Hepatitis research and treatment最新文献

Each phase of hepatitis B infection stimulates distinct viral kinetics and host immune responses resulting in liver damage and hepatic fibrosis. Our objective has been to correlate host inflammatory immune response including circulating Th1 and Th2 cytokines in patients with chronic hepatitis B infection with liver histopathology. Sixty-four patients with chronic hepatitis B without previous treatment were recruited. The liver histology and histological activity index were assessed for various degrees of necroinflammation and hepatic fibrosis. We determined circulating levels of the Th1 and Th2 cytokines. Forty-six males and 18 females at a median age of 34.5 years were studied. HBeAg was present in 28/64 (43.75%) of the patients. In patients negative for HBeAg, IL-10 and IFN-gamma were significantly correlated with degrees of necroinflammation (r = 0.34, r = 0.38, resp.; P < 0.05). Moreover, TNF-alpha was significantly correlated with degrees of fibrosis (r = 0.35; P < 0.05), and IL-10 and TNF-alpha were significantly correlated with significant fibrosis (r = 0.39, r = 0.35, resp.; P < 0.05). These correlations were found in the HBeAg negative group as opposed to the HBeAg positive group. In HBeAg negative patients, circulating cytokines IL-10 and IFN-gamma were correlated with degrees of necroinflammation, whereas IL-10 and TNF-alpha were correlated with significant fibrosis.

The interindividual variations in the capacity of transforming growth factor- β 1 (TGF- β 1) production have been ascribed to genetic polymorphisms in TGF- β 1 gene. As pathogenesis of HBV has a genetic background, this preliminary study was designed to assess the impact of TGF- β 1 (T29C) on the susceptibility of Egyptians to HBV infection. Genotyping was performed using single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian hepatitis B patients and 50 healthy controls. TGF- β 1 plasma levels were measured using Enzyme-linked immunosorbent assay (ELISA). The frequency of CC genotype was significantly higher (P < 0.05) in HBV patients compared to controls. On the contrary, TC genotype did not show significant difference in both groups. TT genotype was significantly higher (P < 0.01) in controls than HBV patients. Our current preliminary data revealed that the frequency of the genotypes in the controls were within Hardy-Weinberg equilibrium (HWE) while the patients group was out of HWE (P < 0.01). TGF- β 1 was significantly (r = -0.684; P < 0.001) deceased in the sera of patients as compared to normal subjects. Depending on our preliminary work, CC genotype may act as a host genetic factor in the susceptibility to HBV infection in Egyptians. Taken together, the current data pointed to the importance of polymorphism of TGF- β 1 gene (T29C) in HBV infection.

Aim. We analyzed the pretreatment natural killer (NK) cell functions with the aim of predicting the sustained virological response (SVR) or the interleukin (IL) 28B polymorphism that is strongly associated with the treatment response. Methods. The peripheral NK cells from chronic hepatitis patients with HCV genotype 1 and high virus titers were activated using a Toll-like receptor (TLR) 4 ligand and IFN- α . The cell surface markers were evaluated using a flow cytometric analysis, and IFN- γ production was evaluated using an enzyme-linked immunosorbent assay (ELISA). The genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on the DNA collected from each patient. Results. The production of IFN- γ was significantly higher in the SVR patients compared with the no-response (NR) patients, whereas the cell surface markers were similar between the SVR and the NR patients. There were no significant differences found in the IL28B genotype distribution associated with the production of IFN- γ . Conclusion. Differences in the NK cell functions were observed between the SVR patients and the NR patients, suggesting that NK cells play a potential role in the treatment response independent of the IL28B genotype.

HD-03/ES is a herbal formulation used for the treatment of hepatitis B. However, the molecular mechanism involved in the antihepatitis B (HBV) activity of this drug has not been studied using in vitro models. The effect of HD-03/ES on hepatitis B surface antigen (HBsAg) secretion and its gene expression was studied in transfected human hepatocarcinoma PLC/PRF/5 cells. The anti-HBV activity was tested based on the inhibition of HBsAg secretion into the culture media, as detected by HBsAg-specific antibody-mediated enzyme assay (ELISA) at concentrations ranging from 125 to 1000  μ g/mL. The effect of HD-03/ES on HBsAg gene expression was analyzed using semiquantitative multiplex RT-PCR by employing specific primers. The results showed that HD-03/ES suppressed HBsAg production with an IC50 of 380  μ g/mL in PLC/PRF/5 cells for a period of 24 h. HD-03/ES downregulated HBsAg gene expression in PLC/PRF/5 cells. In conclusion, HD-03/ES exhibits strong anti-HBV properties by inhibiting the secretion of hepatitis B surface antigen in PLC/PRF/5 cells, and this action is targeted at the transcription level. Thus, HD-03/ES could be beneficial in the treatment of acute and chronic hepatitis B infections.

Objectives. This study was performed to define the overall treatment response rates and treatment completion rates among the population of Hepatitis C infected patients at an urban VA Medical Center. Additionally, we examined whether pretreatment liver biopsy is a positive predictor for treatment completion and if the presence of mental health disorders is a negative predictor for treatment completion. Methods. Retrospective chart review was performed on the 375 patients that were treated for HCV and met the study inclusion parameters between January 1, 2003 and April 1, 2008 at our institution. Clinical data was obtained from the computerized patient record system and was analyzed for respective parameters. Results. Sustained virological response was achieved in 116 (31%) patients. 169 (45%) patients completed a full treatment course. Also, 44% of patients who received a pre-treatment liver biopsy completed treatment versus 46% completion rates for patients who did not receive a pretreatment liver biopsy. Baseline ICD9 diagnosis of a mental health disorder was not associated with higher treatment discontinuation rates. Conclusions. In conclusion, pretreatment liver biopsy was not a positive predictor for treatment completion, and the presence of mental health disorders was not a negative predictor for treatment completion.

Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; liver manifestations and hepatitis are examples of them. Parvovirus B19 hepatitis associated aplastic anemia and its coinfection with other hepatotropic viruses are relatively underrecognized, and there is sufficient evidence in the literature suggesting that B19 infections can cause a spectrum of liver diseases from elevation of transaminases to acute hepatitis to fulminant liver failure and even chronic hepatitis. It can also cause fatal macrophage activation syndrome and fibrosing cholestatic hepatitis. Parvovirus B19 is an erythrovirus that can only be replicate in pronormoblasts and hepatocytes, and other cells which have globosides and glycosphingolipids in their membrane can also be affected by direct virus injury due to nonstructural protein 1 persistence and indirectly by immune mediated injury. The virus infection is suspected in bone marrow aspiration in cases with sudden drop of hemoglobin and onset of transient aplastic anemia in immunosuppressed or immunocompetent patients and is confirmed either by IgM and IgG positive serology, PCR analysis, and in situ hybridization in biopsy specimens or by application of both. There is no specific treatment for parvovirus B19 related liver diseases, but triple therapy regimen may be effective consisting of immunoglobulin, dehydrohydrocortisone, and cyclosporine.

Chronic hepatitis C virus (HCV) infection is associated with 50% incidence of insulin resistance (IR) that is fourfold higher than that in non-HCV population. IR impairs the outcome of antiviral treatment. The molecular mechanisms of IR in HCV are not entirely clear. Experimental and clinical data suggested that hepatitis C virus per se is diabetogenic. However, presence of HCV alone does not affect IR. It was proposed that IR is mediated by proinflammatory cytokines, mainly by TNF-alpha. TNF-alpha potentiates interferon-gamma-induced transcriptional activation of indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan- (TRP-) kynurenine (KYN) metabolism. Upregulation of TRP-KYN metabolism was reported in HCV patients. KYN and some of its derivatives affect insulin signaling pathways. We hypothesized that upregulation of TRP-KYN metabolism might contribute to the development of IR in HCV. To check this suggestion, we evaluated serum concentrations of TRP and KYN and HOMA-IR and HOMA-beta in 60 chronic HCV patients considered for the treatment with IFN-alpha. KYN and TRP concentrations correlated with HOMA-IR and HOMA-beta scores. Our data suggest the involvement of KYN and its metabolites in the development of IR in HCV patients. TRP-KYN metabolism might be a new target for prevention and treatment of IR in HCV patients.

Background. Cirrhosis may lead to a poor health-related quality of life (HRQOL), which should be taken into consideration when addressing the cirrhotic outpatient. Methods. Prospective cohort study evaluating predictors of HRQOL in outpatients with cirrhosis. Patients with overt hepatic encephalopathy at baseline were excluded. HRQOL was evaluated at baseline using the six point Chronic Liver Disease Questionnaire. Predictors of low quality of life scores (<4 points) and mortality were analyzed using multivariable logistic regression. Results. In total, 92 patients were included (mean age 61 years, 59% male). Nineteen patients died (mean duration of follow-up 20 months). The mean Child-Pugh score was 6.9. Twenty percent had a poor HRQOL judged by the Chronic Liver Disease Questionnaire score and 45% had covert hepatic encephalopathy. The only predictors of poor HRQOL were the Child-Pugh score (β=0.45;P = 0.013), nonalcoholic etiology of cirrhosis (β=-2.34;P = 0.009), and body mass index (β=-0.20;P = 0.023). The body mass index predicted poor HRQOL independently of the presence of ascites and albumin level. Conclusions. The body mass index was associated with a low HRQOL. This suggests that malnutrition may be an important target in the management of patients with cirrhosis.

Aim. To gain an insight into the effect of HCV replication-associated interference with the IFN system on hepatic mRNA expression involved in IFN production. Methods. Relative mRNA expression of TLR3/RIG-I signaling genes involved in IFN- β production was correlated with positive- and negative-strand HCV RNAs in pretreatment liver tissues responsive and nonresponsive to peginterferon and ribavirin for chronic hepatitis C genotype 1. Treatment response was analyzed for per protocol population at weeks 12 (n = 45) and 24 (n = 40) and at 24 weeks aftertreatment (n = 38). Results. HCV replication had no relation to the expression of TLR3, RIG-I, TRIF, IPS-1, IRF3, and IFN- β mRNAs in responders. In striking contrast, positive- and/or negative-strand HCV showed positive correlations with TLR3, RIG-I, TRIF, IPS-1, and IRF3 mRNAs in week-12 nonresponders; with RIG-I, TRIF, IPS-1, and IRF3 mRNAs in week-24 nonresponders; and with TLR3, RIG-I, and IRF3 mRNAs in posttreatment nonresponders. Thus mRNA expression of TLR3/RIG-I signaling genes was increased in relation to viral replication in nonresponders. Conclusions. The findings in IFN nonresponders may imply a host feedback response to severe impairment of the IFN system associated with HCV replication.

Giant cell hepatitis is common manifestation in pediatric liver diseases, but quite uncommon in adults, only about 100 cases reported in the English literature in the last two decades. Data for the present review were identified by a structured PubMed/MEDLINE search from 1963 to December 2012, using keywords postinfantile giant cell hepatitis (PIGCH), adult giant cell hepatitis, and syncytial giant cell hepatitis in adults and liver. We report a case of postinfantile giant cell hepatitis along with the review related to the etiology and respective outcome, as the literature in the last 20 years suggests. This condition is probably due to idiosyncratic or cytopathic response of individual to various hepatocytic stimuli. It is purely a histomorphological diagnosis and does not establish the etiology. Autoimmune liver diseases are most common etiology, in around 40% of cases, but various viruses, drugs, posttransplant condition, and other causes also have been reported. Prognosis depends upon the etiology. In this paper, we emphasized various causative factors of PIGCH and their respective outcome in patients affected by them. We also highlighted the possible pathogenesis and histopathological spectrum of this entity on the basis of description given in various studies and our limited experience of few cases.