detected in decompensated cirrhosis and HCC patients. AA genotype presented more frequently in late stages of HCV chronically ill patients, while, CC genotype had no significant association with staging of liver disease and had low frequency especially in late stages of liver disease.

Hepatocellular carcinoma and estrogen receptors: Polymorphisms and isoforms relations and implications

Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and its incidence continues to increase worldwide. HCC is a disease with multifactorial causes and genetic variability has been discussed as a risk factor for its development. Liver is a hormone-sensitive organ and therefore is influenced by gonadal hormones, such as estrogen. Estrogen is known to participate in various biological functions, but its role in development of HCC, on the other hand, is controversial and presents evidence suggesting a role as both a carcinogen and protective effect in liver. Estrogen way of action is mediated by estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), that belong to a family of nuclear receptors that may regulate the expression of many genes. The ER subtypes exert a variety of roles in many stages of liver disease and may play a part in the process of signal transduction, according to some studies. However, the many functions of ER subtypes in hepatic diseases, in special of the ERβ, are yet to be clarified.The genetic modifications related to HCC are not yet fully clarified and accumulation of multiple genetic alterations appears to have an important role in carcinogenesis of HCC. The presence of some certain single nucleotide polymorphism (SNP) may have a functional repercussion related to final product of a gene, which can be measured and may participate in some alterations related to a pathological condition.Our hypothesis is based on the fact that liver tissue express ER and its different variants exert multiple functions in various stages of liver disease and participate in an extremely complicated signal transduction process, therefore we believe that the presence of one or more SNPs of ESR1 and ESR2 genes may be related with the increase of risk in developing and the severity of HCC, as well as in the response to different treatments. The confirmation of our hypothesis by scientific studies may provide knowledge of markers that act as prognostic factors of this disease, as well as enabling alternatives to development of anti tumoral therapies.

Prophylactic effects of humic acid-glucan combination against experimental liver injury.

Aim:Despite intensive research, liver diseases represent a significant health problem and current medicine does not offer a substance able to significantly inhibit the hepatotoxicity leading to various stages of liver disease. Based on our previously published studies showing the protective effects of a glucan-humic acid (HA) combination, we focused on the hypothesis that the combination of these two natural molecules can offer prophylactic protection against experimentally induced hepatotoxicity.Materials and Methods:Lipopolysaccharide, carbon tetrachloride, and ethanol were used to experimentally damage the liver. Levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase, glutathione, superoxide dismutase, and malondialdehyde, known to correspond to the liver damage, were assayed.Results:Using three different hepatotoxins, we found that in all cases, some samples of HA and most of all the glucan-HA combination, offer strong protection against liver damage.Conclusion:Glucan-HA combination is a promising agent for use in liver protection.

Tracing the Spread of Hepatitis C Virus in Turkey: A Phylogenetic Analysis

Background/Aims: Molecular epidemiology of hepatitis C virus (HCV) shows that HCV genotypes are unique with respect to their nucleotide sequence, geographical distribution and clinical relationship. Methods: In this study we enrolled 67 HCV-infected individuals with various stages of liver disease from four geographical regions of Turkey. A partial NS5B region of the HCV genome was sequenced and subjected to phylogenetic analysis to determine the circulating HCV genotypes and subtypes. Results: The results showed that HCV genotype 1 (subtype1b) is the main genetic variant of HCV in Turkey but did not reveal any Turkish indigenous phylogenetic cluster. Phylogenetic analysis showed that Turkish strains have their closest matches from both Asia (Japan) and Europe/USA. Conclusions: In view of Turkey's geographic position, HCV-1b transmission from Europe is not exceptional. This study could not establish a clear role of other HCV genotypes prevalent in neighboring Asian countries in Turkey's HCV transmission, which would need to be confirmed by further regional epidemiological studies.

A Study of Plasma D-Dimer Levels in Various Stages of Liver Disease

Aim: Defects in the process of coagulation and fibrinolysis is a common feature of various types of liver disease. The present study sought to evaluate the utility of D Dimer, a stable product of fibrinolysis in assessing this aspect of liver function. In the present study we estimated the D-Dimer levels to determine the status of coagulation defect and bleeding tendency. Materials and methods: Ninety-nine patients with chronic liver disease were classified into groups A, B and C based upon the Child-Pugh scores. This score was calculated based upon values of serum bilirubin, serum albumin, internationalized normal ratio (INR), as well the severity of ascitis and hepatic encephalopathy. Plasma D-Dimer was estimated using an immuno-turbidimetry. The results were analyzed using the student’s ‘t’ test as well as ANOVA. Results: The plasma D-Dimer levels were found to be increased significantly with severity of liver disease (p<0.005). Prothrombin time and INR increased significantly while fibrinogen decreased significantly from A to C groups (p<0.05). Conclusion: Apart from coagulation defects, increased fibrinolytic activity could be one of the important factors responsible for the bleeding tendency in liver disease. D- Dimer can therefore be looked upon as an important parameter for the assessment of fibrinolytic status in chronic liver disease. It should be used in conjunction with the parameters of coagulation in order to assess the bleeding tendency in these patients.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Diagnostic Value of the13C Methacetin Breath Test in Various Stages of Chronic Liver Disease

The accuracy of the 13C-methacetin breath test (13C-MBT) in differentiating between various stages of liver disease is not clear. A cross-sectional study of Asian patients was conducted to examine the predictive value of the 13C-MBT in various stages of chronic liver diseases. Diagnostic accuracy of the breath test was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve analysis. Seventy-seven patients (47 men/30 women, mean age 50 ± 16 years) were recruited. Forty-seven patients had liver cirrhosis (Child Pugh A = 11, Child Pugh B = 15, and Child Pugh C = 21), 21 had fibrosis, and 9 had chronic inflammation. The sensitivity and positive predictive value for liver fibrosis, cirrhosis (all stages), Child-Pugh A, Child-Pugh B, and Child-Pugh C were 65% and 56%, 89% and 89%, 67% and 42%, 40% and 40%, and 50% and 77%, respectively. Area under curve values for fibrosis was 0.62 (0.39–0.86), whilst that for cirrhosis (all stages) was 0.95 (0.91–0.99). The 13C-methacetin breath test has a poor predictive value for liver fibrosis but accurately determines advanced cirrhosis.

Hepatocellular carcinoma-associated protein markers investigated by MALDI-TOF MS

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. The initial hepatocellular alterations that precede the appearence of HCC include chronic viral hepatitis/cirrhosis, foci of phenotypically altered hepatocytes and, subsequently, dysplastic hepatocytes that form foci and nodules. These changes cause a discrepancy in the microenvironment of liver cells, which may result in changes in the protein expression profile of the cells. The aim of the present study was to investigate differences between the protein expression profiles at various stages of liver disease in order to better understand the mechanisms of HCC and to identify potential biomarkers for its early diagnosis. The proteins of specific cells were obtained from HCC tissue sections and pre-cancerous lesions using a manual microdissection technique, and were investigated by a two dimensional gel electrophoresis (2-DE) MALDI-TOF MS proteomics approach. Select identified proteins were reconfirmed by immunohistochemistry. A total of 95 differentially expressed proteins, with an over 2-fold disparity in expression levels between cells of varying morphology during the stages of hepatocarcinogenesis, were detected by 2-DE. Among these 95 proteins, 80 were determined to be involved in numerous cell functions, including cell growth and proliferation, protein synthesis and metabolism, apoptosis and signal transduction. These identified proteins, which include stratifin (14-3-3), transgelin 2, heat-shock protein (HSP)70, HSP27, manganese superoxide dismutase, prohibitin, DJ1, α-enolase, peroxiredoxin 6, aldo-keto reductase family member B10, phosphoglycerate kinase 1, α-1-antitrypsin and nm23-H1, may play a role in the development of HCC. Protein expression profiles differed markedly between the HCC tissue samples and pre-cancerous lesions, suggesting that alterations in protein expression occurred frequently during the process of hepatocarcinogenesis. Analysis of the differential expression of proteins related to the development of HCC may help elucidate the molecular mechanisms of the disease. These proteins may also serve as candidate biomarkers for early HCC diagnosis.

Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution

HIV-related enhancement of gut microbial translocation is associated with progression of hepatic fibrosis. Although hepatic macrophages (Kupffer cells) clear most microbial translocation products and can be infected by HIV, their fate in HIV progression has not been carefully investigated. We studied Kupffer cell density (KCD) in 76 HIV-hepatitis C virus coinfected patients investigated at various stages of liver disease and CD4(+) lymphocyte depletion (and restoration). KCD averaged 23 cells per high-powered field (range 4.4-52.2) and was highest in portal and periportal regions as compared with centrilobular regions (P < 0.001). No differences were detected in KCD by age, liver fibrosis stage, or hepatic inflammatory score. Compared with individuals without apparent HIV-related immunosuppression, however, KCD was substantially lower in persons with lower peripheral blood CD4(+) lymphocyte counts (P = 0.027) and lowest among those with deepest CD4(+) lymphocyte nadir (P = 0.006). After the initial liver biopsy, eight patients began antiretroviral therapy and had immune restoration (> or = 2-fold increase in peripheral CD4(+) lymphocyte count) and a second histologic evaluation with a median of 36.8 months later (range 28.1-58.4 months); KCD increased in all (P = 0.007). Given the central role of Kupffer cells in controlling microbial translocation, these data suggest Kupffer cell loss needs to be considered in the pathogenesis of liver fibrosis in HIV-hepatitis C virus coinfected persons. The abundance of portal and periportal Kupffer cells is suggestive of their contribution to fibrosis in periportal regions in chronic viral hepatitis.

Subgenotypes of hepatitis B virus genotype C do not correlate with disease progression of chronic hepatitis B in Taiwan

Hepatitis B virus (HBV) genotype C (HBV/C) has two subgenotypes: HBV/Cs and Ce. The prevalence and clinical implications of subgenotype Cs and Ce in Taiwanese HBV carriers remain unknown. Subgenotypes of HBV/C were determined in 242 Taiwanese HBV carriers with various stages of liver disease. The clinical as well as virologic features between patients with HBV/Cs and HBV/Ce infection were further compared. HBV/Ce was the predominant subgenotype in Taiwan. The prevalence of HBV/Ce was 93.6% in the inactive carriers group, 84.2% in chronic hepatitis patients, 81.2% in cirrhosis patients, 92.5% in hepatocellular carcinoma (HCC) patients without cirrhosis and 91.9% in HCC patients with cirrhosis. There was no significant difference in the distribution of the HBV/C subgenotypes among patients with different stages of liver disease. Subgenotypes of HBV/C may not have a clinical impact on the disease progression of chronic hepatitis B in Taiwan.

Distribution of hepatitis B virus genotypes in Guizhou and analysis of clinical significance

To investigate the distribution of HBV genotypes in Guizhou and study the relationship between the genotype and the progression of liver disease. Totally 693 patients with chronic HBV infection, from 4 areas of Guizhou, including 292 asymptomatic HBV carriers (ASC), 276 cases with chronic hepatitis (CH), 76 liver cirrhosis (LC), 49 hepatocellular carcinoma (HCC) were examined. The HBV genotype was determined by restriction fragment length polymorphism analysis and the relationship between HBV genotype and the progression of liver disease was studied by multifactor analysis such as HBsAg positivity, HBV DNA load and ALT level. Of the 693 patients, 6 (0.87%), 449 (64.79%), 233 (33.62%), and 5 (0.72%) belonged to genotype A, B, C and D, respectively. There was a statistically siganificant difference in the distribution of genotype B among Kaili (96.4%), Zunye (78.79%), Duyun (76.19%) and Guiyang (53.66%) areas (P less than 0.01). Genotype C was more prevalent in Guiyang than in other three areas (45.68% vs. 23.8%, 45.68% vs. 13.13%, 45.68% vs. 3.96%, P less than 0.01, respectively). There were also statistically significant difference in distribution of genotype B and C in various stages of liver disease (P less than 0.01). Genotype B showed a decreasing trend from ASC, CH, LC to HCC and genotype C was more frequent in patients with CH (45.92%) than in those with ASC (20.6%), LC (17.17%) and HCC (16.31%). The ALT levels and the mean ages were significantly higher and older in patients with genotype C than those in genotype B. The HBeAg positivity was significantly lower in genotype C than that in genotype B (48.07% vs 61.90%, P less than 0.01). Genotype A, B, C and D exist in Guizhou. Genotype B predominates and genotype C was the second common. The geographic distribution of genotype B and C are different in some areas of Guizhou. Compared with genotype B, genotype C is associated with the development of more severe liver damage.

Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan

The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. We therefore studied the prevalence of HFE mutations and their impact on the progression of chronic viral hepatitis in Taiwan. H63D and C282Y mutations were screened by using polymerase chain reaction followed by restriction fragment length polymorphism in 152 chronic hepatitis B patients with various stages of liver disease, 87 chronic hepatitis C patients with various stages of liver disease, and 49 healthy controls. The distribution of each allele frequency was then compared among different groups of patients and in various stages of liver disease. All three groups of patients were C282Y wild type and the majority of H63D mutations were heterozygotes. Although statistically not significant, allele frequencies of H63D mutation in hepatitis B-related liver cirrhosis (6%) and hepatitis C-related liver cirrhosis (9.1%) were higher than those in healthy control (2%). After adjustment for age and sex, hepatitis B patients with H63D heterozygosity had a higher likelihood of cirrhosis than those with H63D wild type (odds ratios (OR): 3.2, confidence interval (CI): 0.49-20.5, P = 0.22). Similarly, hepatitis C patients with H63D homozygosity had a higher likelihood of cirrhosis compared with those with H63D wild type (OR: 2.35, CI : 0.19-28.5, P = 0.52). Almost all Taiwanese are C282Y wild type. H63D heterozygote and homozygote, occurring in less than 5% of the subjects, tended to be associated with the development of liver cirrhosis, irrespective of viral etiology. Screening for H63D mutation might be considered in patients with chronic viral hepatitis in Taiwan.

Finally... Real Utility Scores for Hepatitis C Patients!

Chong and colleagues (1) used gold-standard methods to assess health-state utilities in 193 outpatients at various stages of liver disease due to chronic hepatitis C (HCV) infection. They showed worsening of health-state utility scores with progression of disease from mild to moderate chronic hepatitis, to compensated cirrhosis, to decompensated cirrhosis and to hepatocellular carcinoma. They also confirmed improvement in health-state utility scores after liver transplantation and with sustained virological response (SVR) to treatment of HCV infection. Patients with HCV infection had lower health-state utility scores than the general Canadian population (PÃ0.001) and significantly poorer quality of life compared with population norms in the United States (PÃ0.005).

Hepatitis C virus (HCV) hypervariable region 1 complexity does not correlate with severity of liver disease, HCV type, viral load or duration of infection

Backgroud/Aims: Several studies have suggested that infection with a highly heterogeneous population of hepatitis C virus correlates with a low response rate to interferon. It is still debated, however, whether or not this heterogeneity might be associated with liver disease severity. The aim of this study was to analyse hepatitis C virus genome complexity in patients with various stages of liver disease. Methods: We used polymerase chain reaction-single strand conformation polymorphism (SSCP) analysis to estimate the degree of complexity of the hypervariable region (HVR1) in 95 anti-HCV and serum HCV-RNA positive patients. They were divided into two groups according to Knodell's histological activity index (HAI) grading: 22 with HAI <4 and 73 with HAI > -4, including 19 with cirrhosis. Results: The number of visible SSCP bands ranged from 1 to 7. There was no significant difference in the number of SSCP bands between patients with HAI <4 and patients with HAI > -4 (median number of bands was 4 in both groups). The number of SSCP bands was not correlated to the biochemical activity, the genotype, the HCV-RNA titre or the duration of hepatitis C virus infection. Conclusions: The HCV-HVR1 complexity profile alone does not correlate with the severity of liver disease, whatever, the biological and virological profile of the viral infection.