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Sample records for 1b chronic hepatitis

  1. Replication of a chronic hepatitis B virus genotype F1b construct.

    PubMed

    Hernández, Sergio; Jiménez, Gustavo; Alarcón, Valentina; Prieto, Cristian; Muñoz, Francisca; Riquelme, Constanza; Venegas, Mauricio; Brahm, Javier; Loyola, Alejandra; Villanueva, Rodrigo A

    2016-03-01

    Genotype F is one of the less-studied genotypes of human hepatitis B virus, although it is widely distributed in regions of Central and South American. Our previous studies have shown that HBV genotype F is prevalent in Chile, and phylogenetic analysis of its full-length sequence amplified from the sera of chronically infected patients identified it as HBV subgenotype F1b. We have previously reported the full-length sequence of a HBV molecular clone obtained from a patient chronically infected with genotype F1b. In this report, we established a system to study HBV replication based on hepatoma cell lines transfected with full-length monomers of the HBV genome. Culture supernatants were analyzed after transfection and found to contain both HBsAg and HBeAg viral antigens. Consistently, fractionated cell extracts revealed the presence of viral replication, with both cytoplasmic and nuclear DNA intermediates. Analysis of HBV-transfected cells by indirect immunofluorescence or immunoelectron microscopy revealed the expression of viral antigens and cytoplasmic viral particles, respectively. To test the functionality of the ongoing viral replication further at the level of chromatinized cccDNA, transfected cells were treated with a histone deacetylase inhibitor, and this resulted in increased viral replication. This correlated with changes posttranslational modifications of histones at viral promoters. Thus, the development of this viral replication system for HBV genotype F will facilitate studies on the regulation of viral replication and the identification of new antiviral drugs.

  2. Hemoglobin Decrease with Iron Deficiency Induced by Daclatasvir plus Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b

    PubMed Central

    Shigefuku, Ryuta; Hattori, Nobuhiro; Watanabe, Tsunamasa; Matsunaga, Kotaro; Hiraishi, Tetsuya; Tamura, Tomohiro; Noguchi, Yohei; Fukuda, Yasunobu; Ishii, Toshiya; Okuse, Chiaki; Sato, Akira; Suzuki, Michihiro; Itoh, Fumio

    2016-01-01

    Background Decreased hemoglobin (Hb) level has been supposed to be a relatively rare side effect of a combination therapy against hepatitis C virus that consists of the NS5A inhibitor daclatasvir (DCV) and the NS3/4A protease inhibitor asunaprevir (ASV). Methods The study was conducted in 75 patients with genotype 1b chronic hepatitis C virus infection who had started combination therapy with DCV and ASV at St. Marianna University School of Medicine Hospital between September 2014 and December 2014. Results Among the patients examined, decreased Hb level by ≥1.5 g/dL from the values at treatment initiation was observed in 11 individuals. This was accompanied by decreased mean corpuscular volume, and iron and ferritin levels. Conclusions These findings suggest that the mechanism of the phenomenon is caused by iron deficiency. The underlying mechanism and clinical impacts will need to be further examined. PMID:26990758

  3. Delayed Viral Clearance after 6-Week Treatment with Peginterferon Plus Ribavirin in a Patient with Chronic Hepatitis C Virus Genotype 1b

    PubMed Central

    Sato, Akira; Ishii, Toshiya; Adachi, Kayo; Takahashi, Hideaki; Sano, Fumiaki; Matsumoto, Nobuyuki

    2016-01-01

    Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy. Spontaneous clearance of hepatitis C virus RNA can occur following antiviral failure in patients with persistently low viral loads, and virological follow-up is therefore necessary in chronic hepatitis C virus infection, even after antiviral failure. PMID:27721727

  4. [Update chronic viral hepatitis].

    PubMed

    Ziegenhagen, D J

    2016-03-01

    More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade. PMID:27111951

  5. Historical treatment of chronic hepatitis B and chronic hepatitis C.

    PubMed Central

    Ferenci, P

    1993-01-01

    Interferon is currently considered to be the only accepted effective treatment for chronic viral hepatitis. A history of the treatment of chronic hepatitis B and C before the use of interferon is presented here. Hepatitis B virus does not seem to be directly cytopathic and the disease is known to be modulated largely by the host's immune response. Experience with immunosuppressant and immunostimulant drugs and a wide variety of antiviral agents, however, has indicated that none of these are of any benefit in patients with chronic hepatitis B, with the possible exception of adenine arabinoside. In view of the much more recent identification of the hepatitis C virus, studies of therapy for chronic hepatitis C are inevitably less extensive. A pilot study using acyclovir in patients with chronic non-A, non-B hepatitis did not show any benefit, although the treatment period may have been too short for the results to be conclusive. The only agent other than alpha interferon to be tried in chronic hepatitis C is ribavirin, which may have some activity. Many of the agents studied in chronic hepatitis B should also be investigated for the treatment of patients with chronic hepatitis C. PMID:8314494

  6. Pregnancy and pregnancy outcome in hepatitis C type 1b.

    PubMed

    Jabeen, T; Cannon, B; Hogan, J; Crowley, M; Devereux, C; Fanning, L; Kenny-Walsh, E; Shanahan, F; Whelton, M J

    2000-09-01

    A large cohort of rhesus-negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti-D immunoglobulin in 1977-8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age- and parity-matched control group of rhesus-positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme-linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV-RNA-positive (type 1b) on PCR testing. In the 20 years post-infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR-positive women. Of the children born to HCV-RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV-RNA-positive mothers apart from one single exception in the antibody-positive HCV-RNA-negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

  7. Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication

    PubMed Central

    Murata, Ayato; Genda, Takuya; Ichida, Takafumi; Amano, Nozomi; Sato, Sho; Tsuzura, Hironori; Sato, Shunsuke; Narita, Yutaka; Kanemitsu, Yoshio; Shimada, Yuji; Hirano, Katsuharu; Iijima, Katsuyori; Wada, Ryo; Nagahara, Akihito; Watanabe, Sumio

    2016-01-01

    AIM To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication. METHODS In this study, we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response (SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios (HRs) of AKR1B10 expression for hepatocellular carcinoma (HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test. RESULTS Of the 303 chronic hepatitis C patients, 153 (50.5%) showed scarce hepatic AKR1B10 expression, quantified as 0%, which was similar to the expression in control normal liver tissues. However, the remaining 150 patients (49.5%) exhibited various degrees of AKR1B10 expression in the liver, with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years (range 1.0-10.0 years), 8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression (≥ 8%) was an independent risk factor for HCC development (HR = 15.4, 95%CI: 1.8-132.5, P = 0.012). The 5-year cumulative incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression, respectively (P < 0.001). During the follow-up period after viral eradication, patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression. CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR. PMID:27672277

  8. Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication

    PubMed Central

    Murata, Ayato; Genda, Takuya; Ichida, Takafumi; Amano, Nozomi; Sato, Sho; Tsuzura, Hironori; Sato, Shunsuke; Narita, Yutaka; Kanemitsu, Yoshio; Shimada, Yuji; Hirano, Katsuharu; Iijima, Katsuyori; Wada, Ryo; Nagahara, Akihito; Watanabe, Sumio

    2016-01-01

    AIM To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication. METHODS In this study, we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response (SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios (HRs) of AKR1B10 expression for hepatocellular carcinoma (HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test. RESULTS Of the 303 chronic hepatitis C patients, 153 (50.5%) showed scarce hepatic AKR1B10 expression, quantified as 0%, which was similar to the expression in control normal liver tissues. However, the remaining 150 patients (49.5%) exhibited various degrees of AKR1B10 expression in the liver, with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years (range 1.0-10.0 years), 8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression (≥ 8%) was an independent risk factor for HCC development (HR = 15.4, 95%CI: 1.8-132.5, P = 0.012). The 5-year cumulative incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression, respectively (P < 0.001). During the follow-up period after viral eradication, patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression. CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.

  9. Chronic Hepatitis C.

    PubMed

    Tran, Tram T.; Martin, Paul

    2001-12-01

    Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin. PMID:11696276

  10. Epclusa Approved for Chronic Hepatitis C

    MedlinePlus

    ... news/fullstory_159609.html Epclusa Approved for Chronic Hepatitis C Combination drug treats six major forms of ... to treat the six major strains of chronic hepatitis C virus (HCV). Epclusa combines sofosbuvir, FDA-approved ...

  11. Identification and characterization of a natural inter-genotypic (2b/1b) recombinant hepatitis C virus in Japan.

    PubMed

    Yokoyama, Koji; Takahashi, Masaharu; Nishizawa, Tsutomu; Nagashima, Shigeo; Jirintai, Suljid; Yotsumoto, Shigeru; Okamoto, Hiroaki; Momoi, Mariko Y

    2011-09-01

    A hepatitis C virus (HCV) strain (HC10-0804) recovered from a 12-year-old Japanese female with chronic hepatitis C segregated into discordant genotypes, 2b and 1b, in the 5'UTR/core and NS5B regions, respectively, thus suggesting an inter-genotypic recombination. The HC10-0804 isolate had a genomic length of 9,423 nucleotides (nt), excluding the poly(U) tract at the 3' terminus, and encoded a single open reading frame (ORF) for a polyprotein of 3,014 amino acids (aa). Based on Simplot and Bootscan analyses, the crossover point from 2b to 1b was estimated at nt 3443/3444 (aa 1034/1035), just after the beginning of the NS3 region. Comparison of the entire genomic sequence showed that the HC10-0804 strain was only 90.2% identical to the previously reported 2b/1b recombinant strain (SE-03-07-1689) from the Philippines, whose putative crossover point was 24 nt downstream of that of HC10-0804. These results indicate the circulation of a novel inter-genotypic (2b/1b) recombinant HCV in Japan.

  12. Hepatitis C virus (HCV) genotype 2a has a better virologic response to antiviral therapy than HCV genotype 1b

    PubMed Central

    Wang, Meng; Zhang, Yi; Li, Zhiqin; Zhang, Hongyu; Zhang, Zhen; Yue, Dongli; Zhou, Rong; Li, Xiaogang; Wu, Shuhuan; Li, Jiansheng

    2015-01-01

    The standard treatment, pegylated interferon (PEG-IFN) plus ribavirin (RBV), for patients with chronic hepatitis C (CHC), does not provide a sustained virologic response (SVR) in a large majority of patients. In the present study, 211 treatment-naïve patients with the hepatitis C virus (HCV) genotype 1b and 2a were recruited and treated weekly with PEG-IFN plus RBV to determine the response of HCV genotype 1b and 2a patients to standard antiviral treatment. Virologic responses were assessed by TaqMan at week 4, 12, 24, 48 and 24 weeks of treatment. Patients with HCV genotype 2a had a significantly higher rapid virologic response (RVR), early virologic response, end-of-treatment response and SVR, and a lower relapse rate than patients with HCV genotype 1b. Multivariate logistic regression analysis showed that the HCV genotype 2a patients had a HCV RNA level ≤ 5.70 log10 IU/ml, a fibrosis stage < S3, and that HLA-A02 expression and RVR were independent factors of SVR that may improve HCV clearance. PMID:26221288

  13. Forced expression of Hnf1b/Foxa3 promotes hepatic fate of embryonic stem cells.

    PubMed

    Yahoo, Neda; Pournasr, Behshad; Rostamzadeh, Jalal; Hakhamaneshi, Mohammad Saeed; Ebadifar, Asghar; Fathi, Fardin; Baharvand, Hossein

    2016-05-20

    Embryonic stem (ES) cell-derived hepatocytes have the potential to be used for basic research, regenerative medicine, and drug discovery. Recent reports demonstrated that in addition to conventional differentiation inducers such as chemical compounds and cytokines, overexpression of lineage-specific transcription factors could induce ES cells to differentiate to a hepatic fate. Here, we hypothesized that lentivirus-mediated inducible expression of hepatic lineage transcription factors could enhance mouse ES cells to hepatocyte-like cells. We screened the effects of candidate transcription factors Hnf1b, Hnf1a, Hnf4a, Foxa1, Foxa3 and Hex, and determined that the combination of Hnf1b/Foxa3 promoted expression of several hepatic lineage-specific markers and proteins, in addition to glycogen storage, ICG uptake, and secretion of albumin and urea. The differentiated cells were engraftable and expressed albumin when transplanted into a carbon tetrachloride-injured mouse model. These results demonstrated the crucial role of Hnf1b and Foxa3 in hepatogenesis in vitro and provided a valuable tool for the efficient differentiation of HLCs from ES cells. PMID:27107701

  14. Chronic urticaria following acute hepatitis A.

    PubMed

    Griffin, Paul M; Kevat, Dev A S; McCarthy, James S; Woods, Marion L

    2012-09-18

    Urticaria has a documented association with the prodromal phases of hepatitis A, B and, although still contentious, likely hepatitis C. Despite the documented association there are few actual reported cases of urticaria occurring with hepatitis A infection and in all of the cases reported so far the urticaria preceded the diagnosis of hepatitis A and was acute rather than chronic. We describe a case of urticaria occurring following acute infection with hepatitis A, which persisted beyond 6 weeks and therefore was by definition chronic. Although chronic urticaria has been reported to be associated with other forms of viral hepatitis, to the best of our knowledge this has not been reported previously with hepatitis A.

  15. Evaluation of Interferon Resistance in Newly Established Genotype 1b Hepatitis C Virus Cell Culture System

    PubMed Central

    Taniguchi, Miki; Tasaka-Fujita, Megumi; Nakagawa, Mina; Watanabe, Takako; Kawai-Kitahata, Fukiko; Otani, Satoshi; Goto, Fumio; Nagata, Hiroko; Kaneko, Shun; Nitta, Sayuri; Murakawa, Miyako; Nishimura-Sakurai, Yuki; Azuma, Seishin; Itsui, Yasuhiro; Mori, Kenichi; Yagi, Shintaro; Kakinuma, Sei; Asahina, Yasuhiro; Watanabe, Mamoru

    2016-01-01

    Background and Aims: The hepatitis C virus (HCV) genotype 1b is known to exhibit treatment resistance with respect to interferon (IFN) therapy. Substitution of amino acids 70 and 91 in the core region of the 1b genotype is a significant predictor of liver carcinogenesis and poor response to pegylated-IFN-α and ribavirin therapy. However, the molecular mechanism has not yet been clearly elucidated because of limitations of the HCV genotype 1b infectious model. Recently, the TPF1-M170T HCV genotype 1b cell culture system was established, in which the clone successfully replicates and infects Huh-7-derived Huh7-ALS32.50 cells. Therefore, the purpose of this study was to compare IFN resistance in various HCV clones using this system. Methods: HCV core amino acid substitutions R70Q and L91M were introduced to the TPF1-M170T clone and then transfected into Huh7-ALS32.50 cells. To evaluate the production of each virus, intracellular HCV core antigens were measured. Results were confirmed with Western blot analysis using anti-NS5A antibodies, and IFN sensitivity was subsequently measured. Results: Each clone was transfected successfully compared with JFH-1, with a significant difference in intracellular HCV core antigen (p < 0.05), an indicator of continuous HCV replication. Among all clones, L91M showed the highest increase in the HCV core antigen and HCV protein. There was no significant resistance against IFN treatment in core substitutions; however, IFN sensitivity was significantly different between the wildtype core and JFH-1 (p < 0.05). Conclusions: A novel genotype 1b HCV cell culture was constructed with core amino acid substitutions, which demonstrated IFN resistance of genotype 1b. This system will be useful for future analyses into the mechanisms of HCV genotype 1b treatment. PMID:27047766

  16. [Occult hepatitis B virus infection in chronic hepatitis C].

    PubMed

    Jang, Jae Young; Park, Eui Ju

    2013-09-01

    Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.

  17. Characterization of ursodeoxycholic and norursodeoxycholic acid as substrates of the hepatic uptake transporters OATP1B1, OATP1B3, OATP2B1 and NTCP.

    PubMed

    König, Jörg; Klatt, Sabine; Dilger, Karin; Fromm, Martin F

    2012-08-01

    Ursodeoxycholic acid (UDCA) is the only approved treatment for primary biliary cirrhosis, and norursodeoxycholic acid (norUDCA) is currently tested in clinical trials for future treatment of primary sclerosing cholangitis because of beneficial effects in cholestatic Mdr2 knock-out mice. Uptake of UDCA and norUDCA into hepatocytes is believed to be a prerequisite for subsequent metabolism and therapeutic action. However, the molecular determinants of hepatocellular uptake of UDCA and norUDCA are poorly understood. We therefore investigated whether UDCA and norUDCA are substrates of the hepatic uptake transporters OATP1B1, OATP1B3, OATP2B1 and Na(+) -taurocholate co-transporting polypeptide (NTCP), which are localized in the basolateral membrane of hepatocytes. Uptake of [(3) H]UDCA and [(14) C]norUDCA into Human embryonic kidney (HEK) cells stably expressing OATP1B1, OATP1B3, OATP2B1 or NTCP was investigated and compared with uptake into vector control cells. Uptake ratios were calculated by dividing uptake into transporter-transfected cells by uptake into respective control cells. Uptake ratios of OATP1B1-, OATP1B3- and OATP2B1-mediated UDCA and norUDCA uptake were at maximum 1.23 and 1.49, respectively. Uptake of UDCA was significantly higher into HEK-NTCP cells only at the lowest tested concentration (1 μM, p < 0.001) compared with the control cells with an uptake ratio of 1.34-fold. NorUDCA was not significantly transported by NTCP. The low uptake rates suggest that OATP1B1, OATP1B3, OATP2B1 and NTCP are not relevant for hepatocellular uptake and effects of UDCA and norUDCA in human beings.

  18. Sofosbuvir for treatment of chronic hepatitis C.

    PubMed

    Kattakuzhy, Sarah; Levy, Rachel; Kottilil, Shyam

    2015-04-01

    Chronic hepatitis C is a leading cause of liver-related morbidity and mortality worldwide. If untreated, chronic hepatitis C can progress to advanced liver fibrosis, cirrhosis, liver failure, hepatocellular carcinoma and death. Until recently, treatment of hepatitis C predominantly constituted an immunomodulatory agent, peg-interferon-alfa and ribavirin. In 2011, the first class of directly acting antiviral agents, HCV NS3/4A serine protease inhibitors, was added to peg-interferon-alfa and ribavirin with increased efficacy. In the past year, an NS5B inhibitor, sofosbuvir, has emerged as a potent agent with pangenotypic efficacy, resulting in the first interferon-free regimen for the treatment of hepatitis C. This review summarizes the data that resulted in regulatory approval of sofosbuvir and highlights the future of hepatitis C therapy with sofosbuvir as the backbone of a highly effective antiviral regimen.

  19. Acute viral E hepatitis with chronic liver disease (autoimmune hepatitis).

    PubMed

    Desai, H G; Naik, A S

    2005-03-01

    A 36 years old male presented with anorexia, jaundice and ascites. He was suffering from acute viral E hepatitis. In view of ascites, he was investigated for associated asymptomatic chronic liver disease (CLD). The CLD was diagnosed as cirrhosis with autoimmune hepatitis and was treated with steroid with good response. He is maintaining good health with low dose steroid, on follow up for 1 year.

  20. Advances in therapeutics for chronic hepatitis B.

    PubMed

    Yang, Ninghan; Bertoletti, Antonio

    2016-03-01

    Chronic hepatitis B infection remains a major disease burden globally, and leads to high risk of hepatocellular carcinoma development. Current therapies of nucleot(s)ide analogues and interferon alpha treatment remain limited in their efficacy. Several key findings in the hepatitis B virus (HBV) life cycle have led to the development of novel antiviral drugs to inhibit viral replication and persistence. In addition, recent studies on HBV-specific innate and adaptive immune responses have advanced development of immunotherapy to restore immune mediated virus control in chronic hepatitis B patients. In this review, we discuss potential new therapeutic strategies targeting HBV or the host immune system that might lead to a sustained cure for chronic hepatitis B. PMID:26363922

  1. 1a/1b subtype profiling of nonnucleoside polymerase inhibitors of hepatitis C virus.

    PubMed

    Nyanguile, Origène; Devogelaere, Benoit; Vijgen, Leen; Van den Broeck, Walter; Pauwels, Frederik; Cummings, Maxwell D; De Bondt, Hendrik L; Vos, Ann M; Berke, Jan M; Lenz, Oliver; Vandercruyssen, Geneviève; Vermeiren, Katrien; Mostmans, Wendy; Dehertogh, Pascale; Delouvroy, Frédéric; Vendeville, Sandrine; VanDyck, Koen; Dockx, Koen; Cleiren, Erna; Raboisson, Pierre; Simmen, Kenneth A; Fanning, Gregory C

    2010-03-01

    The RNA-dependent RNA polymerase (NS5B) of hepatitis C virus (HCV) is an unusually attractive target for drug discovery since it contains five distinct drugable sites. The success of novel antiviral therapies will require nonnucleoside inhibitors to be active in at least patients infected with HCV of subtypes 1a and 1b. Therefore, the genotypic assessment of these agents against clinical isolates derived from genotype 1-infected patients is an important prerequisite for the selection of suitable candidates for clinical development. Here we report the 1a/1b subtype profiling of polymerase inhibitors that bind at each of the four known nonnucleoside binding sites. We show that inhibition of all of the clinical isolates tested is maintained, except for inhibitors that bind at the palm-1 binding site. Subtype coverage varies across chemotypes within this class of inhibitors, and inhibition of genotype 1a improves when hydrophobic contact with the polymerase is increased. We investigated if the polymorphism of the palm-1 binding site is the sole cause of the reduced susceptibility of subtype 1a to inhibition by 1,5-benzodiazepines by using reverse genetics, X-ray crystallography, and surface plasmon resonance studies. We showed Y415F to be a key determinant in conferring resistance on subtype 1a, with this effect being mediated through an inhibitor- and enzyme-bound water molecule. Binding studies revealed that the mechanism of subtype 1a resistance is faster dissociation of the inhibitor from the enzyme.

  2. 1a/1b Subtype Profiling of Nonnucleoside Polymerase Inhibitors of Hepatitis C Virus ▿

    PubMed Central

    Nyanguile, Origène; Devogelaere, Benoit; Vijgen, Leen; Van den Broeck, Walter; Pauwels, Frederik; Cummings, Maxwell D.; De Bondt, Hendrik L.; Vos, Ann M.; Berke, Jan M.; Lenz, Oliver; Vandercruyssen, Geneviève; Vermeiren, Katrien; Mostmans, Wendy; Dehertogh, Pascale; Delouvroy, Frédéric; Vendeville, Sandrine; VanDyck, Koen; Dockx, Koen; Cleiren, Erna; Raboisson, Pierre; Simmen, Kenneth A.; Fanning, Gregory C.

    2010-01-01

    The RNA-dependent RNA polymerase (NS5B) of hepatitis C virus (HCV) is an unusually attractive target for drug discovery since it contains five distinct drugable sites. The success of novel antiviral therapies will require nonnucleoside inhibitors to be active in at least patients infected with HCV of subtypes 1a and 1b. Therefore, the genotypic assessment of these agents against clinical isolates derived from genotype 1-infected patients is an important prerequisite for the selection of suitable candidates for clinical development. Here we report the 1a/1b subtype profiling of polymerase inhibitors that bind at each of the four known nonnucleoside binding sites. We show that inhibition of all of the clinical isolates tested is maintained, except for inhibitors that bind at the palm-1 binding site. Subtype coverage varies across chemotypes within this class of inhibitors, and inhibition of genotype 1a improves when hydrophobic contact with the polymerase is increased. We investigated if the polymorphism of the palm-1 binding site is the sole cause of the reduced susceptibility of subtype 1a to inhibition by 1,5-benzodiazepines by using reverse genetics, X-ray crystallography, and surface plasmon resonance studies. We showed Y415F to be a key determinant in conferring resistance on subtype 1a, with this effect being mediated through an inhibitor- and enzyme-bound water molecule. Binding studies revealed that the mechanism of subtype 1a resistance is faster dissociation of the inhibitor from the enzyme. PMID:20071590

  3. Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles

    PubMed Central

    Kinoshita, Chika; Nagano, Tomohisa; Seki, Nobuyoshi; Tomita, Yoichi; Sugita, Tomonori; Aida, Yuta; Itagaki, Munenori; Satoh, Kenichi; Sutoh, Satoshi; Abe, Hiroshi; Tsubota, Akihito; Aizawa, Yoshio

    2016-01-01

    AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins. METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis. RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL

  4. Chronic viral hepatitis: the histology report.

    PubMed

    Guido, Maria; Mangia, Alessandra; Faa, Gavino

    2011-03-01

    In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice.

  5. Chronic hepatitis C: latest treatment options.

    PubMed

    Iosue, Kathleen

    2002-04-01

    The most common chronic bloodborne infection in the United States, hepatitis C virus (HCV) is the most frequent reason for liver transplantation. Unfortunately, most infected individuals don't realize they're HCV positive and only discover the disease after severe liver damage has occurred. Here, update your knowledge on the epidemiology, transmission and risk factors, diagnosis, clinical presentation, and management of chronic HCV. Insight on counseling and quality of life issues for infected patients is also included. PMID:11984417

  6. Direct acting antiviral therapy is curative for chronic hepatitis C/autoimmune hepatitis overlap syndrome

    PubMed Central

    Sahebjam, Farhad; Hajdu, Cristina H; Nortey, Esther; Sigal, Samuel H

    2016-01-01

    Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting anti-viral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology. PMID:27190580

  7. Review article: hepatitis vaccination in patients with chronic liver disease.

    PubMed

    Reiss, G; Keeffe, E B

    2004-04-01

    Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.

  8. Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout mice.

    PubMed

    Gardier, A M; David, D J; Jego, G; Przybylski, C; Jacquot, C; Durier, S; Gruwez, B; Douvier, E; Beauverie, P; Poisson, N; Hen, R; Bourin, M

    2003-07-01

    The role of serotonin (5-HT)1B receptors in the mechanism of action of selective serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout (KO 5-HT1B) mice in order to compare the effects of chronic administration of paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral hippocampus, approximately 20 h after removing the minipump, were not altered by chronic paroxetine treatment in both genotypes. On day 15, in the ventral hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This difference between the two genotypes in the effect of the paroxetine challenge persisted following chronic paroxetine treatment. Conversely, in the medial prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in saline-pretreated mice of both genotypes. Such a challenge produced a further increase in cortical [5-HT]ext compared with that in saline-pretreated groups of both genotypes, but no differences were found between genotypes following chronic treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 micro m paroxetine was perfused locally through the dialysis probe implanted in the ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in acutely or chronically treated wild-type mice. Systemic administration of the mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext in the ventral hippocampus, whereas systemic administration of the selective 5-HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of quantitative microdialysis in

  9. [Autoimmune hepatitis and membranous glomerulonephritis under immune therapy in chronic hepatitis C].

    PubMed

    Paparoupa, Maria; Huy Ho, Ngoc Ahn; Schuppert, Frank

    2016-05-01

    A 63-year-old patient is evaluated for an unclear weight loss with general malaise and fatigue for several months. Serological examination reveales the first diagnosis of a hepatitis-C-virus-genotype-1b-infection with an initial viral load of 980 000 IU / ml. The duration of the infection is suggested to be more than 6 months. Because of the initially elevated anti-nuclear-antibodies (ANA) the diagnosis of an autoimmune hepatitis needs to be excluded. All other liver related autoantibodies and the immunoglobulins (Ig) IgG, IgA and IgM are normal. A liver biopsy is conducted. After a short test with non-pegylated interferon (IFN) liver enzymes remain stable and treatment with pegylated IFN-alfa-2a and ribavirin (RBV) is initiated. The patient is a "rapid viral responder" and his viral load is found under the detection limit within 4 weeks under therapy. On the 16th week, liver enzymes increase rapidly. ANA's and IgG-immunoglobulins are positive. A second lever biopsy does not confirm the diagnosis of autoimmune hepatitis and the treatment is continued under careful observation of all relevant liver parameters. 21 weeks after the initiation of the treatment, massive peripheral edema, hypoproteinemia and proteinuria are observed. The renal biopsy reveales membranous glomerulonephritis. Because of the preserved renal function, no acute immunosuppression is initiated and the treatment gets completed after overall 24 weeks. Liver and renal parameters return quickly back to normal after treatment discharge. This is the first report of a combined autoimmune reaction with development of autoimmune hepatitis and glomerulonephritis under INF and RBV antiviral therapy for a chronic hepatitis-C-infection. The occurrence of autoimmune manifestations should especially be considered in genetically susceptible individuals or those with positive autoimmunity markers. The initiation of INF for the treatment of chronic hepatitis-C-infection has to be critically evaluated since

  10. Sarcoidosis and chronic hepatitis C: a case report.

    PubMed

    Brjalin, Vadim; Salupere, Riina; Tefanova, Valentina; Prikk, Kaiu; Lapidus, Natalia; Jõeste, Enn

    2012-10-28

    Several case reports deal with the relationship between hepatitis C virus (HCV) infection and pulmonary or hepatic sarcoidosis. Most publications describe interferon α-induced sarcoidosis. However, HCV infection per se is also suggested to cause sarcoidosis. The present case report describes a case of biopsy-verified lung and liver sarcoidosis and HCV infection, and the outcome of antiviral therapy. In March 2009, a 25-year-old man presented with moderately elevated liver enzymes without any clinical symptoms. The patient was positive for HCV antibodies and HCV RNA of genotype 1b. Four months later the patient became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and radiography. A short course of corticosteroid treatment relieved symptoms. Three months later, liver biopsy showed noncaseating granulomas consisting of epithelioid histiocytes and giant cells with a small amount of peripheral lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection with coexistence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral therapy with peginterferon α and ribavirin at standard doses was started, which lasted 48 wk, and sustained viral response was achieved. A second liver biopsy showed disappearance of granulomas and chest radiography revealed normalization of mediastinal and perihilar glands. The hypothesis that HCV infection per se may have triggered systemic sarcoidosis was proposed. Successful treatment of HCV infection led to continuous remission of pulmonary and hepatic sarcoidosis. Further studies are required to understand the relationship between systemic sarcoidosis and HCV infection. PMID:23155326

  11. A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis?

    PubMed

    Hayashi, Kazuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Nishimura, Daisaku; Goto, Hidemi; Hirooka, Yoshiki

    2016-08-01

    Reactivation of hepatitis B virus (HBV) in HBV surface antigen (HBsAg)-positive patients treated with cytotoxic chemotherapy is well known. HBV reactivation in patients with HBV and hepatitis C virus (HCV) coinfection caused by direct-acting antiviral (DAA) therapy has also recently been reported. We report a case of acute hepatitis B in a patient with HCV infection after DAA therapy. An 83-year-old woman was referred for chronic hepatitis C. She was infected with HCV genotype 1b and negative for HBsAg at baseline. She received daclatasvir and asunaprevir therapy, and HCV became negative at 4 weeks and remained negative until 6 months after the end of DAA therapy. Acute hepatitis B developed 5 months after ending DAA therapy. Genome sequencing revealed the subgenotype as B1, and the serological subtype as adr. T118 K mutation at the S region as an immune escape mutant was identified. These virologic features led to HBV reactivation. The presence of hepatitis B core antibody or HBs antibody was not determined before DAA therapy, so prior HBV infection status was unclear. This case is speculated to represent HBV reactivation in a patient with previously resolved HBV induced by DAA therapy, based on virologic analysis and clinical status. The risk might be very low, but DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. When acute hepatitis emerges in patients who have received DAA therapy for HCV, HBV reactivation should be considered to allow early initiation of anti-HBV therapy. PMID:27329484

  12. If You Have Chronic Hepatitis B Virus (HBV) Infection

    MedlinePlus

    If you have chronic hepatitis B virus (HBV) infection . . . If you have chronic hepatitis B virus (HBV) infection, you are not alone. Today, approximately one ... receive pneumococcal polysaccharide vac- cine.  Get vaccinated against hepatitis A. Hepati- tis A can further damage your ...

  13. Chronic hepatitis B virus infection.

    PubMed

    McMahon, Brian J

    2014-01-01

    All providers, regardless of specialty, should perform screening for HBV on high-risk persons, especially those born in endemic countries. The primary care physician can perform the initial evaluation and follow-up of patients with chronic HBV by following the algorithm in this article and consulting with specialists when appropriate. Chronically infected patients should be followed on a regular basis, preferably every 6 months, with liver function tests, and when appropriate, HBV DNA levels. Those who meet the criteria for high risk for HCC should undergo liver ultrasound every 6 months. Powerful antiviral medications are available that can suppress but not cure HBV and result in resolution of liver inflammation and fibrosis, even cirrhosis, as well as decrease the risk of developing HCC. They should be used in those patients who meet the criteria outlined in the practice guidelines of the major liver societies. PMID:24266913

  14. Omentin serum concentration and hepatic expression in chronic hepatitis C patients - together or apart?

    PubMed

    Kukla, Michał; Waluga, Marek; Adamek, Brygida; Zalewska-Ziob, Marzena; Kasperczyk, Janusz; Gabriel, Aandrzej; Bułdak, Rafał J; Sobala-Szczygieł, Barbara; Kępa, Lucjan; Ziora, Katarzyna; Żwirska-Korczala, Krystyna; Surma, Edward; Sawczyn, Tomasz; Hartleb, Marek

    2015-09-01

    Chronic hepatitis C (CHC) is accompanied by numerous metabolic disorders, partially associated with altered adipokine system regulation. Omentin (intelectin-1) is a novel adipokine known to play a pivotal role in metabolic regulation in CHC. In a group of 63 CHC patients (29 men/34 women) infected with genotype 1b, aged 6.6 ± 14.6 years, serum omentin levels and its gene expression in liver tissue were examined and their association with metabolic and histopathological features was assessed. Serum omentin levels were significantly higher in CHC patients compared to controls (p < 0.001), regardless of sex, body mass index (BMI), insulin sensitivity and lipid concentrations. There was no correlation between serum omentin and omentin hepatic expression. Neither parameter was associated with any histological features. Serum omentin in non-obese CHC patients seems not to be related to metabolic disorders or liver pathology. Omentin hepatic expression shows no relationship with either serum omentin levels or histopathological features. This suggests different mechanisms regulating circulating omentin concentration and omentin hepatic expression in CHC. PMID:26619101

  15. Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-naïve Patients Infected with Genotype 1b Hepatitis C Virus

    PubMed Central

    Wang, Ye; Rao, Hui-Ying; Xie, Xing-Wang; Wei, Lai

    2015-01-01

    Background: It has been reported that several baseline polymorphisms of direct-acting antivirals (DAAs) agents resistance-associated variants (RAVs) would affect the treatment outcomes of patients chronically infected with hepatitis C virus (CHC). The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-naïve GT1b CHC patients. Methods: Direct sequencing and ultra-deep sequencing of the HCV NS3, NS5A, and NS5B gene were performed in baseline serum samples of treatment-naïve patients infected with genotype 1b hepatitis C virus (HCVs). Results: One hundred and sixty CHC patients were studied. Complete sequence information was obtained for 145 patients (NS3), 148 patients (NS5A), and 137 patients (NS5B). Treatment-failure associated variants of DAAs were detected: 56.6% (82/145) of the patients presented S122G for simeprevir (NS3 protease inhibitor); 10.1% (14/148) of the patients presented Y93H for daclatasvir and ledipasvir (NS5A protein inhibitors); 94.2% (129/137) of the patients presented C316N for sofosbuvir (NS5B polymerase inhibitor). Nearly, all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing. Conclusions: The majority of genotype 1b CHC patients in China present a virus population carrying HCV DAAs RAVs. Pretreatment sequencing of HCV genome might need to be performed when patients infected with GT1b HCV receiving DAAs-containing regimens in China. Population sequencing would be quite quantified for the work. PMID:26415801

  16. Patient concerns regarding chronic hepatitis C infections.

    PubMed

    Minuk, G Y; Gutkin, A; Wong, S G; Kaita, K D E

    2005-01-01

    Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them. The most common volunteered concerns of newly diagnosed patients in decreasing order were: disease progression (27%), premature death (19%), infecting family members (13%), side-effects of treatment (11%) and miscellaneous others. In decreasing order, prioritized concerns included: infecting family members, development of liver cancer, infecting others, development of cirrhosis, social stigma of having liver disease, need for liver transplant and loss of employment. The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, modes of viral acquisition and in the case of follow-up patients, duration of follow-up. These results indicate that health care providers who focus counselling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection. PMID:15655048

  17. Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form.

    PubMed

    Schuermans, Wim; Orlent, Hans; Desombere, Isabelle; Descheemaeker, Patrick; Van Vlierberghe, Hans; Geerts, Anja; Verhelst, Xavier; Reynders, Marijke; Padalko, Elizaveta

    2016-01-01

    As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis. PMID:27563879

  18. Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form

    PubMed Central

    Schuermans, Wim; Orlent, Hans; Desombere, Isabelle; Descheemaeker, Patrick; Van Vlierberghe, Hans; Geerts, Anja; Verhelst, Xavier; Reynders, Marijke; Padalko, Elizaveta

    2016-01-01

    As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis. PMID:27563879

  19. Chronic hepatitis e in heart transplant recipients.

    PubMed

    Pischke, S; Stiefel, P; Franz, B; Bremer, B; Suneetha, P V; Heim, A; Ganzenmueller, T; Schlue, J; Horn-Wichmann, R; Raupach, R; Darnedde, M; Scheibner, Y; Taubert, R; Haverich, A; Manns, M P; Wedemeyer, H; Bara, C L

    2012-11-01

    Chronic courses of hepatitis E virus (HEV) infections have been described in immunosuppressed patients. We aimed to study the role of HEV infections in heart transplant recipients (HTR). 274 HTR were prospectively screened for HEV infection using an anti-HEV-IgG ELISA and HEV-PCR. In addition, 137 patients undergoing cardiac surgery (non-HTR) and 537 healthy subjects were studied cross-sectionally. The anti-HEV-IgG seroprevalence was 11% in HTR, 7% in non-HTR and 2% in healthy controls (HTR vs. healthy controls p<0.0001; non-HTR vs. healthy controls p<0.01). Anti-HEV tested positive in 4.0% in control cohorts of other immunocompromised patients (n = 474). Four HTR (1.5%) were chronically infected with HEV as shown by HEV-PCR and all four patients had liver transaminases of >200 IU/L and histological or clinical evidence of advanced liver disease. In three patients ribavirin treatment was successful with a sustained biochemical and virological response while treatment failed in one cirrhotic patient after ribavirin dose reduction. Heart transplant recipients and patients undergoing cardiac surgery have an increased risk for HEV infections. Chronic hepatitis E may explain elevated liver enzymes in heart transplant recipients. Treatment of HEV infection with ribavirin is effective but the optimal dose and duration of ribavirin therapy remains to be determined. PMID:22823202

  20. [Clinical practice guideline for diagnosis and treatment of chronic hepatitis virus hepatitis B. Grupo Colaborativo en Hepatitis B].

    PubMed

    2011-01-01

    This guide sets out the technical criteria for the diagnosis and treatment of chronic hepatitis secondary to viral hepatitis B. The guide intend to reduce the morbidity and mortality of this disease. The Guide give practical definitions to help understand the terminology, describe epidemiology, risk factors, and clinical aspects and the diagnosis of chronic hepatitis B. Finally the guide give recommendations for the management including special circumstances such as patients with cirrhosis, patients coinfected with HIV or coinfected with hepatitis C. The recommendations of the guide become the national guide for the management of chronic hepatitis B

  1. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    PubMed

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

  2. Management issues in chronic viral hepatitis: hepatitis C.

    PubMed

    Sievert, William

    2002-04-01

    The natural history of chronic hepatitis C virus (HCV) infection and intervention with antiviral therapy are closely linked issues that cause the greatest controversy and concern for the person infected with HCV, as well as for the clinician involved in the assessment and treatment of people with chronic HCV infection. The outstanding challenge of natural history is to identify the person who is likely to develop serious liver disease, and to make that determination early in the course of chronic HCV infection when treatment is likely to be of the greatest benefit. Significant advances in the therapy of chronic HCV infection have occurred over the past decade. A sustained virological response (SVR), defined as undetectable HCV-RNA in blood 6 months after completing antiviral treatment, is the best indicator of a beneficial treatment effect. Relapse, breakthrough or non-response should all be regarded as unsuccessful outcomes of therapy. Interferons are still the mainstay of antiviral therapy for chronic HCV infection. The combination of interferon and ribavirin has improved SVR by decreasing the relapse rate. Treatment responses vary according to host factors such as age and gender, fibrotic severity and to viral factors like genotype and viral load. Patients with genotype 1 HCV and a high viral load require 12 months of treatment to achieve a SVR in approximately 30%, compared to those with genotypes 2 or 3 who achieve a SVR in approximately 65% after 6 months. Patients who relapse after an end-of-treatment response to interferon monotherapy have a good chance of responding to combination interferon and ribavirin given for 6 months, but a longer treatment course should be considered in less optimal cases. At present, the treatment of those with non-response is less clear, but there is interest in more intense forms of interferon therapy, such as induction dosing or pegylated interferon in combination with ribavirin. Clinicians need to be aware of the common side

  3. Chronic hepatitis: a retrospective study in 34 dogs.

    PubMed Central

    Fuentealba, C; Guest, S; Haywood, S; Horney, B

    1997-01-01

    The aims of this study were to characterize the histological changes observed in 34 accessioned cases of canine chronic hepatitis and to correlate these changes with the clinical pathological data. Cases of chronic hepatitis were subdivided into 6 categories: chronic active hepatitis (10/34), chronic persistent hepatitis (7/32), chronic cholestatic hepatitis (6/34), fibrosing hepatitis with cirrhosis (3/34), chronic cholangiohepatitis (3/34), and miscellaneous secondary hepatitis (5/34). Iron accumulation was a consistent finding in all livers examined. Although all cases of chronic hepatitis had elevated liver enzymes, no correlation was detected between biochemical parameters and the severity of morphologic changes. Similarly, no correlation was detected between rhodanine staining for copper and morphologic or biochemical indicators of cholestasis. However, presence of copper correlated well with reticulo-fibrosis (r = 0.8) and bile duct hyperplasia, suggesting that changes in the hemodynamics of the hepatic acini due to fibrosis could influence storage of copper. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. PMID:9187802

  4. Novel spiroketal pyrrolidine GSK2336805 potently inhibits key hepatitis C virus genotype 1b mutants: from lead to clinical compound.

    PubMed

    Kazmierski, Wieslaw M; Maynard, Andrew; Duan, Maosheng; Baskaran, Sam; Botyanszki, Janos; Crosby, Renae; Dickerson, Scott; Tallant, Matthew; Grimes, Rick; Hamatake, Robert; Leivers, Martin; Roberts, Christopher D; Walker, Jill

    2014-03-13

    Rapid clinical progress of hepatitis C virus (HCV) replication inhibitors, including these selecting for resistance in the NS5A region (NS5A inhibitors), promises to revolutionize HCV treatment. Herein, we describe our explorations of diverse spiropyrrolidine motifs in novel NS5A inhibitors and a proposed interaction model. We discovered that the 1,4-dioxa-7-azaspiro[4.4]nonane motif in inhibitor 41H (GSK2236805) supported high potency against genotypes 1a and 1b as well as in genotype 1b L31V and Y93H mutants. Consistent with this, 41H potently suppressed HCV RNA in the 20-day RNA reduction assay. Pharmacokinetic and safety data supported further progression of 41H to the clinic.

  5. Chronic Hepatitis D; at a Standstill?

    PubMed

    Rizzetto, Mario

    2016-01-01

    Chronic hepatitis D (CHD) is a severe liver disease with worldwide distribution caused by the hepatitis D virus (HDV). Therapy of CHD is at a standstill. It still relies on interferon (IFN), introduced empirically in the 1980s; results are limited. With the peghilated IFNs that are now in use, only 25% of CHD reach a sustained viral response, that is, clear the HDV-RNA 6 months after stopping therapy. However, HDV remains infectious and ready to reactivate at very low titers undetectable by current assays, if the HBsAg persists in serum; relapses of hepatitis D post-therapy are frequent and further diminish the therapeutic response. The major obstacle to CHD therapy is the minimalist nature of the HDV. It does not encode for any enzymatic function but is replicated by host RNA polymerases deceived to recognize the viral RNA as it were a cellular DNA; therefore, it has no replicative machinery of its own to be targeted by antivirals. The only help required from hepatitis B virus (HBV) is the HBsAg coat to attach to hepatocytes and assembly in the virion; HBV antivirals that decrease HBV-DNA but leave HBsAg unaffected are of no avail in CHD. Novel therapeutic strategies are under evaluation. Myrcludex B, a peptidic inhibitor of HBV entry, was used with some success in vitro in the mouse to block the Na+-tauro chocolate cotransporting polypeptide and prevent entry of the HD virion into hepatocytes. The nuclei acid polymer REP-2139 was shown to distinctly diminish serum HBsAg and HDV-RNA by blocking HBsAg entry and inhibiting its intracellular synthesis. Prenylation of the large HD-antigen is critical for its interaction with the HBsAg in the assembly of the virion. A proof of concept study in humans has shown that the prenylation inhibitor lonafarnib reduced HDV-viremia. PMID:27170382

  6. Steatosis and chronic hepatitis C infection: mechanisms and significance.

    PubMed

    Harrison, Stephen A

    2005-10-01

    The co-existence of chronic hepatitis C and hepatic steatosis is well known, occurring in roughly 50% of patients infected with the hepatitis C virus. Recent interest has focused on the pathophysiologic mechanisms explaining the genesis of hepatic steatosis in the setting of chronic hepatitis C. Data suggest that both viral and host metabolic factors are involved in this process. Additionally, it has become evident that the efficacy of current antiviral therapy is decreased in the setting of co-existent steatosis or steatohepatitis, predominantly in genotype non-3 patients. Several potential explanations for this have been proposed and include underlying viral resistance and host-mediated insulin resistance, enhanced fibrosis, altered immune responses, and decreased bioavailability of interferon-based therapy. This review focuses on our current understanding of the mechanisms for steatosis development in the setting of chronic hepatitis C infection and the proposed mechanisms for the observed decreased efficacy of current antiviral therapy in this patient population.

  7. Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

    PubMed

    Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

    2014-05-12

    We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

  8. Genome-wide analysis for identification of adaptive diversification between hepatitis C virus subtypes 1a and 1b.

    PubMed

    Li, Yan; Wang, Ruirui; Du, Xiaogang; Zhang, Mingwang; Xie, Meng

    2016-07-01

    Hepatitis C virus (HCV) is a major cause of liver disease and has been estimated to infect approximately 2%-3% of the world's population. HCV genotype 1 is the subject of intense research and clinical investigations because of its worldwide prevalence and poor access to treatment for patients in developing countries and marginalized populations. The predominant subtypes 1a and 1b of HCV genotype 1 present considerable differences in epidemiological features. However, the genetic signature underlying such phenotypic functional divergence is still an open question. Here, we performed a genome-wide evolutionary study on HCV subtypes 1a and 1b. The results show that adaptive selection has driven the diversification between these subtypes. Furthermore, the major adaptive divergence-related changes have occurred on proteins E1, NS4B, NS5A, and NS5B. Structurally, a number of adaptively selected sites cluster in functional regions potentially relevant to (i) membrane attachment and (ii) the interactions with viral and host cell factors and the genome template. These results might provide helpful hints about the molecular determinants of epidemiological divergence between HCV 1a and 1b.

  9. Chronic hepatitis B virus in the Philippines.

    PubMed

    Gish, Robert G; Sollano, Jose D; Lapasaran, Alex; Ong, Janus P

    2016-05-01

    Multiple studies have shown a high prevalence of chronic hepatitis B (CHB) infection in the Philippines, not only in high-risk populations but also in the general population. The most recent national study estimated HBsAg seroprevalence to be 16.7%, corresponding to an estimated 7.3 million CHB adults. The factors underlying the high prevalence of CHB and its sequelae include the inadequate use of vaccination for prevention and the lack of treatment for many Filipinos. Because without medical monitoring and treatment of CHB the risk of progression to liver failure and death is 25-30%, the ultimate medical and societal costs will be very high if the Philippines fails to properly address hepatitis B infection. It will be very important to move forward with programs that can help to ensure universal vaccination of newborns, screening and vaccination nationwide, and monitoring and treatment for CHB persons. It will also be crucial to address transmission of HBV in the health-care setting (via contaminated needles and syringes and inadequately sterilized hospital equipment) and via injection drug use and tattooing. Because of the relatively low average per capita income and the lack of coverage by PhilHealth of outpatient visits and medications, there is an urgent need to move forward with a nationally supported program that includes education for both the general public and health-care workers on liver disease and screening for hepatitis viruses, followed by, as appropriate, vaccination or treatment, with expanded government coverage for these for all those who could not otherwise afford it. PMID:26643262

  10. Daclatasvir: A Review in Chronic Hepatitis C.

    PubMed

    Keating, Gillian M

    2016-09-01

    The hepatitis C virus (HCV) NS5A replication complex inhibitor daclatasvir (Daklinza(®)) is indicated for use in combination with sofosbuvir, with or without ribavirin, in a pangenotypic all-oral regimen. In patients with chronic HCV genotype 1 or 3 infection without cirrhosis, a 12-week regimen of daclatasvir plus sofosbuvir achieved high sustained virological response rates 12 weeks' post-treatment (SVR12), regardless of prior treatment experience, according to the results of the AI444040 and ALLY-3 trials. In the ALLY-3+ trial, high SVR12 rates were achieved with a 12- or 16-week regimen of daclatasvir plus sofosbuvir and ribavirin in patients with chronic HCV genotype 3 infection and advanced fibrosis or compensated cirrhosis. A daclatasvir plus sofosbuvir-based regimen demonstrated efficacy in patients with chronic HCV genotype 1, 3 or 4 infection and advanced cirrhosis or post-transplant recurrence in the ALLY-1 trial, and in patients co-infected with HCV genotype 1, 3 or 4 and HIV-1 in the ALLY-2 trial. Results of clinical trials were supported by real-world data from early-access programmes that included high numbers of patients who would have been excluded from phase 3 trials because of advanced disease and/or concomitant medical conditions. Daclatasvir plus sofosbuvir with or without ribavirin was generally well tolerated. In conclusion, an all-oral regimen comprising daclatasvir plus sofosbuvir with or without ribavirin is an important option for use in treatment-naive or treatment-experienced patients with chronic HCV genotype 1, 3 or 4 infection, including in patients with advanced liver disease, post-transplant recurrence and HIV-1 co-infection. PMID:27550544

  11. Cell culture replication of a genotype 1b hepatitis C virus isolate cloned from a patient who underwent liver transplantation.

    PubMed

    Koutsoudakis, George; Perez-del-Pulgar, Sofia; Coto-Llerena, Mairene; Gonzalez, Patricia; Dragun, Jakub; Mensa, Laura; Crespo, Gonzalo; Navasa, Miguel; Forns, Xavier

    2011-01-01

    The introduction of the genotype 2a isolate JFH1 was a major breakthrough in the field of hepatitis C virus (HCV), allowing researchers to study the complete life cycle of the virus in cell culture. However, fully competent culture systems encompassing the most therapeutically relevant HCV genotypes are still lacking, especially for the highly drug-resistant genotype 1b. For most isolated HCV clones, efficient replication in cultured hepatoma cells requires the introduction of replication-enhancing mutations. However, such mutations may interfere with viral assembly, as occurs in the case of the genotype 1b isolate Con1. In this study, we show that a clinical serum carrying a genotype 1b virus with an exceptionally high viral load was able to infect Huh7.5 cells. Similar to previous reports, inoculation of Huh7.5 cells by natural virus is very inefficient compared to infection by cell culture HCV. A consensus sequence of a new genotype 1b HCV isolate was cloned from the clinical serum (designated Barcelona HCV1), and then subjected to replication studies. This virus replicated poorly in a transient fashion in Huh7.5 cells after electroporation with in vitro transcribed RNA. Nonetheless, approximately 3 weeks post electroporation and thereafter, core protein-positive cells were detected by immunofluorescence. Surprisingly, small amounts of core protein were also measurable in the supernatant of electroporated cells, suggesting that HCV particles might be assembled and released. Our findings not only enhance the current method of cloning in vitro HCV replication-competent isolates, but also offer valuable insights for the realization of fully competent culture systems for HCV. PMID:21887279

  12. Cell Culture Replication of a Genotype 1b Hepatitis C Virus Isolate Cloned from a Patient Who Underwent Liver Transplantation

    PubMed Central

    Koutsoudakis, George; Perez-del-Pulgar, Sofia; Coto-Llerena, Mairene; Gonzalez, Patricia; Dragun, Jakub; Mensa, Laura; Crespo, Gonzalo; Navasa, Miguel; Forns, Xavier

    2011-01-01

    The introduction of the genotype 2a isolate JFH1 was a major breakthrough in the field of hepatitis C virus (HCV), allowing researchers to study the complete life cycle of the virus in cell culture. However, fully competent culture systems encompassing the most therapeutically relevant HCV genotypes are still lacking, especially for the highly drug-resistant genotype 1b. For most isolated HCV clones, efficient replication in cultured hepatoma cells requires the introduction of replication-enhancing mutations. However, such mutations may interfere with viral assembly, as occurs in the case of the genotype 1b isolate Con1. In this study, we show that a clinical serum carrying a genotype 1b virus with an exceptionally high viral load was able to infect Huh7.5 cells. Similar to previous reports, inoculation of Huh7.5 cells by natural virus is very inefficient compared to infection by cell culture HCV. A consensus sequence of a new genotype 1b HCV isolate was cloned from the clinical serum (designated Barcelona HCV1), and then subjected to replication studies. This virus replicated poorly in a transient fashion in Huh7.5 cells after electroporation with in vitro transcribed RNA. Nonetheless, approximately 3 weeks post electroporation and thereafter, core protein-positive cells were detected by immunofluorescence. Surprisingly, small amounts of core protein were also measurable in the supernatant of electroporated cells, suggesting that HCV particles might be assembled and released. Our findings not only enhance the current method of cloning in vitro HCV replication-competent isolates, but also offer valuable insights for the realization of fully competent culture systems for HCV. PMID:21887279

  13. Chronic treatment with the vasopressin 1b receptor antagonist SSR149415 prevents the dysphoria associated with nicotine withdrawal in rats

    PubMed Central

    Qi, Xiaoli; Guzhva, Lidia; Ji, Yue; Bruijnzeel, Adriaan W.

    2015-01-01

    Nicotine addiction is a chronic brain disorder that is characterized by dysphoria upon smoking cessation and relapse after brief periods of abstinence. It has been hypothesized that the negative mood state associated with nicotine withdrawal is partly mediated by a heightened activity of brain stress systems. Animal studies suggest that blockade of vasopressin 1b (V1b) receptors diminishes high levels of drug intake in dependent animals and attenuates the emotional response to stressors. The goal of the present studies was to investigate the effect of acute and chronic treatment with the V1b receptor antagonist SSR149415 on the negative mood state associated with nicotine withdrawal in rats. An intracranial self-stimulation (ICSS) procedure was used to assess mood states and nicotine dependence was induced using minipumps. The nicotinic receptor antagonist mecamylamine was used to precipitate withdrawal. Mecamylamine elevated the brain reward thresholds of the nicotine dependent rats, which reflects a negative mood state. Mecamylamine did not affect the brain reward thresholds of the saline-treated control rats. Chronic treatment with SSR149415 completely prevented the elevations in brain reward thresholds associated with nicotine withdrawal while acute treatment only partly prevented nicotine withdrawal. These data suggest that chronic treatment with V1b receptor antagonists may prevent the dysphoria associated with smoking cessation and thereby improve relapse rates. PMID:26112757

  14. Chronic treatment with the vasopressin 1b receptor antagonist SSR149415 prevents the dysphoria associated with nicotine withdrawal in rats.

    PubMed

    Qi, Xiaoli; Guzhva, Lidia; Ji, Yue; Bruijnzeel, Adriaan W

    2015-10-01

    Nicotine addiction is a chronic brain disorder that is characterized by dysphoria upon smoking cessation and relapse after brief periods of abstinence. It has been hypothesized that the negative mood state associated with nicotine withdrawal is partly mediated by a heightened activity of brain stress systems. Animal studies suggest that blockade of vasopressin 1b (V1b) receptors diminishes high levels of drug intake in dependent animals and attenuates the emotional response to stressors. The goal of the present studies was to investigate the effect of acute and chronic treatment with the V1b receptor antagonist SSR149415 on the negative mood state associated with nicotine withdrawal in rats. An intracranial self-stimulation (ICSS) procedure was used to assess mood states and nicotine dependence was induced using minipumps. The nicotinic receptor antagonist mecamylamine was used to precipitate withdrawal. Mecamylamine elevated the brain reward thresholds of the nicotine dependent rats, which reflects a negative mood state. Mecamylamine did not affect the brain reward thresholds of the saline-treated control rats. Chronic treatment with SSR149415 completely prevented the elevations in brain reward thresholds associated with nicotine withdrawal while acute treatment only partly prevented nicotine withdrawal. These data suggest that chronic treatment with V1b receptor antagonists may prevent the dysphoria associated with smoking cessation and thereby improve relapse rates.

  15. Interferon therapy of chronic hepatitis B.

    PubMed

    Brunetto, Maurizia Rossana; Bonino, Ferruccio

    2014-01-01

    Chronic hepatitis B (CHB) results from the inability of the host's immune system to control viral replication. Interferon-α (IFN-α) therapy can convert CHB into inactive hepatitis B virus (HBV) infection in 20-30% of the treated patients. In spite of the low response rate, IFN-α therapy has the advantage of having a limited duration and being effective even after therapy, as demonstrated by a much higher incidence of HBsAg clearance in responders to IFN-α than in naturally occurring inactive HBsAg carriers. IFN-α has multiple antiviral, antiproliferative, and immunomodulatory activities and targets: cellular genes (IFN-stimulated genes) activating different pathways of antiviral defense in infected and noninfected cells, HBV replication blocking the RNA-containing core particle formation and accelerating their decay, degrading pregenomic RNA, and modulating the nuclear viral minichromosome (covalently closed circular DNA) activity by targeting its epigenetic regulation and both innate and adaptive immune response. The interference of viral heterogeneity and genetic polymorphisms of the host on IFN-α susceptibility is under investigation. Only a better understanding of the complex interplay between the different activities of IFN-α would warrant the amelioration of current therapeutic strategies and the design of new therapeutic approaches. The study of on-treatment dynamics of HBV infection by means of combined quantitative monitoring of serum HBV DNA and HBsAg warrant tailoring treatment at the single-patient level and can help to make treatment more cost-effective by using the different combinations of currently available antivirals, including IFN, more appropriately. Integrated molecular and clinical knowledge in a systems medicine fashion is mandatory to further improve antiviral therapy in CHB.

  16. Susceptibilities of Genotype 1a, 1b, and 3 Hepatitis C Virus Variants to the NS5A Inhibitor Elbasvir

    PubMed Central

    Curry, Stephanie; McMonagle, Patricia; Yeh, Wendy W.; Ludmerer, Steven W.; Jumes, Patricia A.; Marshall, William L.; Kong, Stephanie; Ingravallo, Paul; Black, Stuart; Pak, Irene; DiNubile, Mark J.

    2015-01-01

    Elbasvir is an investigational NS5A inhibitor with in vitro activity against multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The barrier to resistance was assessed by the number of resistant colonies selected by exposure to various elbasvir concentrations. In a phase 1b dose-escalating study, virologic responses were determined in 48 noncirrhotic adult men with chronic genotype 1 or 3 infections randomized to placebo or elbasvir from 5 to 50 mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for 5 days. The NS5A gene was sequenced from plasma specimens obtained before, during, and after treatment. Elbasvir suppressed the emergence of resistance-associated variants (RAVs) in vitro in a dose-dependent manner. Variants selected by exposure to high elbasvir concentrations typically encoded multiple amino acid substitutions (most commonly involving loci 30, 31, and 93), conferring high-level elbasvir resistance. In the monotherapy study, patients with genotype 1b had greater reductions in HCV RNA levels than patients with genotype 1a at all elbasvir doses; responses in patients with genotype 3 were generally less pronounced than for genotype 1, particularly at lower elbasvir doses. M28T, Q30R, L31V, and Y93H in genotype 1a, L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3 were the predominant RAVs selected by elbasvir monotherapy. Virologic findings in patients were consistent with the preclinical observations. NS5A-RAVs emerged most often at amino acid positions 28, 30, 31, and 93 in both the laboratory and clinical trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under identifier NCT01532973.) PMID:26303801

  17. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine*

    PubMed Central

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D’Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-01-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  18. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine.

    PubMed

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D'Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-04-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  19. Hepatic inflammation and progressive liver fibrosis in chronic liver disease

    PubMed Central

    Czaja, Albert J

    2014-01-01

    Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to improve outcomes as adjunctive therapies. Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes. Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species. Anti-oxidants (N-acetylcysteine, S-adenosyl-L-methionine, and vitamin E) and angiotensin inhibitors (losartin) have had anti-fibrotic actions in preliminary human studies, and they may emerge as supplemental therapies. Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease. PMID:24627588

  20. Correlation between histologic staging, hepatitis C virus genotypes and clinical features in HCV chronic hepatitis: evidence of a new pattern.

    PubMed

    Di Tommaso, L; Macchia, S; Morandi, L; Leoncini, S; Pession, A; Dal Monte, P R; Foschini, M P

    2003-07-01

    Genome heterogeneity may be related to the wide variability of clinical and pathological features in hepatitis C virus (HCV)-related chronic liver disease. This paper addresses the possible association between HCV subtypes and clinical and histological features of chronically infected patients. Sixty-eight consecutive liver biopsies of chronic hepatitis constituted the basis of the study. HCV genotyping was performed on frozen tissue. Grading of necroinflammatory activity and staging of fibrosis were histologically assessed. Serologic HCV-RNA and liver function were assessed at the same time. All information was compared with clinical data including age, sex, HCV serology, and probable data and route of infection. Two cases were excluded as inadequate tissue was available. Five cases were negative to HCV-RNA in both serum and tissue. In 61 cases HCV RNA was present at the same time in serum and liver tissue. Forty-four patients were men (72%) and 17 (28%) were women. Two peaks of age were observed: 1 in the 4th decade of life, the 2nd in the 7th. The 2 groups had different HCV genotypes. Patients with genotypes 1b (mean age 50.7 years), 2c (mean age 61.3 years), and a subgroup of coinfections (mean age 60 years) were older than patients with genotypes 1a (mean age 35.5 years), 3 (mean age 36 years), and a subgroup of coinfections (mean age 33 years). Patients with genotypes 1b, 2, or 2c and a subgroup of coinfections more frequently had a history of blood transfusion and or surgical intervention dating up to 49 years previously. Patients with HCV 1a, 3, and a subgroup of coinfections frequently admitted a period of intravenous drug abuse. Patients with advanced liver disease, i.e., severe fibrosis and cirrhosis, showed the same 2 peaks of incidence: in the 4th and 7th decades of life, the first group mainly comprising patients with HCV types 1a and 3, the second, patients with HCV types 1b and 2c. Both these groups shared a clinical history of a long

  1. Successful treatment of activated occult hepatitis B in a non-responder chronic hepatitis C patient

    PubMed Central

    2011-01-01

    We reported a 23 years old male with chronic hepatitis C virus infection, discontinued from pegylated interferon/ribavirin combination therapy due to a lack of early virological response. He has developed activation of occult hepatitis B virus that was successfully treated by a one year of lamivudine therapy. PMID:22078891

  2. Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors

    PubMed Central

    Saludes, Verónica; Bracho, Maria Alma; Valero, Oliver; Ardèvol, Mercè; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Martró, Elisa

    2010-01-01

    Background Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy −especially among genotype 1 infected patients−, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Methodology Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1–E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A “leave-one-out” cross-validation method was used to assess the reliability of the discriminant models. Principal Findings Lower alanine transaminase levels (ALT, p = 0.009), a higher number of quasispecies variants in the E1–E2 region (number of haplotypes, nHap_E1–E2) (p = 0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p = 0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1–E2, and gamma-glutamyl transferase and ALT levels. Conclusions and Significance Discriminant analysis has been shown as a useful tool to predict treatment outcome using

  3. Studies on immunoregulatory mechanisms in acute and chronic hepatitis B.

    PubMed Central

    Lemm, G; Salzer, K; Warnatz, H

    1983-01-01

    Patients with acute hepatitis B and HBV-induced chronic hepatitis as well as normal control persons participated in the study. Hepatitis patients of both groups have decreased OKT4+/OKT8+T cell ratios due to an percental increase of OKT8+T cells in peripheral blood compared to the data of controls. Lymphocyte cultures of chronic hepatitis patients show reduced DNA synthesis after stimulation by allogeneic non-T cells, PHA, Con A and PWM. PWM-induced immunoglobulin secretion by B cells, determined by means of a reverse haemolytic plaque assay (RHPA) and a solid phase ELISA, showed comparable results in hepatitis B patients and controls. The AMLR, which is thought to reflect an autologous immunoregulatory phenomenon, is slightly impaired in cultures of hepatitis B patients in comparison to controls. Con A-induced suppressor cell activity on T cell reactions is decreased in hepatitis, whereas suppressor cell activity on B cell activation is within the same range as in cultures of controls. It is concluded from these data, that suppressor cell activity on T cell function is impaired in hepatitis B, whereas B cell functions and suppressor cell activity on B cell function are in the normal range. The results with the functional assays and the finding of increased proportions of OKT8+T cells in hepatitis B are considered to reflect properties of different T cell subpopulations, responsible for different immunoregulatory functions. PMID:6222854

  4. Evaluation of interleukin -1B (+3954) gene polymorphism in patients with chronic and aggressive periodontitis: A genetic association study

    PubMed Central

    Masamatti, Sujata S.; Kumar, Ashish; Baron, Tarun Kumar A.; Mehta, Dhoom S.; Bhat, Kishore

    2012-01-01

    Background: IL-1 cytokines have central roles in the pathogenesis of periodontal disease. Polymorphism in the locus +3954 (C/T) of the human IL-1B gene has been shown to affect the levels of this cytokine. Aim: The aim of the present study was to investigate the association between the IL-1 B (+3954) gene polymorphism and the occurrence of different clinical forms of periodontitis. Materials and Methods: Genomic DNA was obtained from 90 individuals and amplified using the PCR with specific primers flanking the locus +3954 of IL-1B. PCR products were submitted to restriction endonuclease digestion and analyzed by gel electrophoresis, allowing for the determination of the genotypes and detection of the polymorphism. Statistical Analysis: Fisher's exact test was used for comparing the frequency of genotype distributions between groups. Results: The chronic periodontitis group displayed a higher percentage of T alleles (38%) when compared to the aggressive periodontitis group (20%) and to the control group (19%). Conclusion: Our study data states that polymorphism in the locus +3954 of IL-1B gene could be a risk factor for chronic periodontitis in a sample of Indian population of Karnataka state. PMID:22919211

  5. Baseline factors associated with treatment response in patients infected with hepatitis C virus 1b by stratification of IL28B polymorphisms.

    PubMed

    Ling, Qihua; Chen, Jianjie; Zhou, Hua; Zhong, Jun; Chen, Yiyun; Ye, Qingyan; Zhuo, Yunhui; Min, Niehong; Shang, Binyi

    2015-04-01

    Although the single-nucleotide polymorphism (SNP) rs12979860 in the IL28B gene is a better predictor of sustained virological response to treatment of chronic hepatitis C (CHC) than other baseline factors, some CHC patients with the favorable C allele cannot achieve a sustained virological response when treated with peginterferon plus ribavirin. The aim of this study was to examine baseline factors as predictors of rapid virological response (RVR) and complete early virological response (cEVR) to peginterferon alfa-2a plus ribavirin treatment in Chinese CHC patients with hepatitis C virus (HCV) genotype 1b, with emphasis on the difference between the rs129860 CC and CT/TT genotypes. A total of 337 treatment-naïve patients participated in this study. All patients were treated with peginterferon alfa-2a plus ribavirin at standard dosage. Serum samples from all patients were collected at baseline, week 4, and week 12 for testing of laboratory parameters, and IL28B genotypes were determined. Multivariate analysis showed that among rs12979860 CC genotype patients, glucose level and aspartate amino transferase (AST) activity were inversely associated with RVR, while abnormal platelet count and allergy inversely associated with cEVR. Among rs12979860 CT genotype patients, age below 40 years and short infection duration were associated with RVR, while age below 40 years, short infection duration, high body mass index (BMI), and no history of allergies were associated with cEVR. The baseline factors associated with the response to CHC treatment may depend on the IL28B genotype. Refinement of the baseline predictors based on IL28B genotypes may be useful for management of HCV infection. PMID:25687192

  6. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity

    PubMed Central

    Labonté, Eric D.; Pfluger, Paul T.; Cash, James G.; Kuhel, David G.; Roja, Juan C.; Magness, Daniel P.; Jandacek, Ronald J.; Tschöp, Matthias H.; Hui, David Y.

    2010-01-01

    Decrease in fat catabolic rate on consuming a high-fat diet contributes to diet-induced obesity. This study used group 1B phospholipase A2 (Pla2g1b)-deficient mice, which are resistant to hyperglycemia, to test the hypothesis that Pla2g1b and its lipolytic product lysophospholipid suppress hepatic fat utilization and energy metabolism in promoting diet-induced obesity. The metabolic consequences of hypercaloric diet, including body weight gain, energy expenditure, and fatty acid oxidation, were compared between Pla2g1b+/+ and Pla2g1b−/− mice. The Pla2g1b−/− mice displayed normal energy balance when fed chow, but were resistant to obesity when challenged with a hypercaloric diet. Obesity resistance in Pla2g1b−/− mice is due to their ability to maintain elevated energy expenditure and core body temperature when subjected to hypercaloric diet, which was not observed in Pla2g1b+/+ mice. The Pla2g1b−/− mice also displayed increased postprandial hepatic fat utilization due to increased expression of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-δ, PPAR-γ, cd36/Fat, and Ucp2, which coincided with reduced postprandial plasma lysophospholipid levels. Lysophospholipids produced by Pla2g1b hydrolysis suppress hepatic fat utilization and down-regulate energy expenditure, thereby preventing metabolically beneficial adaptation to a high-fat diet exposure in promoting diet-induced obesity and type 2 diabetes.—Labonté, E. D., Pfluger, P. T., Cash, J. G., Kuhel, D. G., Rojas, J. C., Magness, D. P., Jandacek, R. J., Tschöp, M. H., Hui, D. Y. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity. PMID:20215528

  7. Cytokine profiles and hepatic injury in occult hepatitis C versus chronic hepatitis C virus infection.

    PubMed

    Mousa, N; Eldars, W; Eldegla, H; Fouda, O; Gad, Y; Abousamra, N; Elmasry, E; Arafa, M

    2014-01-01

    Occult hepatitis C virus (HCV) infection is a new entity that should be considered when diagnosing patients with abnormal liver functions of unknown origin. This work was carried out to evaluate T-helper 1/T-helper 2 (Th1/Th2) cytokine profiles in patients with occult HCV infection versus chronic hepatitis C (CHC) infection, also to investigate any association between theses cytokines and liver histological features in both groups. Serum levels of Th1 cytokines (IL-2, IFN-gamma) and Th2 (IL-4 and IL-10) were measured in 35 patients with occult HCV infection compared to 50 patients with chronic hepatitis C infection and 30 healthy controls. We have found that Th1 cytokines were significantly increased in patients with CHC infection than in both occult HCV infection and control groups (p less than 0.001). On the other hand, serum IL-4 levels were higher in occult HCV infection than in CHC and control groups (p less than 0.001). Furthermore, serum IL-10 levels were higher in both patient groups vs control group (pless than 0.001), with no significant difference between CHC and occult HCV groups. Finally, only serum IL-10 levels were significantly higher among patients with high activity (A2-A3) than those with low activity (A0-A1) in both CHC and occult HCV groups (p=0.038, p=0.025, respectively). Patients with occult HCV infection exhibited a distinct immunoregulatory cytokine pattern that is shifted towards the Th2 arm.

  8. [Chronic hepatitis B: anatomo-clinical, serologic and developmental aspects].

    PubMed

    da Silva, L C; Carrilho, F J; da Fonseca, L E; Faggion, P; Arroyo, S E; Tavares, S M; Granato, C F; Vianna, M R; Alves, V A; Gayotto, L C

    1989-01-01

    Few data on chronic hepatitis B (CHB) have been published in our country, despite the fact that it is responsible for more than 50% of all types of chronic hepatitis. From 1968 to 1988, 164 patients were attended with the diagnosis of CHB, from whom 136 (82.9%) were male. Only 11 (8.1%) admitted homosexual behavior. Twenty six out of 39 (66.7%) health professionals were medical doctors; among them 12 (46.2%) were surgeons. The mode of transmission was unknown in 55% of the cases, but vertical and sexual transmissions were also frequent. Commercial gammaglobulin, used with prophylactic purpose, was probably responsible for eight cases between 1972 and 1975. The most frequent forms of CH were chronic active hepatitis (CAH) and liver cirrhosis (LC): 72 or 43.9% and 53 or 32.3%, respectively. The predominance of HBeAg (66.4%) was observed in all forms of CHB. Repeated biopsies showed that chronic lobular hepatitis (CLH) and chronic persistent hepatitis (CPH) may occasionally progress to CAH. This form may persist as such for some years or progress to cirrhosis. In a few cases the evolution to CPH was observed. In the long term follow-up of our patients, the appearance of hepatocellular carcinoma was observed in 8 (4.9%). PMID:2561546

  9. Characteristics of an outpatient chronic hepatitis B virus infection cohort

    PubMed Central

    de Assis, Danyenne Rejane; Tenore, Simone de Barros; Pinho, João Renato Rebello; Lewi, David Salomão; Ferreira, Paulo Roberto Abrão

    2015-01-01

    ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID:26154539

  10. Hepatitis C virus genotypes: epidemiological and clinical associations. Benelux Study Group on Treatment of Chronic Hepatitis C.

    PubMed

    Kleter, B; Brouwer, J T; Nevens, F; van Doorn, L J; Elewaut, A; Versieck, J; Michielsen, P P; Hautekeete, M L; Chamuleau, R A; Brénard, R; Bourgeois, N; Adler, M; Quint, W G; Bronkhorst, C M; Heijtink, R A; Hop, W J; Fevery, J; Schalm, S W

    1998-02-01

    In a cohort of 292 chronic hepatitis C patients living in the Benelux countries the relationship between viral genotype and geographical origin, route of transmission, clinical characteristics and severity of liver disease was analyzed. HCV-RNA isolates could be classified by the Line Probe Assay (LiPA) as 1a, 1b, 2, 3, 4 or 5 in 286 (98%) cases. Patients of European origin were predominantly infected with HCV subtype 1b (164/254, 65%, CI 58-70%), as were patients of Asian origin (7/13, 54%). Patients originating from Surinam (South America) had predominantly type 2 (9/10, 90%), whereas Africans were mainly infected with type 4 (7/9, 77%). Blood transfusion was the mode of transmission in 142 (50%) patients, intravenous drug abuse (IVDA) in 40 (14%), occupational needle accident or tattoo in 11 (4%); no obvious source of infection was found in 93 (33%). In patients infected by blood transfusion, subtype 1b was predominant (70%, CI 61-77%), whereas subtypes la and 3 were predominant in those infected by IVDA (25% and 45%, respectively, p<0.001). Cirrhosis was observed in 68 (24%) patients; in multivariate analysis, factors independently related to cirrhosis were: the duration of infection, age and prior hepatitis B. No significant relationship was found between the severity of fibrosis or liver inflammation and the HCV (sub)types. In summary, in this large cohort of patients in the Benelux countries the hepatitis C virus (sub)type present was clearly related to the country of origin and the route of transmission, but not to the severity of liver disease. PMID:9548265

  11. The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1.

    PubMed

    Shu, Nan; Hu, Mengyue; Ling, Zhaoli; Liu, Peihua; Wang, Fan; Xu, Ping; Zhong, Zeyu; Sun, Binbin; Zhang, Mian; Li, Feng; Xie, Qiushi; Liu, Xiaodong; Liu, Li

    2016-01-01

    Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation.

  12. The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1.

    PubMed

    Shu, Nan; Hu, Mengyue; Ling, Zhaoli; Liu, Peihua; Wang, Fan; Xu, Ping; Zhong, Zeyu; Sun, Binbin; Zhang, Mian; Li, Feng; Xie, Qiushi; Liu, Xiaodong; Liu, Li

    2016-01-01

    Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation. PMID:27624558

  13. The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1

    PubMed Central

    Shu, Nan; Hu, Mengyue; Ling, Zhaoli; Liu, Peihua; Wang, Fan; Xu, Ping; Zhong, Zeyu; Sun, Binbin; Zhang, Mian; Li, Feng; Xie, Qiushi; Liu, Xiaodong; Liu, Li

    2016-01-01

    Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation. PMID:27624558

  14. Amino Acid Polymorphisms Within the Entire HCV NS5A Region in Estonian Chronic HCV 1b Patients With Different Treatment Response

    PubMed Central

    Kuznetsova, Tatiana; Tallo, Tatjana; Brjalin, Vadim; Reshetnjak, Irina; Salupere, Riina; Priimagi, Ljudmilla; Katargina, Olga; Smirnova, Maria; Jansons, Juris; Tefanova, Valentina

    2013-01-01

    Background A substantial proportion of hepatitis C virus (HCV)-1b infected patients do not response to pegylated interferon-α plus ribavirin (PegIFNα/RBV) combination therapy that was partially associated with mutations in the non-structural 5A (NS5A) protein. Objectives Analysis of NS5A polymorphisms in HCV genotype 1b pre-treatment serum samples from Estonian patients and their effect on the treatment response. Patients and Methods Twenty-nine complete NS5A sequences obtained from patients with chronic HCV-1b infection who had received combined therapy with PegIFNα-2a/RBV were analyzed and compared with the prototype strain HCV-J. Twelve patients achieved a sustained virological response (SVR), 15 were non-SVR and 2 patients stopped treatment because of side effects. Results No significant difference in total number of amino acid mutations was observed between isolates from SVR and non-SVR patients in any known regions of the NS5A protein. However, specific amino acid substitutions at positions 1989 and 2283 correlated significantly with SVR, mutations at positions 1979, 2107, 2171 and 2382 were associated with non-response to treatment and amino acid substitution at position 2319 was observed in relapsers. At phylogenetic analysis, NS5A nucleotide sequences have been subdivided into four groups characterized by the different treatment response. Twenty-four novel nucleotide polymorphisms and 11 novel amino acid polymorphisms were identified based on the phylogenetic tree topology. Conclusions Specific amino acid substitutions correlating with the treatment response were found. Polymorphisms revealed by phylogenetic analysis may define the signature patterns for treatment susceptible and treatment resistant strains prevalent in Estonia. PMID:24358043

  15. Resistance management in chronic hepatitis B complicated by renal failure.

    PubMed

    Wiegand, J; Karlas, T; Schiefke, I; Krasselt, U; Bock, T; Mössner, J; Tillmann, H L

    2010-07-01

    Therapy of chronic hepatitis B has improved by the invention of the potent nucleos(t)ide analogues entecavir, telbivudine and tenofovir disoproxil. Due to increasing prevalence of lamivudine resistance the appropriate first line therapy may prevent emergence of any new resistance and avoid combination therapy. The present case describes a complex history of chronic hepatitis B in the setting of renal failure after two renal transplants illustrating why lamivudine should not be used as first line treatment option any more. Instead, entecavir offers high antiviral potency, low risk for resistance and possible individual dose titration by an oral solution.

  16. Current treatment of choice for chronic hepatitis C infection

    PubMed Central

    Yasin, Tareq; Riley, Thomas R; Schreibman, Ian R

    2011-01-01

    More than three million Americans have chronic hepatitis C infection, and the disease remains one of the most common blood-borne infections in the US. Treatment is focused on the chronic form of the disease, because the acute one tends to be self-limiting. In this article, we review the recent literature regarding the most effective therapy against hepatitis C infection, to confirm the current treatment of choice for the disease. We conclude that combination therapy with pegylated interferon and ribavirin remains the initial treatment of choice. New research focusing on adjuvant therapies, such as protease and polymerase inhibitors, has yielded early data that appear to be promising. PMID:21694905

  17. Vasculitis as a Presenting Manifestation of Chronic Hepatitis B Virus Infection: A Case Report

    PubMed Central

    Singh, Harpreet; Sukhija, Gagandeep; Kaur, Parminder; Govil, Nikhil

    2016-01-01

    Hepatitis B virus is responsible for causing hepatic complications like acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma along with some uncommon immune mediated extrahepatic manifestations. Vasculitis remains an uncommon extrahepatic complication of hepatitis B virus infection. Herein we report a case of hepatitis B infection that presented with leucocytoclastic vasculitis as an initial manifestation and managed successfully with entacavir therapy. PMID:27042512

  18. Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1B.

    PubMed

    Owen, C; Lees, E K; Mody, N; Delibegović, M

    2015-02-01

    Protein tyrosine phosphatase 1B (PTP1B) regulates various signalling pathways including insulin, leptin, IGF-1 and growth hormone (GH) signalling. Transmission of the GH signal depends on Janus kinase 2 (JAK2), which is how PTP1B is thought to modulate GH signalling in the liver, based on studies utilising global PTP1B knockout mice (Ptp1b(-/-)). Here, we investigated the liver-specific role of PTP1B in GH signalling, using liver-specific Ptp1b(-/-) mice (alb-crePtp1b(-/-)), under physiological (chow) or insulin resistant (high-fat diet [HFD]) feeding conditions. Body weight and adiposity were comparable between female alb-crePtp1b(-/-) and Ptp1b(fl/fl) control mice. On chow diet, under 48-hour fasting GH-resistant conditions, GH stimulation in vivo led to a robust stimulation of the JAK-STAT signalling pathway. Alb-crePtp1b(-/-) mice exhibited significantly higher GH-induced JAK2 phosphorylation and SOCS3 gene expression post-GH stimulation. However, STAT3, STAT5 and ERK1/2 phosphorylation and SOCS2 gene expression were similar between groups. Interestingly, GH-induced mTOR phosphorylation was significantly higher in alb-crePtp1b(-/-) mice 5-min post-GH stimulation compared to controls, revealing this part of the pathway under direct control of PTP1B. Under ad lib HFD-fed conditions, GH-induced STAT5 phosphorylation significantly increased in alb-crePtp1b(-/-) mice only, with no alterations in the controls. Overall, our data demonstrate that liver-specific PTP1B deletion leads to significant alterations in GH signalling with increased JAK2, STAT5 and mTOR phosphorylation and SOCS3 gene expression.

  19. Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment.

    PubMed

    Takahashi, M; Yamada, G; Miyamoto, R; Doi, T; Endo, H; Nishimoto, H; Fujiki, S; Shimomura, H; Mizuno, M; Tsuji, T

    1992-10-01

    We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.

  20. Expression of fibrosis-related genes in canine chronic hepatitis.

    PubMed

    Kanemoto, H; Ohno, K; Sakai, M; Nakashima, K; Takahashi, M; Fujino, Y; Tsujimoto, H

    2011-07-01

    Molecular regulation of fibrosis in chronic canine hepatitis is poorly understood. The authors employed quantitative polymerase chain reaction (PCR) to determine the expression levels of genes reported to be related to fibrosis in other species (human, mouse, and rat) and to elucidate the relationship of these genes with the degree of fibrosis and the presence or absence of ascites and/or jaundice in dogs with hepatitis. Nine fibrosis-related genes were assayed: PDGFB, PDGFD, MMP2, TIMP1, THBS1, COL1A1, COL3A1, TGFB1, and TGFB2. Liver samples of 15 dogs with chronic hepatitis and 4 healthy control dogs were obtained via laparoscopic biopsy and subjected to histologic and quantitative PCR analyses. The expression of all 9 genes showed significant positive correlation (P<.01, r>.70) with the degree of fibrosis. Furthermore, the expression levels of all genes except TGFB1 were significantly higher (P<.05) in dogs with hepatic failure-related symptoms (ascites/jaundice). Results suggest that these 9 genes are integral to the development of fibrosis in canine chronic hepatitis.

  1. Chronic hepatitis C: This and the new era of treatment.

    PubMed

    Bertino, Gaetano; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Demma, Shirin; Ruggeri, Maria Irene; Scuderi, Laura; Malaguarnera, Giulia; Bertino, Nicoletta; Rapisarda, Venerando; Di Carlo, Isidoro; Toro, Adriana; Salomone, Federico; Malaguarnera, Mariano; Bertino, Emanuele; Malaguarnera, Michele

    2016-01-18

    Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.

  2. The serology of chronic hepatitis B infection revisited.

    PubMed Central

    Maruyama, T; McLachlan, A; Iino, S; Koike, K; Kurokawa, K; Milich, D R

    1993-01-01

    The serology of chronic hepatitis B infection has been established through the use of commercial immunoassays to measure the structural antigens of the hepatitis B virus and their respective antibodies in serum. However, the commercial assays have not been designed to detect serum antibodies in the presence of an excess of circulating antigens. A series of serum samples from 200 HBeAg-positive, chronically infected hepatitis B patients with varying degrees of liver disease were analyzed using novel immunoassays designed to detect antibodies in the presence of circulating viral antigens. All patients, regardless of their liver disease, were seronegative for antibodies specific for the envelope antigens or the secreted nucleoprotein antigen (HBeAg) when the commercial assays were used. In contrast, virtually all chronically infected patients with liver disease and approximately 50% of patients without liver disease demonstrated anti-HBe and anti-envelope antibodies when sera were tested in the more sensitive immunoassays. Furthermore, asymptomatic patients could be serologically distinguished from symptomatic patients based on antibody fine specificity, titer, and IgG subclass. This study revealed that the majority of chronically infected hepatitis B patients produce a variety of antibodies for many years, and are not immunologically unresponsive, as suggested by the current assays. Images PMID:8514870

  3. Chronic Hepatitis C Infection in a Rural Medicaid HMO

    ERIC Educational Resources Information Center

    Calvert Jr., James F.; Goldenberg, Paula C.; Schock, Cathy

    2005-01-01

    Chronic hepatitis C infection (CHCI) is an increasingly common problem, affecting about 2% of the US population. The cost and complexity of treatment and difficulties in communicating with the infected population are of concern to insurers and health planners. Purpose: To describe the clinical features of patients with CHCI in a rural…

  4. Limited hepatitis B virus replication space in the chronically hepatitis C virus-infected liver.

    PubMed

    Wieland, S F; Asabe, S; Engle, R E; Purcell, R H; Chisari, F V

    2014-05-01

    We compared the kinetics and magnitude of hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-naive and chronically HCV-infected chimpanzees in whose livers type I interferon-stimulated gene (ISG) expression is strongly induced. HBV infection was delayed and attenuated in the HCV-infected animals, and the number of HBV-infected hepatocytes was drastically reduced. These results suggest that establishment of HBV infection and its replication space is limited by the antiviral effects of type I interferon in the chronically HCV-infected liver.

  5. Hepatic folate metabolism in the chronic alcoholic monkey

    SciTech Connect

    Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

    1981-05-01

    To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of /sup 3/H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected.

  6. Epigenetic Repression of CCDC37 and MAP1B Links Chronic Obstructive Pulmonary Disease to Lung Cancer

    PubMed Central

    Tessema, Mathewos; Yingling, Christin M.; Picchi, Maria A.; Wu, Guodong; Liu, Yushi; Weissfeld, Joel L.; Siegfried, Jill M.; Tesfaigzi, Yohannes; Belinsky, Steven A.

    2015-01-01

    Introduction Lung cancer and chronic obstructive pulmonary disease (COPD) share environmental risk factors. COPD also increases the risk of lung cancer; however, the molecular mechanisms are unclear. Methods An epigenome-wide association study of lung tumors and cancer-free lung tissue (CFLT) pairs from non-small cell lung cancer (NSCLC) cases with (n=18) or without (n=17) COPD was conducted using the HumanMethylation450 beadchip (HM450K). COPD-associated methylation of top-ranked genes was confirmed in a larger sample set, independently validated, and their potential as sputum-based biomarkers was investigated. Results Methylation of CCDC37 and MAP1B was more prevalent in lung tumors from COPD than non-COPD cases [54/71 (76%) vs. 20/46 (43%), p=0.0013] and [48/71 (68%) vs. 17/46 (37%), p=0.0035], respectively, after adjustment for age, sex, smoking status, and tumor histology. HM450K probes across CCDC37 and MAP1B promoters showed higher methylation in tumors than CFLT with the highest methylation seen in tumors from COPD cases (p<0.05). These results were independently validated using The Cancer Genome Atlas data. CCDC37 methylation was more prevalent in sputum from COPD than non-COPD smokers (p<0.005) from two cohorts. CCDC37 and MAP1B expression was dramatically repressed in tumors and CFLT from COPD than non-COPD cases, p<0.02. Conclusions The reduced expression of CCDC37 and MAP1B associated with COPD likely predisposes these genes to methylation that in turn, may contribute to lung cancer. PMID:26200272

  7. Management of hepatitis C in patients with chronic kidney disease

    PubMed Central

    Carvalho-Filho, Roberto J; Feldner, Ana Cristina CA; Silva, Antonio Eduardo B; Ferraz, Maria Lucia G

    2015-01-01

    Hepatitis C virus (HCV) infection is highly prevalent among chronic kidney disease (CKD) subjects under hemodialysis and in kidney transplantation (KT) recipients, being an important cause of morbidity and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on management and treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon (PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes

  8. Amantadine Therapy for Chronic Hepatitis C

    PubMed Central

    Smith, Jill P; Riley, Thomas R; Devenyi, Attila; Bingaman, Sandra I; Kunselman, Allen

    2004-01-01

    OBJECTIVE Although treatment of hepatitis C has improved, up to 50% do not respond to standard therapy with interferon regimes or cannot tolerate the treatment due to side effects. The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferon. DESIGN A prospective double-blind randomized placebo-controlled trial. SETTING Outpatient research clinic of a teaching hospital. PATIENTS/PARTICIPANTS One hundred fifty-two patients with confirmed hepatitis C with abnormal liver enzymes, detectable hepatitis C RNA in the blood, and abnormal liver histology by biopsy were randomized to receive treatment or placebo. MEASUREMENTS AND MAIN RESULTS Patients received either amantadine 100 mg twice daily by mouth or placebo for 6 months. After 6 months, placebo-treated patients were crossed over and treated with amantadine for 6 months and amantadine-treated subjects received 6 additional months of therapy. Amantadine therapy resulted in a significant decline in serum alanine aminotransferase compared to placebo (P = .03). Nine percent cleared the virus at the end of therapy and 6.8% had a sustained virologic response 6 months after discontinuation of amantadine, but this was not statistically significant. Side effects were minimal, and the social quality of life survey improved with 12 months of amantadine (P = .02). CONCLUSIONS Oral amantadine may provide a safe alternative treatment for those patients who are intolerant or unresponsive to interferon. PMID:15209605

  9. Fentanyl pharmacokinetics is not dependent on hepatic uptake by organic anion-transporting polypeptide 1B1 in human beings.

    PubMed

    Ziesenitz, Victoria C; König, Sonja K; Mahlke, Nina; Jantos, Ricarda; Skopp, Gisela; Weiss, Johanna; Haefeli, Walter E; Mikus, Gerd

    2013-07-01

    A recent study investigating the pharmacokinetics of fentanyl in Sprague-Dawley rats suggested fentanyl to be a substrate of rat organic anion-transporting polypeptide Oatp. In human beings, the most important OATP for the pharmacokinetics of many drugs is OATP1B1. Therefore, genetic variants of OATP1B1 (SLCO1B1) might modulate fentanyl pharmacokinetics and efficacy in human beings. Sixteen healthy male and female volunteers, homozygous for SLCO1B1*1a (genetic wild-type) (n = 11) or *15 (deficient haplotype carrying the single-nucleotide polymorphisms rs2306283 and rs4149056 and exhibiting altered transport activity; n = 5), were included in this randomized crossover study. The participants received fentanyl (5 μg/kg) intravenously alone or with the OATP inhibitor rifampicin (600 mg single oral dose). The pharmacokinetics of fentanyl and norfentanyl were determined by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In addition, fentanyl uptake in vitro was evaluated in OATP1B1 overexpressing HEK293 cells and compared to a mock-transfected cell line. In the clinical trial, fentanyl clearance was 18.8 ± 8.2 mL/min. kg in SLCO1B1*1a and 19.5 ± 1.8 mL/min/kg in SLCO1B1*15 carriers and not significantly different between the genotypes. During rifampicin, fentanyl clearance was 15.0 ± 4.4 mL/min/kg in SLCO1B1*1a and 16.7 ± 5.9 mL/min/kg in SLCO1B1*15 carriers (p > 0.5). In addition, in vitro data also indicate that fentanyl is not transported by OATP1B1. In conclusion, our data indicate that OATP1B1 has no impact on fentanyl pharmacokinetics in human beings.

  10. Antiviral therapy for chronic hepatitis B in China.

    PubMed

    Zheng, Xin; Wang, Junzhong; Yang, Dongliang

    2015-02-01

    The vaccination program against hepatitis B virus (HBV) has greatly reduced the incidence of HBV infection. However, almost one-fourth of the HBV infected patients worldwide are still located in China. The healthcare burden from chronic HBV infection is a big challenge for the Chinese government and clinicians. Antiviral therapy plays a central role in controlling chronic HBV infection and preventing the disease progression. However, due to the specific economic and medical system issues, the first-line antiviral agents recommended by the AASLD and EASL have not been widely used for Chinese patients. In this review, we will discuss some key issues in the area of antiviral treatment for chronic hepatitis B in China. PMID:25540038

  11. Distribution of Hepatitis B Virus Genotypes in Azerbaijani Patients With Chronic Hepatitis B Infection

    PubMed Central

    Bokharaei-Salim, Farah; Keyvani, Hossein; Monavari, Seyed Hamidreza; Esghaei, Maryam; Fakhim, Shahin; Ataei Pirkooh, Angila; Behnava, Bita

    2014-01-01

    Background: Hepatitis B virus (HBV) has been classified into ten genotypes (A-J) based on genome sequence divergence, which is very important for etiological and clinical investigations. HBV genotypes have distinct geographical distributions worldwide. Objectives: The aim of this study was to investigate the distribution of HBV genotypes among Azerbaijani patients with chronic hepatitis B, came from the Republic of Azerbaijan country to Iran to receive medical care. Patients and Methods: One hundred and three patients with chronic HBV infection, referred to hospitals related to Iran University of Medical Sciences and Tehran Hepatitis Center from August 2011 to July 2014, were enrolled in this cross sectional study. About 3-milliliter of peripheral blood was taken from each patient. After viral DNA extraction, HBV genotypes were tested using the INNO-LiPA™ HBV kit (Innogenetics, Ghent, Belgium). HBV genotyping was confirmed using sequencing of hepatitis B surface antigen (HBsAg) and polymerase (pol) regions of HBV. Results: The mean age of patients was 35.9 ± 11.7 years (19-66). Of 103 patients, 72 (69.9%) were male. In the present study, the predominant HBV genotype was D (93.2%) followed by genotype A (5.8%) and concurrent infection with A and D genotypes (0.97%). Conclusions: The main and frequent HBV genotype among Azerbaijani patients with chronic hepatitis B virus infection was genotype D followed by genotype A. PMID:25685166

  12. Hepatitis B flares in chronic hepatitis B: pathogenesis, natural course, and management.

    PubMed

    Chang, Ming-Ling; Liaw, Yun-Fan

    2014-12-01

    Hepatitis B flare, defined as an event with abrupt rise of alanine aminotransferase (ALT) levels to >5 times the upper limit of normal during chronic hepatitis B virus (HBV) infection, is considered to be the result of a human leukocyte antigen-I restricted, cytotoxic T lymphocyte mediated immune response against HBV and its downstream mechanisms. It may occur spontaneously, during or after antiviral therapy and in the setting of immunosuppression and/or chemotherapy. The clinical spectrum of hepatitis B flares varies from asymptomatic to symptomatic and typical overt acute hepatitis, even with hepatic decompensation or failure. Flares may also occur in viraemic patients with cirrhosis with higher incidence of decompensation/mortality, hence requiring immediate antiviral therapy. An upsurge of serum HBV DNA and hepatitis B surface antigen levels usually precedes the abrupt rise of ALT levels. Rising or stable and high HBV DNA during flares represent ineffective immune clearance and further hepatocytolysis, even hepatic decompensation, may occur. Such patients require immediate antiviral therapy. In contrast, bridging hepatic necrosis and/or alpha-fetoprotein levels >100 ng/ml or decreasing HBV DNA during flares represent a more effective immune clearance and frequently leads to seroclearance of HBV DNA and/or hepatitis B e antigen with remission. If patients are non-cirrhotic and there is no concern of developing decompensation, patients may be observed for 3-6 months before deciding on the need of antiviral therapy. Severe and repeated flares are prone to develop into decompensation or lead to the development of cirrhosis, thus a timely treatment to prevent the hepatitis B flare is better than to cope with the flare. Screening, monitoring and prophylactic or pre-emptive antiviral therapy is mandatory for patients who are going to receive immunosuppressants or chemotherapy.

  13. Hepatitis B-Related Concerns and Anxieties Among People With Chronic Hepatitis B in Australia

    PubMed Central

    Hajarizadeh, Behzad; Richmond, Jacqui; Ngo, Naomi; Lucke, Jayne; Wallace, Jack

    2016-01-01

    Background The psychological wellbeing of people with chronic hepatitis B (CHB) may be negatively affected due to the chronic and transmissible nature of the disease, and possible serious complications (e.g. cirrhosis and liver cancer). There are limited data investigating concerns and anxieties among people living with CHB. Objectives This study examined feelings about having hepatitis B among people with CHB, including hepatitis B-related concerns and anxieties. Patients and Methods Using convenience sampling, people with CHB attending four public liver clinics and one general practice in three Australian jurisdictions between April and September 2013 completed a self-administered questionnaire about their feelings about having hepatitis B. Results Ninety-three people completed the survey. Mean age was 45 years, 57% were men, and 93% were born overseas (75% from Asia). Seventy-six percent of participants reported having hepatitis B-related concerns and anxieties. The most common concerns were of developing liver cancer (57%), and infecting other people (53%). Thirty-five percent of participants were unwilling to talk to anyone about their hepatitis B while 25% changed how they lived as a result of having hepatitis B. Lower educational level was associated with feeling scared of hepatitis B (adjusted Odds Ratio [OR]: 4.04; 95%CI: 1.09, 14.90; P = 0.04), and an unwillingness to talk to anyone about hepatitis B (adjusted OR: 4.41; 95%CI: 1.09, 17.83; P = 0.04). Very good English proficiency was associated with a higher likelihood of participants changing how they lived (adjusted OR: 12.66; 95%CI: 2.21, 72.42; P < 0.01), and seeing life differently as a result of having hepatitis B (adjusted OR: 21.10; 95%CI: 3.70, 120.19; P < 0.01). Health professionals were the key person for 34% of participants in helping them cope with having hepatitis B, while 18% reported that no one supported them. Conclusions Hepatitis B-related concerns and anxieties are prevalent among

  14. Hepatitis B-Related Concerns and Anxieties Among People With Chronic Hepatitis B in Australia

    PubMed Central

    Hajarizadeh, Behzad; Richmond, Jacqui; Ngo, Naomi; Lucke, Jayne; Wallace, Jack

    2016-01-01

    Background The psychological wellbeing of people with chronic hepatitis B (CHB) may be negatively affected due to the chronic and transmissible nature of the disease, and possible serious complications (e.g. cirrhosis and liver cancer). There are limited data investigating concerns and anxieties among people living with CHB. Objectives This study examined feelings about having hepatitis B among people with CHB, including hepatitis B-related concerns and anxieties. Patients and Methods Using convenience sampling, people with CHB attending four public liver clinics and one general practice in three Australian jurisdictions between April and September 2013 completed a self-administered questionnaire about their feelings about having hepatitis B. Results Ninety-three people completed the survey. Mean age was 45 years, 57% were men, and 93% were born overseas (75% from Asia). Seventy-six percent of participants reported having hepatitis B-related concerns and anxieties. The most common concerns were of developing liver cancer (57%), and infecting other people (53%). Thirty-five percent of participants were unwilling to talk to anyone about their hepatitis B while 25% changed how they lived as a result of having hepatitis B. Lower educational level was associated with feeling scared of hepatitis B (adjusted Odds Ratio [OR]: 4.04; 95%CI: 1.09, 14.90; P = 0.04), and an unwillingness to talk to anyone about hepatitis B (adjusted OR: 4.41; 95%CI: 1.09, 17.83; P = 0.04). Very good English proficiency was associated with a higher likelihood of participants changing how they lived (adjusted OR: 12.66; 95%CI: 2.21, 72.42; P < 0.01), and seeing life differently as a result of having hepatitis B (adjusted OR: 21.10; 95%CI: 3.70, 120.19; P < 0.01). Health professionals were the key person for 34% of participants in helping them cope with having hepatitis B, while 18% reported that no one supported them. Conclusions Hepatitis B-related concerns and anxieties are prevalent among

  15. Establishment of a set of double transfectants coexpressing organic anion transporting polypeptide 1B3 and hepatic efflux transporters for the characterization of the hepatobiliary transport of telmisartan acylglucuronide.

    PubMed

    Ishiguro, Naoki; Maeda, Kazuya; Saito, Asami; Kishimoto, Wataru; Matsushima, Soichiro; Ebner, Thomas; Roth, Willy; Igarashi, Takashi; Sugiyama, Yuichi

    2008-04-01

    In the hepatic uptake of organic anions, organic anion transporting polypeptide (OATP) 1B1 is believed to be mainly involved. We have constructed a set of double-transfected cells coexpressing OATP1B1 and hepatic efflux transporters and characterized the transcellular transport of several anions. Recent reports have also suggested the importance of OATP1B3 in the hepatic uptake of some compounds. However, there is little information about OATP1B3-selective substrate and no good tool for the evaluation of efflux transporters of OATP1B3 substrates. In the present study, we found an OATP1B3-selective substrate and established a novel set of double transfectants expressing OATP1B3. Telmisartan acylglucuronide (tel-glu) is a main metabolite of telmisartan, an angiotensin II receptor antagonist. Tel-glu is recognized by hepatobiliary transport systems and efficiently distributed to liver. Several studies using rat and human hepatocytes and transporter-expressing cells revealed that OATP1B3 was responsible for the hepatic uptake of tel-glu in humans. By using double transfectants expressing OATP1B3, we investigated the transcellular transport of tel-glu as well as estradiol 17beta-d-glucuronide (E(2)17betaG) and cholecystokinin octapeptide (CCK-8) to identify the responsible efflux transporters in their biliary excretion. Vectorial basal-to-apical transport of tel-glu was observed in all kinds of double transfectants expressing OATP1B3. In contrast, basal-to-apical transport of E(2)17betaG and CCK-8 was seen only in the OATP1B3/MRP2 double transfectant compared with OATP1B3-expressing cells. Therefore, the newly established set of double transfectants expressing OATP1B3 combined with OATP1B1-expressing double transfectants can be used as a powerful tool for the rapid identification of hepatic uptake and efflux transporters of organic anions.

  16. Construction and characterization of infectious hepatitis C virus chimera containing structural proteins directly from genotype 1b clinical isolates.

    PubMed

    Lu, Jie; Tao, Wanyin; Li, Rui; Xiang, Yu; Zhang, Nan; Xiang, Xiaogang; Xie, Qing; Zhong, Jin

    2013-08-15

    HCV genotype is a major determinant of clinical outcome, and GT1b HCV infection is the most difficult to treat and also the predominant genotype in East Asia and Europe. We developed 1b/JFH-1 inter-genotypic recombinants containing the structural genes (Core, E1, E2), p7 and the 1stTMD of NS2 directly from GT1b clinical isolates. Through a cloning selection strategy, we obtained 4 functional clones from 3 cases of GT1b patients' sera, which could produce infectious viruses in Huh7.5.1 cells. Sequencing analysis of recovered viruses from serial passage and reverse genetics revealed that adaptive mutations in the GT1b-originated region were enough for the enhancement of infectivity. A monoclonal antibody to E2 and original patient sera could efficiently block 3 of the viruses (26C3mt, 52B6mt and 79L9) while had little effect on 26C6mt viruses. The availability of 1b/JFH-1 chimeric viruses will be important for studies of isolate-specific neutralization and useful in evaluating antiviral therapies.

  17. The clinical outcomes of chronic hepatitis C in South Korea

    PubMed Central

    Ok, Kyeong Sam; Jeong, Sook-Hyang; Jang, Eun Sun; Kim, Young Seok; Lee, Youn Jae; Kim, In Hee; Cho, Sung Bum; Bae, Si Hyun; Lee, Han Chu

    2016-01-01

    Abstract This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region. From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival. During the median follow-up of 39.0 months (range 18.0–81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150  × 109/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002). The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy. PMID:27583874

  18. Current treatments for chronic hepatitis B virus infections.

    PubMed

    Zoulim, Fabien; Lebossé, Fanny; Levrero, Massimo

    2016-06-01

    Over 240 million people worldwide are chronically infected with hepatitis B virus (HBV) and although a prophylactic vaccine and effective antiviral therapies are available, no cure exists. Curative regimens are urgently needed because up to one million deaths per year are caused by HBV-related liver cancer and end-stage liver disease. HBV is an hepatotropic virus which belongs to the Hepadnaviridae family and replicates its DNA genome via a reverse transcriptase mechanism. Effective therapies have been developed for chronic hepatitis B (CHB) infection in the last two decades. They rely on the use of interferon alpha and its pegylated formulation, and on nucleos(t)ide analogs that inhibit viral polymerase activity. Their results are discussed in this review as well as future perspectives. PMID:27318098

  19. Hepatic expression of tumour necrosis factor-alpha in chronic hepatitis B virus infection.

    PubMed Central

    Hussain, M J; Lau, J Y; Williams, R; Vergani, D

    1994-01-01

    AIM--To determine the hepatic expression of tumour necrosis factor-alpha (TNF alpha) in patients with chronic hepatitis B virus (HBV) infection. METHODS--Frozen liver biopsy sections from 19 patients with chronic HBV infection were studied, 12 of whom were HBeAg positive and 10 serum HBV DNA positive. Hepatic expression of TNF alpha was determined using immunohistochemistry. RESULTS--Only infiltrating mononuclear cells showed immunoreactive staining for TNF alpha (median 2, range 0-3; n = 19) which appeared as diffuse positive staining material in the cytoplasm. Patients with active liver disease, assessed histologically and biochemically, had a higher level of expression, both in the number of TNF alpha positive cells and the proportion of TNF alpha positive infiltrating mononuclear cells. There was no correlation between the expression of TNF alpha and serological parameters of viral infection (HBeAg and HBV DNA status and HBV DNA concentrations). CONCLUSION--Hepatic expression of TNF alpha is increased in chronic HBV infection and is related to the activity of liver disease and not to the level of HBV replication. Images PMID:7876386

  20. Chronic hepatitis C: This and the new era of treatment

    PubMed Central

    Bertino, Gaetano; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Demma, Shirin; Ruggeri, Maria Irene; Scuderi, Laura; Malaguarnera, Giulia; Bertino, Nicoletta; Rapisarda, Venerando; Di Carlo, Isidoro; Toro, Adriana; Salomone, Federico; Malaguarnera, Mariano; Bertino, Emanuele; Malaguarnera, Michele

    2016-01-01

    Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. PMID:26807205

  1. Study of Hepatic Osteodystrophy in Patients with Chronic Liver Disease

    PubMed Central

    Karoli, Yogesh; Fatima, Jalees; Manhar, Mohammad

    2016-01-01

    Introduction Chronic Liver Disease (CLD) is a major cause of morbidity and mortality worldwide. It involves haemodynamic and metabolic complications. Hepatic Osteodystrophy is a metabolic bone disease that may occur in individuals with chronic liver disease. It can significantly affect morbidity and quality of life of these patients. Fractures are also associated with an excess mortality. It has been an under recognized and inadequately studied complication among Indian population. An early diagnosis is essential to correct reversible risk factors which predispose to bone mass loss. Aim To assess the prevalence of metabolic bone disease and identify the risk factors associated with hepatic osteodystrophy in patients with cirrhosis. Materials and Methods This was an observational, cross-sectional, hospital based study conducted at a medical college hospital. All patients more than 20-year-old, diagnosed with chronic liver disease/Cirrhosis were enrolled. They were subjected to haematological, biochemical investigations, evaluation of Vitamin D and other hormonal parameters. Bone Mineral Density (BMD) was estimated by Dual Energy X-ray Absorptiometry (DEXA). Results A total of 72 patients with mean age 50.04±11.24 years were included in the study. Amongst causes of chronic liver disease were alcoholic liver disease 22 (30.6%), CLD due to hepatitis B 24 (33.3%) and chronic hepatitis C 26 (36.1%). Twenty one (29.2%) patients had normal BMD while 51 (70.8%) had a low BMD. Out of these 51 patients, 36 (70.6%) were diagnosed of osteopenia and 15 (29.4%) others were found to have osteoporosis. Vitamin D levels and severity of liver disease had correlation with low BMD. Conclusion Low BMD is highly prevalent in patients with chronic liver disease of variable aetiologies. We advocate more randomised and prospective studies to be conducted on homogeneous groups with chronic liver disease in its various stages. In view of numerous therapeutic options available both for liver

  2. Combination treatment with interferon and ribavirin for chronic hepatitis C.

    PubMed

    Davis, G L

    1999-11-01

    Interferon was the first drug shown to be effective in patients with chronic hepatitis C, but initial treatment regimens achieved sustained loss of virus in only a small minority of patients. The combination of IFN with ribavirin now makes sustained response rates of 30% to 40% possible. This is quite a remarkable achievement for a pharmacologic treatment of a chronic viral infection. It is now reasonable to assume that early treatment and eradication of chronic hepatitis C might reduce the growing burden of hepatitis C and its complications on the healthcare system. Future researchers will strive to optimize combination treatment regimens. Longer treatment courses and intensified induction regimens using either daily dosing, high doses, or both may improve long-term response, but this remains speculative. Other forms of IFN may improve response or increase the ease of drug administration. Conjugation of biologic compounds to polyethylene glycol can result in significant prolongation of plasma half-life while maintaining the properties of the parent molecule. Some biologic properties may be altered, however, so pegylated IFN must continue to be evaluated in clinical trials. There is limited clinical data on other recombinant or natural interferons in combination with oral ribavirin, however, these may prove to be equally effective. Combinations of IFN with one or more other antiviral, anti-inflammatory, or immune modulatory agents will need to be studied. Although amantidine is not effective against hepatitis C as a single agent or in combination with IFN, the combination of IFN, ribavirin, and rimantidine has been shown to have antiviral activity superior to the IFN-ribavirin combination against influenza virus and possibly against HCV. PMID:11291252

  3. Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

    PubMed

    Keeffe, Emmet B

    2006-01-01

    A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

  4. Prevalence of hepatic steatosis and associated factors in Iranian patients with chronic hepatitis C

    PubMed Central

    Poortahmasebi, Vahdat; Emami Aleagha, Mohammad Sajad; Amiri, Mehdi; Qorbani, Mostafa; Farahmand, Mohammad; Asayesh, Hamid; Alavian, Seyed Moayed

    2016-01-01

    Background: Hepatic steatosis is commonly observed in patients with chronic hepatitis C (CHC). Many studies indicate a relationship between steatosis and fibrosis progression. The aim of this study was to analyze the prevalence of hepatic steatosis and related factors in Iranian CHC patients. Methods: One hundred and fifteen consecutive patients with CHC were enrolled which were treatment- naïve. The patients were divided into groups with and without steatosis according to the result of liver biopsy (58.3% and 41.7%, respectively). Demographic, histological, biochemical and virological factors were examined and compared in all patients. Results: In terms of host factors, body mass index (BMI), triglyceride, fasting blood glucose (FBG), necroinflammatory activity and severity in fibrosis of CHC patients with steatosis was significantly higher than the patients without steatosis. Of viral factors, HCV viral load was not significantly altered in patients with steatosis. Moreover, HCV genotypes did not meet such association. Using multivariate regression analysis, parameters of BMI values, FBG level and stage of fibrosis were independently associated with steatosis. Conclusion: Our data indicate that CHC patients are more susceptible to development of hepatic steatosis. Based on our results, grade of steatosis appears to be associated with hepatic fibrosis progression rate in CHC patients. PMID:27390692

  5. Primary Hepatic Small-Cell Carcinoma Developed during Antiviral Treatment for Chronic Hepatitis B

    PubMed Central

    Kim, Suk Bae

    2015-01-01

    Previously reported cases of primary hepatic small-cell carcinoma were all detected at progressed state with associated symptoms. Therefore, the natural course of primary hepatic small-cell carcinoma remains unknown. This case shows the natural course of primary hepatic small-cell carcinoma. We detected a 1.2 cm hypodense nodule 6 months ago in a patient with cirrhosis who had been taking entecavir. It was suspected to be a regenerating or degenerating nodule. Three months later, liver computed tomography (CT) revealed that the mass was increased to 2.1 cm with the same characteristics. The patient wanted to do a follow-up CT scan after 3 months instead of a biopsy. Another 3 months later, the mass was markedly increased, involving the whole left lobe and was confirmed as small-cell carcinoma on biopsy. Here, we report the first case of primary hepatic small-cell carcinoma developed during treatment for chronic hepatitis B with cirrhosis. PMID:26951743

  6. New insights in the management of chronic hepatitis B.

    PubMed

    Gill, Upkar S; Kennedy, Patrick Tf

    2015-04-01

    Chronic hepatitis B (CHB) remains a global healthcare challenge, complicated by the development of cirrhosis and hepatocellular carcinoma, accounting for approximately 600,000 deaths per year. Hepatitis B is a DNA virus, which utilises a covalently closed circular (ccc) DNA to act as a transcriptional template for the virus. The persistence of cccDNA in the nucleus of infected hepatocytes accounts for HBV chronicity. Quantitative hepatitis B surface antigen (qHBsAg) acts as a surrogate for the level of cccDNA and therefore may provide useful information around treatment response and viral immune control. Current antiviral therapies are limited in their ability to achieve HBsAg loss, which is considered the 'gold-standard' treatment endpoint. This article focuses on the unmet needs in CHB today; a better definition of disease phase, the timing of therapeutic intervention, optimising treatment strategies with current therapies and the development of novel agents; all with HBsAg loss as the therapeutic goal. PMID:25824074

  7. Change of hepatitis B virus DNA distribution associated with the progression of chronic hepatitis.

    PubMed

    Michitaka, K; Horiike, N; Nadano, S; Onji, M; Ohta, Y

    1988-08-01

    Hepatitis B virus (HBV) DNA was detected by in situ hybridization in 53 out of 74 liver specimens from patients with chronic HBV infection. The distribution of HBV DNA was classified into three patterns: diffuse (HBV DNA distributed diffusely, within the section of specimen), lobular (HBV DNA was present in 1/3-2/3 of the section) and spotty. All three specimens from asymptomatic HBV carriers showed the diffuse pattern. In the advanced stage of liver disease (chronic active hepatitis with severe activity and liver cirrhosis), a decreased number of specimens showed the diffuse pattern, whereas the number of specimens with the lobular pattern increased. From these data, we conclude that HBV may replicate diffusely in the liver in the early stage of chronic liver disease, and the site of HBV replication becomes localized in the advanced stage of the disease. The main target cells of immunocytes may be hepatocytes undergoing HBV replication, because HVB DNA was frequently detected in areas of focal, piecemeal and bridging hepatic necrosis. PMID:3419292

  8. [Chronic Hepatitis E Virus Infection and Treatment in Organ Transplant Recipients].

    PubMed

    Chen, Shu; Wei, Feixue; Wu, Ting; Xia, Ningshao

    2015-05-01

    Hepatitis E, caused by hepatitis E virus (HEV) infection, usually leads to an acute clinical course, and is the most common diagnosis among cases of acute viral hepatitis. From 2008, there have been increasing reports of chronic HEV infection in immunocompromised patients such as organ transplant recipients. Without intervention with antiviral treatment, approximately 60% of HEV infections in organ transplant recipients evolve into chronic HEV infections. Of these chronic hepatitis E patients, 10% may develop liver fibrosis and progress to liver cirrhosis. This article reviews chronic HEV infection and treatment in organ transplant recipients.

  9. Immune regulation in chronic hepatitis C virus infection.

    PubMed

    Hartling, Hans Jakob; Ballegaard, Vibe Cecilie; Nielsen, Nick Schou; Gaardbo, Julie Christine; Nielsen, Susanne Dam

    2016-11-01

    The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs. Thus, the major immune players during chronic HCV infection are characterized by a decrease of cytotoxic function and increase of inhibitory functions. This may be an approach to diminish intrahepatic and systemic inflammation. Finally, there has been increasing awareness of regulatory functions of epigenetic changes in chronic HCV infection. A vast amount of studies have revealed the complexity of immune regulation in chronic HCV infection, but the interplay between immune regulation in virus and host remains incompletely understood. This review provides an overview of regulatory functions of HCV-specific T cells, NK cells, Tregs, IL-10, and TGF-β, as well as epigenetic changes in the setting of chronic HCV infection.

  10. Nutritional support in the treatment of chronic hepatic encephalopathy.

    PubMed

    Milke García, María del Pilar

    2011-06-01

    The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease becomes more advanced. The deterioration in the nutritional status and its associated metabolic derangements has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions may be drawn about the benefit of protein restriction. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive and harmful protein depletion and must be avoided. PMID:22228881

  11. Recent Advances in Antiviral Therapy for Chronic Hepatitis C

    PubMed Central

    Tamori, Akihiro; Enomoto, Masaru; Kawada, Norifumi

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide health problem. Chronic infection induces continuous inflammation in the liver, progression of hepatic fibrosis, eventual cirrhosis, and possible hepatocellular carcinoma. Eradication of the virus is one of the most important treatment aims. A number of promising new direct-acting antivirals (DAAs) have been developed over the past 10 years. Due to their increased efficacy, safety, and tolerability, interferon-free oral therapies with DAAs have been approved for patients with HCV, including those with cirrhosis. This review introduces the characteristics and results of recent clinical trials of several DAAs: NS3/4A protease inhibitors, NS5A inhibitors, and NS5B inhibitors. DAA treatment failure and prognosis after DAA therapy are also discussed. PMID:27022210

  12. Hepatic encephalopathy in acute-on-chronic liver failure.

    PubMed

    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  13. Direct Acting Antivirals for the Treatment of Chronic Viral Hepatitis

    PubMed Central

    Karayiannis, Peter

    2012-01-01

    The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years have heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus (HBV, HCV, and HDV). The introduction of direct acting antivirals (DDAs) for the treatment of HBV carriers has permitted the long-term use of these compounds for the continuous suppression of viral replication, whilst in the case of HCV in combination with the standard of care [SOC, pegylated interferon (PegIFN), and ribavirin] sustained virological responses (SVRs) have been achieved with increasing frequency. Progress in the case of HDV has been slow and lacking in significant breakthroughs.This paper aims to summarise the current state of play in treatment approaches for chonic viral hepatitis patients and future perspectives. PMID:24278700

  14. Urine from chronic hepatitis B virus carriers: implications for infectivity.

    PubMed

    Knutsson, M; Kidd-Ljunggren, K

    2000-01-01

    Horizontal transmission of hepatitis B virus (HBV) without apparent sexual or parenteral exposure is common in hyperendemic areas. In most cases, the route of transmission is unknown. To investigate urine as a potential source of infection, serum and urine from 56 chronic hepatitis B surface antigen (HBsAg) carriers were examined for the presence of HBV DNA using the polymerase chain reaction (PCR). Thirty-four of the patients were anti-hepatitis B e antigen (anti-HBe) positive and 22 were hepatitis B e antigen (HBeAg) positive. HBV DNA was detected in serum from 46 patients (82%) and in urine from 28 patients (50%). Most HBeAg-positive patients had HBV DNA detectable in urine (91%), whereas urine samples from anti-HBe-positive patients were found to contain HBV DNA to a lesser extent (24%). When comparing HBV DNA from serum and urine by an end-point titration PCR, a titration difference averaging 10(3) was found between serum and urine. A significant female predominance was also noted among the positive urine samples (P < 0.05), which was not correlated to the presence of haematuria. Detection of HBV DNA may indicate active viral replication, and thereby infectivity. Because a high proportion of chronic HBV carriers were found to have HBV DNA in urine, it is suggested that irrespective of HBeAg/anti-HBe status, urine should be regarded as a potential route of transmission and therefore be investigated further as a means of horizontal and nosocomial transmission of HBV.

  15. Hepatitis B Virus Core-Related Antigens as Markers for Monitoring Chronic Hepatitis B Infection▿

    PubMed Central

    Wong, Danny Ka-Ho; Tanaka, Yasuhito; Lai, Ching-Lung; Mizokami, Masashi; Fung, James; Yuen, Man-Fung

    2007-01-01

    A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (r = 0.820), intrahepatic total HBV DNA (r = 0.700), and covalently closed circular DNA (cccDNA) (r = 0.664; for all, P values were <0.001). A higher HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (<300 copies/ml) at the end of treatment, 20 (65%) still had detectable HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of <40,000 kU/ml at baseline and <200 kU/ml at week 24 were associated with a higher chance of having undetectable HBV DNA at week 48. In conclusion, serum HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver. PMID:17942661

  16. Hepatitis B virus core-related antigens as markers for monitoring chronic hepatitis B infection.

    PubMed

    Wong, Danny Ka-Ho; Tanaka, Yasuhito; Lai, Ching-Lung; Mizokami, Masashi; Fung, James; Yuen, Man-Fung

    2007-12-01

    A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (r = 0.820), intrahepatic total HBV DNA (r = 0.700), and covalently closed circular DNA (cccDNA) (r = 0.664; for all, P values were <0.001). A higher HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (<300 copies/ml) at the end of treatment, 20 (65%) still had detectable HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of <40,000 kU/ml at baseline and <200 kU/ml at week 24 were associated with a higher chance of having undetectable HBV DNA at week 48. In conclusion, serum HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver.

  17. Microsomal antibodies in active chronic hepatitis and other disorders

    PubMed Central

    Rizzetto, M.; Swana, G.; Doniach, Deborah

    1973-01-01

    An autoantibody reacting with microsomal membranes has been characterized by a distinctive immunofluorescence pattern on proximal renal tubules and hepatocytes. The microsomal nature of the antigen was demonstrated by absorption and quantitative complement fixation studies. These results showed the antibodies to be quite distinct from the mitochondrial antibodies found in primary biliary cirrhosis. Microsomal antibodies have so far been detected in sixteen cases, of whom twelve had liver disorders. These antibodies, although rare, may provide a serological marker for a small proportion of active chronic hepatitis cases differing in several respects from other recognized subgroups in this disease. ImagesFIG. 1FIG. 5 PMID:4587503

  18. Effects of He-Ne laser acupuncture-point irradiation on serology hepatitis virus markers in chronic hepatitis B

    NASA Astrophysics Data System (ADS)

    Wang, Yue-lan; Huang, Bing-chen; Ni, Liu-da

    1993-03-01

    For most of the patients with chronic hepatitis B the immunologic function is deficient. Immunopotentiation and immunoregulation can be used as effective treatments. Laser irradiation can potentiate the cellular immune function of the human body and has good effects on improving clinical symptoms, cutting short the process of diseases, and promoting HBsAg negative change. Thereby we have a randomized opportunity to study the effect of He-Ne laser acupoint irradiation on serological HBV markers (HBVM) in chronic hepatitis B (CHB).

  19. Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir

    PubMed Central

    Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

    2015-01-01

    Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising <1%, 1 to 40%, or >40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. PMID:26643326

  20. Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir.

    PubMed

    Krishnan, Preethi; Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

    2016-02-01

    Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising <1%, 1 to 40%, or >40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. PMID:26643326

  1. Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis

    PubMed Central

    Kamar, Nassim; Lhomme, Sébastien; Abravanel, Florence; Marion, Olivier; Peron, Jean-Marie; Alric, Laurent; Izopet, Jacques

    2016-01-01

    Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection. PMID:27537905

  2. Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis.

    PubMed

    Kamar, Nassim; Lhomme, Sébastien; Abravanel, Florence; Marion, Olivier; Peron, Jean-Marie; Alric, Laurent; Izopet, Jacques

    2016-01-01

    Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection. PMID:27537905

  3. Characterization of hepatitis B virus genotypes in chronically infected patients.

    PubMed

    Basaras, M; Arrese, E; Blanco, S; Sota, M; de las Heras, B; Cisterna, R

    2007-12-01

    Genomic mutations occurring during reverse transcription of hepatitis B virus (HBV) could explain its genetic diversity and account for 8 genetically distinct genotypes that are geographically distributed quite differently. The main objectives of this study were to determine the prevalence of hepatitis B virus genotypes in patients with chronic hepatitis B and to see if there was a relationship between genotypes and risk factors for transmission based on HBeAg status. A total of 14 serum samples were analyzed using INNO-LIPA HBV genotyping assay. Genotype D was the most prevalent (64.3%) followed by genotype A (28.6%). There was one case of co-infection (D/E genotypes) that was confirmed by PCR sequencing. All patients except one were HBeAg-negative and anti-HBe-positive. The risk factors for HBV transmission were unknown in half of the cases; in the other half, sexual, transfusion, maternal or interfamilial transmission were observed. The results show that genotype D is the most prevalent genotype in our hospital, followed by genotype A. On the other hand, no relationship was found between HBeAg status and genotype.

  4. Cirrhosis due to chronic hepatitis E infection in a child post-bone marrow transplant.

    PubMed

    Halac, Ugur; Béland, Kathie; Lapierre, Pascal; Patey, Natacha; Ward, Pierre; Brassard, Julie; Houde, Alain; Alvarez, Fernando

    2012-05-01

    Chronic hepatitis E virus (HEV) infection occurs in immunosuppressed adults. We detected HEV ribonucleic acid in serum of an adolescent patient who had undergone bone marrow transplantation and subsequently presented with persistently increased aminotransferases and histologic chronic hepatitis, and eventually developed cirrhosis. Phylogenetic analysis revealed these HEV strains were similar to swine genotype 3a, suggesting a possible zoonosis. PMID:22341950

  5. [Significant laparoscopy and ultrasound findings in chronic hepatic porphyria].

    PubMed

    Fengler, J D; Binus, R; Hintsche-Kilger, B; Baumgarten, R

    1990-09-01

    In the years from 1983 to 1989 we diagnosed in altogether 69 patients a chronic hepatic porphyria. As a rule the light microscopic and sonographic findings in the liver use to be uncharacteristic. Yet, unexpectedly by sonography in eight patients findings, suspicious for metastases, were stated. Multiple coin lesions with a marginal edge mostly rich in echoes were impressing. The laparoscopy resulted in grey/blue-discoloured depressions in an otherwise even surface of the liver, thus suggesting mass necroses respectively rebuilding processes. Subclinical stages of a chronic hepatic porphyria could have been proved by the partial red-fluorescence of bioptates and a corresponding porphyrin secretion. The histological changes of the liver were--in contrary to the impressing laparoscopic picture--rather insignificant. In case of a successful intervention the pathological porphyrin secretion was done in about eight months. Mostly, more than a year used to pass away till the sonographic findings normalized. The seldom described phenomena use to conceal the danger of a false interpretation and an unnecessary stress for the patient. More over the causes and the development of these peculiar porphyria findings are unclear; they need in an discussion among medical special branches.

  6. Natural regression of fibrosis in chronic hepatitis B

    PubMed Central

    Ohkoshi, Shogo; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko; Kamimura, Kenya; Yano, Masahiko

    2016-01-01

    The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B (CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBeAg seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma (HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been (pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosis-induced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue. PMID:27350724

  7. [Therapeutic vaccination in chronic hepatitis B: chance or utopia?].

    PubMed

    Flisiak, Robert; Prokopowicz, Danuta

    2003-12-01

    Current therapy of chronic hepatitis B with interferon-a or lamivudine is directed first of all to reduce viral replication. Unfortunately these relatively expensive therapeutic methods can eliminate the infection in only one third of patients. However the pathogenesis of chronic infection with hepatitis B virus is related mostly to the deficits of specific immune response both cellular and humoral. Therefore research on therapeutic vaccination have been started recently. It was supported by development in the last years vaccines, that applied prophylactically demonstrated extraordinary immunogenicity and efficiency. Short story on research related to use of this low cost method for the fight against one of the most common infectious disease was presented in this paper. Experimental studies and small number of clinical trials with recombinant and lipopeptide vaccines, and the most recent based on viral DNA, demonstrated their safety and simultaneously enriched knowledge on the disease pathogenesis. This therapy did not lead to elimination of the infection in the proportion greater than interferon-a or lamivudine, but enables to faster reduction of its activity. Clinical trials including combined use of current therapeutical standards and vaccine immunotherapy, can be expected in coming years.

  8. Association between inherited monogenic liver disorders and chronic hepatitis C

    PubMed Central

    Piekuse, Linda; Kreile, Madara; Zarina, Agnese; Steinberga, Zane; Sondore, Valentina; Keiss, Jazeps; Lace, Baiba; Krumina, Astrida

    2014-01-01

    AIM: To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS: This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Case-control analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail. PMID:24575168

  9. Comparison of effects of hepatitis E or A viral superinfection in patients with chronic hepatitis B

    PubMed Central

    Ke, Weimin; Xie, Junqiang; Zhao, Zhixin; Xie, Dongying; Gao, Zhiliang

    2010-01-01

    Purpose To compare the demographics, liver function, and prognosis of Chinese patients infected with chronic hepatitis B (CHB) and superinfected with hepatitis E virus (HEV) or hepatitis A virus (HAV). Patients and methods Among 188 patients with CHB, 136 with HEV superinfection and 52 with HAV superinfection were treated at our hospital between March 1999 and October 2007 for clinical features suggestive of acute hepatitis. The patients’ age, sex, incidence of liver failure, and mortality were recorded. The tested biochemical indices and markers of liver function included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), prothrombin activity (PTA), and the serum levels of HBeAg, HBeAb, and HBV DNA. Results There were significant differences between the age and sex distributions of the two groups (P < 0.05). More patients in the CHB + HEV group had complications (94.9 vs. 61.5%, P < 0.001), and hepatic failure (39.7 vs. 11.5%, P = 0.002). Additionally, the mortality among the CHB + HEV group was significantly higher (33.8 vs. 1.9%, P < 0.001). Conclusions The comparison of clinical outcomes revealed that patients with HBV + HEV had more advanced baseline liver disease and a poorer prognosis than those with HBV + HAV. Because there is no vaccine against HEV, patients with CHB should take appropriate precautions against superinfection with HEV, such as consumption of boiled water and well-cooked food, in regions where it is endemic. PMID:21063485

  10. 78 FR 63218 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Chronic Hepatitis C Virus... availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection: Developing Direct... of development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C....

  11. Effect of Hepatitis C Virus Genotype 1b Core and NS5A Mutations on Response to Peginterferon Plus Ribavirin Combination Therapy.

    PubMed

    Nakamoto, Shingo; Imazeki, Fumio; Arai, Makoto; Yasui, Shin; Nakamura, Masato; Haga, Yuki; Sasaki, Reina; Kanda, Tatsuo; Shirasawa, Hiroshi; Yokosuka, Osamu

    2015-01-01

    We examined whether hepatitis C virus (HCV) genotype 1b core- and NS5A-region mutations are associated with response to peginterferon α-2b plus ribavirin combination therapy. A total of 103 patients with high HCV genotype 1b viral loads (≥ 100 KIU/mL) were treated with the combination therapy. Pretreatment mutations in the core region and interferon sensitivity determining region (ISDR) in the NS5A region were analyzed. In univariate analysis, arginine and leucine at positions 70 and 91 in the core region, defined as double wild (DW)-type, were associated with early virologic response (p = 0.002), sustained virologic response (SVR) (p = 0.004), and non-response (p = 0.005). Non-threonine at position 110 was associated with SVR (p = 0.004). Multivariate analysis showed the following pretreatment predictors of SVR: hemoglobin level ≥ 14 g/dL (odds ratio (OR) 6.2, p = 0.04); platelet count ≥ 14 × 10⁴/mm³ (OR 5.2, p = 0.04); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio < 0.9 (OR 6.17, p = 0.009); DW-type (OR 6.8, p = 0.02); non-threonine at position 110 (OR 14.5, p = 0.03); and ≥ 2 mutations in the ISDR (OR 12.3, p = 0.02). Patients with non-DW-type, non-threonine at position 110, and < 2 ISDR mutations showed significantly lower SVR rates than others (11/45 (24.4%) vs. 27/37 (73.0%), respectively; p < 0.001). SVR can be predicted through core and NS5A region mutations and host factors like hemoglobin, platelet count, and AST/ALT ratio in HCV genotype 1b-infected patients treated with peginterferon and ribavirin combination therapy. PMID:26370958

  12. Direct-acting antivirals for the treatment of chronic hepatitis C in patients with chronic kidney disease

    PubMed Central

    Kohli, Anita; Alshati, Ali; Georgie, Fawaz; Manch, Richard; Gish, Robert G.

    2016-01-01

    All-oral, direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of chronic hepatitis C (CHC) treatment but their effectiveness and safety among patients with chronic kidney disease (CKD) remains poorly understood. Our aim was to assess the efficacy and safety of DAAs for treatment of CKD patients. The National Library of Medicine through PubMed was searched for studies evaluating the efficacy of DAAs for the treatment of patients with CKD stages 4 or 5, as defined by the Kidney Disease Outcomes Quality Initiative guidelines [i.e. glomerular filtration rate (GFR) 15–29 ml/min per 1.73 m2 and GFR <15 ml/min per 1.73 m2, respectively, or hemodialysis or peritoneal dialysis]. Randomized clinical trials (RCTs) and relevant cohort studies were included if they were published in English and included sustained viral response after 12 weeks (SVR12) as a primary or secondary endpoint. After applying inclusion and exclusion criteria, eight studies (one RCT and seven cohort studies) following 350 patients were selected. For patients with CKD stage 4 or 5, ± hemodialysis, the overwhelming majority of DAA regimens were well-tolerated and resulted in SVR12 rates of 90–100%. Most studies were small, with the exception of one RCT evaluating elbasvir and grazoprevir. Overall, treatment of CHC in patients with CKD is highly effective with SVR12 rates similar to those seen in patients without CKD and with acceptable adverse event profiles. In patients with hepatitis C virus (HCV) genotype (GT) 1a, 1b or 4 and Stage 4 or 5 CKD, the best evidence available is for the use of elbasvir and grazoprevir. This combination as well as the combination of paritaprevir/ritonavir/ombitasvir/dasabuvir for HCV GT-1b are recommended. More studies are needed to assess efficacy and adverse effects of DAAs and their impact on CKD patients and to fully elucidate the effect of curing CHC on the natural history and sequelae of renal disease in CHC patients with CKD. PMID

  13. Successful Interferon Therapy Reverses Enhanced Hepatic Progenitor Cell Activation in Patients with Chronic Hepatitis C.

    PubMed

    Noritake, Hidenao; Kobayashi, Yoshimasa; Ooba, Yukimasa; Matsunaga, Erika; Ohta, Kazuyoshi; Shimoyama, Shin; Yamazaki, Satoru; Chida, Takeshi; Kawata, Kazuhito; Sakaguchi, Takanori; Suda, Takafumi

    2015-12-01

    The enhanced accumulation of hepatic progenitor cells (HPCs) is related to the risk of progression to hepatocellular carcinoma (HCC). Interferon (IFN) treatment reduces HCC risk in patients with chronic hepatitis C virus (HCV) infection. However, the underlying mechanisms remain unclear. The aim of this study was to examine the effects of IFN treatment on HPC activation in HCV patients. Immunohistochemical detection and computer-assisted quantitative image analyses of cytokeratin 7 (CK7) were performed to evaluate HPC activation in paired pre- and post-treatment liver biopsies from 18 HCV patients with sustained virological response (SVR) to IFN-based therapy and from 23 patients without SVR, as well as normal liver tissues obtained from surgical resection specimens of 10 patients. Pretreatment HCV livers showed increased CK7 immunoreactivity, compared with normal livers (HCV: median, 1.38%; normal: median, 0.69%, P=0.006). IFN treatment reduced hepatic CK7 immunoreactivity (median, 1.57% pre-IFN vs. 0.69% post-IFN, P=0.006) in SVR patients, but not in non-SVR patients. The development of HCC following IFN treatment was encountered in 3 non-SVR patients who showed high post-IFN treatment CK7 immunoreactivity (>4%). Successful IFN therapy can reverse enhanced HPC activation in HCV patients, which may contribute to the reduced risk of HCC development in these patients.

  14. Preliminary results of individual therapy of chronic hepatitis C by Ukrain and interferon-alpha.

    PubMed

    Voltchek, I; Sologub, T; Nowicky, J W; Grigoryeva, T; Belozyorova, L; Belopolskaya, M; Semenyako, N; Lamanova, E

    2000-01-01

    The effects of Ukrain and recombinant human interferon-alpha 2b (IFN) on the state of the thiol-disulfide ratio (SH/SS) of the blood (Russian Federation patent no. 2150700) were studied in vitro using the amperometric titration method. The blood of 73 chronic hepatitis C (CHC) hepatitis C virus (HCV)-RNA-positive patients was examined. Ukrain was tested in doses of 0.05-2.0 micrograms/ml and IFN in 20-1000 U/ml of blood. After in vitro examination, 59 patients were treated: 28 with Ukrain and 31 with IFN. The first group of 16 patients (including eight with HCV genotype 1b) was treated with individually selected optimal doses of Ukrain (0.5-2.5 mg every second day). The second group of 12 patients was treated with doses of 2.5 mg Ukrain independent of in vitro test results. The third group of 31 patients was treated with individually selected optimal doses of IFN (0.5-2 MU 3 times a week). It was found that 79.4% of CHC patients were sensitive to Ukrain in vitro and 65.1% were sensitive to IFN. CHC patients with genotype 1b were sensitive to IFN only in 16.7% of cases while the figure for Ukrain was 92.3%. CHC patients with other HCV genotypes (3, 1a, 2) were sensitive to Ukrain in 86.7% of cases and to IFN in 70.6%. After 1 month of individual therapy with Ukrain, 87.5% of CHC patients, including six of eight cases with HCV genotype 1b, became PCR-HCV negative. In the group receiving the standard dose of Ukrain, virological response was only 33.3%. After 1 month, 74.2% of CHC patients treated with individual doses of IFN became PCR-HCV negative and after 3 months 90.3% were PCR-HCV negative. The prognostic significance of the method for screening preparations for the treatment of CHC patients was 89.8%. Treatment with Ukrain was without serious negative effects and the number of side effects of IFN in individual therapy was significantly reduced. Ukrain can be used in the treatment of CHC patients, alone or in combination with IFN preparations; in the cases with

  15. Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

    PubMed Central

    2010-01-01

    Background The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area. Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population. Methods We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing. Results Sixty-two point seven (62.7%) of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4%) and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C) genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -31T (rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer. Conclusions The H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was not associated with

  16. Hepatitis B Splice-Generated Protein Antibodies in Syrian Chronic Hepatitis B Patients: Incidence and Significance

    PubMed Central

    Al-Hanafi, Nour; Monem, Fawza

    2014-01-01

    Background: Previous studies have suggested hepatitis B splice-generated protein (HBSP), when expressed, is involved in the pathogenesis of HBV infection. Objectives: We aimed to evaluate anti-HBSP incidence and association with several HBV infection parameters in a group of Syrian chronic hepatitis B patients. Patients and Methods: Eighty treatment-naïve HBsAg-positive adult chronic hepatitis B patients' sera were included in our prospective targeted study. Liver function, virological and histological tests results were obtained from patients’ medical files. Three variants of a 20-mer HBSP-derived peptide were designed based on HBV genome sequences obtained from Syrian patients' sera (GenBank Accession No. JN257148-JN257217). Microtiter plate wells were coated with the synthetic peptides and used to detect anti-HBSP antibodies by an optimized indirect enzyme-linked immunosorbent assay (ELISA). Samples were considered positive when showed optical density (OD) values higher than the cut-off value for at least one peptide variant. Results: Seven out of eighty (9%) CHB patients were positive for anti-HBSP antibodies. Mean OD values were not significantly different between HBeAg-positive and -negative patients (P > 0.05). OD values showed weak positive correlation with ALT and AST values (P < 0.05), and weak to moderate positive correlation with liver biopsy staging ranks (P < 0.05). No significant correlation was revealed with viral load values or liver biopsy grading ranks (P > 0.05). Conclusions: We introduced an anti-HBSP antibodies ELISA, designed for locally circulating HBV strains. Correlation observed of Anti-HBSP with liver fibrosis staging regardless of viral replication and liver inflammation suggests anti-HBSP antibodies as possible indicator for HBV-associated liver fibrosis. PMID:24829585

  17. Antibody to Hepatitis B Core Antigen Levels in the Natural History of Chronic Hepatitis B

    PubMed Central

    Jia, Wei; Song, Liu-Wei; Fang, Yu-Qing; Wu, Xiao-Feng; Liu, Dan-Yang; Xu, Chun; Wang, Xiao-Mei; Wang, Wen; Lv, Dong-Xia; Li, Jun; Deng, Yong-Qiong; Wang, Yan; Huo, Na; Yu, Min; Xi, Hong-Li; Liu, Dan; Zhou, Yi-Xing; Wang, Gui-Qiang; Xia, Ning-Shao; Zhang, Ming-Xiang

    2014-01-01

    Abstract Previous studies have revealed antibody to hepatitis B core antigen (anti-HBc) levels as a predictor of treatment response in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in both interferon and nucleos(t)ide analog therapy cohorts. However, there is no information about anti-HBc levels in the natural history of CHB. This study aimed to define anti-HBc levels of different phases in the natural history of CHB. Two hundred eleven treatment-naive CHB patients were included in the study. They were classified into 4 phases: immune tolerance (IT) phase (n = 39), immune clearance (IC) phase (n = 48), low or no-replicative (LR) phase (n = 55), and HBeAg-negative hepatitis (ENH, n = 69). Fifty patients who were HBsAg negative and anti-HBc positive were also recruited as past HBV infection (PBI) control group. Anti-HBc levels were measured by a newly developed double-sandwich immunoassay. Correlation of anti-HBc levels with alanine aminotransferase (ALT) and other HBV-related markers within each phase was performed. Serum anti-HBc levels were statistically significant between patients in different phases of CHB (P < 0.001). The median anti-HBc levels were: IT (3.17 log10 IU/mL), IC (4.39 log10 IU/mL), LR (3.29 log10 IU/mL), ENH (4.12 log10 IU/mL), and PBI (0.61 log10 IU/mL). There existed a strong correlation in IC (r = 0.489, P < 0.001), a poor correlation in ENH (r = 0.275, P = 0.042), and no correlation in patients with ALT reached 5 times upper limit of normal (r = 0.120, P = 0.616). Anti-HBc levels show significant differences during the natural course of CHB. These results may provide some potentially useful insights into hepatitis B pathogenesis and immune activation against hepatitis B virus. PMID:25546679

  18. [Correction of dyslipidemia in patients with chronic hepatitis C, combined with diabetes type 2].

    PubMed

    Derbak, M; Boldizhar, P

    2014-01-01

    The article shows the results of treatment of 118 patients with chronic hepatitis C (CHC) which is associated with type 2 diabetes mellitus (DM). When planning therapeutic interventions in chronic hepatitis C in patients with diabetes, it is considered the presence of visceral obesit , dyslipidemia, and hepatic steatosis. The efficacy of different treatment regimens was studied. Found that the usage of ursodeoxycholic acid and ademetionin in HCV patients with diabetes type 2 receiving standard antiviral therapy (SAVT), significantly make a positive effect on the level of dyslipidemia. The normalization of lipid profile allows for a full course of SAVT, which reduces the frequency of relapse. It is also noted that the simultaneous use of ademetionin and ursodeoxycholic acid in treatment of chronic hepatitis C leads to a reduction of side effects of SAVT. Metabolic therapy may be recommended for patients with chronic hepatitis C in combination with type 2 diabetes in case of SAVT, and at its contraindications or intolerance.

  19. [Correction of dyslipidemia in patients with chronic hepatitis C, combined with diabetes type 2].

    PubMed

    Derbak, M; Boldizhar, P

    2014-01-01

    The article shows the results of treatment of 118 patients with chronic hepatitis C (CHC) which is associated with type 2 diabetes mellitus (DM). When planning therapeutic interventions in chronic hepatitis C in patients with diabetes, it is considered the presence of visceral obesit , dyslipidemia, and hepatic steatosis. The efficacy of different treatment regimens was studied. Found that the usage of ursodeoxycholic acid and ademetionin in HCV patients with diabetes type 2 receiving standard antiviral therapy (SAVT), significantly make a positive effect on the level of dyslipidemia. The normalization of lipid profile allows for a full course of SAVT, which reduces the frequency of relapse. It is also noted that the simultaneous use of ademetionin and ursodeoxycholic acid in treatment of chronic hepatitis C leads to a reduction of side effects of SAVT. Metabolic therapy may be recommended for patients with chronic hepatitis C in combination with type 2 diabetes in case of SAVT, and at its contraindications or intolerance. PMID:24523328

  20. Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B.

    PubMed

    Seto, W-K; Wong, D K-H; Fung, J; Huang, F-Y; Liu, K S-H; Lai, C-L; Yuen, M-F

    2014-11-01

    Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n=52), immune clearance (IC group, n=105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n=97), HBeAg-negative quiescent group (ENQ group, n=95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n=55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r=0.874, p<0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r=0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r=0.537, p<0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p<0.001) and HBsAg (5.05/5.96 log mIU/mL, p<0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability.

  1. Disease burden of chronic hepatitis C among immigrants in Canada.

    PubMed

    Chen, W; Krahn, M

    2015-12-01

    Immigrants with chronic hepatitis C (CHC) in Canada have doubled risk of hepatocellular carcinoma. To measure the burden of CHC among immigrants in Canada. A decision analytic model was developed to compare immigrants with CHC and age-matched immigrants without CHC for survival years, quality-adjusted life-years (QALYs) and medical costs per life year. Hepatitis C epidemiology among immigrants was based on hepatitis C prevalence in their home countries. A cohort of immigrant patients was retrospectively followed up to estimate fibrosis stage distribution, treatment patterns and prognosis of compensated cirrhosis. Other model variables were based on published sources. Base case analysis, one-way sensitivity analysis and probabilistic sensitivity analysis were performed to measure the burden of CHC and assess the impact of uncertainty associated with model variables on the burden of CHC. CHC could reduce survival by 9.6 years [95% credible interval (CI): 8.0-10.9 years], reduce QALYs by 9.5 years (95% CI: 6.0-13.8 years) and increase medical costs per life year by $1950 (95% CI: $1518 to $2486, 2006 Canadian dollars). Because nearly half of immigrants with CHC were not diagnosed until the development of cirrhosis, the burden of CHC was highly sensitive to the risks of liver-related complications and mortality but insensitive to pegylated interferon plus ribavirin. The burden of CHC among immigrants in Canada is substantial mainly due to liver-related complications and mortality. The delay in diagnosis was another important contributor to the burden of CHC among immigrants. PMID:26110922

  2. Disease burden of chronic hepatitis C among immigrants in Canada.

    PubMed

    Chen, W; Krahn, M

    2015-12-01

    Immigrants with chronic hepatitis C (CHC) in Canada have doubled risk of hepatocellular carcinoma. To measure the burden of CHC among immigrants in Canada. A decision analytic model was developed to compare immigrants with CHC and age-matched immigrants without CHC for survival years, quality-adjusted life-years (QALYs) and medical costs per life year. Hepatitis C epidemiology among immigrants was based on hepatitis C prevalence in their home countries. A cohort of immigrant patients was retrospectively followed up to estimate fibrosis stage distribution, treatment patterns and prognosis of compensated cirrhosis. Other model variables were based on published sources. Base case analysis, one-way sensitivity analysis and probabilistic sensitivity analysis were performed to measure the burden of CHC and assess the impact of uncertainty associated with model variables on the burden of CHC. CHC could reduce survival by 9.6 years [95% credible interval (CI): 8.0-10.9 years], reduce QALYs by 9.5 years (95% CI: 6.0-13.8 years) and increase medical costs per life year by $1950 (95% CI: $1518 to $2486, 2006 Canadian dollars). Because nearly half of immigrants with CHC were not diagnosed until the development of cirrhosis, the burden of CHC was highly sensitive to the risks of liver-related complications and mortality but insensitive to pegylated interferon plus ribavirin. The burden of CHC among immigrants in Canada is substantial mainly due to liver-related complications and mortality. The delay in diagnosis was another important contributor to the burden of CHC among immigrants.

  3. Association between celiac disease and chronic hepatitis C

    PubMed Central

    Casella, Giovanni; Viganò, Davide; Romano Settanni, Carlo; Morelli, Olivia; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio

    2016-01-01

    Celiac disease is characterized by a gluten-induced damage of the small bowel in sensitive individuals that may cause malabsorption. Non-intestinal inflammatory diseases may trigger immunologic gluten intolerance in susceptible people and the HCV virus may be considered as a suitable candidate. Interferon therapy could precipitate symptom onset in subjects with silent celiac disease. In fact, symptoms such as diarrhea, anemia, and weight loss may occur during interferon therapy and are associated with serological positivity of anti-tranglutaminase antibodies. To date, considering the available literature data, it is very difficult to support a firm association between HCV chronic hepatitis and celiac disease. Thus, such a serological screening in HCV patients before starting interferon therapy should not be recommended. However, serology for celiac disease must be considered in patients who develop diarrhea and/or weight loss during such therapy. PMID:27458507

  4. Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection.

    PubMed

    Tang, L; Ward, H; Kattakuzhy, S; Wilson, E; Kottilil, S

    2016-01-01

    Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world-in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.

  5. Association between celiac disease and chronic hepatitis C.

    PubMed

    Casella, Giovanni; Viganò, Davide; Romano Settanni, Carlo; Morelli, Olivia; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio

    2016-01-01

    Celiac disease is characterized by a gluten-induced damage of the small bowel in sensitive individuals that may cause malabsorption. Non-intestinal inflammatory diseases may trigger immunologic gluten intolerance in susceptible people and the HCV virus may be considered as a suitable candidate. Interferon therapy could precipitate symptom onset in subjects with silent celiac disease. In fact, symptoms such as diarrhea, anemia, and weight loss may occur during interferon therapy and are associated with serological positivity of anti-tranglutaminase antibodies. To date, considering the available literature data, it is very difficult to support a firm association between HCV chronic hepatitis and celiac disease. Thus, such a serological screening in HCV patients before starting interferon therapy should not be recommended. However, serology for celiac disease must be considered in patients who develop diarrhea and/or weight loss during such therapy. PMID:27458507

  6. Dysregulation of male sex hormones in chronic hepatitis C patients.

    PubMed

    El-Serafi, A T; Osama, S; El-Zalat, H; EL-Deen, I M

    2016-02-01

    Chronic hepatitis C (HCV) infection is a serious problem all over the world and has a special importance in Egypt, where the prevalence of infection is 14.7% of population. In males, HCV is associated with sexual dysfunction and changes in the semen parameters. This study aimed at estimation of a panel of the most important related hormones in the serum of patients and illustration of their correlation to the routine laboratory investigations. The four studied hormones showed alteration in the patients in comparison with the controls. While androstenedione, prolactin and testosterone were significantly increased in patients, dehydroepiandrosterone sulphate was decreased. These changes in the hormones were not related to the liver functions, pathological grade or even viral load. We hypothesised a model of how HCV can induce these hormonal changes and recommended to add these hormones to the follow-up panel of male patients with HCV.

  7. HBV and HAV infection in chronic hepatitis in Argentina.

    PubMed

    Tanno, H; Fay, O H; Roncoroni, M; Palazzi, J

    1981-01-01

    Sera of 155 chronic hepatitis (CH) patients in Argentina were tested for the presence of HBsAg, anti-HBs, anti-HBc, and anti-HAV. Our purpose was to define the role that both virus A and B might play in the etiology and pathogenesis of this condition. The patients were divided into two groups: group I (57) HBsAg-negative; group II (98) HBsAg-positive. The control group consisted of 1,209 healthy blood donors from Banco Central de Sangre de Rosario; 286/1,209 (24%) had viral markers for HBV. In group I, 38/57 (67%) had anti-HBs and/or anti-HBc, but none had anti-HBs alone. Group II showed a higher percentage of males (P less than 0.05). We found similar incidence of anti-HAV among group I, group II, and the control group.

  8. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    PubMed Central

    Fan, Lin; Owusu-Edusei, Kwame; Schillie, Sarah F.; Murphy, Trudy V.

    2014-01-01

    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection. PMID:25548510

  9. Quantification of liver fibrosis in chronic hepatitis B virus infection

    PubMed Central

    Jieanu, CF; Ungureanu, BS; Săndulescu, DL; Gheonea, IA; Tudorașcu, DR; Ciurea, ME; Purcărea, VL

    2015-01-01

    Chronic hepatitis B virus infection (HBV) is considered a global public issue with more than 78.000 people per year dying of its evolution. With liver transplantation as the only viable therapeutic option but only in end-stage disease, hepatitis B progression may generally be influenced by various factors. Assessing fibrosis stage plays an important part in future decisions on the patients’ wealth with available antiviral agents capable of preventing fibrosis passing to an end-stage liver disease. Several methods have been taken into consideration as an alternative for HBV quantification status, such as imaging techniques and serum based biomarkers. Magnetic resonance imaging, ultrasound, and elastography are considered non-invasive imaging techniques frequently used to quantify disease progression as well as patients future prognostic. Consequently, both direct and indirect biomarkers have been studied for differentiating between fibrosis stages. This paper reviews the current standings in HBV non-invasive liver fibrosis quantification, presenting the prognostic factors and available assessment procedures that might eventually replace liver biopsy. PMID:26351528

  10. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  11. Redox mechanisms in hepatic chronic wound healing and fibrogenesis

    PubMed Central

    Novo, Erica; Parola, Maurizio

    2008-01-01

    Reactive oxygen species (ROS) generated within cells or, more generally, in a tissue environment, may easily turn into a source of cell and tissue injury. Aerobic organisms have developed evolutionarily conserved mechanisms and strategies to carefully control the generation of ROS and other oxidative stress-related radical or non-radical reactive intermediates (that is, to maintain redox homeostasis), as well as to 'make use' of these molecules under physiological conditions as tools to modulate signal transduction, gene expression and cellular functional responses (that is, redox signalling). However, a derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, can play a significant role in the pathogenesis of major human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis. This review has been designed to first offer a critical introduction to current knowledge in the field of redox research in order to introduce readers to the complexity of redox signalling and redox homeostasis. This will include ready-to-use key information and concepts on ROS, free radicals and oxidative stress-related reactive intermediates and reactions, sources of ROS in mammalian cells and tissues, antioxidant defences, redox sensors and, more generally, the major principles of redox signalling and redox-dependent transcriptional regulation of mammalian cells. This information will serve as a basis of knowledge to introduce the role of ROS and other oxidative stress-related intermediates in contributing to essential events, such as the induction of cell death, the perpetuation of chronic inflammatory responses, fibrogenesis and much more, with a major focus on hepatic chronic wound healing and liver fibrogenesis. PMID:19014652

  12. Antibody-directed complement-mediated cytotoxicity to hepatocytes from patients with chronic hepatitis B.

    PubMed Central

    Michalak, T I; Lau, J Y; McFarlane, B M; Alexander, G J; Eddleston, A L; Williams, R

    1995-01-01

    The susceptibility of hepatocytes from patients with chronic hepatitis B to complement-dependent cytotoxicity mediated by heterologous antibodies to hepatitis B virus core (anti-HBc) and surface (anti-HBs) antigens and to hepatic asialoglycoprotein receptor was examined using a microcytotoxicity assay. The anti-HBc-induced cytotoxicity was found to be markedly enhanced against hepatocytes isolated from patients with chronic active hepatitis (72.6 +/- 9.5% (mean +/- s.e.m.); n = 6) over that against hepatocytes from individuals with chronic persistent hepatitis or inactive liver cirrhosis (40.6 +/- 18.6%; n = 4) (P = 0.019). Overall, values of the anti-HBc-directed cytotoxicity were higher in patients positive for HBcAg in hepatocytes and seropositive for hepatitis B virus e antigen (HBeAg). Hepatocytotoxicity was also exerted by anti-HBs and anti-asialoglycoprotein receptor antibodies in the presence of complement, but it was not seemingly related to disease activity. These results indicate that hepatitis B virus core and surface antigens and asialoglycoprotein receptor at the hepatocyte surface can be recognized by antibodies, and raise the possibility that complement-dependent cytolysis may contribute to the injury of hepatitis B virus-infected hepatocytes. The data also suggest that liver cells of patients with severe chronic hepatitis might be more susceptible to anti-HBc antibody-directed complement-mediated cytotoxicity than those with inactive liver histology. PMID:7743660

  13. Chronic hepatitis type B in childhood: longitudinal study of 35 cases.

    PubMed Central

    Bortolotti, F; Cadrobbi, P; Crivellaro, C; Bertaggia, A; Alberti, A; Realdi, G

    1981-01-01

    Clinical, virological, and histological features of hepatitis B virus infection have been examined in 35 children, aged 1 to 11 years, known to be hepatitis B surface antigen (HBsAg) carriers for at least six months when entering the study. Only 10 patients had a history of acute unresolved hepatitis: in the remaining cases the detection of HBsAg had been an occasional finding. Although 77% of the patients were asymptomatic, all had evidence of hepatic involvement and liver history showed the features of chronic persistent hepatitis in 18 cases and of chronic active hepatitis in 16 cases, with associated cirrhosis in two of them. One patient had only minimal histological changes. A high percentage of children with both chronic persistent and chronic active hepatitis had evidence of active virus replication throughout the observation period. During the follow-up study of one to eight years (mean 3.1 +/- 1.7 years), transaminase levels became consistently normal in five patients with chronic persistent hepatitis, and inflammatory infiltrates disappeared in three of them. However, only one of these children cleared HBsAg from serum. Eleven of 16 patients with chronic active hepatitis received immunosuppressive treatment but only one of them achieved a complete and protracted remission, although active viral replication persisted. On the other hand, two of five untreated patients reached complete remission after two and three years of follow-up respectively and one of them cleared HBsAg three years later. These results would suggest the possibility of a spontaneous complete remission of HBsAg positive chronic active hepatitis in children but also raise doubts about the usefulness of immunosuppressive therapy in such patients. PMID:7262628

  14. Extrahepatic manifestations of chronic hepatitis C virus infection

    PubMed Central

    Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne C.; Saadoun, David

    2016-01-01

    During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID:26862398

  15. Chronic hepatitis C: an age wave of disease burden.

    PubMed

    McHutchison, John G; Bacon, Bruce R

    2005-10-01

    There are at least 2.7 million individuals in the United States, most of them in their 40s and 50s, who are chronically infected with hepatitis C virus (HCV). As these infected individuals get older, about 20% will develop cirrhosis, and a significant fraction of those with cirrhosis (about 1 in 10) will then develop serious decompensated liver disease or hepatocellular carcinoma. Currently, HCV is the primary cause of death in 8000 to 12 000 people every year; the virus is also the primary reason for liver transplantation in the United States. Although the number of new cases of HCV infection has been dropping steadily since the introduction of improved blood-supply screening, the "age wave" of existing chronic HCV in baby boomers is expected to contribute to a substantial rise in morbidity, mortality, and costs over the next 2 decades. Although it is difficult to predict which HCV-infected patients will progress to serious liver disease, the availability of a combination drug regimen (peginterferon alfa plus ribavirin) that essentially "cures" the disease in more than half of treated patients now provides clinicians and pharmacists in managed care settings with the tools needed to diminish the impact of the anticipated wave of liver disease. This article reviews the epidemiology, natural history, clinical and economic burden, and screening and treatment options for HCV. PMID:16232012

  16. Ophthalmological side effects of interferon therapy of chronic hepatitis C

    PubMed Central

    Medhat, Eman; Esmat, Gamal; Hamza, Eman; Abdel Aziz, Amr; Fouad Fathalah, Waleed; Zakaria, Zeinab; Mostafa, Sameh

    2016-01-01

    Background Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity. Methods We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment. Results IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy. Conclusions Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately it’s asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important. PMID:27275462

  17. Telaprevir-based triple therapy following partial splenic arterial embolization for chronic hepatitis C with thrombocytopenia can reduce carcinogenesis and improve hepatic function reserve

    PubMed Central

    ISHIKAWA, TORU; ABE, SATOSHI; KOJIMA, YUICHI; HORIGOME, RYOKO; SANO, TOMOE; IWANAGA, AKITO; SEKI, KEIICHI; HONMA, TERASU; YOSHIDA, TOSHIAKI

    2015-01-01

    Thrombocytopenia in patients with chronic hepatitis C negatively impacts interferon (IFN)-based treatment. The aim of this study was to evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy including IFN for patients who have undergone partial splenic arterial embolization (PSE). Ten patients with thrombocytopenia who were infected with hepatitis C virus (HCV) genotype 1b received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN)α2b and ribavirin following PSE. A sustained virological response (SVR) was seen in 9 of the 10 patients who could be assessed. Early relapse was seen in 1 patient who had the IL-28B minor allele and a null response to pretreatment. The α-fetoprotein levels of the patients decreased from 17.94±7.30 ng/ml prior to PSE to 4.33±2.41 ng/ml at 6 months after triple therapy (P=0.08). Furthermore, serum albumin levels improved significantly from 3.68±0.49 g/dl pre-PSE to 4.13±0.34 g/dl at 12 months after triple therapy (P=0.043). PSE contributed to the treatment success of triple therapy, particularly for patients who were either treatment-naïve, had a history of relapse or the IL28B major allele. This strategy can reduce carcinogenesis and improve hepatic function reserve. PMID:26622488

  18. [Autoimmune hepatitis].

    PubMed

    Marcais, O; Larrey, D

    1994-01-01

    Acute and chronic autoimmune hepatitis are uncommon inflammatory liver diseases, mainly occurring in young women, in association with hypergammaglobulinemia and serum autoantibodies. Different types have been described: type 1 characterized by anti-smooth muscle and anti-nuclear antibodies; type 2 characterized by anti-LKM1 antibodies; type 3 characterized by anti-SLA antibodies. Other types, still not clearly defined, may exist. Autoimmune hepatitis are associated with HLA A1 B8 DR3 and HLA DR4. Without any treatment, the disease leads to cirrhosis and, uncommonly, to fulminant hepatitis. Large doses of corticosteroids usually allow to control the disease. Relapse of hepatitis is frequent after corticosteroid withdrawal. Concomitant administration of immunosuppressive agents such as azathioprine allows to reduce corticosteroid dosage and contributes to maintain the remission of the disease. Liver transplantation may be indicated in cases of severe cirrhosis or fulminant hepatitis.

  19. The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors

    PubMed Central

    Duncan, Marilyn J.; Hester, James M.; Hopper, Jason A.; Franklin, Kathleen M.

    2010-01-01

    Age-related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5-HT1B receptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin-releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin-selective reuptake inhibitor, fluoxetine, would attenuate the age-related changes in SCN VIP mRNA expression and 5-HT1B receptors. In situ hybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age-related increase in SCN 5-HT1B receptors at ZT6, and decreases SCN 5-HT1B receptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5-HT1B receptors are differentially regulated; the age-related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment. PMID:20525077

  20. The Woodchuck, a Nonprimate Model for Immunopathogenesis and Therapeutic Immunomodulation in Chronic Hepatitis B Virus Infection.

    PubMed

    Roggendorf, Michael; Kosinska, Anna D; Liu, Jia; Lu, Mengji

    2015-12-01

    The woodchuck hepatitis virus (WHV) and its host, the eastern woodchuck, is a very valuable model system for hepatitis B virus infection. Many aspects of WHV replication and pathogenesis resemble acute and chronic hepatitis B infection in patients. Since the establishment of immunological tools, woodchucks were used to develop new therapeutic vaccines and immunomodulatory approaches to treat chronic hepadnaviral infections. Combination therapy of nucleos(t)ide analogs, with prime-boost vaccination and triple therapy, including immunomodulatory strategies by blocking the interaction of the programmed death-1 (PD-1) receptor with its ligand inducing a potent T-cell response in chronic WHV carrier woodchucks, suppression of viral replication, and complete elimination of the virus in 30% of the animals. Both strategies may be used for future therapies in patients with chronic hepatitis B. PMID:26511761

  1. Chronic Hepatitis C: An Overview of Evidence on Epidemiology and Management from a Brazilian Perspective

    PubMed Central

    Castro, Rodolfo; Perazzo, Hugo; Grinsztejn, Beatriz; Veloso, Valdilea G.; Hyde, Chris

    2015-01-01

    Chronic hepatitis C remains one of the main causes of chronic liver disease worldwide and presents a variable natural history ranging from minimal changes to advanced fibrosis and cirrhosis and its complications, such as development of hepatocellular carcinoma. Approximately, 1.45 million people are estimated to be infected by HCV in Brazil representing a major public health issue. The aim of this paper was to review the epidemiology and management of chronic hepatitis C from a Brazilian perspective. The management of chronic hepatitis C has been challenged by the use of noninvasive methods to stage liver fibrosis as an alternative to liver biopsy and the high cost of new interferon-free antiviral treatments. Moreover, the need of cost-effectiveness analysis in hepatitis C and the recent changes in treatment protocols were discussed. PMID:26693356

  2. Glucose abnormalities in Asian patients with chronic hepatitis C.

    PubMed

    Bo, Qingyan; Orsenigo, Roberto; Wang, Junyi; Griffel, Louis; Brass, Clifford

    2015-01-01

    Many studies have demonstrated a potential association between type 2 diabetes (T2D) and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D) and their risk factors between Asian and non-Asian chronic hepatitis C (CHC) patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries). This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025) as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%), and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08). Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had no impact on viral response to peginterferon plus ribavirin.

  3. Interaction of IL1B and IL1RN polymorphisms, smoking habit, gender, and ethnicity with aggressive and chronic periodontitis susceptibility

    PubMed Central

    Ribeiro, Magali Silveira Monteiro; Pacheco, Renata Botelho Antunes; Fischer, Ricardo Guimarães; Macedo, Jacyara Maria Brito

    2016-01-01

    Background: Although the interleukin-1 (IL-1) plays a critical role in the pathogenesis of periodontitis, associations between IL1 gene cluster polymorphisms and the disease remains unclear. Aims: To investigate the importance of IL1B-511C>T (rs16944), IL1B +3954C>T (rs1143634), and IL1RN intron 2 variable number tandem repeat (VNTR) (rs2234663) polymorphisms, individually or in combination, as the risk factors of periodontitis in a Southeastern Brazilian population with a high degree of miscegenation. Subjects and Methods: A total of 145 individuals, with aggressive (aggressive periodontitis [AgP], n = 43) and chronic (chronic periodontitis [CP], n = 52) periodontitis, and controls (n = 50) were genotyped by polymerase chain reaction (PCR) (IL1RN intron 2 VNTR) or PCR-restriction fragment length polymorphism (PCR-RFLP) (IL1B-511 C>T and IL1B + 3954C>T) techniques. Statistical Analysis: The independent t-test, Chi-square, and Fisher's exact tests were used. The SNPStats program was used for haplotype estimation and multiplicative interaction analyses. Results: The IL1B +3954T allele represented risk for CP (odds ratio [OR] = 2.84), particularly in smokers (OR = 4.43) and females (OR = 6.00). The minor alleles IL1RN*2 and *3 increased the risk of AgP (OR = 2.18), especially the IL1RN*2*2 genotype among  white Brazilians (OR = 7.80). Individuals with the combinations of the IL1B + 3954T and IL1RN*2 or *3-containing genotypes were at increased risk of developing CP (OR = 4.50). Considering the three polymorphisms (rs16944, rs1143634, and rs2234663), the haplotypes TC2 and CT1 represented risk for AgP (OR = 3.41) and CP (OR = 6.39), respectively. Conclusions: Our data suggest that the IL1B +3954C>T and IL1RN intron 2 VNTR polymorphisms are potential candidates for genetic biomarkers of periodontitis, particularly in specific groups of individuals. PMID:27630500

  4. Interaction of IL1B and IL1RN polymorphisms, smoking habit, gender, and ethnicity with aggressive and chronic periodontitis susceptibility

    PubMed Central

    Ribeiro, Magali Silveira Monteiro; Pacheco, Renata Botelho Antunes; Fischer, Ricardo Guimarães; Macedo, Jacyara Maria Brito

    2016-01-01

    Background: Although the interleukin-1 (IL-1) plays a critical role in the pathogenesis of periodontitis, associations between IL1 gene cluster polymorphisms and the disease remains unclear. Aims: To investigate the importance of IL1B-511C>T (rs16944), IL1B +3954C>T (rs1143634), and IL1RN intron 2 variable number tandem repeat (VNTR) (rs2234663) polymorphisms, individually or in combination, as the risk factors of periodontitis in a Southeastern Brazilian population with a high degree of miscegenation. Subjects and Methods: A total of 145 individuals, with aggressive (aggressive periodontitis [AgP], n = 43) and chronic (chronic periodontitis [CP], n = 52) periodontitis, and controls (n = 50) were genotyped by polymerase chain reaction (PCR) (IL1RN intron 2 VNTR) or PCR-restriction fragment length polymorphism (PCR-RFLP) (IL1B-511 C>T and IL1B + 3954C>T) techniques. Statistical Analysis: The independent t-test, Chi-square, and Fisher's exact tests were used. The SNPStats program was used for haplotype estimation and multiplicative interaction analyses. Results: The IL1B +3954T allele represented risk for CP (odds ratio [OR] = 2.84), particularly in smokers (OR = 4.43) and females (OR = 6.00). The minor alleles IL1RN*2 and *3 increased the risk of AgP (OR = 2.18), especially the IL1RN*2*2 genotype among  white Brazilians (OR = 7.80). Individuals with the combinations of the IL1B + 3954T and IL1RN*2 or *3-containing genotypes were at increased risk of developing CP (OR = 4.50). Considering the three polymorphisms (rs16944, rs1143634, and rs2234663), the haplotypes TC2 and CT1 represented risk for AgP (OR = 3.41) and CP (OR = 6.39), respectively. Conclusions: Our data suggest that the IL1B +3954C>T and IL1RN intron 2 VNTR polymorphisms are potential candidates for genetic biomarkers of periodontitis, particularly in specific groups of individuals.

  5. [The stage of portal blood flow in patients with hemoblastosis combined with chronic hepatitis].

    PubMed

    Pospelova, T I; Koptev, V D; Volkova, I I; Loseva, M I; Ageeva, T A; Soldatova, G S

    2008-01-01

    109 patients with hemoblastosis (HB) were examined. Average age was 31.8 +/- 1.4 years in group of lymphogranulomatosis patients, and 44 +/- 5.3 years in group of acute leukemia patients. Group of 46 patients with clinical laboratory signs of hepatic lesion was marked out. Since features of portal blood flow (PBF) revealed at dopplerography did not depend on hepatitis aetiology, all patients with chronic hepatitis were analyzed in one group. These patients were examined clinicobiochemically: functional hepatic tests, markers of viral hepatitis B and C, ultrasonic abdominal scanning, PBF dopplerography, puncture biopsy of hepar. All patients had PBF disturbances such as decrease of portal vein blood flow, increase of venous drainage of hepar and spleen. The degree of disturbances intensity increased depending on degree of chronic hepatitis activity (the index of histological activity) and hepatic fibrosis stage. Thus, presence of chronic hepatitis in HB patients regardless of aetiology, is the factor aggravating patients' stage and corrupting PBF. PBF disturbances (decrease of arterial and venous inflow and increase of venous outflow) and development of fibrous changes apparently related with compression of vessels by connective tissue around central veins, inside of lobules and among of hepatic cells. Consequence of it is including anastomosises in blood flow which leads to redistribution of PBF and portal hypertension forming. PMID:18494289

  6. Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C

    PubMed Central

    Sultana, Camelia; Oprişan, Gabriela; Teleman, Monica Delia; Dinu, Sorin; Oprea, Cristiana; Voiculescu, Mihai; Ruta, Simona

    2016-01-01

    AIM To determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients. METHODS One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5' allelic discrimination assay; Applied Biosystems). RESULTS Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P < 0.001), urban residence (P = 0.004), IL28B CC genotype (P < 0.001), absence of core mutations (P = 0.005), achievement of rapid virologic response (P < 0.001) and early virological response (P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P < 0.001), absence of core substitutions (P = 0.04) and IL28B CC genotype (P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%. CONCLUSION HCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease. PMID:27729747

  7. CLINICAL AND GENETIC PREDICTORS AND PROGNOSTIC MODEL OF RAPIDLY PROGRESSIVE HEPATIC FIBROSIS IN CHRONIC HEPATITIS C.

    PubMed

    Dubinskaya, G; Sizova, L; Koval, T; Kovalyova, Е; Kaydashev, I

    2016-07-01

    The search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender - ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) - ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity - ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) - ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) - ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin - ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase - ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity - 85.5%, specificity - 68.3%, total number of the appropriate assignments - 76.8%, positive and negative predictive value - 72,6% and 82.7%,, respectively, the AUC ROC-curve - 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual

  8. CLINICAL AND GENETIC PREDICTORS AND PROGNOSTIC MODEL OF RAPIDLY PROGRESSIVE HEPATIC FIBROSIS IN CHRONIC HEPATITIS C.

    PubMed

    Dubinskaya, G; Sizova, L; Koval, T; Kovalyova, Е; Kaydashev, I

    2016-07-01

    The search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender - ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) - ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity - ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) - ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) - ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin - ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase - ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity - 85.5%, specificity - 68.3%, total number of the appropriate assignments - 76.8%, positive and negative predictive value - 72,6% and 82.7%,, respectively, the AUC ROC-curve - 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual

  9. Anti-cyclic citrullinated peptide and rheumatoid factor in patients with chronic hepatitis B and hepatitis B carriers

    PubMed Central

    Dalkılıç, Ediz; Öksüz, Mustafa Ferhat; Tufan, Ayşe Nur; Özbek, Aysun; Nizamoğlu, Ali; Dolarslan, Mürside Esra; Coşkun, Belkıs Nihan; Pehlivan, Yavuz

    2015-01-01

    Objective Rheumatoid factor (RF) positivity that may occur in a number of patients with hepatitis B (HBV) infection poses challenges in terms of differential diagnosis with rheumatoid arthritis (RA). On the other hand, antibodies to cyclic citrullinated peptide (anti-CCP) may prove to be an important marker for differential diagnosis of the two conditions. This study aimed to assess anti-CCP and RF positivity among patients with hepatitis B and rheumatoid arthritis. Material and Methods Anti-CCP and RF seropositivity was assessed in 61 patients with HBV infection (32 patients with chronic hepatitis, 29 patients with inactive HBV carrier status) and 40 patients with RA as the control group. Results RF positivity was found in 18.7% and 34.4% of the patients with chronic hepatitis B and inactive HBV carrier status, respectively. On the other hand, only one patient with chronic HBV had low positive anti-CCP. RF was positive in 24 (60%) and anti-CCP was positive in 26 (65%) patients among the 40 patients with RA. Conclusion Anti-CCP may be helpful in the differential diagnosis between RA and chronic HBV infection or inactive HBV carrier status.

  10. Resetting the transcription factor network reverses terminal chronic hepatic failure.

    PubMed

    Nishikawa, Taichiro; Bell, Aaron; Brooks, Jenna M; Setoyama, Kentaro; Melis, Marta; Han, Bing; Fukumitsu, Ken; Handa, Kan; Tian, Jianmin; Kaestner, Klaus H; Vodovotz, Yoram; Locker, Joseph; Soto-Gutierrez, Alejandro; Fox, Ira J

    2015-04-01

    The cause of organ failure is enigmatic for many degenerative diseases, including end-stage liver disease. Here, using a CCl4-induced rat model of irreversible and fatal hepatic failure, which also exhibits terminal changes in the extracellular matrix, we demonstrated that chronic injury stably reprograms the critical balance of transcription factors and that diseased and dedifferentiated cells can be returned to normal function by re-expression of critical transcription factors, a process similar to the type of reprogramming that induces somatic cells to become pluripotent or to change their cell lineage. Forced re-expression of the transcription factor HNF4α induced expression of the other hepatocyte-expressed transcription factors; restored functionality in terminally diseased hepatocytes isolated from CCl4-treated rats; and rapidly reversed fatal liver failure in CCl4-treated animals by restoring diseased hepatocytes rather than replacing them with new hepatocytes or stem cells. Together, the results of our study indicate that disruption of the transcription factor network and cellular dedifferentiation likely mediate terminal liver failure and suggest reinstatement of this network has therapeutic potential for correcting organ failure without cell replacement.

  11. [Chronic hepatitis C: standard of care and perspective].

    PubMed

    Aghemo, Alessio; De Nicola, Stella

    2016-07-01

    Chronic hepatitis C (HCV) is a major health problem with more than 150 million people infected worldwide. It is the leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation in western countries. Nowadays the disease is curable in most patients as the development of directly acting antivirals against HCV allows between 90 and 95% of patients who receive treatment to achieve viral eradication. This innovation has been made possible by the understanding of the HCV life cycle as well as the development of in vitro models of HCV replication, that have led to the discovery of 3 key steps in the HCV life cycle that can be targeted to halt viral replication. Drugs targeting the NS3 Protease, the NS5A protein as well as the NS5B polymerase are now commercially available in Europe. By combining these drugs for 12 or 24 weeks, most HCV-positive patients can be cured of their infection. Still the treatment cascade requires at the moment expert management, due to the relative complexity and need for individualization of the current regimens, as well as the need for monitoring for side effects during treatment. This, together with low diagnostic rates in the general population and high pricing of directly acting antivirals is a major hurdle to universal treatment of HCV and emphasizes the need for simplier pangenotypic, ribavirin free anti-HCV regimens that are now in advanced phase of development and should enter the field in the next 12-18 months. PMID:27571464

  12. Management of Chronic Hepatitis B Infection in India.

    PubMed

    Amarapurkar, Deepak N; Madan, Kaushal; Kapoor, Dharmesh

    2015-11-01

    Chronic hepatitis B (CHB) infection is a substantial global health problem with highest prevalence observed in the sub-Saharan Africa and East Asia. India lies in the intermediate endemicity zone with prevalence ranging from 0.1% to 11.7%. The predominant route of transmission is horizontal and the most commonly occurring genotypes are A and D. The high mortality and morbidity associated with CHB constitutes significant health and economic burden in developing countries like India. Antiviral agents decrease HBV DNA load and prevent disease progression. Several regional and country expert associations have developed treatment guidelines for appropriate management of CHB; however, various factors like prevalence, disease awareness, immunization status, cost implications, availability of resources, type of transmission and emerging significance of HBV genotypes have influenced the management of CHB in a country. This article focuses on expert's recommendations on CHB management including initiation, monitoring and termination of treatment with emphasis on borderline cases. The article also throws light on the challenges to optimum management and provides preferred therapeutic approaches in Indian perspective. PMID:27608783

  13. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    PubMed Central

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-01-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host’s immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host’s immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  14. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection.

    PubMed

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-07-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far. PMID:27635192

  15. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    PubMed Central

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-01-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host’s immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host’s immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far. PMID:27635192

  16. Emperipolesis is a potential histological hallmark associated with chronic hepatitis B.

    PubMed

    Hu, Y; Jiang, L; Zhou, G; Liu, S; Liu, Y; Zhang, X; Zhao, S; Wu, L; Yang, M; Ma, L; Wang, X; Zhao, J

    2015-01-01

    Although emperipolesis exists in infectious liver diseases, the diagnostic value of emperipolesis in chronic hepatitis B is not exactly known. The aim of this study is to evaluate the histological characteristics and laboratory parameters of emperipolesis in chronic hepatitis B. Totally 402 patients with hepatitis B and other liver diseases were processed in a retrospective assessment. Inflammatory severity of hepatitis B was evaluated with Ishak Scoring System. Immunofluorescent staining was performed for CD8 (T cells), CD20 (B cells), CD56 (NK cells), CD68 (macrophages) and MPO (neutrophils). Emperipolesis was observed in 74.0% of patients with chronic hepatitis B (CHB) and 82.8% of patients with acute hepatitis B (AHB). In emperipolesis, CD8(+) T cell was the main cell type. Patients with emperipolesis in CHB got high scores of inflammatory activity. Among patients with CHB, emperipolesis was present with higher serum ALT, AST and GGT levels. HBV DNA Load in patients with emperipolesis was as 10 times high as those without emperipolesis. HBeAb was significantly correlated with the evidence of emperipolesis. In chronic hepatitis B, emperipolesis was associated with severity of liver injury. The presence of emperipolesis was an indicator of active liver inflammation. PMID:26511703

  17. Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment

    PubMed Central

    Aygen, Bilgehan; Yildiz, Orhan; Akhan, Sila; Gunal, Ozgur; Taheri, Serpil; Zararsiz, Gokmen; Sayan, Murat; Rustemoglu, Aydin; Altinok, Elif Sargin

    2014-01-01

    Background Interleukin (IL) 28B single nucleotide polymorphisms may play a role in the clearance of hepatitis C virus (HCV). We aimed to evaluate the treatment response of chronic HCV infection patients to pegile interferon (pegIFN) and ribavirin treatment with regard to IL28B rs12979860 C/T polymorphism. Methods A total of 186 patients (mean age, 55.6 ± 10 years; 65.1% female) who underwent pegIFN and ribavirin treatment for chronic HCV infection were studied. We analyzed demographics, HCV genotype, baseline alanine aminotransferase (ALT) levels, histopathological data, viral load before treatment and at 4, 12, 24, 48, and 72 weeks from the treatment start, and IL28B genotype. IL28B polymorphism was genotyped using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in all the subjects. Results One hundred forty-five (86.8%) patients were infected with viral genotype 1b, and 13.2% were infected with viral genotype 4. The rates of C/C, C/T, and T/T genotypes were 22.6%, 52.7%, and 24.7% respectively. The percentage of patients with a viral load over 400,000 IU/mL was higher in the C/T group (P = 0.020). Of the patients, 44.6% provided sustained virological response (SVR) to pegIFN and ribavirin combination treatment. The frequency of T allele was 41% in patients with SVR, whereas 59% patients provided no response (P < 0.001). SVR was obtained in 66.7%, 42.9%, and 28.3% of CC, CT, and TT groups (P = 0.001). The rates of rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and SVR were higher in the CC group than other groups (P = 0.216, P < 0.001, P = 0.001, P = 0.001, respectively). The relapse and null response (NR) rates were higher in TT group and partial response rate (PR) was higher in CT group. Conclusions IL28B rs12979860 C/T gene polymorphism affects the response to antiviral treatment in the patients with chronic HCV genotypes 1b and 4 infections.

  18. Distribution of natural resistance to NS3 protease inhibitors in hepatitis C genotype 1a separated into clades 1 and 2 and in genotype 1b of HIV-infected patients.

    PubMed

    Bagaglio, S; Uberti-Foppa, C; Messina, E; Merli, M; Hasson, H; Andolina, A; Galli, A; Lazzarin, A; Morsica, G

    2016-04-01

    Naturally occurring resistance-associated variants (RAVs) within the protease domain of hepatitis C virus (HCV) genotype (G) 1a separated into clades 1 and 2, and G1b were investigated in 59 HIV/HCV coinfected patients. RAVs were detected in 10/23 G1a/clade 1 and 1/19 G1b (p 0.0059). A similar frequency of RAVs was found when comparing G1a/clade 2 and G1b (p 0.1672). A cross-resistance to the macrocyclic compounds simeprevir and paritaprevir was detected in two G1a/clade 2 and 1 G1b sequences and none of G1a/clade 1 sequences. The simultaneous characterization of subtype and natural RAVs by population analysis of the NS3 domain by may add important information for anti-HCV treatment strategies including protease inhibitors.

  19. Circulating and Hepatic Fas Expression in HCV-Induced Chronic Liver Disease and Hepatocellular Carcinoma

    PubMed Central

    El Bassiouny, Azza E. I.; El-Bassiouni, Nora E. I.; Nosseir, Mona M. F.; Zoheiry, Mona M.K.; El-Ahwany, Eman G.; Salah, Faten; Omran, Zeinab S.O.; Ibrahim, Raafat A.

    2008-01-01

    Apoptosis is central for control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death-inducing ligands CD95/Fas occur. This study aimed to study the role of serum soluble Fas and hepatic Fas expression as early predictors of advancement of chronic hepatitis C disease. The current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 30 cases of liver cirrhosis (LC) and HCV, and 20 cases of hepatocellular carcinoma (HCC) and HCV admitted to Theodor Bilharz Research Institute, Giza, Egypt. Fifteen wedge liver biopsies, taken during laparoscopic cholecystectomy, were included in the study as normal controls. Assessment of serum soluble Fas level (sFas) and other laboratory investigations, including liver function tests, serologic markers for viral hepatitis, and serum alpha-fetoprotein level (alpha-FP), were determined for all cases. Histopathologic study and immunohistochemistry using monoclonal antibody for CD95 were also done. The sFas was significantly increased in CHC, LC, and HCC cases compared with normal controls (P < .01). The increase of sFas in HCC was also significantly higher than that of CHC (P < .01). However, positive hepatic expression of Fas antigen was higher in CHC than LC with no significant difference; meanwhile, it was significantly lower in HCC (P < .01) compared with CHC. In conclusion, circulating and hepatic Fas expression in chronic hepatitis C infection illustrate the mechanism of liver injury caused by death receptors throughout the multistep process of fibrosis/carcinogenesis. Not only the higher degree of hepatic fibrosis, but also the lower expression of Fas protein, are correlated with the increased incidence of HCC. PMID:18679533

  20. Racial Disparities in Treatment Rates for Chronic Hepatitis C

    PubMed Central

    Vutien, Philip; Hoang, Joseph; Brooks, Louis; Nguyen, Nghia H.; Nguyen, Mindie H.

    2016-01-01

    Abstract Chronic hepatitis C (CHC) disproportionately affects racial minorities in the United States (US). Although prior studies have reported lower treatment rates in Blacks than in Caucasians, the rates of other minorities remain understudied. We aimed to examine antiviral treatment rates by race and to evaluate the effect of other demographic, medical, and psychiatric factors on treatment rates. We performed a population-based study of adult CHC patients identified via ICD-9CM query from OptumInsight's Data Mart from January 2009 to December 2013. Antiviral treatment was defined by pharmaceutical claims for interferon and/or pegylated-interferon. A total of 73,665 insured patients were included: 51,282 Caucasians, 10,493 Blacks, 8679 Hispanics, and 3211 Asians. Caucasians had the highest treatment rate (10.7%) followed by Blacks (8.8%), Hispanics (8.8%), and Asians (7.9%, P < .001). Hispanics had the highest cirrhosis rates compared with Caucasians, Blacks, and Asians (20.7% vs 18.3%, 17.1%, and 14.3%, respectively). Caucasians were the most likely to have a psychiatric comorbidity (20.1%) and Blacks the most likely to have a medical comorbidity (44%). Asians were the least likely to have a psychiatric (6.4%) or medical comorbidity (26.9%). On multivariate analysis, racial minority was a significant predictor of nontreatment with odds ratios of 0.82 [confidence interval (CI): 0.74–0.90] for Blacks, 0.87 (CI: 0.78–0.96) for Hispanics, and 0.73 (CI: 0.62–0.86) for Asians versus Caucasians. Racial minorities had lower treatment rates than Caucasians. Despite fewer medical and psychiatric comorbidities and higher incomes and educational levels, Asians had the lowest treatment rates. Hispanics also had lower treatment rates than Caucasians despite having higher rates of cirrhosis. Future studies should aim to identify underlying racial-related barriers to hepatitis C virus treatment besides socioeconomic status and medical or psychiatric comorbidities

  1. Web-based Distributed Medical Information System for Chronic Viral Hepatitis

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Qin, Tuan-fa; Jiang, Jian-ning; Lu, Hui; Ma, Zong-e.; Meng, Hong-chang

    2008-11-01

    To make a long-term dynamic monitoring to the chronically ill, especially patients of HBV A, we build a distributed Medical Information System for Chronic Viral Hepatitis (MISCHV). The Web-based system architecture and its function are described, and the extensive application and important role are also presented.

  2. Chronic hepatitis E virus infection in a pediatric female liver transplant recipient.

    PubMed

    Passos-Castilho, Ana Maria; Porta, Gilda; Miura, Irene K; Pugliese, Renata P S; Danesi, Vera L B; Porta, Adriana; Guimarães, Teresa; Seda, João; Antunes, Eduardo; Granato, Celso F H

    2014-12-01

    We describe a case of chronic hepatitis E virus (HEV) infection in a 13-year-old female liver transplant recipient with recurrent increased aminotransferase levels and acute cellular rejection. This finding demonstrates that chronic HEV infection can occur and should be further investigated in immunocompromised patients in Latin America.

  3. Experimental murine chronic hepatitis: results following intrahepatic inoculation of human uveitis mycoplasma-like organisms.

    PubMed Central

    Johnson, L. A.; Wirostko, E.; Wirostko, B. M.

    1993-01-01

    Mycoplasma-like organisms (MLO) are non-cultivated intracellular cell-wall deficient pathogenic bacteria with a distinctive ultrastructural appearance. Diagnosis of MLO disease depends on finding the organisms in parasitized cells using a transmission electron microscope. MLO are a well studied cause of transmissible chronic plant disease responsive to antibiotics. MLO have recently been found to cause human chronic uveitis, orbital, and retinal disease with autoimmune features. Ophthalmic leucocytes in these patients display MLO parasitization. Inoculation of human uveitis MLO into mouse eyelids produced chronic uveitis. MLO also disseminated to produce randomly distributed lethal systemic disease including chronic hepatitis. MLO parasitized leucocytes were present in all disease sites. Direct intrahepatic inoculation of human hepatic pathogens is a simple and efficient technique to produce murine hepatitis. This report describes the delayed onset widespread inflammatory liver disease produced by direct intrahepatic inoculation of human chronic uveitis MLO in 12 of 20 mice versus 0 in 40 controls (P < 0.05). The liver disease was accompanied by elevated serum SGOT levels, splenomegaly, and accelerated mortality. All 12 inflamed livers displayed MLO parasitized leucocytes versus 0 of 10 control livers. The resemblance of human chronic active hepatitis, massive hepatic necrosis, and post-necrotic cirrhosis to the MLO induced murine liver disease, the role of molecular biologic techniques in the detection and classification of those bacteria, and in therapy of MLO disease are discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8398804

  4. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

    PubMed

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully. PMID:27649152

  5. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

    PubMed

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

  6. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

    PubMed Central

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully. PMID:27649152

  7. Dysregulation of hepatic fatty acid metabolism in chronic kidney disease

    PubMed Central

    Jin, Kyubok; Norris, Keith; Vaziri, Nosratola D.

    2013-01-01

    Background Chronic kidney disease (CKD) results in hypertriglyceridemia which is largely due to impaired clearance of triglyceride-rich lipoproteins occasioned by downregulation of lipoprotein lipase and very low-density lipoprotein (LDL) receptor in the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-related protein in the liver. However, data on the effect of CKD on fatty acid metabolism in the liver is limited and was investigated here. Methods Male Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy (CRF) or sham operation (control) and observed for 12 weeks. The animals were then euthanized and their liver tissue tested for nuclear translocation (activation) of carbohydrate-responsive element binding protein (ChREBP) and sterol-responsive element binding protein-1 (SREBP-1) which independently regulate the expression of key enzyme in fatty acid synthesis, i.e. fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) as well as nuclear Peroxisome proliferator-activated receptor alpha (PPARα) which regulates the expression of enzymes involved in fatty acid oxidation and transport, i.e. L-FABP and CPT1A. In addition, the expression of ATP synthase α, ATP synthase β, glycogen synthase and diglyceride acyltransferase 1 (DGAT1) and DGAT2 were determined. Results Compared with controls, the CKD rats exhibited hypertriglyceridemia, elevated plasma and liver tissue free fatty acids, increased nuclear ChREBP and reduced nuclear SREBP-1 and PPARα, upregulation of ACC and FAS and downregulation of L-FABP, CPT1A, ATP synthase α, glycogen synthase and DGAT in the liver tissue. Conclusion Liver in animals with advanced CKD exhibits ChREBP-mediated upregulation of enzymes involved in fatty acid synthesis, downregulation of PPARα-regulated fatty acid oxidation system and reduction of DGAT resulting in reduced fatty acid incorporation in triglyceride. PMID:23045433

  8. Antineutrophil Cytoplasmic Antibody Frequency in Chronic Hepatitis B Patients

    PubMed Central

    Calhan, Turan; Kahraman, Resul; Altunoz, Mustafa Erhan; Ozbakır, Fatma; Ozdil, Kamil; Sokmen, Hacı Mehmet

    2014-01-01

    Background. Chronic hepatitis B (CHB) is a viral disease, common across the world, and associated with several extraintestinal manifestations including vasculitis. Antineutrophil cytoplasmic antibodies (ANCAs) are sensitive and specific markers for vasculitides. There is limited data available in the literature on whether ANCA formation is stimulated by CHB infection. In the present study we aimed to identify the frequency of ANCA in CHB patients. Methods. A total of 174 subjects were included in the study (87 CHB patients, 87 control subjects). Perinuclear-ANCA (P-ANCA), cytoplasmic-ANCA (C-ANCA), myeloperoxidase ANCA (MPO-ANCA), and proteinase 3-ANCA (PR3-ANCA) were studied. IFA was used for P-ANCA and C-ANCA assays, and ELISA was used for MPO-ANCA and PR3-ANCA assays. Results. ANCA positivity was high in both groups (31% in the CHB group and 26% among controls). There were no significant differences between the groups for P-ANCA and MPO-ANCA (P = 0.6 and P = 0.6, resp.). Frequency of borderline positive C-ANCA and all positive PR3-ANCA (positive + borderline positive) was significantly higher in the CHB group (P = 0.009 and P = 0.005, resp.). Conclusions. In the present study, the frequency of ANCA was high in both groups. The CHB group had a relatively higher frequency of ANCA positivity compared to controls. Borderline positive C-ANCA and positive PR3-ANCA were significantly higher in the CHB group. These results suggest that ANCA may have a high prevalence in Turkey. Patients with CHB should be evaluated particularly for C-ANCA and PR3-ANCA in the presence of vasculitic complaints and lesions. PMID:25161336

  9. Spontaneous and antiviral-induced cutaneous lesions in chronic hepatitis B virus infection

    PubMed Central

    Grigorescu, Ioana; Dumitrascu, Dan Lucian

    2014-01-01

    AIM: To describe spontaneous, or interferon (IFN)- or immunization-induced skin lesions in hepatitis B virus (HBV) infection. METHODS: A comprehensive literature search of all the papers presenting case reports of dermatological lesions in patients with chronic HBV infection was carried out. We included only patients with histologically proven skin lesions that appeared in the normal course of hepatitis B infection, or after immunization for hepatitis B or antiviral treatment. RESULTS: We found 44 papers on this topic, reporting 151 cases. About 2% of patients with hepatitis B infection, mainly men, presented with skin lesions. Among patients with chronic hepatitis B, vasculitis and essential mixed cryoglobulinemia seemed to be the most frequent skin lesion (53.3%), followed by papular changes, rashes and Gianotti-Crosti syndrome, skin carcinoma and Henoch-Schönlein purpura were rare. IFN treatment seemed to be effective against HBV-associated and immunoglobulin-complex-mediated disease (vasculitis). Two cutaneous lesions (lichen planus and granuloma annulare) were described after hepatitis B vaccination. Systemic lupus and lupus-like lesions were the most frequently encountered lesions after antiviral treatment. Immunosuppressive and steroid therapy ameliorates lichen planus lesions in 50% of cases. CONCLUSION: Vasculitis was the most frequent spontaneous skin lesion found in chronic hepatitis B. Lichen planus was most frequent after immunization and lupus/lupus-like lesions after IFN. PMID:25400473

  10. Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice.

    PubMed

    Rogers, Arlin B; Boutin, Samuel R; Whary, Mark T; Sundina, Nataliya; Ge, Zhongming; Cormier, Kathleen; Fox, James G

    2004-01-01

    Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.

  11. Trends in the Incidence Rates of Chronic Hepatitis B in Poland in the Years 2005 - 2013

    PubMed Central

    Stawinska-Witoszynska, Barbara; Zysnarska, Monika; Krzywinska-Wiewiorowska, Małgorzata; Wojtyła-Buciorab, Paulina; Krzyzaniak, Alicja; Wieckowska, Barbara

    2016-01-01

    Background The prevalence of newly-diagnosed cases of chronic hepatitis is decisive for the overall incidence rate of hepatitis B observed in Poland. Objectives We aimed to determine the chronic hepatitis B incidence trends in Poland, taking into consideration the ages, genders, and environments of the patients. Methods The study is based on aggregated data from Polish descriptive epidemiological studies for the period of 2005 to 2013 (i.e., hepatitis B incidence numbers and ratios, including mixed HBV and HCV infections) as published in the annual bulletins Choroby zakazne i zatrucia w Polsce (Infectious diseases and poisonings in Poland] drawn up by the laboratory for the monitoring and analysis of epidemiological status of the department of epidemiology at the national institute of public health - national institute of hygiene (NIPH-NIH). Poland, a central European country situated in the humid continental climate zone, is classified as a highly developed country. In the analyzed period, the Polish population consisted of about 38 million people, more than 19 million of whom were women, and more than 18 million of whom were men. Among European countries, Poland has the smallest number of national and ethnic minorities. For the purposes of epidemiological supervision, a special definition of acute hepatitis B was adopted in Poland in 2005, which facilitated separate registration of acute and chronic cases. Results A significantly increasing chronic hepatitis B incidence trend was observed in the population of Poland, with considerable increases in incidence rates for both men and women alike. The incidence rates for inhabitants of both urban and rural areas also showed an increasing tendency. Chronic hepatitis B occurred more frequently in men and in urban areas. For each of the five-year age groups encompassing patients between 20 and 54 years of age, the increase in the incidence rate proved to be significant. Conclusions The registered increase in the

  12. The Prevalence of Hepatitis C Virus Core Amino Acid 70 Substitution and Genotypes of Polymorphisms Near the IFNL3 Gene in Iranian Patients With Chronic Hepatitis C

    PubMed Central

    Kadjbaf, Danesh; Keshvari, Maryam; Alavian, Seyed Moayed; Pouryasin, Ali; Behnava, Bita; Salimi, Shima; Mehrnoush, Leila; Karimi Elizee, Pegah; Sharafi, Heidar

    2016-01-01

    Background Molecular studies have demonstrated that the hepatitis C virus (HCV) genotype and host genetics play predictive roles in the management of patients infected with HCV. Objectives This study aimed to investigate the HCV genotype, core amino acid (aa) 70 substitution, and polymorphisms near the IFNL3 gene (including rs12979860 and rs8099917) among Iranian patients with chronic hepatitis C (CHC). Patients and Methods In this cross-sectional study, the molecular profiles of the HCV genotype, core aa 70 substitution, and rs12979860 and rs8099917 polymorphisms and plasma HCV RNA levels were determined in 429 CHC patients including 141 hemophilic, 84 thalassemic, and 204 non-hemophilic, non-thalassemic patients. Results The hepatitis C virus subtype 1a was the most common subtype in the study population. Core aa substitution Arg70Gln was strongly associated with cirrhosis (OR = 2.49; 95% CI = 1.13 - 5.50; P = 0.020). Core aa 70 substitutions were more frequently observed in patients with the HCV subtype 1b than in patients with any other HCV subtypes (P < 0.001). Core aa 70 substitutions were also more common in patients with the rs12979860 TT genotype than in patients with non-TT genotypes (17.3% vs. 8.5%, P = 0.022) and also in rs8099917 non-TT genotypes than in the TT genotype (14.0% vs. 7.0%, P = 0.026). The HCV genotypes and rs8099917 polymorphisms were correlated in which HCV subtype 1b was in favor of rs8099917 GG and HCV subtype 3a favored rs8099917 TT (P = 0.021). Furthermore, the rs12979860 TT and rs8099917 GG genotypes showed significantly lower HCV RNA levels than the other genotypes (P < 0.001). Conclusions There is an as yet unexplained association between HCV and host parameters with unknown mechanisms in patients with chronic HCV infection. The assessments of core aa 70 substitution and polymorphisms near the IFNL3 gene could offer promising steps to improve the management of patients with HCV.

  13. The Prevalence of Hepatitis C Virus Core Amino Acid 70 Substitution and Genotypes of Polymorphisms Near the IFNL3 Gene in Iranian Patients With Chronic Hepatitis C

    PubMed Central

    Kadjbaf, Danesh; Keshvari, Maryam; Alavian, Seyed Moayed; Pouryasin, Ali; Behnava, Bita; Salimi, Shima; Mehrnoush, Leila; Karimi Elizee, Pegah; Sharafi, Heidar

    2016-01-01

    Background Molecular studies have demonstrated that the hepatitis C virus (HCV) genotype and host genetics play predictive roles in the management of patients infected with HCV. Objectives This study aimed to investigate the HCV genotype, core amino acid (aa) 70 substitution, and polymorphisms near the IFNL3 gene (including rs12979860 and rs8099917) among Iranian patients with chronic hepatitis C (CHC). Patients and Methods In this cross-sectional study, the molecular profiles of the HCV genotype, core aa 70 substitution, and rs12979860 and rs8099917 polymorphisms and plasma HCV RNA levels were determined in 429 CHC patients including 141 hemophilic, 84 thalassemic, and 204 non-hemophilic, non-thalassemic patients. Results The hepatitis C virus subtype 1a was the most common subtype in the study population. Core aa substitution Arg70Gln was strongly associated with cirrhosis (OR = 2.49; 95% CI = 1.13 - 5.50; P = 0.020). Core aa 70 substitutions were more frequently observed in patients with the HCV subtype 1b than in patients with any other HCV subtypes (P < 0.001). Core aa 70 substitutions were also more common in patients with the rs12979860 TT genotype than in patients with non-TT genotypes (17.3% vs. 8.5%, P = 0.022) and also in rs8099917 non-TT genotypes than in the TT genotype (14.0% vs. 7.0%, P = 0.026). The HCV genotypes and rs8099917 polymorphisms were correlated in which HCV subtype 1b was in favor of rs8099917 GG and HCV subtype 3a favored rs8099917 TT (P = 0.021). Furthermore, the rs12979860 TT and rs8099917 GG genotypes showed significantly lower HCV RNA levels than the other genotypes (P < 0.001). Conclusions There is an as yet unexplained association between HCV and host parameters with unknown mechanisms in patients with chronic HCV infection. The assessments of core aa 70 substitution and polymorphisms near the IFNL3 gene could offer promising steps to improve the management of patients with HCV. PMID:27630727

  14. Re-designing Orem's Self-care Theory for Patients with Chronic Hepatitis

    PubMed Central

    Hasanpour-Dehkordi, Ali; Mohammadi, Nooredin; Nikbakht-Nasrabadi, Alireza

    2016-01-01

    Background: Hepatitis is an inflammatory disease which has many adverse effects on patients’ life because of its chronic nature. Since Orem's theory of self-care is a grounded theory, the concepts and applications of this theory in patients with chronic hepatitis who have special needs may lead to some challenges. The purpose of this study was to explore self-care in patients with chronic hepatitis. Methods/Design: A directed content analysis was used in this qualitative study. Participants were recruited from a metropolitan area. Data were collected through semi-structured interviews. The verbatim transcripts of the participants’ interviews were analyzed according to directed content analysis. Results: In this study, four themes, suggested by Orem, were drawn from the data according to directed content analysis. The codes generated from the data were classified into concepts and then the concepts were assigned into these four themes. These themes were needs in the matrix of time and place, self-care agency, need for change in self-care and consequences of hepatitis. Conclusion: The use of Orem's self-care theory cannot meet the need for self-care in hepatitis patients because these patients have vital sexual, respect and belonging, physical, economical, and psychological-behavioral needs, and lack adequate knowledge about self-care. Consequently, the specific self-care model developed in this study helps health professionals identify self-care activities in patients with chronic hepatitis. PMID:27803560

  15. Involvement of MAP3K8 and miR-17-5p in Poor Virologic Response to Interferon-Based Combination Therapy for Chronic Hepatitis C

    PubMed Central

    Tsubota, Akihito; Mogushi, Kaoru; Aizaki, Hideki; Miyaguchi, Ken; Nagatsuma, Keisuke; Matsudaira, Hiroshi; Kushida, Tatsuya; Furihata, Tomomi; Tanaka, Hiroshi; Matsuura, Tomokazu

    2014-01-01

    Despite advances in chronic hepatitis C treatment, a proportion of patients respond poorly to treatment. This study aimed to explore hepatic mRNA and microRNA signatures involved in hepatitis C treatment resistance. Global hepatic mRNA and microRNA expression profiles were compared using microarray data between treatment responses. Quantitative real-time polymerase chain reaction validated the gene signatures from 130 patients who were infected with hepatitis C virus genotype 1b and treated with pegylated interferon-alpha and ribavirin combination therapy. The correlation between mRNA and microRNA was evaluated using in silico analysis and in vitro siRNA and microRNA inhibition/overexpression experiments. Multivariate regression analysis identified that the independent variables IL28B SNP rs8099917, hsa-miR-122-5p, hsa-miR-17-5p, and MAP3K8 were significantly associated with a poor virologic response. MAP3K8 and miR-17-5p expression were inversely correlated with treatment response. Furthermore, miR-17-5p repressed HCV production by targeting MAP3K8. Collectively, the data suggest that several molecules and the inverse correlation between mRNA and microRNA contributed to a host genetic refractory hepatitis C treatment response. PMID:24819603

  16. Hepatic necroinflammation and severe liver fibrosis in patients with chronic hepatitis B with undetectable HBV DNA and persistently normal alanine aminotransferase.

    PubMed

    Alam, M M; Mahtab, M A; Akbar, S M F; Kamal, M; Rahman, S

    2014-12-01

    Both consensus and controversy remains regarding surrogacy of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and alanine aminotransferase (ALT), however, these markers are used to ascertain the extent of liver damages and to guide therapeutic options in patients with chronic hepatitis B. However, little is known about liver histology of patients with chronic hepatitis B with undetectable HBV DNA and persistently normal ALT. Thirty-five incidentally-detected patients with chronic HBV infection (assessed by expression of hepatitis B surface antigen for more than 6 months) with undetectable HBV DNA and normal serum ALT were enrolled in this study. Liver biopsy specimens were taken from all patients and the extent of hepatic necroinflammation and liver fibrosis were evaluated. Moderate degree of hepatic necroinflammation was detected in 2 of 35 patients and severe hepatic fibrosis was seen in 6 of 35 patients. Two patients with undetectable HBV DNA and sustained normal ALT had moderate hepatic necroinflammation and severe hepatic fibrosis. In spite of undetectable HBV DNA for prolonged period and persistently normal ALT, some patients with chronic hepatitis B express evidences of progressive liver diseases. Large scale studies in different races and geographical regions should be accomplished to develop insights about management of these patients. Studies about extent of liver diseases in these patients should be accomplished in Treatment recommendation and management strategies should be developed for these patients. PMID:26402972

  17. Incidence, risk factors, and outcome of chronic rejection during antiviral therapy for posttransplant recurrent hepatitis C.

    PubMed

    Fernández, Inmaculada; Ulloa, Esperanza; Colina, Francisco; Abradelo, Manuel; Jiménez, Carlos; Gimeno, Alberto; Meneu, Juan Carlos; Lumbreras, Carlos; Solís-Herruzo, José Antonio; Moreno, Enrique

    2009-08-01

    Antiviral therapy for recurrent hepatitis C in liver transplantation has been associated with the development of chronic rejection. The aim of this study was to assess the incidence, evolution, and risk factors associated with the development of chronic rejection during posttransplant hepatitis C virus antiviral therapy. Seventy-nine patients with posttransplant recurrent hepatitis C who were treated with pegylated interferon and ribavirin were prospectively followed. Liver biopsy was performed before antiviral therapy was initiated and when liver tests worsened during therapy. Pretransplant and posttransplant factors were analyzed as potential risk factors for the development of chronic rejection. Seven of 79 patients (9%) developed chronic rejection during antiviral therapy. The mean time from the start of treatment to the development of chronic rejection was 5.8 months (3-12 months). An analysis of factors associated with the development of chronic rejection showed that the use of cyclosporine as immunosuppression therapy (6 of 19 patients who received cyclosporine developed chronic rejection in comparison with only 1 of 57 patients who received tacrolimus; P = 0.0013), achievement of sustained virological response (P = 0.043), and ribavirin discontinuation (P = 0.027) were associated with the development of chronic rejection. In conclusion, the development of chronic rejection during posttransplant pegylated interferon and ribavirin therapy is a severe complication. The use of cyclosporine, ribavirin discontinuation, and viral infection elimination seem to be associated with the development of this complication. Liver Transpl 15:948-955, 2009. (c) 2009 AASLD.

  18. Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment.

    PubMed

    Kim, Jun Hyung; Kim, Mi Na; Han, Kwang-Hyub; Kim, Seung Up

    2015-04-01

    Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases (CLD) is crucial, as liver fibrosis is important in determining the prognosis of liver diseases. Currently, liver biopsy (LB) is considered the gold standard for staging liver fibrosis or cirrhosis. However, utilization of LB in clinical practice is often limited because of its invasive nature, sampling error and interobserver variability. Recently, transient elastography (TE) was introduced as a noninvasive, highly reproducible technique for assessing the degree of liver fibrosis. After extensive studies, TE is now regarded as a reliable surrogate marker for grading the severity of liver fibrosis in patients with CLD. In the past few years, the role of TE in monitoring liver stiffness and determining prognosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who are undergoing antiviral treatment has been investigated. In patients with CHB, liver stiffness values decrease with antiviral treatment. TE can also be used to predict the incidence of liver-related events during antiviral treatment. In patients with CHC, TE can be used to monitor potential regression of liver fibrosis after antiviral treatment and may predict the treatment outcome of CHC. In addition, TE is an adjunct tool for distinguishing inactive hepatitis B virus carriers from patients with chronic active hepatitis. This review article discusses the important findings from recent studies focusing on the clinical application of TE in patients with chronic viral hepatitis who are undergoing antiviral treatments. PMID:24976523

  19. Chronic hepatitis B in 2014: Great therapeutic progress, large diagnostic deficit

    PubMed Central

    Niederau, Claus

    2014-01-01

    This review analyzes progress and limitations of diagnosis, screening, and therapy of patients with chronic hepatitis B infection. A literature review was carried out by framing the study questions. Vaccination in early childhood has been introduced in most countries and reduces the infection rate. Treatment of chronic hepatitis B can control viral replication in most patients today. It reduces risks for progression and may reverse liver fibrosis. The treatment effect on development of hepatocellular carcinoma is less pronounced when cirrhosis is already present. Despite the success of vaccination and therapy chronic hepatitis B remains a problem since many infected patients do not know of their disease. Although all guidelines recommend screening in high risk groups such as migrants, these suggestions have not been implemented. In addition, the performance of hepatocellular cancer surveillance under real-life conditions is poor. The majority of people with chronic hepatitis B live in resource-constrained settings where effective drugs are not available. Despite the success of vaccination and therapy chronic hepatitis B infection remains a major problem since many patients do not know of their disease. The problems in diagnosis and screening may be overcome by raising awareness, promoting partnerships, and mobilizing resources. PMID:25206267

  20. Fanconi syndrome and chronic renal failure in a chronic hepatitis B monoinfected patient treated with tenofovir.

    PubMed

    Magalhães-Costa, Pedro; Matos, Leopoldo; Barreiro, Pedro; Chagas, Cristina

    2015-07-01

    Tenofovir disoproxil fumarate (TDF) is one of the first-line treatment options in chronic hepatitis B (CHB). Despite its efficacy in suppressing viral load and a high resistance barrier, long life maintenance therapy is required. Registration studies demonstrated TDF to be a safe drug. However, post-marketing experience reported cases of serious nephrotoxicity associated with hypophosphatemia, osteomalacia and, even more recently, Fanconi syndrome associated with TDF therapy in CHB monoinfected patients.Here the authors report a case of a 40 year-old male, with a CHB monoinfection, that, three years after TDF therapy, developed a progressive chronic kidney disease with a serious hypophosphatemia and a secondary osteomalacia that was manifested by bone pain and multiple bone fractures. Further investigational analyses unveiled a proximal renal tubular dysfunction, which fulfilled most of the diagnostic criteria for a Fanconi syndrome. After TDF withdrawal and oral supplementation with phosphate and calcitriol, his renal function stabilized (despite not returning to normal), proximal renal tubular dysfunction abnormalities resolved as well as osteomalacia. In conclusion, physicians should be aware that, in CHB monoinfected patients under TDF therapy, serious renal damage is possible and preventable by timely monitoring serum creatinine and phosphate. PMID:26228957

  1. Seed Sequence-Matched Controls Reveal Limitations of Small Interfering RNA Knockdown in Functional and Structural Studies of Hepatitis C Virus NS5A-MOBKL1B Interaction

    PubMed Central

    Chung, Hyo-Young; Gu, Meigang; Buehler, Eugen; MacDonald, Margaret R.

    2014-01-01

    ABSTRACT Hepatitis C virus (HCV) is a widespread human pathogen causing liver cirrhosis and cancer. Similar to the case for other viruses, HCV depends on host and viral factors to complete its life cycle. We used proteomic and yeast two-hybrid approaches to elucidate host factors involved in HCV nonstructural protein NS5A function and found that MOBKL1B interacts with NS5A. Initial experiments with small interfering RNA (siRNA) knockdown suggesting a role in HCV replication led us to examine the interaction using biochemical and structural approaches. As revealed by a cocrystal structure of a core MOBKL1B-NS5A peptide complex at 1.95 Å, NS5A binds to a hydrophobic patch on the MOBKL1B surface. Biosensor binding assays identified a highly conserved, 18-amino-acid binding site in domain II of NS5A, which encompasses residues implicated in cyclophilin A (CypA)-dependent HCV RNA replication. However, a CypA-independent HCV variant had reduced replication in MOBKL1B knockdown cells, even though its NS5A does not interact with MOBKL1B. These discordant results prompted more extensive studies of MOBKL1B gene knockdowns, which included additional siRNAs and specifically matched seed sequence siRNA controls. We found that reduced virus replication after treating cells with MOBKL1B siRNA was actually due to off-target inhibition, which indicated that the initial finding of virus replication dependence on the MOBKL1B-NS5A interaction was incorrect. Ultimately, using several approaches, we found no relationship of the MOBKL1B-NS5A interaction to virus replication. These findings collectively serve as a reminder to investigators and scientific reviewers of the pervasive impact of siRNA off-target effects on interpretation of biological data. IMPORTANCE Our study illustrates an underappreciated shortcoming of siRNA gene knockdown technology. We initially identified a cellular protein, MOBKL1B, as a binding partner with the NS5A protein of hepatitis C virus (HCV). MOBKL1B si

  2. [CHARACTERISTIC OF ALTERATIONS OF ARTERIES IN PATIENTS WITH ISCHEMIC HEART DISEASE AND CHRONIC HEPATITIS C].

    PubMed

    Guliaev, N I; Kuznetsov, V V; Poltareĭko, D S; Qleksiuk, I B; Gordienko, A V; Barsukov, A V

    2015-01-01

    The article presents an assessment of degree and type of atherosclerosis of coronary and non-coronary vessels in old patients with ischemic heart disease associated with chronic viral hepatitis C (VHC), the incidence of myocardial infarction and the possibility of participation chronic VHC in atherogenesis. Patients with ischemic heart disease have correlation of atherosclerosis of arteries with age, hypercholesterinemia. Patients without chronic VHC more often give a higher risk of myocardial infarction, especially in early period (1-1,5 years) of onset of ischemic heart disease clinical implications. Patients with ischemic heart disease associated with chronic viral hepatitis C more often have generalized alterations in vessels, multifocal type of alteration. So, participation of VHC in atherogenesis is most probably connected with maintenance of chronic immune inflammation in vascular endothelium.

  3. Changes of Some Hormones Levels in Patients With Hepatitis B Virus-Related Chronic Liver Disease

    PubMed Central

    Serin, Ayfer; Akarsu, Mesut; Akpinar, Hale; Simsek, Ilkay

    2013-01-01

    Background The purpose of the study was to evaluate some of the hormones in patients with chronic liver disease and cirrhosis. Methods The men patients with chronic hepatitis B (Group 1), liver cirrhosis secondary to hepatitis B (Group 2), were included in this study. Additionally, a control group of healthy volunteers (Group 3) was formed. We investigated serum levels of Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Total testosterone (T. TES), Free-testosterone (F. TES), Estradiol (E2), Androstenedione (ANDR), Dihydroepiandrosterone (DHEA), Progesterone (PPOGES), Prolactin (PRL), Sex hormone binding protein (SHGB) were measured by radioimmunoassay and chemiluminescent immunoassay methods. Result A total of 73 patients with chronic liver disease and cirrhosis were included in the study. Patients were grouped as cirrhosis (n = 28), chronic hepatitis B (n = 41) according to the type of their chronic liver disease. Serum F.TEST level in patient groups (group 1, group 2) was found to be lower than control group (P = 0.045, P = 0.047). Serum LH value was found to be higher in patient group (group 2) than control group (P = 0.048). Serum estradiol was higher in the group 2 compared to the control group (P = 0.046). Conclusions The described disturbances of some of the observed hormones (LH, E2, F. TES) are complex, particularly in their relationship by which the clinical picture of the hepatitis B related cirrhotic patients and chronic liver disease can be explained.

  4. [The frequency of the e-antigen in acute and chronic hepatitis (author's transl)].

    PubMed

    Fay, O H; Tanno, H; Roncoroni, M; Findor, J; Igartua, E B; Domecq, R

    1975-08-01

    Five groups of patients were studied: (a) 88 HBsAg-positive cases of acute viral hepatitis (AVH) who completely cured within 90 days; (b) 75 cases of acute HBsAg-negative hepatitis with early resolution; (c) 15 AVH patients who became chronic; (d) 94 HBsAg-positive cases of chronic hepatitis (CH) and liver cirrhosis; (e) HBsAg-negative cases with CH. The e-antigen was investigated in every patient and was found in 9 of the AVH cases with favorable evolution, and in 8 of the AVH patients evolving to chronicity. Amont the CH and cirrhosis group, 48 of the HBsAg carriers were positive while e-antigen could not be detected in any of the HBsAg-negative ones. The high incidence of e-antigen carriers among patients with chronic hepatitis and liver cirrhosis as well as among those with AVH who later entered the chronic stage of the disease, deserves especial consideration. A possible role of e-antigen in the evolution to chronicity and a prognostic significance is suggested.

  5. Influence of Hepatic Inflammation on FibroScan Findings in Diagnosing Fibrosis in Patients with Chronic Hepatitis B.

    PubMed

    Zeng, Xianghua; Xu, Cheng; He, Dengming; Zhang, Huiyan; Xia, Jie; Shi, Dairong; Kong, Lingjun; He, Xiaoqin; Wang, Yuming

    2015-06-01

    Hepatic inflammation may affect the performance of FibroScan. This prospective study investigated the influence of hepatic inflammation on liver stiffness measurement (LSM) values by assessing FibroScan and liver biopsy findings in 325 patients with chronic hepatitis B. Liver fibrosis and inflammation were classified into five stages (S0-S4) and grades (G0-G4) according to the Scheuer scoring system. LSM values were correlated with fibrosis stage and inflammation grade (r = 0.479, p < 0.001, and r = 0.522, p < 0.001, respectively). Although LSM values increased in parallel with inflammation grade, no significant differences were found between patients with significant fibrosis (S2-S4) (p > 0.05). For inflammation grades G0, G1, G2 and G3, areas under receiver operating characteristic curves of FibroScan for significant fibrosis were 0.8267 (p < 0.001), 0.6956 (p < 0.001), 0.709 (p = 0.0012) and 0.6947 (p = 0.137), respectively. Inflammation has a significant influence on LSM values in patients with chronic hepatitis B with mild fibrosis, but not in those with significant fibrosis.

  6. Pioneering a Global Cure for Chronic Hepatitis C Virus Infection.

    PubMed

    Vilarinho, Silvia; Lifton, Richard P

    2016-09-22

    This year's Lasker∼Debakey Clinical Medical Research Award honors Ralf Bartenschlager, Charles Rice, and Michael Sofia, pioneers in the development of curative and safe therapies for the 170 million people with hepatitis C virus infection. PMID:27634325

  7. Abbott RealTime PCR assay is useful for evaluating virological response to antiviral treatment for chronic hepatitis C.

    PubMed

    Ikezaki, Hiroaki; Furusyo, Norihiro; Ihara, Takeshi; Hayashi, Takeo; Ogawa, Eiichi; Toyoda, Kazuhiro; Taniai, Hiroaki; Kainuma, Mosaburo; Murata, Masayuki; Hayashi, Jun

    2011-12-01

    This study was done to evaluate the utility of the Abbott RealTime PCR assay (ART) for the monitoring of chronic hepatitis C patients. The serum samples of 183 patients infected with hepatitis C virus (HCV) genotype 1b who had completed a 48-week period of pegylated interferon (PEG-IFN) alpha-2b plus ribavirin treatment were prospectively analyzed. Serum HCV RNA levels were measured both by ART and by the Roche COBAS Amplicor Monitor test, version2.0 (CAM) at baseline and at weeks 4, 12, 24, 36, and 48 of treatment, and at 24 weeks after the end of treatment (EOT). A significant positive correlation of pretreatment HCV RNA levels was found between ART and CAM (r = 0.595, P < 0.0001). Of the 183 patients, 66 (36.0%) achieved a sustained virological response (SVR). The logarithmic decline of the HCV RNA level from the pretreatment level determined by ART in SVR patients was significantly higher than that in non-SVR patients at all time points tested. The logarithmic decline determined by CAM in SVR patients was significantly higher than that in non-SVR patients only at week 4, but there was no significant difference at other weeks. Of 124 patients who were HCV RNA-negative at EOT by ART, 58 (46.8%) had a relapse of viremia at 24 weeks after EOT, whereas 77 of 143 patients (53.8%) who were HCV RNA-negative at EOT by CAM had a relapse. The relapse rate was lower when determined by ART than by CAM, but not significantly so. ART is more useful than CAM for evaluating the virological response to antiviral treatment for chronic hepatitis C. PMID:21528383

  8. Diurnal variation in 5-HT1B autoreceptor function in the anterior hypothalamus in vivo: effect of chronic antidepressant drug treatment

    PubMed Central

    Sayer, Tamsin J O; Hannon, Serina D; Redfern, Peter H; Martin, Keith F

    1999-01-01

    Intracerebral microdialysis was used to examine the function of the terminal 5-hydroxytryptamine (5-HT) autoreceptor in the anterior hypothalamus of anaesthetized rats at two points in the light phase of the light–dark cycle.Infusion of the 5-HT1A/1B agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU24969) 0.1, 1.0 and 10 μM through the microdialysis probe led to a concentration-dependent decrease (49, 56 and 65% respectively) in 5-HT output. The effect of RU24969 (1 and 5 μM) was prevented by concurrent infusion of methiothepin (1 and 10 μM) into the anterior hypothalamus via the microdialysis probe. Infusion of methiothepin alone (1.0 and 10 μM) increased (15 and 142% respectively) 5-HT output.Infusion of RU24969 (5 μM) through the probe at mid-light and end-light resulted in a quantitatively greater decrease in 5-HT output at end-light compared with mid-light.Following treatment with either paroxetine hydrochloride (10 mg kg−1 i.p.) or desipramine hydrochloride (10 mg kg−1 i.p.) for 21 days the function of the terminal 5-HT1B autoreceptor was more markedly attenuated at end-light.The data show that, as defined by the response to RU24969, the function of the 5-HT1B receptors that control 5-HT output in the anterior hypothalamus is attenuated following chronic desipramine or paroxetine treatment in a time-of-day-dependent manner. PMID:10372820

  9. Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee.

    PubMed Central

    Govindarajan, S.; Fields, H. A.; Humphrey, C. D.; Margolis, H. S.

    1986-01-01

    A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:3511726

  10. Polymorphisms of interleukin-1R receptor antagonist genes in patients with chronic hepatitis B in Iran

    PubMed Central

    Ranjbar, Mitra; Alizadeh, Amir Houshang Mohammad; Hajilooi, Mehrdad; Mousavi, Seyed Mohsen

    2006-01-01

    AIM: To investigate the relationships between polymorphisms of interleukin-1R receptor antagonist genes and susceptibility to chronic hepatitis B in Iran population. METHODS: Genomic DNA was extracted from the peripheral blood of 80 patients with chronic hepatitis B (57 males, 23 females) aged 12-77 years (mean 36.1 ± 13.8 years) and 147 normal controls (96 males, 51 females) aged 6-75 years (mean 41 ± 18.7 years) who referred to a liver clinic of Tehran and then subjected to polymerase chain reaction (PCR) amplification. PCR products were resolved on a 3% agarose gel and stained with ethidium bromide. RESULTS: Only three of the five kinds of polymorphism (2/2, 2/4, and 4/4) were found in this study. The frequencies of 2/2, 2/4, and 4/4 were 12.5%, 17.5%, 70% respectively in chronic hepatitis B patients and 6.8%, 24.5%, and 68.7% respectively in controls. IL-1 R allele 2 was detected in 30% of chronic hepatitis B patients and in 31.3% of controls, while IL-1 R allele 4 was detected in 87.5% of chronic hepatitis B patients and in 93.2% of controls. The frequency of IL-1R alleles 2 and 4 was detected in 21.25% and 78.75% of the patients and 19.04% and 80.96% of the controls, respectively. CONCLUSION: Our results suggest that the carriage of IL-1R receptor antagonist alleles 2, 4, 6 may not play any role in the development of HBV infection. Large population-based studies are needed to investigate the role of IL-1 polymorphisms in the pathogenesis of developing chronic hepatitis B. PMID:16937503

  11. Treatment of Chronic Viral Hepatitis in Woodchucks by Prolonged Intrahepatic Expression of Interleukin-12▿

    PubMed Central

    Crettaz, Julien; Otano, Itziar; Ochoa, Laura; Benito, Alberto; Paneda, Astrid; Aurrekoetxea, Igor; Berraondo, Pedro; Rodríguez-Madoz, Juan Roberto; Astudillo, Aurora; Kreppel, Florian; Kochanek, Stefan; Ruiz, Juan; Menne, Stephan; Prieto, Jesus; Gonzalez-Aseguinolaza, Gloria

    2009-01-01

    Chronic hepatitis B is a major cause of liver-related death worldwide. Interleukin-12 (IL-12) induction accompanies viral clearance in chronic hepatitis B virus infection. Here, we tested the therapeutic potential of IL-12 gene therapy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), an infection that closely resembles chronic hepatitis B. The woodchucks were treated by intrahepatic injection of a helper-dependent adenoviral vector encoding IL-12 under the control of a liver-specific RU486-responsive promoter. All woodchucks with viral loads below 1010 viral genomes (vg)/ml showed a marked and sustained reduction of viremia that was accompanied by a reduction in hepatic WHV DNA, a loss of e antigen and surface antigen, and improved liver histology. In contrast, none of the woodchucks with higher viremia levels responded to therapy. The antiviral effect was associated with the induction of T-cell immunity against viral antigens and a reduction of hepatic expression of Foxp3 in the responsive animals. Studies were performed in vitro to elucidate the resistance to therapy in highly viremic woodchucks. These studies showed that lymphocytes from healthy woodchucks or from animals with low viremia levels produced gamma interferon (IFN-γ) upon IL-12 stimulation, while lymphocytes from woodchucks with high viremia failed to upregulate IFN-γ in response to IL-12. In conclusion, IL-12-based gene therapy is an efficient approach to treat chronic hepadnavirus infection in woodchucks with viral loads below 1010 vg/ml. Interestingly, this therapy is able to break immunological tolerance to viral antigens in chronic WHV carriers. PMID:19116251

  12. Acute and chronic effect of ethanol on hepatic albumin synthesis in rat liver in vitro

    SciTech Connect

    Ohtake, H.; Kato, S.; Murawaki, Y.; Kishimoto, Y.; Wakushima, T.; Hirayama, C.

    1986-08-01

    To study the effects of ethanol and its metabolite on albumin metabolism, we examined the hepatic albumin synthesis and secretion in male Wistar rats in vitro, following acute and chronic ethanol administration. After acute ethanol administration, proalbumin synthesis in rat liver in vitro, declined to 47% of the control level at 4 hrs, the lowest level, and increased thereafter to slightly higher than the control level at 16 hrs. On the other hand, chronic ethanol administration for 4 weeks, increased proalbumin synthesis to 1.5 times that of the control level. In the acute ethanol group, a significant negative correlation was observed between proalbumin radioactivity and the concentration of hepatic ethanol and acetaldehyde. The variation between proalbumin radioactivity and hepatic ethanol concentration was wider than the variation between proalbumin and hepatic acetaldehyde. In the chronic ethanol group, ethanol was not detected in the liver. No significant differences from the proalbumin/albumin ratio were seen at any time point after acute or chronic ethanol administration. These findings suggest that the effects of ethanol on hepatic albumin synthesis differ with the method of ethanol administration, and acetaldehyde and/or ethanol is involved in the reduction in albumin synthesis, however, proalbumin-albumin conversion is not disturbed.

  13. Prevalence and severity of depression in chronic viral hepatitis in Iran

    PubMed Central

    Mirabdolhagh Hazaveh, Mojgan; Dormohammadi Toosi, Taraneh; Nasiri Toosi, Mohsen; Tavakoli, Amir; Shahbazi, Fatemeh

    2015-01-01

    Aim: The aim of this study was to compare the prevalence and severity of depression in chronic hepatitis B (CHB) patients, chronic hepatitis C (CHC) patients, and healthy participants. Methods: Two hundred and fifty-three persons participated in this cross-sectional study between 2011 and 2012 in Imam Khomeini Hospital. The prevalence and severity of depression were assessed using the Hamilton Scale. Results: There was significantly higher prevalence of depression in CHC patients (35.9%) than in healthy participants (11.3%) and CHB patients (19.8%) (both P < 0.01). However, CHB and CHC patients did not differ significantly in their depression prevalence after excluding inactive hepatitis B surface antigen (HBsAg) carriers (29.3% vs. 35.9%; P > 0.05). Inactive HBsAg carriers differed significantly from CHB patients—excluding inactive HBsAg carriers—in depression prevalence (10.0% vs. 29.3%; P < 0.05). No statistically significant difference was found in depression severity between all groups (P > 0.05). Conclusion: Depression screening in chronic hepatitis B and chronic hepatitis C patients may be beneficial in disease management. PMID:25663386

  14. Chronic hepatitis C virus infections in brazilian patients: association with genotypes, clinical parameters and response to long term alpha interferon therapy

    PubMed

    Bassit; Da Silva LC; Ribeiro-Dos-Santos; Maertens; Carrilho; Fonseca; Alves; Gayotto; Pereira; Takei; Chamone; Saez-Alquezar

    1999-05-01

    The present study assessed the clinical significance of hepatitis C virus (HCV) genotypes and their influence on response to long term recombinant-interferon-alpha (r-IFN-alpha) therapy in Brazilian patients. One hundred and thirty samples from patients previously genotyped for the HCV and with histologically confirmed chronic hepatitis C (CH-C) were evaluated for clinical and epidemiological parameters (sex, age, time of HCV infection and transmission routes). No difference in disease activity, sex, age or mode and time of transmission were seen among patients infected with HCV types 1, 2 or 3. One hundred and thirteen of them were treated with 3 million units of r-IFN-alpha, 3 times a week for 12 months. Initial response (IR) was significantly better in patients with genotype 2 (100%) and 3 (46%) infections than in patients with genotype 1 (29%) (p < 0. 005). Among subtypes, difference in IR was observed between 1b and 2 (p < 0.005), and between 1b and 3a (p < 0.05). Sustained response (SR) was observed in 12% for (sub)type 1a, 13% for 1b, 19% for 3a, and 40% for type 2; significant differences were found between 1b and 2 (p < 0.001), and between 1b and 3a (p < 0.05). Moreover, presence of cirrhosis was significantly associated with non response and response with relapse (p < 0.05). In conclusion, non-1 HCV genotype and lack of histological diagnosis of cirrhosis were the only baseline features associated with sustained response to treatment. These data indicate that HCV genotyping may have prognostic relevance in the responsiveness to r-IFN-alpha therapy in Brazilian patients with chronic HCV infection, as seen in other reports worldwide. PMID:10529839

  15. Protracted anaphylaxis developed after peginterferon α-2a administration for chronic hepatitis C

    PubMed Central

    Sakatani, Akihiko; Doi, Yoshinori; Matsuda, Takaaki; Sasai, Yasutaka; Nishida, Naohiro; Sakamoto, Megumi; Uenoyama, Naoto; Matsumoto, Yoshiya; Kinoshita, Kazuo

    2015-01-01

    Peginterferon is a key drug used to treat chronic viral hepatitis that is known for causing various side effects. Side effects occurring immediately after administration include headache, nausea, and influenza-like symptoms, such as fever and joint pain. However, reports of anaphylactic shock are extremely rare. Here we report a patient with protracted anaphylaxis who suffered shock symptoms after peginterferon α-2a administration for chronic hepatitis C. Although the patient improved temporarily with shock treatment, symptoms of anaphylaxis recurred. As peginterferon is often administered on an outpatient basis, it is important to recognize life-threatening side effects that may develop in a protracted manner. PMID:25759556

  16. Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss

    PubMed Central

    Clugston, Robin D.; Huang, Li-Shin; Blaner, William S.

    2015-01-01

    The alcohol-induced depletion of hepatic retinoid stores correlates with the progression of liver injury; however, the mechanisms underlying alcohol’s effects have not been fully elucidated. Our goal was to gain a mechanistic understanding of alcohol-induced hepatic retinoid depletion. Wild-type and mutant mice were continuously fed alcohol through Lieber-DeCarli liquid diets, with matched control animals pair fed an isocaloric alcohol-free diet to ensure equal nutrient and calorie intake between groups. A systematic analysis of tissue retinol and retinyl ester levels was performed with HPLC, complemented by gene and protein expression analyses. Our results delineated 2 phases of alcohol-induced depletion of hepatic retinoid. Initially, ∼15% of hepatic retinoid content was mobilized from the liver, causing extrahepatic tissue retinoid levels to increase. Subsequently, there was a precipitous drop in hepatic retinoid content (>60%), without further retinoid accumulation in the periphery. Follow-up studies in mutant mice revealed roles for RBP, CRBP1, and CD36 in retinoid mobilization and extrahepatic retinoid uptake, as well as a role for CYP2E1 in the catabolism of hepatic retinoid. In summary, alcohol has a biphasic effect on hepatic retinoid stores, characterized by an initial phase of rapid mobilization to extrahepatic tissues followed by extensive catabolism within the liver.—Clugston, R. D., Huang, L.-S., Blaner, W. S. Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss. PMID:25985802

  17. Hepatitis B Virus Genotype Distribution and Genotype-Specific BCP/preCore Substitutions in Acute and Chronic Infections in Argentina

    PubMed Central

    González López Ledesma, María Mora; Mojsiejczuk, Laura Noelia; Rodrigo, Belén; Sevic, Ina; Mammana, Lilia; Galdame, Omar; Gadano, Adrian; Fainboim, Hugo; Campos, Rodolfo; Flichman, Diego

    2015-01-01

    Aim In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections). Results Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896. Discussion HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying

  18. Neutralizing antibodies in patients with chronic hepatitis C and correlation to liver cirrhosis and estimated duration of infection.

    PubMed

    Pedersen, Jannie; Lundbo, Lene Fogt; Krarup, Henrik; Bukh, Jens; Weis, Nina

    2016-10-01

    Although chronic hepatitis C virus (HCV) infection accounts for 30% of individuals with cirrhotic livers worldwide, factors influencing disease progression are far from elucidated. The aim of this study was to determine whether the level of neutralizing antibodies (NAbs) correlated with the development of cirrhosis in patients with chronic HCV infection, genotype 1, when adjusting for estimated duration of infection. Thirty-nine patients with chronic hepatitis C, with either no/mild fibrosis (n = 23) or cirrhosis (n = 16), were enrolled from two university hospitals in Denmark. Duration of HCV infection was estimated based on patient information and/or anti-HCV seroconversion. Serial dilutions of purified serum/plasma derived IgGs were tested for their ability to neutralize six HCV-genotype 1 cell-culture strains. The results were expressed as the lowest IgG concentration yielding ≥50% neutralization (NAb50 -titer). A significant difference in HCV NAb50 -titers among the six genotype 1a/1b recombinants was found. In patients with cirrhosis, a tendency for higher level of NAbs was observed compared to patients with no/mild fibrosis, although not statistical significant. Stratifying the two groups revealed that being infected >25 years resulted in higher levels of NAbs in both. Furthermore, by correlating estimated duration of HCV infection to NAb50 -titers a significant result was found against two recombinants. The NAb titer does not differ significantly between HCV patients with either no/mild fibrosis or cirrhosis but show a tendency for increasing level with increased duration of infection. NAbs might contribute as a biological marker to increase the accuracy of patient based information on duration of HCV infection. J. Med. Virol. 88:1791-1803, 2016. © 2016 Wiley Periodicals, Inc.

  19. Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis

    SciTech Connect

    D'Arienzo, A.; Celentano, L.; Scuotto, A.; Di Siervi, P.; Lombardi, V.; Squame, G.; Mazzacca, G.

    1988-07-01

    In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function tests were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.

  20. The effect of standard therapy on mean platelet volume in patients with chronic hepatitis C

    PubMed Central

    Uslu, Ali Ugur; Aydin, Bahattin; Balta, Sevket; Yonem, Ozlem; Uncu, Tunahan; Seven, Dogan

    2016-01-01

    Introduction Chronic hepatitis C (CHC) infection is a systemic disorder that can lead to liver inflammation, fibrosis, cirrhosis, and hepatocellular cancer. The mean platelet volume (MPV) is widely used as an inflammatory marker to evaluate the platelet function and the status of systemic inflammation. Aim To determine the pre- and post-treatment MPV values in CHC patients who were administered a 48-week antiviral therapy based on systemic inflammation. Material and methods We enrolled 28 patients, diagnosed with CHC genotype 1b, who received a 48-week antiviral therapy and attended regular follow-up, and 28 healthy individuals. In diagnosing CHC, a positive anti-HCV for a minimum duration of 6 months and a positive serum HCV RNA were accepted as the criteria. The patients were assigned to one of two groups based on their group 1 (pre-treatment values) and group 2 (post-treatment values) after 3 months therapy. We analysed and compared the blood samples of all of the groups. Results The MPV value was 8.89 ±1.20 in group 1 and 8.00 ±1.07 in group 2, and 8.21 ±1.18 in the control group. The value in group 1 was detected to be statistically significantly different from that in group 2 and the control group (p < 0.0001, p = 0.045, respectively). No statistically significant difference was observed between group 2 and the control group (p = 0.455). Conclusions The results of this study suggest that MPV could represent an inexpensive marker for use in assessing low-grade inflammation in patients with CHC.

  1. Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience

    PubMed Central

    CLEO Study Group; Ascione, Antonio; Adinolfi, Luigi Elio; Amoroso, Pietro; Andriulli, Angelo; Armignacco, Orlando; Ascione, Tiziana; Babudieri, Sergio; Barbarini, Giorgio; Brogna, Michele; Cesario, Francesco; Citro, Vincenzo; Claar, Ernesto; Cozzolongo, Raffaele; D’Adamo, Giuseppe; D’Amico, Emilio; Dattolo, Pellegrino; De Luca, Massimo; De Maria, Vincenzo; De Siena, Massimo; De Vita, Giuseppe; Di Giacomo, Antonio; De Marco, Rosanna; De Stefano, Giorgio; De Stefano, Giulio; Di Salvo, Sebastiano; Di Sarno, Raffaele; Farella, Nunzia; Felicioni, Laura; Fimiani, Basilio; Fontanella, Luca; Foti, Giuseppe; Furlan, Caterina; Giancotti, Francesca; Giolitto, Giancarlo; Gravina, Tiziana; Guerrera, Barbara; Gulminetti, Roberto; Iacobellis, Angelo; Imparato, Michele; Iodice, Angelo; Iovinella, Vincenzo; Izzi, Antonio; Liberti, Alfonso; Leo, Pietro; Lettieri, Gennaro; Luppino, Ileana; Marrone, Aldo; Mazzoni, Ettore; Messina, Vincenzo; Monarca, Roberto; Narciso, Vincenzo; Nosotti, Lorenzo; Pellicelli, Adriano Maria; Perrella, Alessandro; Piai, Guido; Picardi, Antonio; Pierri, Paola; Pietromatera, Grazia; Resta, Francesco; Rinaldi, Luca; Romano, Mario; Rossini, Angelo; Russello, Maurizio; Russo, Grazia; Sacco, Rodolfo; Sangiovanni, Vincenzo; Schiano, Antonio; Sciambra, Antonio; Scifo, Gaetano; Simeone, Filomena; Sullo, Annarita; Tarquini, Pierluigi; Tundo, Paolo; Vallone, Alfredo

    2016-01-01

    AIM To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings. METHODS This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL). RESULTS All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin. PMID:27574549

  2. The Association between Helicobacter pylori Infection and Chronic Hepatitis C: A Meta-Analysis and Trial Sequential Analysis

    PubMed Central

    Wang, Juan; Li, Wen-Ting; Zheng, Yi-Xiang; Zhao, Shu-Shan; Li, Ning; Huang, Yan; Zhou, Rong-Rong; Huang, Ze-Bing; Fan, Xue-Gong

    2016-01-01

    Purpose. Helicobacter pylori is a common gastric disease-inducing pathogen. Although an increasing number of recent studies have shown that H. pylori is a risk factor for liver disease, the potential association between H. pylori infection and chronic hepatitis C still remains controversial. The aim of our meta-analysis was to evaluate a potential association between H. pylori infection and chronic hepatitis C. Methods. We searched the PubMed, Embase, CNKI, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases between January 1, 1994, and May 1, 2015. Results. This study included a total of 1449 patients with chronic hepatitis C and 2377 control cases. The prevalence of H. pylori was significantly higher in patients with chronic hepatitis C than in those without chronic hepatitis C. The pooled odds ratio was 2.93. In a subgroup analysis, the odds ratios were 4.48 for hepatitis C virus- (HCV-) related cirrhosis and 5.45 for hepatocellular carcinoma. Conclusion. Our study found a strong association between H. pylori and chronic hepatitis C, particularly during the HCV progression stage; thus, we recommend active screening for H. pylori in patients with chronic hepatitis C. PMID:26904112

  3. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  4. Vitamin E treatment for children with chronic hepatitis B: A randomized placebo controlled trial

    PubMed Central

    Gerner, Patrick; Posselt, Hans-Georg; Krahl, Andreas; Ballauff, Antje; Innerhofer, Albina; Binder, Christa; Wenzl, Tobias G; Zense, Matthias; Hector, Ariadne; Dockter, Gerhard; Adam, Rüdiger; Neubert, Jenny; Claßen, Martin; van Gemmern, Robert; Wirth, Stefan

    2008-01-01

    AIM: To evaluate the safety and efficacy of vitamin E in children with chronic hepatitis B. METHODS: We randomly assigned patients with chronic hepatitis B, positive for hepatitis B e antigen (HBeAg), to receive either vitamin E or placebo once daily for 6 mo in a 3:1 ratio and double-blind manner. The primary end point was HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum hepatitis B virus DNA, and the appearance of antibodies against HBeAg 12 mo after therapy. RESULTS: At baseline visit, 49 patients had normal and 43 had increased serum aminotransferase levels. Twenty-nine patients did not respond to previous treatment with interferon-α or lamivudine. Seventy-six children completed the study; 16 were non-compliant (n = 7), lost to follow-up (n = 7), or started another antiviral treatment (n = 3). Intention-to-treat analysis showed HBeAg seroconversion in 16 children (23.2%) treated with vitamin E and two (8.7%) in the placebo group (P = 0.13). Vitamin E was well tolerated. CONCLUSION: There is only a tendency that vitamin E may promote HBeAg seroconversion. Therefore larger studies are needed to clarify the role of antioxidants in the therapy of chronic hepatitis B. PMID:19084935

  5. [Risk factors for the progression of chronic hepatitis C virus infection].

    PubMed

    Valladares Alvarez, Guillermo

    2003-01-01

    The Hepatitis C virus has emerged over the last two decades as the cause of the second greatest viral infection epidemic after the human immunodeficiency virus (HIV). A significant characteristic of the infection with the Hepatitis C virus is the variable course of its natural history. About 80% of the people who acquire this agent develop a chronic infection, with varying degree of liver damage, including cirrhosis and even hepatocelular carcinoma. However, only a minority progresses towards more severe forms. Several factors associated with the host seem to influence the progression of Hepatitis C into cirrhosis. The most important are alcohol abuse, the age in which the infection is acquired, duration of the infection, overweight, male sex and coinfection with Hepatitis A or B or HIV. Evidence of the role of iron levels in the liver, tobacco or the source of infection are less clear. The factors associated with the agent do not seem to play any role in the progression of the disease. Additional studies with adequate control groups are required to confirm the participation of the above mentioned host factors and to identify others which could influence the natural history of the Hepatitis C infection. A reduction in the ingestion of alcohol, overweight and tobacco consumption could contribute to the treatment of HVC chronic infection, as well as vaccination against Hepatitis A and B.

  6. Expression of the hepatitis B virus genome in chronic hepatitis B carriers and patients with hepatocellular carcinoma

    SciTech Connect

    Bowyer, S.M.; Dusheiko, G.M.; Schoub, B.D.; Kew, M.C.

    1987-02-01

    The authors examined the methylation status of CCGG sites in hepatitis B virus (HBV) DNA to determine whether methylation could be responsible for the selective expression of the HBV surface gene in chronic hepatitis B infection and hepatocellular carcinoma. Infected liver tissue from patients with low levels of viral replication was analyzed for HBV DNA copy number per haploid cell genome. Total cellular DNA, with sufficient HBV DNA, was digested with the restriction endonucleases Msp I and Hpa II, to determine whether the HBV DNA was methylated, or HindIII, to determine whether the HBV DNA was integrated or episomal. The cleavage fragments were analyzed by Southern blotting and hybridization to /sup 32/P-labeled HBV DNA. In replicative chronic hepatitis B, hypomethylation of the HBV genome correlated with HBV expression in both virions and infected tissue. In carriers with nonreplicative infection, it was difficult to ascertain the role of methylation as copy number was low. HBV DNA copy number was also low in 17 out of 29 of the rumor tissues tested and as many as 14 out of 16 of the adjacent non-neoplastic tissues tested. Integrated sequences were hypermethylated in the PLC/PRF/5 cell line and in six of the tumor tissues suggesting that methylation plays a role in HBV gene repression. However, since DNA from five other tumors was hypomethylated, the belief that methylation per se is an absolute determinant of HBV core gene repression does not hold for human hepatocellular carcinoma tissue.

  7. Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

    PubMed

    Li, Xi; Wiesen, Eric; Diorditsa, Sergey; Toda, Kohei; Duong, Thi Hong; Nguyen, Lien Huong; Nguyen, Van Cuong; Nguyen, Tran Hien

    2016-02-01

    Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine.

  8. Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review.

    PubMed

    Zhou, Xinying; de Man, Robert A; de Knegt, Robert J; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2013-09-01

    Hepatitis E virus (HEV) infection has emerged as a global public health issue. Although it often causes an acute and self-limiting infection with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Therefore, there is an urgent need to properly evaluate the clinical impact of HEV in these patients. This article aims to review the prevalence, infection course, and management of HEV infection after solid organ transplantation by performing a comprehensive literature review. In addition, an in-depth emphasis of this clinical issue and a discussion of future development are also presented. PMID:23813631

  9. Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck.

    PubMed

    Kosinska, Anna D; Liu, Jia; Lu, Mengji; Roggendorf, Michael

    2015-02-01

    Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model. PMID:25535101

  10. Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C

    PubMed Central

    Manolakopoulos, Spilios; Zacharakis, George; Zissis, Miltiadis; Giannakopoulos, Vassilis

    2016-01-01

    Daclatasvir (Daklinza™), a new oral direct-acting antiviral, is an inhibitor of hepatitis C virus NS5A protein and has recently been approved in the United States, Europe and Japan in chronic hepatitis C. It shows potent pangenotypic activity and moderately high genetic barrier to resistance improving the sustained virological response (SVR) rates. In COMMAND phase 2 trials, daclatasvir demonstrated high SVR rates in HCV genotype 1-4 chronically infected patients treated with peginterferon-a (pegIFNα) plus ribavirin (RBV). Furthermore, it produced even higher response rates in all-oral combination with sofosbuvir, an interferon-free regimen, with or without ribavirin, in patients with advanced liver disease, HCV/HIV coinfection, liver transplantation in ALLY studies and other real-world studies. This narrative review provides information on the pharmacological properties, role, efficacy and safety of daclatasvir-containing regimens in chronic hepatitis C patients. Daclatasvir administered once-daily in combination with sofosbuvir is an effective 12-week treatment in adult patients with chronic hepatitis C and is generally safe and well tolerated. PMID:27366028

  11. Chronic Hepatitis C and Antiviral Treatment Regimens: Where Can Psychology Contribute?

    ERIC Educational Resources Information Center

    Evon, Donna M.; Golin, Carol E.; Fried, Michael W.; Keefe, Francis J.

    2013-01-01

    Objective: Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology…

  12. Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck.

    PubMed

    Kosinska, Anna D; Liu, Jia; Lu, Mengji; Roggendorf, Michael

    2015-02-01

    Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model.

  13. Myasthenia Crisis Induced by Pegylated-Interferon in Patient With Chronic Hepatitis C: A Case Report.

    PubMed

    Baik, Su Jung; Kim, Tae Hun; Kim, Hye In; Rhie, Jeong Yeon

    2016-05-01

    Myasthenia gravis is occasionally associated with thymoma that needs surgical resection and may progress to severe respiratory failure. We experienced a rare case of myasthenia crisis during antiviral therapy for chronic hepatitis C, in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care.A 47-year-old-male patient complained of sudden diplopia 1 week after stopping 11-week administration of pegylated-interferon and ribavirin for chronic hepatitis C. Ophthalmologic examinations revealed ptosis on the right eyelid and restricted right eye movement. Myasthenia gravis was confirmed by positive repetitive nerve stimulation test and positive serum antiacetylcholine receptor antibody test, and mediastinal thymoma was found on chest CT scan. The ocular myasthenia gravis progressed to respiratory failure even after discontinuing antiviral treatment but eventually recovered with thymectomy, anticholinesterase administration, steroid pulse therapy, and prolonged ventilator care. We describe the clinical features of this life-threatening complication of interferon treatment along with previous myasthenia crisis cases by interferon for chronic hepatitis C.In patients with chronic hepatitis C who is going to receive interferon-based antiviral treatment, physicians need to keep in mind the potential life-threatening manifestations of myasthenia gravis before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability. PMID:27227948

  14. Therapeutic Strategies and New Intervention Points in Chronic Hepatitis Delta Virus Infection

    PubMed Central

    Guo, Zhimin; King, Thomas

    2015-01-01

    Chronic hepatitis delta virus infection (CHD) is a condition arising from super-infection of hepatitis B virus (HBV)-infected patients, resulting in a more rapid advance in liver pathology and hepatocellular carcinoma than is observed for HBV mono-infection. Although hepatitis delta virus (HDV) is structurally simple, its life cycle involves the complex participation of host enzymes, HBV-derived surface antigen (HBsAg), and HDV-auto-ribozyme and hepatitis delta antigen (HDAg) activities. Unsatisfactory clinical trial results with interferon-based therapies are motivating researchers to adjust and redirect the approach to CHD drug development. This new effort will likely require additional structural and functional studies of the viral and cellular/host components involved in the HDV replication cycle. This review highlights recent work aimed at new drug interventions for CHD, with interpretation of key pre-clinical- and clinical trial outcomes and a discussion of promising new technological approaches to antiviral drug design. PMID:26295228

  15. Reproductive History and Chronic Hepatic Steatosis in the Michigan Study of Women's Health Across the Nation

    PubMed Central

    Harlow, Siobán D.; Kong, Shengchun; Karvonen-Gutierrez, Carrie; Ylitalo, Kelly; Nan, Bin

    2015-01-01

    Abstract Background: Reproductive history, particularly maternal age at most recent birth, may reflect lower risk for chronic disease and mortality due to socioeconomic factors, lifestyle behaviors, or genetics. Reproductive history has not been examined with respect to hepatic steatosis, the most common liver disease in the United States. Our objective was to examine the association between reproductive history and hepatic steatosis. Methods: We examined the association between reproductive history characteristics—specifically age at most recent birth—and the odds of moderate to severe hepatic steatosis using a population-based retrospective cohort study of women who underwent hepatic ultrasound at the Michigan site of the Study of Women's Health Across the Nation (n=331). Results: Women who gave birth at ≥35 years of age comprised 19% of the study population and were similar to other women regarding sociodemographic history and health behaviors. In multivariable analyses adjusting for age, race/ethnicity, chronic disease, and medications associated with hepatic steatosis, age at birth ≥35 years was associated with significantly decreased odds of hepatic steatosis (adjusted odds ratio [OR] 0.41, 95% confidence interval [CI] 0.20–0.87), which was attenuated after adjustment for waist circumference (OR 0.51, 95% CI 0.24–1.10). Other reproductive factors including gravidity, parity, miscarriages and abortions, recall of gestational weight gain, breastfeeding, age at first birth, and age at final menstrual period were not associated with hepatic steatosis. Conclusions: Women who were older at their most recent birth had a reduced odds of hepatic steatosis, possibly associated with their lower waist circumference. PMID:25548857

  16. Hepatitis B surface antigen-specific cell-mediated immune responses in human chronic hepatitis B surface antigen carriers.

    PubMed Central

    Beutner, K R; Tiku, M L; Ogra, P L

    1978-01-01

    The presence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), the nature of T-cell function, and specific cell-mediated immunity to HBsAg were determined and evaluated serially in groups of subjects with chronic HBsAg carrier states and in seronegative controls. The techniques of in vitro lymphocyte transformation, spontaneous rosette formation, radioimmunoassay, reverse passive hemagglutination, passive hemagglutination, rheophoresis, and liver function tests were employed for these studies. For the lymphocyte transformation assay, multiple concentrations of phytohemagglutinin and purified HBsAg were used as stimulants. Cell-mediated immunity to HBsAg was detectable in 50% of the chronic HBsAg carriers (responders) at one or more concentrations of HBsAg. The remaining carriers (nonresponders) and controls failed to manifest HBsAg-specific lymphocyte transformation activity. The profile of the responders was characterized by elevated serum glutamic pyruvic transaminase levels, the presence of anti-HBe, high HBsAg titers, and the conspicuous absence of HBeAg in the serum. The nonresponders were characterized by normal serum glutamic pyruvic transaminase levels, the presence of HBeAg and anti-HBe, and lower HBsAg titers. These observations demonstrate the presence of specific cell-mediated immunity to HBsAg in chronic HBsAg carriers who manifest biochemical evidence of liver disease. PMID:80380

  17. [Meglumine acridonacetate in combined antiviral treatment of HBeAg-positive chronic hepatitis B].

    PubMed

    Stel'makh, V V; Okovityĭ, S V; Romantsov, M G; Tuan, N Kh; Oiungerel, M

    2013-06-01

    647 patients with HBeAg positive chronic hepatitis B who have not previously received antiviral therapy were participated in randomized, post-marketing, double-blinded, placebo-controlled clinical trial. Interferon inducer cycloferon was presented as study drug. 323 patients with chronic hepatitis B (HBV) with "wild" HBeAg(+) strain of HBV were treated with cycloferon and Lamivudin for 48 weeks. Control group included 324 patients with similar pathology, treated with Lamivudin and placebo for 48 weeks. The study has shown the benefit of cycloferon+lamivudin treatment in comparison with lamivudin monotherapy. Improving of liver histology in 48 weeks of the therapy was observed in 71% of patients in Study group in comparison with 57% in control group (p<0.01). Combined therapy has resulted in decrease of relapse by 24 week of the follow-up period (13% vs. 86%, p<0.001). The higher efficacy of cycloferon+lamivudin in patients with HBeAg positive chronic hepatitis B has proven the role of own antiviral effect of interferon inducer cycloferon, interferon effect of cycloferon in the elimination of virus-infected hepatocytes, as well as the presence of an immunomodulatory effect of the preparation, aimed at the elimination of HBeAg and HBsAg with the following seroconversion. 48-week course of combined antiviral therapy of HBeAg-positive patients with chronic hepatitis B is recommended as first-line therapy for patients with HBeAg-positive chronic hepatitis B, who have not previously received nucleoside analogues, as well as alternative therapy of Lamivudin-refractory patients. PMID:23863208

  18. Distribution of the HLA class I allele in chronic hepatitis C and its association with serum ALT level in chronic hepatitis C.

    PubMed

    Kondo, Yasuteru; Kobayashi, Koju; Kobayashi, Tomoo; Shiina, Masaaki; Ueno, Yoshiyuki; Satoh, Takaomi; Shimosegawa, Tooru

    2003-10-01

    An essential process for resolution of viral infections is the efficient recognition and elimination of intracellular virus. Recognition of viral antigens in the form of short peptides associated with HLA class I molecule is a major task of CD8+ cytotoxic T lymphocytes. In this study, we have evaluated the frequency of the HLA class I alleles in patients with chronic hepatitis C. HLA-B51, -B52, -B55, -B56, -B61, B70, -Cw1, -Cw3, and -Cw4 are less frequent in patients with chronic hepatitis C than in Japanese individuals. The frequency of HLA-A2 is slightly lower in the patients but tends to be higher in patients with normal alanine aminotransferase (ALT) level than in those with elevated ALT level (p = 0.07). Other HLA alleles are not significantly different between two groups. Comparison of HLA homozygosity at HLA-A and -B or -C or at two or three loci did not show a significant association with levels of serum ALT or with the clinical outcome of interferon therapy in patients with hepatitis C. These results suggest a possibility that the alterations of host response, which depends on genetic background, influence disease activities of HCV infection.

  19. Hepatic and dermatologic manifestations of chronic hypervitaminosis A in adults. Report of two cases.

    PubMed

    Inkeles, S B; Connor, W E; Illingworth, D R

    1986-03-01

    Chronic hypervitaminosis A in adults is a clinical syndrome that can develop over varying periods of time depending on the average daily intake of vitamin A. Two adult cases of chronic hypervitaminosis A are described and illustrate this diverse dosage-duration relationship. Hepatic cirrhosis developed as a manifestation of vitamin A toxicity in one of the patients; this appears to be the first reported case of chronic hypervitaminosis A in an adult induced by the long-term frequent ingestion of beef liver. PMID:2937294

  20. Increased frequency of micronuclei in the lymphocytes of patients chronically infected with hepatitis B or hepatitis C virus

    PubMed Central

    Leite, Samantha Therezinha Almeida Pereira; da Silva, Marilene Borges; Pepato, Marco Andrey; Souto, Francisco José Dutra; dos Santos, Raquel Alves; Bassi-Branco, Carmen Lucia

    2013-01-01

    In this study, we analysed the frequency of micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) and evaluated mutagen-induced sensitivity in the lymphocytes of patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). In total, 49 patients with chronic viral hepatitis (28 HBV-infected and 21 HCV-infected patients) and 33 healthy, non-infected blood donor controls were investigated. The frequencies (‰) of MN, NPBs and NBUDs in the controls were 4.41 ± 2.15, 1.15 ± 0.97 and 2.98 ± 1.31, respectively. The frequencies of MN and NPBs were significantly increased (p < 0.0001) in the patient group (7.01 ± 3.23 and 2.76 ± 2.08, respectively) compared with the control group. When considered separately, the HBV-infected patients (7.18 ± 3.57) and HCV-infected patients (3.27 ± 2.40) each had greater numbers of MN than did the controls (p < 0.0001). The HCV-infected patients displayed high numbers of NPBs (2.09 ± 1.33) and NBUDs (4.38 ± 3.28), but only the HBV-infected patients exhibited a significant difference (NPBs = 3.27 ± 2.40, p < 0.0001 and NBUDs = 4.71 ± 2.79, p = 0.03) in comparison with the controls. Similar results were obtained for males, but not for females, when all patients or the HBV-infected group was compared with the controls. The lymphocytes of the infected patients did not exhibit sensitivity to mutagen in comparison with the lymphocytes of the controls (p = 0.06). These results showed that the lymphocytes of patients who were chronically infected with HBV or HCV presented greater chromosomal instability. PMID:24626305

  1. New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant.

    PubMed

    Fabrizi, Fabrizio; Martin, Paul; Messa, Piergiorgio

    2016-05-01

    The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group (n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients undergoing

  2. Vitamin A deficiency in patients with hepatitis C virus-related chronic liver disease.

    PubMed

    Peres, W A F; Chaves, G V; Gonçalves, J C S; Ramalho, A; Coelho, H S M

    2011-12-01

    Hepatitis C virus (HCV) infection is associated with oxidative stress and vitamin A possesses antioxidant activity. The objective of the present study was to investigate vitamin A nutritional status in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), according to biochemical, functional and dietetic indicators correlating these findings with liver function, liver damage and death. Vitamin A nutritional status was analysed by serum retinol levels, dietetic indicators and functional indicators. A total of 140 patients with HCV-related liver disease were enrolled. Vitamin A deficiency was detected in 54·3 % of all patients, and there was a progressive drop in serum retinol levels from chronic hepatitis C patients towards cirrhosis and HCC patients. Increased total bilirubin, liver transaminases and prothrombin time, presence of hepatic encephalopathy and ascites were related to reduced serum retinol levels, and values ≤ 0·78 μmol/l of serum retinol were associated with liver-related death. A high prevalence of inadequate intake of vitamin A was observed in all stages of chronic liver disease. The functional indicator was not an adequate parameter for evaluating the vitamin A nutritional status. Therefore, serum retinol concentration is related to severity of the disease, liver complications and mortality. The effectiveness of nutritional counselling and measures of intervention in this group in improving vitamin A nutritional status should be examined further in a controlled study. PMID:21736776

  3. The use of mind-body medicine and prayer among adult patients with chronic hepatitis C.

    PubMed

    Richmond, Jacqueline A; Bailey, Donald E; McHutchison, John G; Muir, Andrew J

    2010-01-01

    The use of mind-body medicine by patients with chronic hepatitis C has not been reported. The prevalence and reasons for using mind-body medicine and prayer among a cohort of patients with chronic hepatitis C are described. Use of mind-body medicine and prayer was investigated as a component of a larger exploratory, descriptive study of the use of complementary and alternative medicine by patients with hepatitis C attending a tertiary healthcare facility in the United States. An investigator-designed self-administered questionnaire (n = 149) and semistructured interview (n = 28) were completed by participants. Eighty-eight percent (n = 105) of participants had used mind-body medicine in the past 12 months. The most commonly used therapies were prayer for health reasons (90%), deep breathing (29%), and meditation (29%). Mind-body medicine was most commonly used to relieve tension and promote general well-being. The use of mind-body medicine was widespread among patients with chronic hepatitis C. To provide patient-centered healthcare, health providers need to be aware of the alternative support strategies, including mind-body medicine, used by patients.

  4. Sofosbuvir: a review of its use in patients with chronic hepatitis C.

    PubMed

    Keating, Gillian M

    2014-07-01

    Sofosbuvir (Sovaldi(®)) is a nucleotide hepatitis C virus (HCV) NS5B polymerase inhibitor that has pangenotypic antiviral activity and a high genetic barrier to resistance. This article reviews the clinical efficacy and tolerability of sofosbuvir in patients with chronic hepatitis C and summarizes its pharmacological properties. Interferon-free treatment with sofosbuvir plus ribavirin achieved high sustained virological response (SVR) rates in treatment-naïve and treatment-experienced patients with HCV genotype 2 or 3 infection, and also had efficacy in patients with HCV genotype 1 infection. Sofosbuvir plus ribavirin was also effective in patients co-infected with HCV and HIV, and sofosbuvir plus ribavirin administered prior to liver transplantation prevented recurrent HCV infection in the majority of patients who had HCV RNA levels below the limit of quantification at the time of transplantation. Sofosbuvir plus peginterferon-α-2a and ribavirin achieved high SVR rates in patients with HCV genotype 1 infection, and also appeared effective in patients with HCV genotype 4, 5 or 6 infection. Oral sofosbuvir was generally well tolerated in patients with chronic hepatitis C. The most commonly reported adverse events and laboratory abnormalities were consistent with those expected with ribavirin and peginterferon-α. In conclusion, sofosbuvir represents an important advance in the treatment of chronic hepatitis C.

  5. Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

    PubMed Central

    Tang, Ceen-Ming; Yau, Tung On; Yu, Jun

    2014-01-01

    Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB. PMID:24876747

  6. Searching for chronic hepatitis B patients in a low prevalence area – role of racial origin

    PubMed Central

    Ono-Nita, Suzane Kioko; Carrilho, Flair José; Cardoso, Rita A; Nita, Marcelo Eidi; da Silva, Luiz Caetano

    2004-01-01

    Background Clinical studies for testing new drugs against hepatitis B ought to be carried out in low prevalence areas despite difficulties on patient recruitment. In such areas, relatives of chronic hepatitis B patients are considered to be at risk of acquiring the hepatitis B virus (HBV). The aim of this study was to evaluate the prevalence of HBV markers (anti-HBc, HBsAg and anti-HBs) in familial members of chronic hepatitis B (CHB) patients according to their origin (Asian or Western) in a low prevalence area, the city of São Paulo, Brazil. Methods Twenty three Asian CHB probands and their 313 relatives plus 31 CHB probands of Western origin and their 211 relatives were screened for HBV serological markers; the study was carried out in the outpatient clinic of the University of São Paulo School of Medicine. Results Mother to child transmission was greater in the Asian group whereas sexual transmission was more frequent in the Western group (p < 0.0001). Anti-HBc was positive in 90% and 57% of the Asian and Western parents (p = 0.0432) and in 97% and 33% of the Asian and Western brothers (p = 0.0001), respectively. HBsAg was more frequent among the Asian (66%) than the Western (15%) mothers (p = 0.0260) as well as among the Asian (81%) than the Western (19%) brothers (p = 0.0001). We could detect 110 new HBsAg-positive subjects related to the 54 index patients, being the majority (81%) of Asian origin. Conclusion In low prevalence area of hepatitis B, family members and household contacts of chronic HBV carriers are at high risk for acquiring hepatitis B. PMID:15084223

  7. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    PubMed Central

    Brunetto, Maurizia Rossana; Colombatto, Piero; Bonino, Ferruccio

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an “automatic pilot” for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients. PMID:19195054

  8. Assessment of the Frequency of Autoantibodies in Chronic Viral Hepatitis

    PubMed Central

    Acay, Akif; Demir, Kasim; Asik, Gulsah; Tunay, Havva; Acarturk, Gursel

    2015-01-01

    Objective: To examine the occurrence frequency of auto-antibodies and autoimmune diseases in patients with chronic hepatitis B or C. Methods: A total of 67 patients diagnosed with chronic hepatitis B and 77 patients diagnosed with chronic hepatitis C infection based on HBs Ag, Anti HCV, HBe Ag, Anti HBe Ag, HBV DNA, HCV RNA, liver ultrasound, and liver biopsy results as well as 48 healthy individuals were included in this study. ANA, anti dsDNA, anti LKM, Anti-SMA, AMA, C-ANCA, P-ANCA, anti-SSA, anti-SSB, anti-Scl-70, anti Jo-1, anti-U1snRNP, anti-centromere, anti-Jo-1, anti tpo, and anti tg were studied in all individuals in each study group. Results: ANA positivity was detected in 8 (12%), 15 (19%) and 2 (4%) individuals in HBV, HCV and control groups, respectively. The difference between the groups was significant (P=0.04). Similarly, anti Tg was positive in one subject in HBV group, in 6 subjects (7%) in HCV group, and in one subject among controls, the difference being significant (P=0.04). There were no significant differences between the study groups in the frequency of other auto-antibodies. Conclusion: Similar to studies involving patients who received interferon and/or antiviral agents, an increased frequency of auto-antibodies was also detected in our patient group consisting of interferon and anti-viral naive subjects. The increase in the frequency of auto-antibodies reached statistical significance among individuals with HCV infection. Thus, pre-treatment assessment of auto-antibodies in newly diagnosed cases of chronic hepatitis B or hepatitis C infection may provide beneficial information on the future occurrence of auto-immune responses in these patients. PMID:25878633

  9. Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities.

    PubMed

    Gish, Robert G; Given, Bruce D; Lai, Ching-Lung; Locarnini, Stephen A; Lau, Johnson Y N; Lewis, David L; Schluep, Thomas

    2015-09-01

    The host immune system plays an important role in chronic hepatitis B (CHB), both in viral clearance and hepatocellular damage. Advances in our understanding of the natural history of the disease have led to redefining the major phases of infection, with the "high replicative, low inflammatory" phase now replacing what was formerly termed the "immune tolerant" phase, and the "nonreplicative phase" replacing what was formerly termed the "inactive carrier" phase. As opposed to the earlier view that HBV establishes chronic infection by exploiting the immaturity of the neonate's immune system, new findings on trained immunity show that the host is already somewhat "matured" following birth, and is actually very capable of responding immunologically, potentially altering future hepatitis B treatment strategies. While existing therapies are effective in reducing viral load and necroinflammation, often restoring the patient to near-normal health, they do not lead to a cure except in very rare cases and, in many patients, viremia rebounds after cessation of treatment. Researchers are now challenged to devise therapies that will eliminate infection, with a particular focus on eliminating the persistence of viral cccDNA in the nuclei of hepatocytes. In the context of chronic hepatitis B, new definitions of 'cure' are emerging, such as 'functional' and 'virological' cure, defined by stable off-therapy suppression of viremia and antigenemia, and the normalization of serum ALT and other liver-related laboratory tests. Continued advances in the understanding of the complex biology of chronic hepatitis B have resulted in the development of new, experimental therapies targeting viral and host factors and pathways previously not accessible to therapy, approaches which may lead to virological cures in the near term and functional cures upon long term follow-up. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia

  10. [Prevalence of hepatitis C virus antibodies in chronic hemodialysis and kidney transplantation patients].

    PubMed

    Castillo, L; Díaz, P; Inostroza, J; Espinoza, R; Millaqueo, L; Calderara, M; Pinto, A; Behrens, C; Pereira, O

    1993-09-01

    Hepatitis C virus antibodies were measured in 26 chronic hemodialyzed patients and 43 kidney transplant recipients, using a second generation ELISA method. Fifty four percent of hemodialyzed had a longer duration of dialysis treatment compared with patients with negative antibodies (57.6 +/- 30.5 vs 15.4 +/- 7.3 months), and did not differ in the number of transfusions. Seven patients had elevated serum transaminase values, all with positive antibodies. Thirty five percent of kidney transplant recipients had positive antibodies. In these subjects, no relation was observed between the number of transfusions or length of dialysis treatment and the presence of positive hepatitis C antibodies. PMID:7514806

  11. Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury

    PubMed Central

    Liu, Yanlong; Zhao, Cuiqing; Xiao, Jian; Liu, Liming; Zhang, Min; Wang, Cuiling; Wu, Guicheng; Zheng, Ming-Hua; Xu, Lan-Man; Chen, Yong-Ping; Mohammadi, Moosa; Chen, Shao-Yu; Cave, Matthew; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid β-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis. PMID:27498701

  12. Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury.

    PubMed

    Liu, Yanlong; Zhao, Cuiqing; Xiao, Jian; Liu, Liming; Zhang, Min; Wang, Cuiling; Wu, Guicheng; Zheng, Ming-Hua; Xu, Lan-Man; Chen, Yong-Ping; Mohammadi, Moosa; Chen, Shao-Yu; Cave, Matthew; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid β-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis. PMID:27498701

  13. Hepatic Insulin Resistance Following Chronic Activation of the CREB Coactivator CRTC2.

    PubMed

    Hogan, Meghan F; Ravnskjaer, Kim; Matsumura, Shigenobu; Huising, Mark O; Hull, Rebecca L; Kahn, Steven E; Montminy, Marc

    2015-10-23

    Under fasting conditions, increases in circulating concentrations of glucagon maintain glucose homeostasis via the induction of hepatic gluconeogenesis. Triggering of the cAMP pathway in hepatocytes stimulates the gluconeogenic program via the PKA-mediated phosphorylation of CREB and dephosphorylation of the cAMP-regulated CREB coactivators CRTC2 and CRTC3. In parallel, decreases in circulating insulin also increase gluconeogenic gene expression via the de-phosphorylation and activation of the forkhead transcription factor FOXO1. Hepatic gluconeogenesis is increased in insulin resistance where it contributes to the attendant hyperglycemia. Whether selective activation of the hepatic CREB/CRTC pathway is sufficient to trigger metabolic changes in other tissues is unclear, however. Modest hepatic expression of a phosphorylation-defective and therefore constitutively active CRTC2S171,275A protein increased gluconeogenic gene expression under fasting as well as feeding conditions. Circulating glucose concentrations were constitutively elevated in CRTC2S171,275A-expressing mice, leading to compensatory increases in circulating insulin concentrations that enhance FOXO1 phosphorylation. Despite accompanying decreases in FOXO1 activity, hepatic gluconeogenic gene expression remained elevated in CRTC2S171,275A mice, demonstrating that chronic increases in CRTC2 activity in the liver are indeed sufficient to promote hepatic insulin resistance and to disrupt glucose homeostasis.

  14. Hepatic Insulin Resistance Following Chronic Activation of the CREB Coactivator CRTC2*

    PubMed Central

    Hogan, Meghan F.; Ravnskjaer, Kim; Matsumura, Shigenobu; Huising, Mark O.; Hull, Rebecca L.; Kahn, Steven E.; Montminy, Marc

    2015-01-01

    Under fasting conditions, increases in circulating concentrations of glucagon maintain glucose homeostasis via the induction of hepatic gluconeogenesis. Triggering of the cAMP pathway in hepatocytes stimulates the gluconeogenic program via the PKA-mediated phosphorylation of CREB and dephosphorylation of the cAMP-regulated CREB coactivators CRTC2 and CRTC3. In parallel, decreases in circulating insulin also increase gluconeogenic gene expression via the de-phosphorylation and activation of the forkhead transcription factor FOXO1. Hepatic gluconeogenesis is increased in insulin resistance where it contributes to the attendant hyperglycemia. Whether selective activation of the hepatic CREB/CRTC pathway is sufficient to trigger metabolic changes in other tissues is unclear, however. Modest hepatic expression of a phosphorylation-defective and therefore constitutively active CRTC2S171,275A protein increased gluconeogenic gene expression under fasting as well as feeding conditions. Circulating glucose concentrations were constitutively elevated in CRTC2S171,275A-expressing mice, leading to compensatory increases in circulating insulin concentrations that enhance FOXO1 phosphorylation. Despite accompanying decreases in FOXO1 activity, hepatic gluconeogenic gene expression remained elevated in CRTC2S171,275A mice, demonstrating that chronic increases in CRTC2 activity in the liver are indeed sufficient to promote hepatic insulin resistance and to disrupt glucose homeostasis. PMID:26342077

  15. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality?

    PubMed

    Vanni, Ester; Bugianesi, Elisabetta; Saracco, Giorgio

    2016-02-01

    Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.

  16. Essential role of protein-tyrosine phosphatase 1B in the modulation of insulin signaling by acetaminophen in hepatocytes.

    PubMed

    Mobasher, Maysa Ahmed; de Toro-Martín, Juan; González-Rodríguez, Águeda; Ramos, Sonia; Letzig, Lynda G; James, Laura P; Muntané, Jordi; Álvarez, Carmen; Valverde, Ángela M

    2014-10-17

    Many drugs are associated with the development of glucose intolerance or deterioration in glycemic control in patients with pre-existing diabetes. We have evaluated the cross-talk between signaling pathways activated by acetaminophen (APAP) and insulin signaling in hepatocytes with or without expression of the protein-tyrosine phosphatase 1B (PTP1B) and in wild-type and PTP1B-deficient mice chronically treated with APAP. Human primary hepatocytes, Huh7 hepatoma cells with silenced PTP1B, mouse hepatocytes from wild-type and PTP1B-deficient mice, and a mouse model of chronic APAP treatment were used to examine the mechanisms involving PTP1B in the effects of APAP on glucose homeostasis and hepatic insulin signaling. In APAP-treated human hepatocytes at concentrations that did not induce death, phosphorylation of JNK and PTP1B expression and enzymatic activity were increased. APAP pretreatment inhibited activation of the early steps of insulin signaling and decreased Akt phosphorylation. The effects of APAP in insulin signaling were prevented by suramin, a PTP1B inhibitor, or rosiglitazone that decreased PTP1B levels. Likewise, PTP1B deficiency in human or mouse hepatocytes protected against APAP-mediated impairment in insulin signaling. These signaling pathways were modulated in mice with chronic APAP treatment, resulting in protection against APAP-mediated hepatic insulin resistance and alterations in islet alpha/beta cell ratio in PTP1B(-/-) mice. Our results demonstrate negative cross-talk between signaling pathways triggered by APAP and insulin signaling in hepatocytes, which is in part mediated by PTP1B. Moreover, our in vivo data suggest that chronic use of APAP may be associated with insulin resistance in the liver. PMID:25204659

  17. Chlorogenic acid from honeysuckle improves hepatic lipid dysregulation and modulates hepatic fatty acid composition in rats with chronic endotoxin infusion

    PubMed Central

    Zhou, Yan; Ruan, Zheng; Wen, Yanmei; Yang, Yuhui; Mi, Shumei; Zhou, Lili; Wu, Xin; Ding, Sheng; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong

    2016-01-01

    Chlorogenic acid as a natural hydroxycinnamic acid has protective effect for liver. Endotoxin induced metabolic disorder, such as lipid dysregulation and hyperlipidemia. In this study, we investigated the effect of chlorogenic acid in rats with chronic endotoxin infusion. The Sprague-Dawley rats with lipid metabolic disorder (LD group) were intraperitoneally injected endotoxin. And the rats of chlorogenic acid-LD group were daily received chlorogenic acid by intragastric administration. In chlorogenic acid-LD group, the area of visceral adipocyte was decreased and liver injury was ameliorated, as compared to LD group. In chlorogenic acid-LD group, serum triglycerides, free fatty acids, hepatic triglycerides and cholesterol were decreased, the proportion of C20:1, C24:1 and C18:3n-6, Δ9-18 and Δ6-desaturase activity index in the liver were decreased, and the proportion of C18:3n-3 acid was increased, compared to the LD group. Moreover, levels of phosphorylated AMP-activated protein kinase, carnitine palmitoyltransferase-I, and fatty acid β-oxidation were increased in chlorogenic acid-LD group compared to LD rats, whereas levels of fatty acid synthase and acetyl-CoA carboxylase were decreased. These findings demonstrate that chlorogenic acid effectively improves hepatic lipid dysregulation in rats by regulating fatty acid metabolism enzymes, stimulating AMP-activated protein kinase activation, and modulating levels of hepatic fatty acids. PMID:27013782

  18. Beneficial IL28B genotype associated with lower frequency of hepatic steatosis in patients with chronic hepatitis C

    PubMed Central

    Tillmann, Hans L.; Patel, Keyur; Muir, Andrew J.; Guy, Cynthia D.; Li, Josephine H.; Lao, Xiang Qian; Thompson, Alexander; Clark, Paul J.; Gardner, Stephen D.; McHutchison, John G.; McCarthy, Jeanette J.

    2013-01-01

    BACKGROUND IL28B polymorphisms have been associated with both treatment induced and spontaneous clearance of hepatitis C virus (HCV). We previously found that LDL cholesterol levels were higher in chronic hepatitis C (CHC) patients with the CC genotype at the rs12979860 polymorphism, located proximal to the IL28 gene. Here we analyzed the association of steatosis with IL28B genotype in treatment naïve patients with CHC. METHODS Two independent cohorts of 145 genotype 1 infected patients from an antifibrotic study and 180 genotype 1 patients from Duke were analyzed for presence and severity of steatosis in relation to the rs12979860 polymorphism at the IL28B locus. TaqMan assay based genotyping classified three groups CC, CT and TT. RESULTS CC genotype was associated with a lower prevalence of steatosis. In the antifibrotic study steatosis was found in 47.6% (50/105) of IL28B non-CC versus 22.5% (9/40; p=0.008) in CC patients. Similarly, steatosis was found in 67.4% (89/132) of non-CC patients compared to only 39.6% (19/48; p=0.001) of CC patients in the Duke cohort. CONCLUSIONS IL28B CC genotype is associated with less pronounced disturbances of lipid metabolism, as reflected both in serum lipoprotein levels and hepatic steatosis, in HCV infection. PMID:21703198

  19. Role of mouse hepatitis virus (MHV) receptor murine CEACAM1 in the resistance of mice to MHV infection: studies of mice with chimeric mCEACAM1a and mCEACAM1b.

    PubMed

    Hirai, Asuka; Ohtsuka, Nobuhisa; Ikeda, Toshio; Taniguchi, Rie; Blau, Dianna; Nakagaki, Keiko; Miura, Hideka S; Ami, Yasushi; Yamada, Yasuko K; Itohara, Shigeyoshi; Holmes, Kathryn V; Taguchi, Fumihiro

    2010-07-01

    Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV) infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele. mCEACAM1a (1a) has a 10- to 100-fold-higher receptor activity than does mCEACAM1b (1b). To explore the hypothesis that MHV susceptibility is due to the different MHV receptor activities of 1a and 1b, we established a chimeric C57BL/6 mouse (cB61ba) in which a part of the N-terminal immunoglobulin (Ig)-like domain of the mCeacam1a (1a) gene, which is responsible for MHV receptor function, is replaced by the corresponding region of mCeacam1b (1b). We compared the MHV susceptibility of these chimeric mice to that of SJL and B6 mice. B6 mice that are homozygous for 1a are highly susceptible to MHV-A59 infection, with a 50% lethal dose (LD(50)) of 10(2.5) PFU, while chimeric cB61ba mice and SJL mice homozygous for 1ba and 1b, respectively, survived following inoculation with 10(5) PFU. Unexpectedly, cB61ba mice were more resistant to MHV-A59 infection than SJL mice as measured by virus replication in target organs, including liver and brain. No infectious virus or viral RNA was detected in the organs of cB61ba mice, while viral RNA and infectious virus were detected in target organs of SJL mice. Furthermore, SJL mice produced antiviral antibodies after MHV-A59 inoculation with 10(5) PFU, but cB61ba mice did not. Thus, cB61ba mice are apparently completely resistant to MHV-A59 infection, while SJL mice permit low levels of MHV-A59 virus replication during self-limited, asymptomatic infection. When expressed on cultured BHK cells, the mCEACAM1b and mCEACAM1ba proteins had similar levels of MHV-A59 receptor activity. These results strongly support the hypothesis that although alleles of mCEACAM1 are the principal determinants of

  20. Beyond interferon: rationale and prospects for newer treatment paradigms for chronic hepatitis C

    PubMed Central

    Cortez, Karoll J.

    2015-01-01

    Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-α based combination therapy to an all-oral, directly acting antiviral therapy. PMID:25553238

  1. Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

    PubMed Central

    Udoh, Uduak S.; Swain, Telisha M.; Filiano, Ashley N.; Gamble, Karen L.; Young, Martin E.

    2015-01-01

    Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease. PMID:25857999

  2. Hepatitis C virus infection in Argentina: Burden of chronic disease

    PubMed Central

    Ridruejo, Ezequiel; Bessone, Fernando; Daruich, Jorge R; Estes, Chris; Gadano, Adrián C; Razavi, Homie; Villamil, Federico G; Silva, Marcelo O

    2016-01-01

    AIM: To estimate the progression of the hepatitis C virus (HCV) epidemic and measure the burden of HCV-related morbidity and mortality. METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed: (1) increased sustained virologic response (SVR); and (2) increased SVR and treatment. RESULTS: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liver-related deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030. CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina. PMID:27239258

  3. Serum Levels of Annexin A2 as a Candidate Biomarker for Hepatic Fibrosis in Patients With Chronic Hepatitis B

    PubMed Central

    Kolgelier, Servet; Demir, Nazlim Aktug; Inkaya, Ahmet Cagkan; Sumer, Sua; Ozcimen, Serap; Demir, Lutfi Saltuk; Pehlivan, Fatma Seher; Arslan, Mahmure; Arpaci, Abdullah

    2015-01-01

    Background: Hepatologists have studied serologic markers of liver injury for decades. Annexins are a prominent group of such markers and annexin A2 (AnxA2) is one of the best characterized annexins. AnxA2 inhibits HBV polymerase among other functions. Its expression is up-regulated in regenerative hepatocytes. Objectives: To determine if serum AnxA2 level has a role in estimating liver damage in chronic HBV infection and investigate whether AnxA2 levels correlate with hepatic fibrosis. Patients and Methods: This study included 173 patients with chronic hepatitis B (CHB) and 51 healthy controls. Liver fibrosis was graded histologically on liver biopsy samples. Blood samples were taken from patients during biopsy and serum AnxA2 levels were measured with ELISA. Results: In a group of adult patients with CHB, AnxA2 values were far higher than those of the control group (P = 0.001). When we assessed AnxA2 levels based on fibrosis stages, serum AnxA2 levels of patients with early stage fibrosis (stages 1 - 3) were significantly higher than those of patients with advanced stage fibrosis (stages 4 - 5; P = 0.001). Conclusions: AnxA2 is a useful biomarker for early stage fibrosis in patients with CHB. PMID:26587036

  4. [Characterization of Serial Passage of 1b/2a Chimera Hepatitis C Virus Cell Culture System Carrying Envelope E1E2 Coding Gene from Hebei Strain of China].

    PubMed

    Lu, Sha; Zhang, Ling; Tao, Gesi; Cai, Min; Bao Lili; LI, Lian; Deng, Yao; Shen, Xiaoling; Tan, Wenjie

    2015-11-01

    To character a novel chimera(1b/2a) hepatitis C virus cell culture (HCVcc) system carrying envelope E1E2 coding gene from Hebei strain of China, chimera HCVcc (cHCVcc) was developed from Huh7.5-CD81 cells after transfection with in vitro transcribed full-length 1b/2a chimera RNA, which carrying envelope E1E2 coding gene from Hebei strain of China. Then the replication, expression and infectious titer of serial passage HCVcc were assessed by Real Time RT-PCR, indirect immunofluorescence assay (IFA) and Western blotting (WB). In addition, chimeric envelope gene from HCVcc was sequenced after serial passage. We found that the number of HCV positive focus increased gradually in cell post-transfection with chimera HCVcc (1b/2a) RNA and reach a peak platform (80% to 90%) at 41 days post-transfection; the expression of HCV protein was also confirmed by WAB during serial passage. At meantime, HCV RNA copy number in the supernatant peaked at 10(4)-10(7) copies/mL and the highest infectious titer of this 1b/2a cHCVcc reinfection were tested as 10(4) ffu/mL. Sequence analysis indicated 6 of adaptive amino acid substitutes occur among chimeric envelope E1E2 during serial passages. We con:luded that a novel 1b/2a chimera HCVcc carrying envelope E1E2 coding gene from Hebei strain of China was developed and its infectious titer increased after serial passage of HCVcc. This novel cHCVcc will be an effective tool for further evaluation of anti-virus drugs and immune effects against the major genotype from Chinese.

  5. [Characterization of Serial Passage of 1b/2a Chimera Hepatitis C Virus Cell Culture System Carrying Envelope E1E2 Coding Gene from Hebei Strain of China].

    PubMed

    Lu, Sha; Zhang, Ling; Tao, Gesi; Cai, Min; Bao Lili; LI, Lian; Deng, Yao; Shen, Xiaoling; Tan, Wenjie

    2015-11-01

    To character a novel chimera(1b/2a) hepatitis C virus cell culture (HCVcc) system carrying envelope E1E2 coding gene from Hebei strain of China, chimera HCVcc (cHCVcc) was developed from Huh7.5-CD81 cells after transfection with in vitro transcribed full-length 1b/2a chimera RNA, which carrying envelope E1E2 coding gene from Hebei strain of China. Then the replication, expression and infectious titer of serial passage HCVcc were assessed by Real Time RT-PCR, indirect immunofluorescence assay (IFA) and Western blotting (WB). In addition, chimeric envelope gene from HCVcc was sequenced after serial passage. We found that the number of HCV positive focus increased gradually in cell post-transfection with chimera HCVcc (1b/2a) RNA and reach a peak platform (80% to 90%) at 41 days post-transfection; the expression of HCV protein was also confirmed by WAB during serial passage. At meantime, HCV RNA copy number in the supernatant peaked at 10(4)-10(7) copies/mL and the highest infectious titer of this 1b/2a cHCVcc reinfection were tested as 10(4) ffu/mL. Sequence analysis indicated 6 of adaptive amino acid substitutes occur among chimeric envelope E1E2 during serial passages. We con:luded that a novel 1b/2a chimera HCVcc carrying envelope E1E2 coding gene from Hebei strain of China was developed and its infectious titer increased after serial passage of HCVcc. This novel cHCVcc will be an effective tool for further evaluation of anti-virus drugs and immune effects against the major genotype from Chinese. PMID:26951010

  6. Liver Shear-Wave Velocity and Serum Fibrosis Markers to Diagnose Hepatic Fibrosis in Patients with Chronic Viral Hepatitis B

    PubMed Central

    Liu, Jianxue; Ji, Yonghao; Ai, Hong; Ning, Bo; Zhao, Junzhi; Zhang, Yaoren

    2016-01-01

    Objective To compare several noninvasive indices of fibrosis in chronic viral hepatitis B, including liver shear-wave velocity (SWV), hyaluronic acid (HA), collagen type IV (CIV), procollagen type III (PCIII), and laminin (LN). Materials and Methods Acoustic radiation force impulse (ARFI) was performed in 157 patients with chronic viral hepatitis B and in 30 healthy volunteers to measure hepatic SWV (m/s) in a prospective study. Serum markers were acquired on the morning of the same day of the ARFI evaluation. Receiver operating characteristic (ROC) analysis was performed to evaluate and compare the accuracies of SWV and serum markers using METAVIR scoring from liver biopsy as a reference standard. Results The most accurate test for diagnosing fibrosis F ≥ 1 was SWV with the area under the ROC curve (AUC) of 0.913, followed by LN (0.744), HA (0.701), CIV (0.690), and PCIII (0.524). The best test for diagnosing F ≥ 2 was SWV (AUC of 0.851), followed by CIV (0.671), HA (0.668), LN (0.562), and PCIII (0.550). The best test for diagnosing F ≥ 3 was SWV (0.854), followed by CIV (0.693), HA (0.675), PCIII (0.591), and LN (0.548). The best test for diagnosing F = 4 was SWV (0.965), followed by CIV (0.804), PCIII (0.752), HA (0.744), and LN (0.662). SWV combined with HA and CIV did not improve diagnostic accuracy (AUC = 0.931 for F ≥ 1, 0.863 for F ≥ 2, 0.855 for F ≥ 3, 0.960 for F = 4). Conclusion The performance of SWV in diagnosing liver fibrosis is superior to that of serum markers. However, the combination of SWV, HA, and CIV does not increase the accuracy of diagnosing liver fibrosis and cirrhosis. PMID:27134527

  7. Paediatrics: Children need optimal management of chronic hepatitis B.

    PubMed

    Chang, Mei-Hwei

    2013-09-01

    Current therapies for chronic HBV infection are focused on adults. However, the timing of primary infection of HBV often occurs during infancy or childhood, particularly in endemic areas. Children have the potential for a long lifespan and should be treated properly and early before complications develop.

  8. Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting.

    PubMed

    Galante, A; Pischke, S; Polywka, S; Luetgehethmann, M; Suneetha, P V; Gisa, A; Hiller, J; Dienes, H P; Nashan, B; Lohse, A W; Sterneck, M

    2015-08-01

    The chronic course of hepatitis E virus (HEV) infections in orthotopic liver transplant (OLT) recipients has been described previously, but prospectively collected data are rare. We aimed to study the role of chronic hepatitis E in OLT in a real-life setting. Therefore, 287 adult OLT recipients (169 male [59%], median age 56 years) were prospectively tested by HEV polymerase chain reaction assay (lower level of detection = 10 IU/mL), irrespective of their level of liver enzymes. In 4 patients (1.4%), chronic HEV infection was diagnosed. All 4 patients were male, and their age (median 48.5 years), the time since transplantation (median 45.5 months), and bilirubin level (median 0.6 mg/dL) did not differ significantly from the total cohort. However, alanine transaminase and aspartame transaminase levels were significantly higher in HEV-infected patients (75-646 U/L, median 216 U/L and 68-317 U/L, median 108 U/L) than in non-infected patients (6-617 U/L, median 41 and 6-355 U/L, median 36; P = 0.004 and 0.040, Mann-Whitney test). In 3 patients, liver biopsy was performed and revealed signs of inflammation and chronic liver disease, as enlarged densely infiltrated portal tracts with mild-to-moderate interface hepatitis. All infected patients were treated with ribavirin with the starting dose adjusted to renal function (400-800 mg/day). In 2 patients, dose reduction was necessary. Transaminases normalized in all 4 patients, and all patients cleared their infection within 3 months of ribavirin treatment. However, 1 patient experienced viral relapse 12 weeks after discontinuation. Ribavirin medication was re-started and viral clearance occurred within 8 weeks and persisted. Sequence analysis of the HEV genome of this patient revealed that he was infected with an HEV variant, which recently has been shown to have a reduced response to ribavirin in cell culture. The risk of chronic HEV infections in OLT recipients in low-endemic countries should not be overestimated. No case

  9. Immunological changes in different patient populations with chronic hepatitis C virus infection

    PubMed Central

    Szereday, Laszlo; Meggyes, Matyas; Halasz, Melinda; Szekeres-Bartho, Julia; Par, Alajos; Par, Gabriella

    2016-01-01

    AIM: To investigate killer inhibitory and activating receptor expression by natural killer (NK), natural killer T-like (NKT-like) and CD8+ T lymphocytes in patients with chronic hepatitis C virus (HCV) infection with elevated and with persistently normal alanine aminotransferase (PNALT). METHODS: The percentage of peripheral blood Treg cells, KIR2DL3, ILT-2, KIR3DL1, CD160, NKG2D, NKG2C expressing NK, T and NKT-like cells, cytokine production and NK cytotoxicity were determined by flow cytometry. Twenty-one patients with chronic HCV infection with elevated alanine aminotransferase, 11 HCV carriers with persistently normal alanine aminotransferase and 15 healthy volunteers were enrolled. RESULTS: No significant differences were observed in the percentage of total T, NK or NKT-like cells between study groups. Comparing the activating and inhibitory receptor expression by NK cells obtained from HCV carriers with PNALT and chronic HCV hepatitis patients with elevated alanine aminotransferase, NKG2D activating receptor expression was the only receptor showing a significant difference. NKG2D expression of NK cells was significantly lower in patients with elevated alanine aminotransferase. The expression of CD160, NKG2D and NKG2C activating receptor by CD8+ T cells were significantly lower in patients with chronic HCV hepatitis than in healthy controls and in HCV carriers with PNALT. Plasma TGF-β1 levels inversely correlated with NKG2D expression by NK cells. In vitroTGF-β1 treatment inhibited NK cells cytotoxic activity and downregulated NKG2D expression. CD8+ T cells from HCV carriers with PNALT showed significantly elevated expression of CD160, NKG2D and NKG2C activating receptors compared to chronic HCV patients with elevated alanine aminotransferase. Enhanced expression of inhibitory KIR2DL3 receptor, and decreased ILT-2 expression on NK cells were also found in chronic hepatitis C patients compared to healthy controls. CONCLUSION: Our study demonstrated a complex

  10. Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting.

    PubMed

    Galante, A; Pischke, S; Polywka, S; Luetgehethmann, M; Suneetha, P V; Gisa, A; Hiller, J; Dienes, H P; Nashan, B; Lohse, A W; Sterneck, M

    2015-08-01

    The chronic course of hepatitis E virus (HEV) infections in orthotopic liver transplant (OLT) recipients has been described previously, but prospectively collected data are rare. We aimed to study the role of chronic hepatitis E in OLT in a real-life setting. Therefore, 287 adult OLT recipients (169 male [59%], median age 56 years) were prospectively tested by HEV polymerase chain reaction assay (lower level of detection = 10 IU/mL), irrespective of their level of liver enzymes. In 4 patients (1.4%), chronic HEV infection was diagnosed. All 4 patients were male, and their age (median 48.5 years), the time since transplantation (median 45.5 months), and bilirubin level (median 0.6 mg/dL) did not differ significantly from the total cohort. However, alanine transaminase and aspartame transaminase levels were significantly higher in HEV-infected patients (75-646 U/L, median 216 U/L and 68-317 U/L, median 108 U/L) than in non-infected patients (6-617 U/L, median 41 and 6-355 U/L, median 36; P = 0.004 and 0.040, Mann-Whitney test). In 3 patients, liver biopsy was performed and revealed signs of inflammation and chronic liver disease, as enlarged densely infiltrated portal tracts with mild-to-moderate interface hepatitis. All infected patients were treated with ribavirin with the starting dose adjusted to renal function (400-800 mg/day). In 2 patients, dose reduction was necessary. Transaminases normalized in all 4 patients, and all patients cleared their infection within 3 months of ribavirin treatment. However, 1 patient experienced viral relapse 12 weeks after discontinuation. Ribavirin medication was re-started and viral clearance occurred within 8 weeks and persisted. Sequence analysis of the HEV genome of this patient revealed that he was infected with an HEV variant, which recently has been shown to have a reduced response to ribavirin in cell culture. The risk of chronic HEV infections in OLT recipients in low-endemic countries should not be overestimated. No case

  11. [A Case of Composite Hepatocellular Carcinoma and Neuroendocrine Carcinoma in a Patient with Liver Cirrhosis Caused by Chronic Hepatitis B].

    PubMed

    Yun, Eun Young; Kim, Tae Hyo; Lee, Sang Soo; Kim, Hong Jun; Kim, Hyun Jin; Jung, Woon Tae; Lee, Ok Jae; Song, Dae Hyun

    2016-08-25

    Primary hepatic neuroendocrine carcinoma (PHNEC) is rare and its origin is not clearly understood. The coexistence of PHNEC and hepaotcellular carcinoma has been reported in only a few cases. We report a rare case of combined PHNEC and hepaotcellular carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B that resulted in aggressive behavior and poor prognosis. PMID:27554219

  12. Sofosbuvir for the treatment of chronic hepatitis C virus infection.

    PubMed

    Temesgen, Z; Talwani, R; Rizza, S A

    2014-06-01

    Sofosbuvir is a nucleotide analogue selective inhibitor of the RNA-directed RNA polymerase (NS5B) enzyme of the hepatitis C virus (HCV) genome. It has shown potent antiviral activity across all HCV genotypes and in a variety of patient populations, including treatment-naive patients; treatment-experienced patients who had failed previous standard therapy; patients with decompensated liver disease, including cirrhosis; and HIV co-infected patients. It is administered as a single, once-daily 400-mg tablet, has no food restrictions, has low potential for drug interactions, and requires no dose adjustment in mild to moderate kidney or liver impairment. When sofosbuvir is combined with pegylated interferon and/or ribavirin, its clinical and laboratory safety profile is similar to that which is expected from pegylated interferon or ribavirin alone. Rates of treatment discontinuation and dose reduction with sofosbuvir-containing regimens were lower than those commonly observed with pegylated interferon and ribavirin.

  13. Chronic alcohol intake upregulates hepatic expression of carotenoid cleavage enzymes and PPAR in rats.

    PubMed

    Luvizotto, Renata A M; Nascimento, André F; Veeramachaneni, Sudipta; Liu, Chun; Wang, Xiang-Dong

    2010-10-01

    Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism. Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15'-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9'10'-monooxygenase 2 (CMO2). CMO1 has been shown to be regulated by several transcription factors, such as the PPAR, retinoid X receptor, and thyroid receptor (TR). The regulation of CMO2 has yet to be identified. The impact of chronic alcohol intake on hepatic expressions of CMO1 and CMO2 and their related transcription factors are unknown. In this study, Fischer 344 rats were pair-fed either a liquid ethanol Lieber-DeCarli diet (n = 10) or a control diet (n = 10) for 11 wk. Hepatic retinoid concentration and expressions of CMO1, CMO2, PPARγ, PPARα, and TRβ as well as plasma thyroid hormones levels were analyzed. We observed that administering alcohol decreased hepatic retinoid levels but increased mRNA concentrations of CMO1, CMO2, PPARγ, PPARα, and TRβ and upregulated protein levels of CMO2, PPARγ, and PPARα. There was a positive correlation of PPARγ with CMO1 (r = 0.89; P < 0.0001) and both PPARγ and PPARα with CMO2 (r = 0.72, P < 0.001 and r = 0.62, P < 0.01, respectively). Plasma thyroid hormone concentrations did not differ between the control rats and alcohol-fed rats. This study suggests that chronic alcohol intake significantly upregulates hepatic expression of CMO1 and, to a much lesser extent, CMO2. This process may be due to alcohol-induced PPARγ expression and lower vitamin A status in the liver.

  14. The clinical outcomes of chronic hepatitis C in South Korea: A prospective, multicenter cohort study.

    PubMed

    Ok, Kyeong Sam; Jeong, Sook-Hyang; Jang, Eun Sun; Kim, Young Seok; Lee, Youn Jae; Kim, In Hee; Cho, Sung Bum; Bae, Si Hyun; Lee, Han Chu

    2016-08-01

    This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region.From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival.During the median follow-up of 39.0 months (range 18.0-81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150  × 10/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002).The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy. PMID:27583874

  15. Interferon lambda genotype and low serum LDL cholesterol levels in patients with chronic hepatitis C infection

    PubMed Central

    Li, Josephine H.; Lao, Xiang Qian; Tillmann, Hans L.; Rowell, Jennifer; Patel, Keyur; Thompson, Alexander; Suchindran, Sunil; Muir, Andrew J.; Guyton, John R.; Gardner, Stephen D.; McHutchison, John G.; McCarthy, Jeanette J.

    2010-01-01

    Background Recently, genetic polymorphisms occurring in the interferon lambda gene region were associated with response to interferon-based treatment of hepatitis C infection. Both infection with the hepatitis C virus and interferon therapy are associated with decreased serum cholesterol and high cholesterol has been associated with increased likelihood to respond to interferon. We sought to determine if the interferon lambda gene variant was also associated with serum lipid levels in chronic hepatitis C patients. We compared genotypes of the rs12979860 polymorphism, located proximal to the IL28 gene, with serum lipid and apolipoprotein levels in 746 subjects with chronic HCV infection, not currently undergoing treatment, using multivariable analysis of variance. Results Levels of total cholesterol (p=6.0×10-4), apolipoprotein B (p=1.3×10-6) and low density lipoprotein (LDL) cholesterol (p=8.9×10-10) were significantly higher in subjects carrying the rs12979860 CC ‘responder’ genotype compared to those with the CT or TT genotype. Levels of triglycerides (p=0.03), apolipoprotein A-I (p=0.06) and apolipoprotein E (p=0.01) were slightly lower in the rs12979860 CC genotype group, while levels of high density lipoprotein cholesterol (p=0.78) and apolipoprotein C-III (p=0.74) did not vary by rs12979860 genotype. Conclusions Our results suggest that low levels of LDL cholesterol in chronic hepatitis C patients may be a marker of host endogenous interferon response to hepatitis C and that subjects with the rs12979860 CC ‘responder’ genotype may have a lower endogenous interferon response to the virus. PMID:20235331

  16. The clinical outcomes of chronic hepatitis C in South Korea: A prospective, multicenter cohort study.

    PubMed

    Ok, Kyeong Sam; Jeong, Sook-Hyang; Jang, Eun Sun; Kim, Young Seok; Lee, Youn Jae; Kim, In Hee; Cho, Sung Bum; Bae, Si Hyun; Lee, Han Chu

    2016-08-01

    This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region.From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival.During the median follow-up of 39.0 months (range 18.0-81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150  × 10/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002).The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy.

  17. Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

    PubMed Central

    2011-01-01

    Background Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients. Methods Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. Results HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001). Conclusions IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development. PMID:22044490

  18. [Chronic hepatitis B: standard of therapy and perspectives].

    PubMed

    Rizzetto, Mario

    2016-07-01

    Infection with the hepatitis B virus (HBV) has much diminished in Italy in the last 25 years; at present, all Italian nationals aged under 36 years are protected from HBV by vaccinal immunity. The problem of the infection has shifted to the immigrants from countries where HBV is still endemic; in this population the prevalence of the infection is high, up to 10% of the immigrants. In the next 5 years the prevalence of HBV is bound to further diminish in the domestic population, for the increment of the age of the subjects protected by mandatory HBV vaccination and for the natural exhaustion of the elderly cohorts of HBsAg carriers which represent the last domestic reservoir of the infection. Most likely, instead, the problem in immigrants will become more important, forcing new strategies to the approach and containment of HBV. Therapy of hepatitis B is not satisfactory; it allows the control of HBV replication and related disease but is not capable of clearing the virus; eradication of the HBsAg is achieved only in few patients. The future target are therapies aimed at eradicating the HBV, not only at containing its replication and disease expression. A miriad new drugs acting directly against functions necessary to the life cycle of the HBV are under study; it is unlikely, however, that they will enter clinical trials in the few years. More promising in the short term, it is the development of prodrugs of antivirals currently in use, of which tenofovir alafenamide (TAF), the prodrug of tenofovir, is the prototype, entering soon into therapeutic routine. PMID:27571465

  19. Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective

    PubMed Central

    Nkuize, Marcel; Sersté, Thomas; Buset, Michel; Mulkay, Jean-Pierre

    2016-01-01

    Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A) and sofosbuvir 400 mg (anti-NS5B), has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-naïve, treatment-experienced, and with advanced liver disease or posttransplant) patients and HIV–hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection. PMID:27350749

  20. Treatment strategies according to genotype for chronic hepatitis B in children

    PubMed Central

    Man Cho, Seung

    2016-01-01

    This review article was requested by editor-in-chief of this journal as ‘pediatric CHB treatment’ for the upcoming special issue. The main objective of chronic hepatitis B (CHB) treatment is diminishing the risk of complications related to chronic liver disease. In Asia, there are already some reports about hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) infected children. The key points of treatment in children with CHB infections are selection of which patients to treat and conformation of the optimal therapy time that would reduce viral resistance. The choice of therapy is determined by the district (Western/Eastern), HBV genotype, medical accessibility, and economic state of the country. Newly developed nucleos(t)ide analogues (NAs) are potent in children with CHB. However, to improve therapeutic efficacy, physicians are recommended to follow treatment guidelines and determine the specific genotype in the CHB patient. In this article, the treatment of pediatric CHB is reviewed according to differences in genotype.

  1. The use of generics to treat chronic hepatitis C: not quite ready for the big stage.

    PubMed

    Sarpel, Dost; Dieterich, Douglas

    2016-07-01

    Recently developed direct acting antivirals have been highly effective in treating patients with chronic hepatitis C infection. Due to their expense, there has been development of generic formulations of these medications in many countries. However, there has been controversy regarding the bioequivalence of generics when compared to brand name medications. Inactive ingredients, which may differ in generic medications, can alter the bioequivalence of the active ingredient as well as provoke intolerance or confusion among patients. There is also concern regarding the quality control and assessment of the manufacturing process of generics. When taken together these issues have the potential to lead to treatment failure. The use of generics to treat chronic hepatitis C will remain controversial, until these issues are adequately addressed. PMID:27306304

  2. [Immunosuppressive therapy in patients with HBeAg-positive chronic active hepatitis B?].

    PubMed

    Maier, K P; Lepiorz, H; Berthold, H; Gerok, W

    1982-08-01

    The course of HBsAg-positive chronic active hepatitis was followed in 36 patients who were treated by immunosuppression and in 45 controls by means of serial determinations of HBeAg titers and by repeated biopsies of the liver. In the treated group remission occurred in 52% (HBeAg negative) resp. 48% (HBeAg positive); in the control group these percentages were almost identical, that is to say 61% resp. 41%. During therapy 5 out of 9 HBeAg positive patients and 7 out of 12 HBeAg negative patients developed cirrhosis of the liver as compared to 5 resp. 10, and 2 resp. 12 patients in the control group. Judging from these results it seems unlikely, that the course of HBsAg positive, chronic-active hepatitis in patients, whose serum shows a positive HBeAg titer by immunodiffusion, might be influenced in a positive way by immunosuppressive therapy.

  3. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin

    PubMed Central

    Jain, K; Lam, W; Waheeb, S; Thai, Q; Heathcote, J

    2001-01-01

    AIM—To assess the ocular effect of interferon alfa 2b prescribed with ribavirin in patients undergoing therapy for chronic hepatitis C.
METHODS—19 patients with chronic hepatitis C who satisfied the follow up criteria were assessed for ocular complications using slit lamp biomicroscopy and indirect ophthalmoscopy before, during, and after the treatment at regular intervals.
RESULTS—8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.
CONCLUSION—Retinopathy was more common in interferon monotherapy non-responders than relapsers when treated with interferon alfa 2b with the addition of ribavirin. The changes were transient, disappearing while the patients were still being treated.

 PMID:11567959

  4. HIV-negative case of bacillary angiomatosis with chronic hepatitis B.

    PubMed

    Kaçar, Nida; Taşli, Levent; Demirkan, Neşe; Ergin, Cağri; Ergin, Seniz

    2010-08-01

    Bacillary angiomatosis (BA) is an infectious disease which occurs predominantly in immunosuppressive patients and rarely in immunocompetent individuals. We had a case of BA who presented with a red cutaneous nodule on his left leg of which histopathological examination revealed marked lobular proliferation of capillaries throughout the interstitium and clusters of bacilli with hematoxylin-eosin and Warthin-Starry stains, respectively. Antibody titer against Bartonella henselae was 1/32. The only systemic disease the patient had was chronic hepatitis B. HIV was negative and no other immunosuppressive status was established. In this case we believe that the immunological differences secondary to chronic hepatitis B could have caused a tendency for the disease development.

  5. NK Cells: A Double-Edged Sword in Chronic Hepatitis B Virus Infection

    PubMed Central

    Maini, Mala K.; Peppa, Dimitra

    2013-01-01

    There is natural enrichment of NK cells in the human liver and this intrahepatic predominance underscores their potential importance in the control of infections with hepatotropic viruses such as hepatitis B virus (HBV). The contribution of innate components during chronic HBV infection has been a relatively under-investigated area. However, recent data have highlighted that NK cells are capable of exerting antiviral and immunoregulatory functions whilst also contributing to the pathogenesis of liver injury via death receptor pathways. We will present an overview of current knowledge regarding the complex biology of NK cells in the context of their antiviral versus pathogenic role in chronic hepatitis B as a clinically relevant avenue for further investigation. PMID:23459859

  6. Observational descriptive study of cutaneous manifestations in patients from Mato Grosso with viral chronic hepatitis*

    PubMed Central

    Rostey, Renato Roberto Liberato; Souto, Francisco José Dutra

    2015-01-01

    BACKGROUND Extrahepatic manifestations are seen in association with chronic infection by hepatitis B or C virus including cutaneous disorders. The frequency of these findings seems to vary among different places and reports. There is a lack of information about this issue in Brazil. OBJECTIVES To estimate the prevalence of cutaneous findings affecting HBV or HCV carriers from a reference outpatient unit in Mato Grosso. METHODS A cross-sectional observational study. RESULTS 108 patients were studied. 88.9% presented some cutaneous findings but must of them were nonrelated to chronic viral infection. Four patients had cutaneous or autoimmune syndromes that may be HBV or HCV related. CONCLUSION In our study we found no statistical association between viral hepatitis and skin diseases. PMID:26734863

  7. Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers

    SciTech Connect

    Dusheiko, G.M.; Hoofnagle, J.H.; Cooksley, W.G.; James, S.P.; Jones, E.A.

    1983-05-01

    It has been postulated that host immune defects are responsible for the development and persistence of the hepatitis B surface antigen (HBsAg) carrier state. The synthesis of both anti-HBs and antibody to hepatitis B core antigen (anti-HBc) in cultures containing peripheral blood mononuclear cells from chronic HBsAg carriers and from control (antibody-positive) patients was measured in the presence of pokeweed mitogen. Similar amounts of polyclonal IgG and IgM were synthesized by cultures containing lymphocytes from chronic carriers and controls. Anti-HBc was detectable in lymphocyte supernatants from 2 of 20 controls and from 21 of 29 carriers. The presence of anti-HBc synthesis in vitro correlated with high serum titers of anti-HBc. In contrast, anti-HBs was detected in lymphocyte supernatants from 6 of 20 controls (predominantly in those who had high serum titers of anti-HBs) but in none of the supernatants from 29 HBsAg carriers. Co-culture experiments were performed using T and B lymphocyte fractions that had been purified by affinity chromatography. B lymphocytes from carriers co-cultured with allogeneic irradiated (''helper'') T lymphocytes from controls synthesized normal amounts of IgG, IgM, and anti-HBc but still did not synthesize detectable amounts of anti-HBs. In the converse experiments, B lymphocytes from controls were co-cultured with irradiated T lymphocytes from carriers. The T lymphocytes from 16 of 24 carriers augmented anti-HBs production by control B cells normally, the remaining eight did not. Finally, mixtures of control B cells and control irradiated T lymphocytes were co-cultured with T lymphocytes from chronic HBsAg carriers. 5 of 12 carriers demonstrated active suppression of anti-HBs production, and in three this suppression was specific, as IgG and IgM production remained normal.

  8. Role of hepatitis C infection in chronic liver disease in Egypt.

    PubMed

    Strickland, G Thomas; Elhefni, Hanaa; Salman, Tary; Waked, Imam; Abdel-Hamid, Mohamed; Mikhail, Nabiel Nh; Esmat, Gamal; Fix, Alan

    2002-10-01

    Hepatitis C virus (HCV) is considered the most common etiology of chronic liver disease (CLD) in Egypt, where prevalence of antibodies to HCV (anti-HCV) is approximately 10-fold greater than in the United States and Europe. Reported are results that show the role of HCV in both overt and occult CLD, the risk factors for CLD and for HCV infection, and the relative importance of chronic HCV, hepatitis B, or both in causing hepatic morbidity. Case patients included 237 new outpatients at the National Liver Institute. Controls comprised 212 sex- and age-matched neighbors without liver disease. Case patients were more likely than controls to report a history of blood transfusions, schistosomiasis, or parenteral therapy for schistosomiasis; to have anti-HCV, HCV RNA, hepatitis B surface antigen, and serum alanine aminotransferase (ALT) elevations; and to have abdominal ultrasound findings of cirrhosis, portal hypertension, and splenomegaly. Anti-HCV-positive case patients were more likely than anti-HCV-negative patients to be male, older, and farmers: to have received a blood transfusion or parenteral therapy for schistosomiasis; to have ALT elevations; and to have ultrasound findings of cirrhosis, portal hypertension, and spleen enlargement. Anti-HCV-positive controls were more likely than anti-HCV-negative controls to have received parenteral therapy for schistosomiasis. These data support the belief that HCV is the predominant cause of CLD in Egypt and suggest there is a large underlying reservoir of HCV-caused liver disease.

  9. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    PubMed

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C. PMID:20460925

  10. Activated natural killer cells accelerate liver damage in patients with chronic hepatitis B virus infection.

    PubMed

    Zheng, Q; Zhu, Y Y; Chen, J; Ye, Y B; Li, J Y; Liu, Y R; Hu, M L; Zheng, Y C; Jiang, J J

    2015-06-01

    Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3-4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.

  11. The relationship between visfatin, liver inflammation, and acute phase reactants in chronic viral hepatitis B.

    PubMed

    Yüksel, Enver; Akbal, Erdem; Koçak, Erdem; Akyürek, Ömer; Köklü, Seyfettin; Ekiz, Fuat; Yılmaz, Barış

    2016-09-01

    Chronic viral hepatitis B (CHB) is an important cause of morbidity and mortality. Adipokine stimulation might play an important role in the pathogenesis of chronic inflammation. The aim of this study was to evaluate serum visfatin concentrations and the relationship between visfatin, fibrosis, liver inflammation, and acute phase reactants in CHB patients.The sampling universe of the study consisted of 41 CHB patients and 25 healthy controls. All patients had positive hepatitis B surface antigen (Hepatitis e antigen (HBeAg) positive n: 7, n: 34 HBeAg negative) for at least 6 months and detectable serum HBV DNA. Serum visfatin concentrations were significantly higher in the CHB patients [18.0 ± 10.9 ng dL(-1)] than in the healthy controls [9.4 ± 1.6 ng dL(-1)] [P < 0.001]. On the other hand, fibrinogen and haptoglobin concentrations were significantly lower in CHB patients. A strong negative correlation was observed between serum visfatin concentration, haptoglobin, and fibrinogen levels; however, there was no significant correlation between visfatin, glucose, alanine aminotransferase, aspartate aminotransferase, BMI, Knodell score, fibrosis score, hepatitis B virus DNA, sedimentation, and C-reactive protein. Visfatin concentrations were elevated and visfatin was negatively correlated with haptoglobin and fibrinogen levels in CHB patients.

  12. Chronic hepatitis B: role of anti-platelet therapy in inflammation control.

    PubMed

    Aiolfi, Roberto; Sitia, Giovanni

    2015-05-01

    Platelets play a known role in the maintenance of vascular homeostasis, but these cells are emerging as important cellular mediators of acute and chronic inflammatory diseases. Platelets are key elements in the pathogenesis of acute and chronic liver disease associated with hepatitis B virus (HBV) infection by promoting the accumulation of virus-specific CD8(+) T cells and nonspecific inflammatory cells into the liver parenchyma. This review discusses major platelet functions in immune and inflammatory responses, with an emphasis on recent pre-clinical studies that suggest that the inhibition of platelet activation pathways represent an alternative therapeutic strategy with potential use in the reduction of virus-specific T cell-mediated chronic inflammation, liver fibrosis and hepatocellular carcinoma in patients who are chronically infected with HBV.

  13. [Salivary glands and oral mucous membrane status in patients with chronic hepatitis].

    PubMed

    Afanas'ev, V V; Muromtsev, A V; Derkach, N V

    2008-01-01

    The status of salivary glands and oral mucous membrane was investigated in 50 patients with chronic active hepatitis against the background of chronic alcoholism. The check up disclosed sialadenosis in 38% of patients and in 54% of patients - such diseases of oral mucous membrane as stomatitis, candidosis and geographic tonque. Besides there were disclosed such disturbances as big and small salivary glands secretion reduction, mixed saliva viscosity increase, increase of protein, P, K, Na and catalase content in it, glycogen hyperaccumulation in gingival tissues. The received data indicated the necessity of dispensary supervision of such patients and their treatment in stomatologist.

  14. New era for management of chronic hepatitis C virus using direct antiviral agents: A review

    PubMed Central

    Elbaz, Tamer; El-Kassas, Mohamed; Esmat, Gamal

    2014-01-01

    The pegylated interferon regimen has long been the lone effective management of chronic hepatitis C with modest response. The first appearance of protease inhibitors included boceprevir and telaprevir. However, their efficacy was limited to genotype 1. Recently, direct antiviral agents opened the gate for a real effective management of HCV, certainly after FDA approval of some compounds that further paved the way for the appearance of enormous potent direct antiviral agents that may achieve successful eradication of HCV. PMID:26257927

  15. Essential Role of Protein-tyrosine Phosphatase 1B in the Modulation of Insulin Signaling by Acetaminophen in Hepatocytes*

    PubMed Central

    Mobasher, Maysa Ahmed; de Toro-Martín, Juan; González-Rodríguez, Águeda; Ramos, Sonia; Letzig, Lynda G.; James, Laura P.; Muntané, Jordi; Álvarez, Carmen; Valverde, Ángela M.

    2014-01-01

    Many drugs are associated with the development of glucose intolerance or deterioration in glycemic control in patients with pre-existing diabetes. We have evaluated the cross-talk between signaling pathways activated by acetaminophen (APAP) and insulin signaling in hepatocytes with or without expression of the protein-tyrosine phosphatase 1B (PTP1B) and in wild-type and PTP1B-deficient mice chronically treated with APAP. Human primary hepatocytes, Huh7 hepatoma cells with silenced PTP1B, mouse hepatocytes from wild-type and PTP1B-deficient mice, and a mouse model of chronic APAP treatment were used to examine the mechanisms involving PTP1B in the effects of APAP on glucose homeostasis and hepatic insulin signaling. In APAP-treated human hepatocytes at concentrations that did not induce death, phosphorylation of JNK and PTP1B expression and enzymatic activity were increased. APAP pretreatment inhibited activation of the early steps of insulin signaling and decreased Akt phosphorylation. The effects of APAP in insulin signaling were prevented by suramin, a PTP1B inhibitor, or rosiglitazone that decreased PTP1B levels. Likewise, PTP1B deficiency in human or mouse hepatocytes protected against APAP-mediated impairment in insulin signaling. These signaling pathways were modulated in mice with chronic APAP treatment, resulting in protection against APAP-mediated hepatic insulin resistance and alterations in islet alpha/beta cell ratio in PTP1B−/− mice. Our results demonstrate negative cross-talk between signaling pathways triggered by APAP and insulin signaling in hepatocytes, which is in part mediated by PTP1B. Moreover, our in vivo data suggest that chronic use of APAP may be associated with insulin resistance in the liver. PMID:25204659

  16. Peripheral blood dendritic cells are phenotypically and functionally intact in chronic hepatitis B virus (HBV) infection

    PubMed Central

    Tavakoli, S; Mederacke, I; Herzog-Hauff, S; Glebe, D; Grün, S; Strand, D; Urban, S; Gehring, A; Galle, P R; Böcher, W O

    2008-01-01

    Persistence of hepatitis B virus (HBV) infection is associated with reduced anti-viral T cell responses. Impaired dendritic cell (DC) function was suggested as the cause of reduced T cell stimulation in chronic HBV carriers. Thus, we compared myeloid (mDC) and plasmacytoid DC (pDC) from chronic HBV carriers and controls. Frequency and phenotype of isolated DC were analysed by fluorescence activated cell sorter staining, DC function by mixed lymphocyte reaction, cytokine bead array, intracellular cytokine staining, enzyme-linked immunosorbent assay and enzyme-linked immunospot. Expression of HBV DNA and mRNA was studied by polymerase chain reaction (PCR). Circulating total DC, mDC or pDC were not reduced in chronic HBV carriers. Isolated mDC and pDC from chronic HBV carriers exhibited similar expression of co-stimulatory molecules and alloreactive T helper cell stimulation as control DC, whether tested directly ex vivo or after in vitro maturation. Secretion of pro- and anti-inflammatory cytokines by CD40 or Toll-like receptor ligand-stimulated patient DC was intact, as was human leucocyte antigen A2-restricted HBV-specific cytotoxic lymphocyte stimulation. Although both DC populations contained viral DNA, viral mRNA was undetectable by reverse transcription–PCR, arguing against viral replication in DC. We found no quantitative, phenotypic or functional impairment of mDC or pDC in chronic hepatitis B, whether studied ex vivo or after in vitro maturation. PMID:18031557

  17. Antiplatelet antibodies contribute to thrombocytopenia associated with chronic hepatitis C virus infection.

    PubMed

    Aref, Salah; Sleem, Tarek; El Menshawy, Nadia; Ebrahiem, Lamiaa; Abdella, Dooa; Fouda, Manal; Samara, Nashwa Abou; Menessy, Aymen; Abdel-Ghaffar, Hassen; Bassam, Ansaf; Abdel Wahaab, Mohamed

    2009-10-01

    Thrombocytopenia is one of the most frequent hematological manifestations of hepatitis C virus (HCV) infection; which typically worsens with progression of the liver disease and can become a major clinical complication. Several mechanisms have been postulated to explain thrombocytopenia in HCV hepatic patients, including immune mechanisms. The aim of the present work is to investigate the role of immune mechanisms as a causative agent of thrombocytopenia in HCV hepatic patients. The study included 50 hepatic patients with HCV infection (30 with thrombocytopenia and 20 with normal platelets counts). Platelets associated glycoprotein specific antibodies were evaluated by flow cytometry and confirmed by quantitative monoclonal immobilization of platelet antibodies (MAIPA). The frequency of platelet associated immunoglobulin (PAIg) in thrombocytopenic HCV positive hepatic patients by FCM was 86.7, 83.3, 46.7 and 33.3% for total PAIg, PAIgG, PAIgM and PAIgA respectively. MAIPA found platelet specific antibodies in 26/30 (86.7%) of patients. The most likely target antigen for platelets antibodies were glycoprotein (GP) IIb/IIIa (30%), followed by GP IIIa (20.5), GP IIb (13.3%), GPIb (13.3%), then GPIa (10%). The platelets count was inversely correlated to the levels of platelets GP specific antibodies (r=-0.42, p=0.024), and significantly parallel to spleen size (p=0.024). Platelet associated glycoprotein specific antibodies represent a common mechanism inducing thrombocytopenia in patients with chronic HCV infections. PMID:19843383

  18. Syncytial giant cell hepatitis in a patient with chronic lymphocytic leukemia

    PubMed Central

    GUPTA, Neil; NJEI, Basile

    2016-01-01

    While it commonly occurs in the pediatric population, syncytial giant cell hepatitis is rare in adults, which is diagnosed histologically by the presence of multinucleated cells in the liver. The literature has recorded only approximately one hundred cases in adults during the past two decades in whom malignancy is rarely associated with giant cell hepatitis. Our patient is a 66-year-old woman who was diagnosed with chronic lymphocytic leukemia (CLL) and subsequently developed syncytial giant cell hepatitis. This disease is usually linked to virus infection, autoimmune diseases, and drug medications. The association between CLL and giant cell hepatitis is rare, with only three cases reported. In most cases viral particles on electron microscopy are reported and the patients usually have a history of chemotherapy and hypogammaglobulinemia. Unlike such cases, our patient developed giant cell hepatitis in the absence of such confounding variables. The treatment for our patient was a high-dose corticosteroid and rituxan, with improvement in liver enzymes. PMID:26147671

  19. Metabolic Manifestations and Complications Associated With Chronic Hepatitis C Virus Infection.

    PubMed

    Wong, Robert J; Gish, Robert G

    2016-05-01

    Chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations that contribute to morbidity and mortality. It is especially important to be aware of metabolic manifestations and serious complications that affect other organs and cancer risks. Chronic HCV infection itself contributes to de novo development of insulin resistance and hepatic steatosis, both of which increase the risk of cardiovascular diseases. Through these metabolic pathways (as well as through other hypothesized mechanisms that involve lipid metabolism, systemic inflammatory signals, and endothelial dysfunction), chronic HCV infection also contributes to significant systemic cardiovascular morbidity and mortality. While chronic HCV infection contributes to incident development of metabolic complications, the presence of concurrent metabolic diseases also contributes to disease progression, such as higher risks of hepatocellular carcinoma and progression to advanced fibrosis, among patients with chronic HCV infection. The implications of these observations are particularly important given the rising prevalence of obesity and metabolic syndrome in the United States and worldwide. Furthermore, concurrent nonalcoholic fatty liver disease, either as a result of underlying metabolic syndrome or as a direct result of HCV-induced fatty liver disease, further complicates the management of chronic HCV-infected patients. Greater awareness is needed toward the systemic manifestations of chronic HCV infection, with focused attention on the associated metabolic manifestations and complications. Successful treatment and cure of chronic HCV infection with the currently available, highly effective antiviral therapies will significantly improve long-term outcomes among these patients. It is also important to recognize and address the associated metabolic manifestations and complications to reduce cardiovascular-related morbidity and mortality. PMID:27499712

  20. Hepatitis B: progress in understanding chronicity, the innate immune response, and cccDNA protection

    PubMed Central

    Shimazaki, Tomoe; Takeda, Rei; Izumi, Takaaki; Umumura, Machiko; Sakamoto, Naoya

    2016-01-01

    Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus. While HBV infection exhibits a variety of clinical presentations, even asymptomatic carriers can develop HCC without liver fibrosis. Current therapeutic options against HBV include pegylated interferon (Peg-IFN) and nucleos(t)ide reverse transcriptase inhibitors (NRTIs), with clinical studies showing a significant association between loss of HBV DNA and a decrease in cancer risk. However, the ultimate goal of HBV therapy is a complete cure of HBV—including the elimination of covalently closed circular DNA (cccDNA)—in order to further decrease the risk of developing HCC. The development of hepatitis B is associated with the host immune response to virus-infected hepatocytes, as HBV is understood to lack direct cytotoxicity. While HBV-specific CD8+ T cells are thus involved in hepatitis development, they also play an important role in eliminating HBV infection. Indeed, the innate immune response during the initial phase of HBV infection is essential to the induction of acquired immunity. However, the innate immune response to HBV infection, including the roles of specific immunocompetent cells and associated molecules, is not well understood. In this review, we focus on the current understanding of the mechanisms underlying hepatitis development by HBV infection. We also address the mechanisms by which HBV protects cccDNA. PMID:27761441

  1. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    PubMed

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  2. Clinical course and management of acute and chronic viral hepatitis during pregnancy.

    PubMed

    Licata, A; Ingrassia, D; Serruto, A; Soresi, M; Giannitrapani, L; Montalto, G; Craxì, A; Almasio, P L

    2015-06-01

    Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.

  3. Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

    PubMed Central

    Lee, Hye Won; Ahn, Sang Hoon

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B (CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-naïve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM (Individual Prediction Model), CU-HCC (Chinese University-HCC), GAG-HCC (Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC (Nomogram-HCC), REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM (Liver Stiffness Measurement)-based model, LSM-HCC, and mREACH-B (modified REACH-B). PMID:27729738

  4. Thymalfasin for the treatment of chronic hepatitis C infection.

    PubMed

    Rustgi, Vinod K

    2007-09-01

    The purpose of this review article is to examine previous and ongoing studies of thymalfasin in combination with peginterferon-alpha2a and peginterferon-alpha2a plus ribavirin in difficult-to-treat hepatitis C virus (HCV) patients. The following studies will be reviewed in detail: (1) Sherman and colleagues conducted a study in 109 HCV RNA positive HVC patients comparing the combination of thymalfasin + IFN versus IFN alone versus placebo. (2) Rustgi et al. evaluated the efficacy and safety of thymalfasin and peg-IFN-alpha2a in 31 genotype 1, high viral load, HCV nonresponders in a 12-week viral kinetic study. (3) Di Bisceglie, Sherman et al. performed a study of previous HCV nonresponders being retreated with either peginterferon-alpha2a plus thymalfasin or peginterferon-alpha2a plus placebo. (4) Poo and colleagues in Mexico evaluated triple combination therapy using thymalfasin, peginterferon-alpha2a, and ribavirin for the treatment of Hispanic HCV nonresponders. PMID:17600289

  5. Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe.

    PubMed

    Ozaras, R; Corti, G; Ruta, S; Lacombe, K; Mondelli, M U; Irwing, W L; Puoti, M; Khalighi, A; Santos, M L; Harxhi, A; Lazarevic, I; Soriano, V; Gervain, J; Leblebicioglu, H; Salmon, D; Arends, J E

    2015-11-01

    The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries. PMID:26166544

  6. Inhibition of Hepatitis C Virus-Like Particle Binding to Target Cells by Antiviral Antibodies in Acute and Chronic Hepatitis C

    PubMed Central

    Steinmann, Daniel; Barth, Heidi; Gissler, Bettina; Schürmann, Peter; Adah, Mohammed I.; Gerlach, J. Tilman; Pape, Gerd R.; Depla, Erik; Jacobs, Dirk; Maertens, Geert; Patel, Arvind H.; Inchauspé, Geneviève; Liang, T. Jake; Blum, Hubert E.; Baumert, Thomas F.

    2004-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis worldwide. The study of antibody-mediated virus neutralization has been hampered by the lack of an efficient and high-throughput cell culture system for the study of virus neutralization. The HCV structural proteins have been shown to assemble into noninfectious HCV-like particles (HCV-LPs). Similar to serum-derived virions, HCV-LPs bind and enter human hepatocytes and hepatoma cell lines. In this study, we developed an HCV-LP-based model system for a systematic functional analysis of antiviral antibodies from patients with acute or chronic hepatitis C. We demonstrate that cellular HCV-LP binding was specifically inhibited by antiviral antibodies from patients with acute or chronic hepatitis C in a dose-dependent manner. Using a library of homologous overlapping envelope peptides covering the entire HCV envelope, we identified an epitope in the N-terminal E2 region (SQKIQLVNTNGSWHI; amino acid positions 408 to 422) as one target of human antiviral antibodies inhibiting cellular particle binding. Using a large panel of serum samples from patients with acute and chronic hepatitis C, we demonstrated that the presence of antibodies with inhibition of binding activity was not associated with viral clearance. In conclusion, antibody-mediated inhibition of cellular HCV-LP binding represents a convenient system for the functional characterization of human anti-HCV antibodies, allowing the mapping of envelope neutralization epitopes targeted by naturally occurring antiviral antibodies. PMID:15308699

  7. Trace element analysis by PIXE in liver samples from dogs with chronic active hepatitis and liver cirrhosis

    NASA Astrophysics Data System (ADS)

    Andersson, Marianne; Ekholm, Ann-Kristin; Sevelius, Ewa

    1990-04-01

    Trace element levels of liver samples obtained from necropsied dogs suffering from hepatitis and/or liver cirrhosis were determined by PIXE. Two different techniques for preparation of the samples were compared: the pellet press method and wet digestion. Both methods gave similar results, but the pellet press method was chosen for the subsequent routine analyses because of its simplicity due to few preparation steps and little risk of contamination. Preliminary results indicate elevated levels of Cu in chronic hepatitis and cirrhosis. In hereditary copper-induced hepatitis (Bedlington hepatitis) Fe and Br levels were increased as well.

  8. Characterization of antiphospholipid antibodies in chronic hepatitis B infection

    PubMed Central

    Yi, Dae Young; Hwang, Seong Gyu; Choi, Jin Jung; Kang, Myung Seo

    2011-01-01

    Background Many infections are associated with antiphospholipid antibodies (aPLs). The purpose of this study was to investigate the prevalence, persistence, clinical significance, and characteristics of aPLs in hepatitis B virus (HBV)-infected patients. Methods This study included 143 patients with HBV infection and 32 healthy individuals as controls. The presence of anticardiolipin antibodies (aCL Ab), anti-β2-glycoprotein I antibodies (β2GPI Ab), and lupus anticoagulant (LA) was assessed. Results The total prevalence of aPLs in HBV-infected patients was 12.6% (18 of 143). Of these 18 patients, 15 had low to medium titers of aCL Ab (10 with IgM, 4 with IgG, and 1 with both isotypes). β2GPI Ab and LA were detected in 3 (2.1%) and 2 (1.4%) patients with HBV infection, respectively. In follow-up specimens from 14 patients with elevated levels of aCL Ab or β2GPI Ab, 10 (71.4%) showed the persistent presence of aPLs. No clinical manifestations related to aPLs were identified. Conclusion In HBV-infected patients, the most frequently detected antiphospholipid antibodies were IgM aCL Ab, which have a weak association with the clinical manifestations of APS. Unlike the transient presence reported for other infection-associated aPLs, most aPLs were persistently detected over a 12-week period in patients with HBV infection. PMID:21461302

  9. [New drugs in the treatment of chronic hepatitis C].

    PubMed

    Jimenez Galan, R; Albacete Ramirez, A; Monje Agudo, P; Borrego Izquierdo, Y; Morillo Verdugo, R

    2014-05-01

    Objetivos: Analizar la eficacia y seguridad de los nuevos agentesantivirales directos (AAD) que formaran parte del arsenal terapéuticopara el tratamiento de la hepatitis C.Método: Se realizó una búsqueda en la base de datos electrónicaPubMed, de artículos publicados Febrero de 2014 quecumplieran los siguientes criterios: ensayos clínicos (EC) en faseII o III y cuyos objetivos fueran evaluar la eficacia y seguridad denuevas generaciones de inhibidores de la proteasa (IP) frente alVHC, excluyendo con boceprevir y telaprevir.Resultados: Se incluyeron de 24 EC que incluyen asociacionesde AAD con ribavirina (RBV) y con o sin peginterferon (PegINF)y asociaciones de varios AAD. Los resultados de daclatasvircon PegINF y RBV no han sido muy satisfactorios. Por el contrario,sofosbuvir es activo en todos los genotipos virales y permiteser administrado en regímenes libres de PegINF. Alrededordel 90% de los pacientes naïve alcanzan respuesta viralsostenida (RVS) , y no llegan al 80% en pretratados. En cuantoa la segunda generación de IP NS3/4A, destacar a simeprevir,con respuestas próximas al 90% en pacientes naïve y cercanasal 80% en pretratados. Entre las combinaciones de AAD evaluadas,sofosbuvir y daclatasvir y sofosbuvir y ledipasvir alcanzanel 100% de respuesta en no respondedores a triple terapiacon boceprevir y telaprevir.Conclusiones: Las nuevas generaciones de AAD frente al VHCvan a suponer un aumento de las tasas de curación en todoslos subtipos de pacientes, a través de regímenes más sencillosy mejor tolerados.

  10. Enveloped particles in the serum of chronic hepatitis C patients

    SciTech Connect

    Petit, Marie-Anne . E-mail: petit@lyon.inserm.fr; Lievre, Marjory . E-mail: marjory.lievre@free.fr; Peyrol, Simone . E-mail: peyrol@laennec.univ-lyon1.fr; De Sequeira, Sylvie . E-mail: desequeira@lyon.inserm.fr; Berthillon, Pascale . E-mail: berthillon@lyon.inserm.fr; Ruigrok, Rob W.H. . E-mail: ruigrok@embl-grenoble.fr; Trepo, Christian . E-mail: trepo@lyon.inserm.fr

    2005-06-05

    HCV particles were isolated from the plasma of chronically infected patients. The virus was analysed by sucrose density gradient centrifugation. The fractions were tested for viral RNA, core antigen and envelope proteins by using a monoclonal antibody directed against the natural E1E2 complex (D32.10). Two populations of particles containing RNA plus core antigen were separated: the first with a density of 1.06-1.08 g/ml did not contain the envelope proteins; the second with a density between 1.17 and 1.21 g/ml expressed both E1 and E2 glycoproteins. Electron microscopy of the enveloped population after immunoprecipitation with D32.10 showed spherical particles with a rather featureless surface and with a diameter around 40 nm. Immuno-gold staining gave evidence that the E1E2 complex was indeed positioned at the surface of these particles.

  11. Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

    PubMed Central

    Doganay, Levent; Fejzullahu, Arta; Katrinli, Seyma; Yilmaz Enc, Feruze; Ozturk, Oguzhan; Colak, Yasar; Ulasoglu, Celal; Tuncer, Ilyas; Dinler Doganay, Gizem

    2014-01-01

    AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B. METHODS: Patient records at a single institution’s hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed. RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site. CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients. PMID:25009391

  12. Chronic hepatitis B virus infection and rubella susceptibility in pregnant women.

    PubMed

    Lao, T T-H; Sahota, D S; Suen, S S H; Lau, T K; Leung, T Y

    2010-10-01

    Increased rubella susceptibility has been shown in subjects from the Asian-Pacific region where chronic hepatitis B virus (HBV) infection is endemic. This study was performed to explore the relationship between chronic HBV infection and rubella susceptibility in the obstetric population. We conducted a retrospective cohort study on 50556 pregnant women delivered in a university obstetric unit from January 1998 to June 2008. The incidence of rubella susceptibility according to maternal HBV carrier status was examined. HBV infection and rubella susceptibility were found in 5105 (10.1%) and 6102 (12.1%) women, respectively. Rubella susceptibility was more common in women with HBV (13.1%vs 12.0%, P = 0.017), even after adjusting for other confounding factors (odds ratio 1.11, 95% confidence interval 1.01-1.21). Advancing age was associated with progressively decreasing odds of rubella susceptibility, from 0.48 at age 20-24 years to 0.34 at age ≥ 40 years in women without HBV infection, but had no effect in women with hepatitis B. In conclusion, our study is the first to demonstrate an association between chronic HBV infection with rubella susceptibility. Further studies are warranted to confirm whether chronic HBV infection, especially that acquired by vertical transmission, may impair the immune response to rubella vaccine or natural infection throughout the reproductive age. PMID:20002301

  13. Analysis of the binding of hepatitis C virus genotype 1a and 1b E2 glycoproteins to peripheral blood mononuclear cell subsets.

    PubMed

    Yamada, Eriko; Montoya, Maria; Schuettler, Christian G; Hickling, Timothy P; Tarr, Alexander W; Vitelli, Alessandra; Dubuisson, Jean; Patel, Arvind H; Ball, Jonathan K; Borrow, Persephone

    2005-09-01

    Hepatitis C virus (HCV) binding to hepatocytes is thought to be mediated via interaction of the E2 glycoprotein with (co-)receptors including CD81 and scavenger receptor class B type I (SR-BI). Here, the expression of CD81 and SR-BI was analysed on peripheral blood mononuclear cell (PBMC) subsets, and the binding of genotype 1 soluble truncated E2 (sE2) proteins to these cells was investigated. All PBMC subsets expressed CD81, although at varying levels. In contrast, SR-BI was only detected on monocytes and dendritic cells (DCs). The genotype 1a H77c sE2 protein showed higher PBMC binding than other genotype 1a/b sE2s. H77c sE2 binding to different PBMC subsets largely paralleled their level of CD81 expression, and could be inhibited by blocking E2-CD81 interaction. However, those PBMC subsets reported to be infected by HCV in vivo (monocytes, DCs and B cells) also exhibited residual, CD81-independent binding, indicating roles for SR-BI/other receptor(s) in mediating haematopoietic cell infection. PMID:16099909

  14. [Coincidence of a chronic Hepatitis C and an autoimmune Hepatitis Type 3 - successful therapy with the new direct-acting antiviral agents].

    PubMed

    Dikopoulos, N; Zizer, E

    2016-08-01

    Chronic hepatitis C infection may be associated with several features of autoimmunity (i. e., detection of different kinds of autoantibodies in the serum). Hepatitis C is also associated with different autoimmune diseases, such as autoimmune thyroiditis, lichen ruber planus, and membranous glomerulonephritis being the most relevant. There are very few cases of a coincidence of chronic hepatitis C with an autoimmune hepatitis, that is usually diagnosed by detection of specific autoantibodies and typical histological features. During the time of interferon-based antiviral therapies, we often faced a therapeutic dilemma as interferon could lead to an exacerbation of the coincident autoimmune disease. So, in these cases, a prophylactic immunosuppression had to be started before initiation of interferon therapy. Meanwhile, in the new era of direct antiviral agents against hepatitis C, highly specific and effective therapeutic options are available. The case report presented here describes the very rare coincidence of a chronic hepatitis C, genotype 1 with an autoimmune hepatitis type 3 diagnosed by the presence of anti-SLA-antibodies. In the past, the patient had several unsuccessful interferon-based therapies without achieving a sustained virological response in parallel with an immunosuppressive treatment with azathioprine. During the further course of the disease, the patient generated a liver cirrhosis CHILD A after only a few years. After the approval of the direct antiviral agents sofosbuvir and daclatasvir in 2014, we conducted an antiviral therapy, including ribavirin, for 24 weeks and fortunately achieved a sustained virological response. Due to the persistent disease activity caused by the autoimmune hepatitis after the end of antiviral therapy, we treated the patient with prednisolone and azathioprine and could induce a stable and persistent remission of the autoimmune disease. PMID:27529527

  15. [Coincidence of a chronic Hepatitis C and an autoimmune Hepatitis Type 3 - successful therapy with the new direct-acting antiviral agents].

    PubMed

    Dikopoulos, N; Zizer, E

    2016-08-01

    Chronic hepatitis C infection may be associated with several features of autoimmunity (i. e., detection of different kinds of autoantibodies in the serum). Hepatitis C is also associated with different autoimmune diseases, such as autoimmune thyroiditis, lichen ruber planus, and membranous glomerulonephritis being the most relevant. There are very few cases of a coincidence of chronic hepatitis C with an autoimmune hepatitis, that is usually diagnosed by detection of specific autoantibodies and typical histological features. During the time of interferon-based antiviral therapies, we often faced a therapeutic dilemma as interferon could lead to an exacerbation of the coincident autoimmune disease. So, in these cases, a prophylactic immunosuppression had to be started before initiation of interferon therapy. Meanwhile, in the new era of direct antiviral agents against hepatitis C, highly specific and effective therapeutic options are available. The case report presented here describes the very rare coincidence of a chronic hepatitis C, genotype 1 with an autoimmune hepatitis type 3 diagnosed by the presence of anti-SLA-antibodies. In the past, the patient had several unsuccessful interferon-based therapies without achieving a sustained virological response in parallel with an immunosuppressive treatment with azathioprine. During the further course of the disease, the patient generated a liver cirrhosis CHILD A after only a few years. After the approval of the direct antiviral agents sofosbuvir and daclatasvir in 2014, we conducted an antiviral therapy, including ribavirin, for 24 weeks and fortunately achieved a sustained virological response. Due to the persistent disease activity caused by the autoimmune hepatitis after the end of antiviral therapy, we treated the patient with prednisolone and azathioprine and could induce a stable and persistent remission of the autoimmune disease.

  16. Posttranscriptional Inhibition of Class I Major Histocompatibility Complex Presentation on Hepatocytes and Lymphoid Cells in Chronic Woodchuck Hepatitis Virus Infection

    PubMed Central

    Michalak, Tomasz I.; Hodgson, Paul D.; Churchill, Norma D.

    2000-01-01

    Woodchuck hepatitis virus (WHV), similar to human hepatitis B virus, causes acute liver inflammation that can progress to chronic hepatitis and hepatocellular carcinoma. WHV also invades cells of the host lymphatic system, where it persists for life. We report here that acute and chronic hepadnavirus hepatitis is characterized by a profound difference in the expression of class I major histocompatibility complex (MHC) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. While acute WHV infection is accompanied by the enhanced hepatocyte surface presentation of class I MHC antigen and upregulated transcription of the relevant hepatic genes, inhibition of class I antigen display on liver cells is a uniform hallmark of chronic WHV infection. This inhibition in chronic hepatitis occurs despite augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain, β2-microglobulin, and transporters associated with antigen processing (TAP1 and TAP2). Further, the class I antigen inhibition is not related to the histological severity of hepatocellular injury, the extent of lymphocytic infiltrations, the level of intrahepatic gamma interferon induction, or the hepatic WHV load. Importantly, the antigen expression is also inhibited on organ lymphoid cells of chronically infected hosts. The results obtained in this study demonstrate that the defective presentation of class I MHC molecules on cells supporting persistent WHV replication is due to viral posttranscriptional interference. This event may diminish the susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the class I MHC-dependent functions of the host immune system. This multifarious effect could be critical for perpetuation of liver damage and evasion of the antiviral immunological surveillance in chronic infection and therefore could be supportive of hepadnavirus persistence. PMID:10775584

  17. Boceprevir in chronic hepatitis C infection: a perspective review.

    PubMed

    Ascione, Antonio

    2012-05-01

    Boceprevir (Victrelis), from the oral α-ketoamide class of slow-binding reversible hepatitis C virus (HCV)-NS3 protease inhibitors, creates a new class of drugs: direct acting antivirals (DDAs). Boceprevir is highly selective against HCV serine protease. Its use is restricted to genotype 1 HCV infection and it must not be used as monotherapy. Boceprevir is given orally, rapidly absorbed, reaching plasma peak concentration within 1-2 h and is metabolized by aldo-ketoreductase and partly by the cytochrome P450 enzyme CYP3A4/5. Administration with drugs that induce or inhibit CYP3A4/5 could decrease or increase its plasma concentration. The optimal dosage is 800 mg three times daily; capsules should be taken with food. Boceprevir was approved by the US Food and Drug Administration and the European Medicines Agency and is indicated in combination with peginterferon plus ribavirin for the treatment of patients with genotype 1 HCV who have not received previous treatment or whose condition has failed to respond to previous therapy. In the Serine Protease Inhibitor Therapy 2 (SPRINT-2) trial (treatment-naïve patients) and RESPOND-2 trial (patients whose condition relapsed or did not respond to previous treatment), the boceprevir-containing regimen was always more effective than standard of care (SOC). Adverse events were similar in the treatment groups, but in the boceprevir treated group, anemia was more frequent, requiring erythropoietin in nearly 40% of cases. Discontinuation of therapy because of adverse events was identical in all treated groups. As for cost effectiveness, two studies showed that boceprevir plus SOC is cost effective with regard to the lifetime incidence of liver complications, quality of life years, and the incremental cost-effectiveness ratio. The management of this therapy is more complex than before for physicians and patients. The educational role of the physician is crucial for successful therapy and counseling should be carefully given

  18. Associated Factors for Metabolic Syndrome in the Older Adults with Chronic Virus Hepatitis in the Community

    PubMed Central

    Kuo, Yuan-Hung; Tsai, Ming-Chao; Kee, Kwong-Ming; Chang, Kuo-Chin; Wang, Jing-Houng; Lin, Chun-Yin; Lin, Sheng-Che; Lu, Sheng-Nan

    2016-01-01

    This study was to evaluate the association between metabolic syndrome (MetS) and chronic virus hepatitis elders in the community. Those subjects with positive hepatitis B surface antigen (HBsAg) and/or anti-hepatitis C virus (anti-HCV) screened in the community before were invited to this study and 451 responded. All participants underwent anthropometric measurements, blood tests, ultrasound and fibroscan examinations. The cut-off of liver stiffness measurement-liver cirrhosis (LSM-LC) was 10 kPa for chronic hepatitis B (CHB) patients and 12 kPa for chronic hepatitis C (CHC) patients, respectively. Among 451 responders, 56 were excluded due to negative HBsAg or anti-HCV. Three hundreds and ninety-five subjects included 228 CHB patients, 156 CHC patients and 11 dual hepatitis patients, had a mean age of 62±12.6 years. Fifty-four (23.7%) CHB patients coexisted with MetS whereas 40 (25.6%) CHC patients also had MetS. Those patients with MetS had more LSM-LC cases than those without (20.4% vs 9.8%, p = 0.04 in CHB patients; 28.2% vs 13.5%, p = 0.037 in CHC patients, respectively). In multivariate logistic analysis, detectable viremia was reversely associated with MetS in CHB patients after adjustment for age, gender and body mass index (odds ratio (OR): 0.42; 95% confidence interval (CI): 0.18–0.99; p = 0.047). Regarding CHC patients, higher LSM level was the only factor contributed to MetS (OR: 1.1; 95% CI: 1.02–1.19; p = 0.012). In conclusion, elder CHB patients coexisted with MetS might experience an inactive virus replication but have an advanced liver fibrosis. In elder CHC patients, only higher LSM level was associated with MetS. PMID:27177024

  19. Chronic Pain and Hepatitis C Virus Infection in Opioid Dependent Injection Drug Users

    PubMed Central

    Tsui, Judith I.; Herman, Debra S.; Kettavong, Malyna; Anderson, Bradley J.; Stein, Michael D.

    2011-01-01

    It is unknown if infection with hepatitis C virus (HCV) is a risk factor for pain among persons who have used injection drugs (IDU). Multivariate regression was used to determine whether HCV was associated with greater likelihood of reporting significant chronic pain and discomfort intolerance in a cohort of 97 opioid dependent IDU. Study results suggest that participants with HCV may be more likely to suffer chronic pain (aOR=1.98; 95% CI: 0.76 to 5.12, p=0.16). Furthermore, HCV was found to be associated with a higher discomfort intolerance scale score, reflecting intolerance to physical discomfort (β=2.34; 95% CI: 0.06 to 4.62, p=0.04). Infection with HCV may be an overlooked cause for chronic pain and discomfort intolerance among opioid dependent IDU. PMID:21491290

  20. The suitability of mindfulness-based stress reduction for chronic hepatitis C.

    PubMed

    Koerbel, Lynn S; Zucker, Donna M

    2007-12-01

    As incidence of chronic hepatitis C (CHC) in the United States increases, management of physical and psychological symptoms over the long term becomes crucial. Research has shown meditation to be a valuable tool in reducing such symptoms for various chronic illnesses. In particular, the Mindfulness-Based Stress Reduction (MBSR) program offers curriculum that has been shown to influence both physiology and perception of disease states. Although there has been no direct research to date on the effectiveness of the MBSR program for CHC, several studies have shown significant findings affecting other chronic conditions, including heart disease, fibromyalgia, and HIV. The purpose of this literature review is to examine recent research, summarize findings, and indicate appropriate inclusion of MBSR as a primary, secondary, and tertiary treatment option in conjunction with biomedical care for those diagnosed with CHC. Thusly, nurses can better inform their clients with this condition.

  1. Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation.

    PubMed

    Serap, Aksoylar; Funda, Ozgenc; Bengu, Kadioglu; Mehmet, Kantar; Nazan, Cetingul; Rasit, Yagci; Savas, Kansoy

    2011-08-01

      We present an 18-yr-old adolescent with acute lymphocytic leukemia, who underwent peripheral blood SCT with serologically and histologically documented chronic hepatitis B infection. Prior and during the transplant process, lamivudine was administered orally and he underwent SCT with a twofold decrease in viral load at the time of transplant from his HLA full matched, HBV natural immune (anti-HBs and anti-HBc positive) donor. Successful engraftment was achieved and three months after SCT, HBV seroconversion was documented accompanied with an ALT flare. Chronic graft-versus-host disease coincided after the transplantation, and he has been on immunosuppressive treatment for 25 months with sustained HBV seroconversion. We assume that adoptive immunity transfer combined with antiviral treatment might also constitute sustained seroconversion in chronic HBV, besides the reported risk of reactivation. PMID:20102530

  2. [Chronic inflammatory demyelinating polyneuropathy associated with chronic liver disease due to type B and type C hepatitis virus].

    PubMed

    Ohyama, T; Okiyama, R; Yamada, M; Mitani, M; Tamaki, M; Endo, M; Kubo, M

    1995-02-01

    A patient with chronic inflammatory demyelinating polyneuropathy (CIDP) associated with type B and type C hepatitis virus infection is reported. A 54-year-old female who had a blood transfusion at the age of 31 years was diagnosed as a carrier of hepatitis B virus at the age of 43. Liver dysfunction was first noted in 1987 and gradually grew worse year by year. Beginning in early June 1992, the patients general fatigue became worse, her serum GOT and GPT levels became elevated, and she complained of a tingling sensation in her arms and legs. Neurological examination revealed moderate sensory disturbance of the glove-and-stocking type in all of her extremities. Deep tendon reflexes were all diminished. Hepatitis C antibody was detected in the serum at this time. On June 12, 1993, progression of her sensory disturbance was found to be associated with generalized muscle weakness. Cerebrospinal fluid studies showed increased protein without pleocytosis. Motor nerve conduction studies revealed marked prolongation of terminal latencies, reduction of conduction velocities, and abnormal temporal dispersion of the motor potentials. No sensory potentials could be evoked at any of the sites stimulated. Sural nerve biopsy showed segmental demyelination and severe loss of large myelinated fibers as well as some onion bulb formation. A diagnosis of CIDP was made. Treatment with corticosteroids was started, but there was little improvement in neurological function. The liver dysfunction progressed further and ultimately the patient died of hepatic failure. An autopsy demonstrated liver cirrhosis, but no malignant tumors were evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669415

  3. Cimicifuga foetida L. plus adefovir effectively inhibits the replication of hepatitis B virus in patients with chronic hepatitis B

    PubMed Central

    DAI, XIUFANG; YI, XIANFU; SUN, ZEQUN; RUAN, PENG

    2016-01-01

    The aim of the present study was to assess the anti-hepatitis B virus (HBV) effect of Cimicifuga foetida L. (C. foetida) in the patients with chronic hepatitis B (CHB). A total of 60 randomly selected patients with CHB were recruited and divided into groups I and II. The patients in group I received a monotherapy of adefovir (ADV), and the patients in group II received a combination therapy of ADV and C. foetida for >48 weeks. Intrahepatic (IH) HBV covalently closed circular DNA (cccDNA), serum HBV DNA, hepatitis B surface antigen (HBsAg), alanine aminotransferase levels and serum interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels were quantified during the test. Following the treatment, a significant reduction of the median IH cccDNA level was identified in group II (P=0.017), but not in group I (P=0.05, and P=0.01 between the 2 groups), and a significant reduction of log10 HBsAg was identified in groups I (P=0.012) and II (P<0.0001, and P=0.20 between the 2 groups). A significant increase of the median serum IFN-γ level was found in group II (P=0.0005), but not in group I (P=0.06, and P=0.004 between the 2 groups), and a significant reduction of the median TGF-β level was identified in groups I (P<0.0001) and II (P<0.0001, and P=0.002 between the 2 groups). A total of 24 patients in group I, and 27 patients in group II achieved a sustained virological response (P=0.0386), and 20 patients in group I and 24 in group II achieved hepatitis B e antigen seroclearance (P=0.0442). In conclusion, C. foetida can effectively inhibit HBV transcription and replication in the patients by stimulating the release of the inflammatory cytokines, such as IFN-γ. PMID:27073640

  4. EXCESS MORTALITY IN PATIENTS WITH ADVANCED CHRONIC HEPATITIS C TREATED WITH LONG-TERM PEGINTERFERON

    PubMed Central

    Di Bisceglie, Adrian M.; Stoddard, Anne M.; Dienstag, Jules L.; Shiffman, Mitchell L.; Seeff, Leonard B.; Bonkovsky, Herbert L.; Morishima, Chihiro; Wright, Elizabeth C.; Snow, Kristin K.; Lee, William M.; Fontana, Robert J.; Morgan, Timothy R.; Ghany, Marc G.

    2011-01-01

    Background/Aims Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The HALT-C Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who had failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis was to describe the frequency and causes of death among this cohort of patients. Methods Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or non-liver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Results Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%) of which 76 were considered liver-related (62%) and 46 non-liver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years, the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, p=0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, p=0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to non-liver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality, and only one death was suspected to be a direct complication of peginterferon. Conclusions Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to non-liver-related causes among patients with bridging fibrosis. PMID:21480316

  5. Chronically infected wild boar can transmit genotype 3 hepatitis E virus to domestic pigs.

    PubMed

    Schlosser, Josephine; Vina-Rodriguez, Ariel; Fast, Christine; Groschup, Martin H; Eiden, Martin

    2015-10-22

    Hepatitis E virus (HEV) causes acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialized nations. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with the consumption of raw and undercooked products from domestic pig and wild boar. As shown recently, naturally acquired HEV gt3 replicates efficiently in experimentally infected wild boar and is transmissible from a wild boar to domestic pigs. Generally, following an acute infection swine suffer from a transient febrile illness and viremia in connection with fecal virus shedding. However, little is known about sub-acute or chronic HEV infections in swine, and how and where HEV survives the immune response. In this paper, we describe the incidental finding of a chronic HEVgt3 infection in two naturally infected European wild boar which were raised and housed at FLI over years. The wild boar displayed fecal HEV RNA excretion and viremia over nearly the whole observation period of more than five months. The animal had mounted a substantial antibody response, yet without initial clearance of the virus by the immune system. Further analysis indicated a subclinical course of HEV with no evidence of chronic hepatitis. Additionally, we could demonstrate that this chronic wild boar infection was still transmissible to domestic pigs, which were housed together with this animal. Sentinel pigs developed fecal virus shedding accompanied by seroconversion. Wild boar should therefore be considered as an important reservoir for transmission of HEV gt3 in Europe. PMID:26344041

  6. Therapeutic Potential of Cell Penetrating Peptides (CPPs) and Cationic Polymers for Chronic Hepatitis B

    PubMed Central

    Ndeboko, Bénédicte; Lemamy, Guy Joseph; Nielsen, Peter. E; Cova, Lucyna

    2015-01-01

    Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. Because current anti-HBV treatments are only virostatic, there is an urgent need for development of alternative antiviral approaches. In this context, cell-penetrating peptides (CPPs) and cationic polymers, such as chitosan (CS), appear of particular interest as nonviral vectors due to their capacity to facilitate cellular delivery of bioactive cargoes including peptide nucleic acids (PNAs) or DNA vaccines. We have investigated the ability of a PNA conjugated to different CPPs to inhibit the replication of duck hepatitis B virus (DHBV), a reference model for human HBV infection. The in vivo administration of PNA-CPP conjugates to neonatal ducklings showed that they reached the liver and inhibited DHBV replication. Interestingly, our results indicated also that a modified CPP (CatLip) alone, in the absence of its PNA cargo, was able to drastically inhibit late stages of DHBV replication. In the mouse model, conjugation of HBV DNA vaccine to modified CS (Man-CS-Phe) improved cellular and humoral responses to plasmid-encoded antigen. Moreover, other systems for gene delivery were investigated including CPP-modified CS and cationic nanoparticles. The results showed that these nonviral vectors considerably increased plasmid DNA uptake and expression. Collectively promising results obtained in preclinical studies suggest the usefulness of these safe delivery systems for the development of novel therapeutics against chronic hepatitis B. PMID:26633356

  7. Is Combination Therapy for Chronic Hepatitis C Toxic for Cardiac Function?

    PubMed Central

    Almawardy, Ramzy; Elhammady, Walid; Mousa, Nasser; Abotaleb, Sherif

    2012-01-01

    Background Many types of cardiovascular complications such as; cardiac arrhythmias, impaired cardiac function, myocardial ischemia and decreased left ventricular function, have been attributed to interferon therapy. Objectives The aim of this study was to evaluate the effects of combination therapy pegylated interferon and ribavirin on left ventricular systolic and diastolic functions in patients with a chronic hepatitis C infection. Patients and Methods A total of 120 patients, eligible for hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin, were included in this study. All patients underwent a full cardiovascular baseline examination including; detailed medical history, thorough clinical examination, 12 lead electrocardiogram (ECG), and echocardiography. A cardiac evaluation was performed at the beginning and six months after starting combination therapy. Results No significant changes regarding cardiac symptoms including; shortness of breath, cough, palpitations, chest pain and hypertension, were found during or six months after starting the combined therapy. ECG findings showed statistically non-significant decreases in the QT interval, while corrected QT showed statistically non-significant increases six months after beginning combined therapy, when compared to their values before treatment. Also with regard to the echocardiography findings, there was no statistically significant difference found between any of the echocardiography parameters six months after starting combined therapy compared to their values before treatment. Conclusions The results of our study suggest that, combination therapy does not cause a significant deterioration in cardiac function in patients with a chronic hepatitis C infection, and it may be used safely in patients without cardiac disease. PMID:23105944

  8. Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and clinical relevance

    PubMed Central

    Croagh, Catherine MN; Desmond, Paul V; Bell, Sally J

    2015-01-01

    The Hepatitis B Virus (HBV) has a worldwide distribution and is endemic in many populations. It is constantly evolving and 10 genotypic strains have been identified with varying prevalences in different geographic regions. Numerous stable mutations in the core gene and in the surface gene of the HBV have also been identified in untreated HBV populations. The genotypes and viral variants have been associated with certain clinical features of HBV related liver disease and Hepatocellular carcinoma. For example Genotype C is associated with later hepatitis B e antigen (HBeAg) seroconversion, and more advanced liver disease. Genotype A is associated with a greater risk of progression to chronicity in adult acquired HBV infections. Genotype D is particularly associated with the precore mutation and HBeAg negative chronic hepatitis B (CHB). The genotypes prevalent in parts of West Africa, Central and South America, E, F and H respectively, are less well studied. Viral variants especially the Basal Core Promotor mutation is associated with increased risk of fibrosis and cancer of the liver. Although not currently part of routine clinical care, evaluation of genotype and viral variants may provide useful adjunctive information in predicting risk about liver related morbidity in patients with CHB. PMID:25848459

  9. Validation of hepascore as a predictor of liver fibrosis in patients with chronic hepatitis C infection.

    PubMed

    Kalantari, Hamid; Hoseini, Hannan; Babak, Anahita; Yaran, Majid

    2011-01-01

    Introduction. Liver biopsy is an invasive determinator for hepatic fibrosis. Serum biomarkers can probably be used as an alternative to liver biopsy in assessment of the degree of fibrosis in patients with chronic Hepatitis C. Method. Eighty patients with chronic Hepatitis C were included in the study using simple nonrandom sampeling metod. After fulfillment of liver biopsy, the patients were categorized according to the METAVIR Scoring system. The Hepascore algorithm is computed based on age, sex, and the serum levels of total bilirubin, δ-glutamyl transferase, α2-Macroglobulin, and hyaluronic acid. The spearman and ROC tests were used. Results. According to the liver biopsy results, 12, 25, 20, 7 and 16 patients had F0, F1, F2, F3, and F4, respectively. With regard to the 0.34 cut-off point Hepascore had 67%, 56%, 64%, and 56% sensitivity, specificity, respectively, positive prediction value (PPV), and negative prediction value (NPV), respectively, for diagnosis of significant fibrosis. For a Hepascore cut-off point 0.61, sensitivity, specificity, respectively, PPV and NPB 82%, 86%, 70%, and 92% in diagnosis of severe fibrosis. For a Hepascore cut-off point 0.84, sensitivity, specificity, PPV and NPB were respectively 100%, 97%, 89%, and 100% for diagnosis of cirrhosis. Conclusion. Hepascore has a high value in diagnosis of the level of fibrosis, particularly cirrhosis. Therefore, it can be used for primary screening of patients to determine the need for liver biopsy.

  10. Validation of Hepascore as a Predictor of Liver Fibrosis in Patients with Chronic Hepatitis C Infection

    PubMed Central

    Kalantari, Hamid; Hoseini, Hannan; Babak, Anahita; Yaran, Majid

    2011-01-01

    Introduction. Liver biopsy is an invasive determinator for hepatic fibrosis. Serum biomarkers can probably be used as an alternative to liver biopsy in assessment of the degree of fibrosis in patients with chronic Hepatitis C. Method. Eighty patients with chronic Hepatitis C were included in the study using simple nonrandom sampeling metod. After fulfillment of liver biopsy, the patients were categorized according to the METAVIR Scoring system. The Hepascore algorithm is computed based on age, sex, and the serum levels of total bilirubin, δ-glutamyl transferase, α2-Macroglobulin, and hyaluronic acid. The spearman and ROC tests were used. Results. According to the liver biopsy results, 12, 25, 20, 7 and 16 patients had F0, F1, F2, F3, and F4, respectively. With regard to the 0.34 cut-off point Hepascore had 67%, 56%, 64%, and 56% sensitivity, specificity, respectively, positive prediction value (PPV), and negative prediction value (NPV), respectively, for diagnosis of significant fibrosis. For a Hepascore cut-off point 0.61, sensitivity, specificity, respectively, PPV and NPB 82%, 86%, 70%, and 92% in diagnosis of severe fibrosis. For a Hepascore cut-off point 0.84, sensitivity, specificity, PPV and NPB were respectively 100%, 97%, 89%, and 100% for diagnosis of cirrhosis. Conclusion. Hepascore has a high value in diagnosis of the level of fibrosis, particularly cirrhosis. Therefore, it can be used for primary screening of patients to determine the need for liver biopsy. PMID:22254137

  11. Hepatitis B Virus Core Promoter Mutations in Patients With Chronic Hepatitis B and Hepatocellular Carcinoma in Bucharest, Romania

    PubMed Central

    Constantinescu, Ileana; Dinu, Andrei-Antoniu; Boscaiu, Voicu; Niculescu, Marius

    2014-01-01

    Background: Accurate and personalized molecular virological diagnosis of hepatitis B virus (HBV) infection is crucial for individualized selection of patients for antiviral therapy in Romania. Objectives: We aimed to investigate HBV mutations in Romanian patients with chronic HBV infection, also to match HBV genotypes with HBV mutations identified and clinical outcomes. Patients and Methods: This was a cross-sectional study. A total of 484 Romanian patients with chronic HBV infection and hepatocellular carcinoma (HCC) were investigated. This was performed in Fundeni Clinical Institute, Bucharest, Romania during January 2005 to August 2010. HBsAg positive patients with chronic HBV infection admitted to Fundeni Clinical Institute were randomly enrolled in the study. Analysis was performed in the Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania. Indirect diagnosis was performed with enhanced chemiluminescence method using Architect i2000SR and HBV-DNA was quantified with COBAS TaqMan HBV PCR. Direct sequencing of the PCR-products was performed with the PCR-product sequencing kit. HBV genotyping was performed with INNO-LiPA DR Amplification and INNO-LiPA HBV precore-core. Results: We detected two HBV genotypes; A (8.1%) and D (60.5%), and a mixture of genotypes A and D (31.4%) (P < 0.001). Basal core promoter (BCP) A1762T/G1764A and precore (PC) G1896A mutations were detected in these Romanian patients with chronic HBV infection. HBV chronic carriers had mainly genotype D (54.4%) and HBV WT (64.0%). BCP A1762T, G1764A and PC G1896A were significantly associated with HCC-tissue HBV sequencing (75.3%) (P < 0.001). PC G1896A alone was detected in HCC-serum HBV sequencing group (66.7%). Conclusions: Genotype D was the main genotype detected in Romanian patients with chronic HBV infection. Genotype D presented both BCP and PC mutations more frequently. PMID:25477976

  12. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  13. Estimating the treatment cascade of chronic hepatitis B and C in Greece using a telephone survey.

    PubMed

    Papatheodoridis, G; Sypsa, V; Kantzanou, M; Nikolakopoulos, I; Hatzakis, A

    2015-04-01

    Accurate diagnosis and treatment rates for chronic hepatitis B (HBV) and C virus (HCV) infections are usually missing. Aim of this study was to estimate the HBV and HCV treatment cascade (proportion and absolute numbers of tested, aware/unaware, infected and treated) in Greek adults. A telephone survey was conducted in a sample representative of the Greek adult general population. Prevalence rates were age-standardized for the Greek adult population and corrected for high-risk individuals not included in the survey. Of the 9974 participants, 5255 (52.7%) had been tested for HBV and 2062 (20.7%) for HCV with the proportion varying according to age and being higher in middle-age groups (P < 0.001). HBsAg was reported positive in 111/5255 (2.11%) and anti-HCV in 26/2062 (1.26%) tested cases. The age-adjusted prevalence was estimated to be 2.39% for HBV and 1.79% for HCV. Taking into account individuals at high risk for viral hepatitis not included in the survey, the 'true' prevalence was estimated to be 2.58% for HBV and 1.87% for HCV. Anti-HBV and anti-HCV treatment had been taken by 36/111 (32.4%) chronic HBV and 15/26 (57.7%) chronic HCV patients. In conclusion, almost 50% of chronic HBV and 80% of chronic HCV patients in Greece may be unaware of their infection, while only 32% or 58% of diagnosed chronic HBV or HCV patients, respectively, have been ever treated. Therefore, intensive efforts are required to improve the efficacy of screening for HBV and particularly for HCV as well as to reduce the barriers to treatment among diagnosed patients. PMID:25209157

  14. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis

    PubMed Central

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  15. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis.

    PubMed

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  16. Predictive Factors in the Incidence of Cirrhosis in Chronic Hepatitis B Virus Infections

    PubMed Central

    Alavian, Seyed Moayed; Imanieh, Mohammad Hadi; Imanieh, Mohammad Hossein

    2016-01-01

    Background Hepatitis B virus (HBV) is among the leading causes of liver cirrhosis worldwide. Predictors of cirrhosis in Iranian chronic hepatitis B (CHB) patients are yet to be clearly identified. Objectives Evaluating the predictive factors of liver cirrhosis in CHB. Patients and Methods A longitudinal study was conducted during 1995 - 2014 on all CHB patients who were referred to Tehran hepatitis center, Tehran, Iran. The patients were assessed during periodic visits through medical history and laboratory data. Logistic regression analyses were used to determine predictors of cirrhosis. Results Two hundred thirty-seven CHB patients were followed for an average duration of 10.6 years, and 41 of these patients developed cirrhosis. The incidence rate of cirrhosis was 2.82/100 person-years. Univariate analyses determined 9 out of 17 factors as significant predictors of outcome in CHB patients. Age of ≥ 45 years, positive hepatitis D virus (HDV), negative HBeAg, platelet count of < 150 (× 109)/L, and HBV DNA level of ≥ 2,000 IU/mL were identified as significant independent predictors of liver cirrhosis in multiple logistic analyses. Conclusions Five predictive factors that are simple and easy to measure may be used as parameters for the prediction of liver cirrhosis in CHB patients. PMID:27330536

  17. Atherosclerosis as Extrahepatic Manifestation of Chronic Infection with Hepatitis C Virus.

    PubMed

    Voulgaris, Theodoros; Sevastianos, Vassilios A

    2016-01-01

    Chronic hepatitis C virus infection is associated with significant morbidity and mortality, as a result of progression towards advanced natural course stages including cirrhosis and hepatocellular carcinoma. On the other hand, the SVR following successful therapy is generally associated with resolution of liver disease in patients without cirrhosis. Patients with cirrhosis remain at risk of life-threatening complications despite the fact that hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced. Furthermore, recent data suggest that the risk of HCC and all-cause mortality is significantly reduced, but not eliminated, in cirrhotic patients who clear HCV compared to untreated patients and nonsustained virological responders. Data derived from studies have demonstrated a strong link between HCV infection and the atherogenic process. Subsequently HCV seems to represent a strong, independent risk factor for coronary heart disease, carotid atherosclerosis, stroke, and, ultimately, CVD related mortality. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus which may influence the life expectancy and the quality of patients' life. PMID:26885388

  18. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

    PubMed Central

    Yuan, Dongdong; Yao, Weifeng; Zhu, Qianqian; Liu, Yue; Chen, Xi; Huang, Yong

    2016-01-01

    Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R) after high (25 mM) or low (5.5 mM) glucose culture. Cell viability, reactive oxygen species (ROS), and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC) or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system. PMID:27656261

  19. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

    PubMed Central

    Yuan, Dongdong; Yao, Weifeng; Zhu, Qianqian; Liu, Yue; Chen, Xi; Huang, Yong

    2016-01-01

    Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R) after high (25 mM) or low (5.5 mM) glucose culture. Cell viability, reactive oxygen species (ROS), and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC) or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  20. Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada

    PubMed Central

    Osiowy, Carla; Giles, Elizabeth; Trubnikov, Max; Choudhri, Yogesh; Andonov, Anton

    2015-01-01

    Objective The prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk. Methods HBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV. Results Nine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections. Conclusion Chronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection. PMID:26406309

  1. Copper-induced hepatitis: the COMMD1 deficient dog as a translational animal model for human chronic hepatitis.

    PubMed

    Favier, R P; Spee, B; Penning, L C; Rothuizen, J

    2011-03-01

    Chronic inflammatory liver disease regardless of aetiology leads to failing regeneration and fibrosis, ending in cirrhosis. Both in man and in animals this worldwide health problem has no definitive cure. Chronic liver injury causes hepatic stellate cells to proliferate and differentiate into matrix-producing cells. New therapeutic options will be developed upon detailed understanding of the molecular mechanisms driving liver fibrosis. This may lead to new anti-fibrotic therapies which need to be tested in suitable models before application in the veterinary and human clinic. On the other side, to restore the failing regenerative capacity of the diseased liver cells, adult progenitor cells are of interest, as an alternative to whole organ transplantation. In order to find the most suitable large animal model it is important to recognise that the typical histopathological reaction pattern of the liver can differ between mammalian species. It is therefore imperative that specialists in veterinary internal medicine and pathology, being familiar with the diseases and pathologies of the liver in different animal species, are teaming-up in finding the best models for veterinary and human liver diseases. Several large animal models have been mentioned, like pigs, sheep, and dogs. Based on the observations that man and dog share the same hepatopathies and have identical clinical, pathological and pathogenetic reaction patterns during the development of liver disease, the dog seems to be a properly suited species to test new therapeutic strategies for pets and their best friends. PMID:22029820

  2. [Titration and genotyping of hepatitis C virus RNA in chronic hepatitis C patients treated with interferon].

    PubMed

    Konishi, M

    1994-02-01

    In order to evaluate the relation of the response to IFN therapy with viral factors, we quantified and typed HCV-RNA in sera and liver specimens from hepatitis C patients treated with IFN by using the single tube polymerase chain reaction. Sustained serum aminotransferase (sALT) normalization was resulted in 11 (19.6%) of the 51 patients. At 6 months after IFN therapy, serum HCV-RNA was negative in 13 of 44 patients. The pretreatment serum HCV-RNA titers tended to be higher in no responders than in complete responders and partial responders. HCV-RNA concentration in the liver correlated with serum HCV-RNA quantity. HCV infections with type I, II, III, IV, II + III, III + IV or II + III + IV were detected in 0, 24, 9, 2, 9, 2 or 3 patients, respectively. Mixed infection with more than 2 genotypes of HCV was found commonly than previously reported. IFN therapy induced complete response in 6 (66.7%) of the 9 patients with type III infection, and this response rate was apparently higher than that in the patients infected with type II or mixed type of HCV. Serum HCV-RNA titers were significantly higher in the patients with type III infection than in the patients with type II or mixed type infection. These findings implied that the determinations of pretreatment serum HCV-RNA titers and HCV-genotypes could be useful to predict sALT improvement and HCV eradication by IFN therapy.

  3. Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection

    PubMed Central

    Reynolds, Tracy D.; Buonocore, Linda; Rose, Nina F.; Rose, John K.

    2015-01-01

    ABSTRACT More than 500,000 people die each year from the liver diseases that result from chronic hepatitis B virus (HBV) infection. Therapeutic vaccines, which aim to elicit an immune response capable of controlling the virus, offer a potential new treatment strategy for chronic hepatitis B. Recently, an evolved, high-titer vaccine platform consisting of Semliki Forest virus RNA replicons that express the vesicular stomatitis virus glycoprotein (VSV G) has been described. This platform generates virus-like vesicles (VLVs) that contain VSV G but no other viral structural proteins. We report here that the evolved VLV vector engineered to additionally express the HBV middle surface envelope glycoprotein (MHBs) induces functional CD8 T cell responses in mice. These responses were greater in magnitude and broader in specificity than those obtained with other immunization strategies, including recombinant protein and DNA. Additionally, a single immunization with VLV-MHBs protected mice from HBV hydrodynamic challenge, and this protection correlated with the elicitation of a CD8 T cell recall response. In contrast to MHBs, a VLV expressing HBV core protein (HBcAg) neither induced a CD8 T cell response in mice nor protected against challenge. Finally, combining DNA and VLV-MHBs immunization led to induction of HBV-specific CD8 T cell responses in a transgenic mouse model of chronic HBV infection. The ability of VLV-MHBs to induce a multispecific T cell response capable of controlling HBV replication, and to generate immune responses in a tolerogenic model of chronic infection, indicates that VLV vaccine platforms may offer a unique strategy for HBV therapeutic vaccination. IMPORTANCE HBV infection is associated with significant morbidity and mortality. Furthermore, treatments for chronic infection are suboptimal and rarely result in complete elimination of the virus. Therapeutic vaccines represent a unique approach to HBV treatment and have the potential to induce long

  4. Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

    PubMed Central

    Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

    2015-01-01

    Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their

  5. Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene

    SciTech Connect

    Wakui, Shin . E-mail: wakui@azabu-u.ac.jp; Yokoo, Kiyofumi; Takahashi, Hiroyuki; Muto, Tomoko; Suzuki, Yoshihiko; Kanai, Yoshikatsu; Hano, Hiroshi; Furusato, Masakuni; Endou, Hitoshi

    2006-02-01

    We previously reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 {mu}g of PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 {mu}g group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunohistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.

  6. Non cell autonomous upregulation of CDKN2 transcription linked to progression of chronic hepatitis C disease.

    PubMed

    Robinson, Mark W; McGuinness, Dagmara; Swann, Rachael; Barclay, Stephen; Mills, Peter R; Patel, Arvind H; McLauchlan, John; Shiels, Paul G

    2013-12-01

    Chronic hepatitis C virus infection (C-HC) is associated with higher mortality arising from hepatic and extrahepatic disease. This may be due to accelerated biological aging; however, studies in C-HC have thus far been based solely on telomere length as a biomarker of aging (BoA). In this study, we have evaluated CDKN2 locus transcripts as alternative BoAs in C-HC. Our results suggest that C-HC induces non-cell-autonomous senescence and accelerates biological aging. The CDKN2 locus may provide a link between C-HC and increased susceptibility to age-associated diseases and provides novel biomarkers for assessing its impact on aging processes in man.

  7. [Anti-hepatitis B vaccination and postvaccinal immunity stimulation in patients with chronic obstructive pulmonary disease].

    PubMed

    Kostinov, M P; Chikina, E Y; Kulakova, N A; Borisova, V N; Magarshak, O O

    2015-01-01

    The problem of the anti-hepatitis B vaccination of patients with chronic obstructive lung disease (COPD) was discussed due to the lack of studies concerning the developing of the postvaccinal immunity, especially when vaccination is combined with the immunomodulating treatment. The data on the vaccination safety and its influence on the clinical course of COPD are also insufficient. Therefore, in this work we investigated the efficiency of the antihepatitis B vaccination in adults with chronic obstructive pulmonary disease under the treatment with the immunomodulating Affonoleikin drug. A total of 93 patients were tested including 59 patients with severe and moderate COPD (aged from 35 to 65 years). 34 of these 59 patients were vaccinated against hepatitis B (Kombioteh) according to 0-1-6 month scheme, and 25 of them were vaccinated against hepatitis B during the treatment with Affinoleikin. The control group, consisted of 34 healthy patients. Our study demonstrated good tolerance and high immune efficiency of the anti-hepatitis B vaccine. However, after the first vaccination the level of HBs-AT was below protective level in patients with COPD compared to healthy patients. Also, 64 to 70 % of patients with COPD were seronegative excluding the patients receiving the Affinoleikin treatment, whose antibody titer was protective after the first vaccine dose, but did not reach the level typical of healthy patients. After the second vaccination we detected low and medium protective antibody levels in 58.9% of patients from the 1st group, whereas 41% were seronegative. Introduction of the third vaccine-dose led to fast and significant increase in the antibody level mainly in high concentrations with 100% seroconversion in all patients. Combined antihepatitis B vaccination and Affinoleikin treatment in patients with COPD leads to faster biosynthesis of HBs- AT in protective concentrations and decrease of seronegative response, but it has no effect on frequency and type of

  8. Treating chronic hepatitis B virus: Chinese physicians’ awareness of the 2010 guidelines

    PubMed Central

    Wei, Lai; Jia, Ji-Dong; Weng, Xin-Hua; Dou, Xiao-Guang; Jiang, Jia-Ji; Tang, Hong; Ning, Qin; Dai, Qing-Qing; Li, Run-Qin; Liu, Jie

    2016-01-01

    AIM: To investigate Chinese physicians’ awareness of the 2010 guidelines on the treatment of chronic hepatitis B virus (HBV) infection. METHODS: This was a quantitative survey that investigated the characteristics and practices of physicians who were treating patients with hepatitis B, the profile of their patients and physician practices regarding the diagnosis and treatment of HBV at the time of the survey. Participants were randomly selected from available databases of Chinese physicians and requested to complete either an online or paper-based survey. Data from the survey responses were analysed. For data validation and interpretation, qualitative indepth interviews were conducted with 39 of the respondents. RESULTS: Five-hundred completed surveys, from 663 physicians were available for analysis. A mean of 175 chronic hepatitis B (CHB) patients was seen by each physician every month, of whom 85 (49%) were treated in line with therapeutic indications stated in the 2010 guidelines. A total of 444 (89%) physicians often (> 60% of the time) adhered to the guidelines. Most physicians used antiviral medications as recommended. For patients with compensated and decompensated cirrhosis, 342 (68%) and 336 (67%) of physicians, respectively, often followed the recommendation to use potent nucleos(t)ide analogues with a high genetic barrier to resistance, using the appropriate treatment more than 60% of the time. Physicians from infectious disease or liver disease departments were better informed than those from gastrointestinal or other departments. CONCLUSION: The majority of Chinese physicians often adhere to Chinese 2010 CHB guidelines and are well-informed about the use of antiviral medications for hepatitis B. PMID:27366303

  9. Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

    PubMed Central

    Ma, Ying; Yuan, Yujun; Ma, Xianglin; Tang, Boru; Hu, Ximei; Feng, Juan; Tian, Li; Ji, Yaohua; Dou, Xiaoguang

    2016-01-01

    The aim of the present study was to investigate the correlation between feature and genotype with regard to the tyrosine-methionine-aspartate-aspartate (YMDD) mutation in chronic hepatitis B patients after lamivudine (LAM) therapy. A total of 30 patients with chronic hepatitis B were recruited, who underwent one year of LAM therapy. The patients' alanine aminotransferase (ALT) level and hepatitis B envelope antigen (HBeAg) seroconversion were evaluated, hepatitis B virus (HBV) DNA was genotyped using a new genotyping method and YMDD mutations were analyzed prior to treatment and at 6 and 12 months after LAM treatment. Furthermore, the secondary protein structure of the HBV DNA polymerase gene (P gene) was analyzed. Following treatment, the results suggested that LAM therapy improved ALT normalization. There was no correlation between clinical effects and ALT level before treatment. After 12 months treatment, the rate of HBeAg loss increased and the rate of HBeAg seroconversion decreased linearly with the rise of baseline ALT level. While ALT normalization and HBeAg seroconversion were highest in patients with HBV genotype B, HBeAg loss and HBVDNA loss were highest in those with genotype C. The effect was predominant in genotype D. No YMDD mutations were identified prior to 6 months of LAM therapy. The rate of YMDD mutations after 12 months LAM therapy was 12.12%. Two patients with rtM204V + rtL180M belonged to genotype C and another patient with rtL180M alone belonged to genotype D. The turn of secondary protein structure of P gene changed to β sheet when a rtM204V mutation occurred, and no change of secondary protein structure was associated with the rtL180M mutation. Thus, the present results indicate that one year of LAM therapy is able to improve ALT normalization. Long-term LAM therapy may induce YMDD mutation and drug resistance. PMID:27446286

  10. Prognostic factors determining the outcome of treatment in chronic hepatitis C.

    PubMed

    Hadziyannis, S J

    2000-01-01

    After a brief introduction in terminology and a distinction between predictors and determinants or response to therapy in chronic hepatitis C, a review of the wide literature on this topic is presented. None of the pretreatment variables or combination of them can be used as an absolute predictor of response in individual patients. Prognostic factors can help in clinical practice for informing and counseling patients of the likelihood of response. Information on pretreatment HCV RNA levels and HCV genotype can improve the cost benefit of therapy. Predictors of response should be properly evaluated in terms of positive predictive value, negative predictive value and accuracy. The strongest hitherto predictor of sustained response to any therapeutic regimen in chronic hepatitis is the clearance of HCV RNA during treatment. Recent data suggest that sequencing of several regions of the HCV genome may provide important prognostic information on the outcome of therapy. In complex and difficult to treat subsets of patients with chronic HCV infection, available data on predictors and determinants of the outcome of treatment are limited. PMID:10925467

  11. Cyclooxygenase-2 Inhibitor Reduces Hepatic Stiffness in Pediatric Chronic Liver Disease Patients Following Kasai Portoenterostomy

    PubMed Central

    Chang, Hye Kyung; Chang, Eun Young; Ryu, Seonae

    2016-01-01

    Purpose The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. Materials and Methods From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. Results Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. Conclusion COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia. PMID:27189282

  12. Hepatic expression levels of interferons and interferon-stimulated genes in patients with chronic hepatitis C: A phenotype-genotype correlation study.

    PubMed

    Noureddin, M; Rotman, Y; Zhang, F; Park, H; Rehermann, B; Thomas, E; Liang, T J

    2015-01-01

    IFNL4 is linked to hepatitis C virus treatment response and type III interferons (IFNs). We studied the functional associations among hepatic expressions of IFNs and IFN-stimulated genes (ISGs), and treatment response to peginterferon and ribavirin. Type I IFNs (IFNA1, IFNB1), type II (IFNG), type III (IFNL1, IFNL2/3), IFNL4 and ISG hepatic expressions were measured by qPCR from in 65 chronic hepatitis C (CHC) patients whose IFNL4-associated rs368234815 and IFNL3-associated rs12989760 genotype were determined. There was a robust correlation of hepatic expression within type I and type III IFNs and between type III IFNs and IFNL4 but no correlation between other IFN types. Expression of ISGs correlated with type III IFNs and IFNL4 but not with type I IFNs. Levels of ISGs and IFNL2/3 mRNAs were lower in IFNL3 rs12979860 CC patients compared with non-CC patients, and in treatment responders, compared with nonresponders. IFNL4-ΔG genotype was associated with high ISG levels and nonresponse. Hepatic levels of ISGs in CHC are associated with IFNL2/3 and IFNL4 expression, suggesting that IFNLs, not other types of IFNs, drive ISG expression. Hepatic IFNL2/3 expression is functionally linked to IFNL4 and IFNL3 polymorphisms, potentially explaining the tight association among ISG expression and treatment response.

  13. Rates and risk factors for hepatitis B reactivation in a cohort of persons in the inactive phase of chronic hepatitis B—Alaska, 2001–2010

    PubMed Central

    Tohme, Rania A.; Bulkow, Lisa; Homan, Chriss E.; Negus, Susan; McMahon, Brian J.

    2015-01-01

    Background A high prevalence of reactivation of hepatitis B has been documented among immunosuppressed individuals in the inactive phase of chronic hepatitis B; However, the proportion of and the risk factors for reactivation are largely unknown among non-immunosuppressed persons. Objectives Estimate the incidence rate of and risk factors for hepatitis B reactivation in a population-based cohort of persons in the inactive phase of chronic hepatitis B in Alaska. Study design A cohort of 414 Alaska Native Persons in the inactive phase of hepatitis B (HBV DNA < 2000 IU/mL and normal alanine aminotransferase (ALT) for 12 months) was followed-up for 10 years. Reactivation of hepatitis B was defined as HBV DNA ≥ 2000 IU/mL and ALT ≥ 40 IU/L. Cox-proportional hazards regression models were used to identify factors associated with reactivation. Results A total of 36 (9%) persons had reactivation during 2984 person-years of follow-up, with an annual incidence of 1.2%. Persons aged ≥50 years (1.8%) at study entry had the highest incidence rates of reactivation although incidence rates were not significantly different by age group. Risk factors for hepatitis B reactivation were male sex (Hazard Ratio (HR) = 2.41; 95% Confidence Interval (CI): 1.17–4.96), HBV DNA ≥ 1000 IU/mL at study entry (HR = 7.61; 95% CI: 2.81–20.6), and HBV genotype B (HR = 6.08; 95% CI: 1.32–28.0). Conclusions The incidence of hepatitis B reactivation was low during the 10 years of follow-up. However, given the higher risk of reactivation than their counterparts, males, and those with HBV DNA ≥ 1000 IU/mL need to be followed-up more frequently. PMID:24001884

  14. Chronic Low Dose Fructose infusion Does Not Reverse Glucagon-Mediated Decrease in Hepatic Glucose Utilization

    PubMed Central

    Johnson, Paulette M.; Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E; Lacy, D. Brooks; McGuinness, Owen P.

    2013-01-01

    Objective An adaptation to chronic total parenteral nutrition (TPN; 75% of non protein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if chronic fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Material/methods Studies were performed in conscious insulin-treated chronically catheterized pancreatectomized dogs that adapted to TPN for 33 h. They were then assigned to one of 4 groups: TPN (C), TPN + fructose (4.4 μmol·kg−1·min−1, F), TPN+ glucagon (0.2 pmol·kg−1·min−1, GGN), or a TPN + fructose and glucagon (F+GGN) for an additional 63h (33–96h). Insulin, fructose and glucagon were infused into the portal vein. During that period all animals received a fixed insulin infusion 0.4mU· kg−1·min−1 (33–96h) and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mM). Results Chronic fructose infusion was unable to further enhance net hepatic glucose uptake (NHGU; μmol·kg−1·min−1) (31.1±2.8 vs. 36.1±5.0; C vs. F) nor was it able to overcome glucagon-mediated decrease in NHGU (10.0±4.4 vs. 12.2±3.9; GGN vs. F+GGN). Conclusion In summary, chronic fructose infusion cannot augment liver glucose uptake during TPN nor can it overcome the inhibitory effects of glucagon. PMID:20940071

  15. Ledipasvir/Sofosbuvir: a review of its use in chronic hepatitis C.

    PubMed

    Keating, Gillian M

    2015-04-01

    The single-tablet regimen of the hepatitis C virus (HCV) NS5A inhibitor ledipasvir and the HCV NS5B polymerase inhibitor sofosbuvir (ledipasvir/sofosbuvir; Harvoni(®)) was recently approved in the US and the EU. The phase III ION trials included treatment-naive (ION-1 and -3) or treatment-experienced (ION-2) patients with chronic HCV genotype 1 infection (≈20 % of patients in ION-1 and -2 had cirrhosis, whereas no patient in ION-3 had cirrhosis). A sustained virological response 12 weeks' post-treatment (SVR12) was seen in 99 % of treatment-naive patients receiving ledipasvir/sofosbuvir for 12 weeks in ION-1, with no additional benefit conferred by the addition of ribavirin or extending the treatment duration to 24 weeks. Moreover, in ION-3, an 8-week regimen achieved an SVR12 rate of 94 % overall and 97 % in the subgroup of patients with a baseline HCV RNA level of <6 million IU/mL. SVR12 rates of 94 and 99 % were seen in treatment-experienced patients who received ledipasvir/sofosbuvir for 12 and 24 weeks in ION-2. Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 infection, in HCV and HIV co-infection and, in combination with ribavirin, in patients with chronic HCV genotype 1 or 4 infection who have decompensated cirrhosis or are liver transplant recipients and in chronic HCV genotype 3 infection. Oral ledipasvir/sofosbuvir was generally well tolerated. In conclusion, ledipasvir/sofosbuvir is an important new single-tablet regimen that represents a significant advance in the treatment of chronic hepatitis C.

  16. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

    SciTech Connect

    Sorrell, M.F.; Nauss, J.M.; Donohue, T.M. Jr.; Tuma, D.J.

    1983-03-01

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate (/sup 14/C)glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring (/sup 14/C)leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, (/sup 14/C)fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration.

  17. Long-term prognosis of chronic hepatitis B virus infection in the childhood

    PubMed Central

    Akbulut, Ulaş Emre; Çakır, Murat

    2014-01-01

    Aim: It was aimed to investigate the modes of transmisson and long-term prognosis of the disease in patients who were followed up with a diagnosis of chronic hepatitis B infection. Material and Methods: The files of the patients who presented to our outpatient clinic between January 2002 and May 2013 and were being followed up with a diagnosis of chronic hepatitis B virus infection were examined retrospectively and the information related with the age, gender, age at the time of diagnosis, mode of transmission, follow-up period, transaminase levels, the amount of hepatitis B virus-deoxyribonucleic acid and treatment and responses to the treatment given were recorded. Results: The age at the time of diagnosis of 150 patients (97 males, 64%) included in the study was 14.95±2.94 years. 59 (39.3%) of the patients were inactive carriers, 61 (40.7%) were in the immunotolerant stage and 30 (20%) were in the immunoreactive stage. Vertical transmission was present in 86 (57.3%) patients, horizontal transmission was present in 41 patients (27.3%) and the mode of transmission was not known in 23 patients (15.3%). Response to treatment was obtained in 26 (72.2%) of 36 patients who received treatment. Lamivudine (4 mg/kg/day) was given to 29 of the patients who were given treatment, interferon-α (IFN-α) (6 MU/m2, three days a week) was given to 3 patients at the same dose and both IFN-α and lamivudine were given to 4 patients. The time to give response to treatment was 24.23±15.23 months (6–50 months). Spontaneous anti-HBe seroconversion occured in four (7.2%) of 55 immuntolerant children who were followed up without treatment. The time to development of seroconversion in these children was 2.50±1.91 years (1–5 years). Conclusions: Chronic hepatitis B virus infection has a more benign prognosis in children compared to adults, though it may lead to development of hepatic failure, cirrhosis and hepatocellular cancer. In addition, a decrease in the frequency of infection

  18. Chronic hepatitis C: treatment, complications, and long-term outcomes in a population of Latino veterans

    PubMed Central

    Santiago-Rolon, Amarilys; Purcell, Dagmary; Grigg, Nicole; Toro, Doris H.

    2016-01-01

    Objectives Chronic hepatitis C (CHC) is a major public health problem in Puerto Rico. It is the most common cause of chronic liver disease and the most frequent indication for liver transplantation in the United States." Our main objectives were to estimate the seroprevalence of CHC infection, to describe the demographic and histological parameters of the infection in our sample population, and to evaluate the treatment outcomes in Puerto Rican veterans. Methods To determine overall seroprevalence, we reviewed all the hepatitis C cases (encompassing from January 1, 2002, to December 31, 2009) of the VA Caribbean Healthcare System, Department of Veterans Affairs. The records of only those individuals who received treatment with pegylated interferon and ribavirin were reviewed to determine risks factors for infection, response rates, adverse events, and outcomes. Results During the study period, there were a total of 1,496 patients identified as being infected with HCV, for an estimated seroprevalence of 2.3%. Of these, approximately 10% (137) were treated with combination therapy and were included in this study. The mean age was 58 (±6.4); 96.4% were men. The most common genotype was type 1. The responses to treatment were generally poor, with only 48.4% of the patients achieving Ssustained virological response. Discussion Though the seroprevalence of chronic hepatitis C in the Latino veteran population of Puerto Rico is high, relatively few patients have received treatment, most probably because of the contraindications of the medications used. Combination therapy with pegylated interferon plus weight-based ribavirin was inefficient and plagued with side effects; as a whole, this therapy was not found to be overly beneficial to our patients. New emerging and approved therapies will change this paradigm, allowing the treatment of a larger population without the side effects of the studied therapy. PMID:26932282

  19. Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model

    PubMed Central

    Bard-Chapeau, Emilie A.; Nguyen, Anh-Tuan; Rust, Alistair G.; Sayadi, Ahmed; Lee, Philip; Chua, Belinda Q; New, Lee-Sun; de Jong, Johann; Ward, Jerrold M.; Chin, Christopher KY.; Chew, Valerie; Toh, Han Chong; Abastado, Jean-Pierre; Benoukraf, Touati; Soong, Richie; Bard, Frederic A.; Dupuy, Adam J.; Johnson, Randy L.; Radda, George K.; Chan, Eric CY.; Wessels, Lodewyk FA.; Adams, David J.

    2014-01-01

    The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC we performed a near saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers, and a bewildering number (2860) of candidate later stage drivers, that were enriched for genes mutated, deregulated, or that function in signaling pathways important for human HCC, with a striking 1199 genes linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC. PMID:24316982

  20. Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients

    PubMed Central

    Wang, Xiao-Ling; Ren, Jian-Ping; Wang, Xue-Qing; Wang, Xiao-Hong; Yang, Shao-Fang; Xiong, Yi

    2016-01-01

    AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes. METHODS: One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed. RESULTS: Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ2 = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ2 = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively

  1. Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

    PubMed

    Ghosh, S; Nandi, M; Pal, S; Mukhopadhyay, D; Chakraborty, B C; Khatun, M; Bhowmick, D; Mondal, R K; Das, S; Das, K; Ghosh, R; Banerjee, S; Santra, A; Chatterjee, M; Chowdhury, A; Datta, S

    2016-08-01

    Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and

  2. Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

    PubMed

    Ghosh, S; Nandi, M; Pal, S; Mukhopadhyay, D; Chakraborty, B C; Khatun, M; Bhowmick, D; Mondal, R K; Das, S; Das, K; Ghosh, R; Banerjee, S; Santra, A; Chatterjee, M; Chowdhury, A; Datta, S

    2016-08-01

    Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and

  3. Association of serum gamma-glutamyl transferase with treatment outcome in chronic hepatitis B patients

    PubMed Central

    Huang, Rui; Yang, Chen-Chen; Liu, Yong; Xia, Juan; Su, Ran; Xiong, Ya-Li; Wang, Gui-Yang; Sun, Zhen-Hua; Yan, Xiao-Min; Lu, Shan; Wu, Chao

    2015-01-01

    AIM: To investigate the association of serum gamma-glutamyl transferase (GGT) levels with chronic hepatitis B infection and hepatitis B e antigen (HBeAg) seroconversion. METHODS: A retrospective study was performed on clinical data collected from patients who had been positive for hepatitis B surface antigen for > 6 mo and who were antiviral-treatment naïve (n = 215) attending the Hepatitis Clinic at Nanjing Drum Tower Hospital between August 2010 and December 2013. Healthy individuals without liver disease (n = 83) were included as controls. Patients were categorized into four groups based on disease status as recommended by the European Association for the Study of the Liver: immune tolerance (IT; n = 47), HBeAg-positive hepatitis (EPH; n = 93), HBeAg-negative hepatitis (ENH; n = 20), and inactive carrier (IC; n = 55). Prediction of complete response (CR) based on serum GGT was also examined in EPH patients (n = 33) treated for 48 wk with nucleos(t)ide analogue (NA) therapy, including lamivudine plus adefovir combination therapy (n = 20) or entecavir monotherapy (n = 13). CR was defined as a serum hepatitis B virus DNA level < 500 copies/mL and HBeAg seroconversion by 48 wk of treatment. RESULTS: Serum GGT levels were significantly increased in EPH and ENH patients relative to the IT, IC, and healthy control groups (P < 0.01 for all). However, no significant difference in serum GGT levels was found between the EPH and ENH groups. Baseline serum GGT levels were significantly higher in patients who achieved CR (7/33; 21.2%) compared to patients in the non-CR group (26/33; 78.8%; P = 0.011). In addition, the decline in serum GGT was greater in CR patients compared to non-CR patients after 24 wk and 48 wk of treatment (P = 0.012 and P = 0.008, respectively). The receiver operating characteristic curve yielded a sensitivity of 85.71% and a specificity of 61.54% at a threshold value of 0.89 times the upper limit of normal for baseline serum GGT in the prediction of CR

  4. Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Gómez-Ambrosi, Javier; Frago, Laura M; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

    2015-11-01

    Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia.

  5. Altered hepatic vasopressin and alpha 1-adrenergic receptors after chronic endotoxin infusion

    SciTech Connect

    Roth, B.L.; Spitzer, J.A.

    1987-05-01

    Sepsis and septic shock are complicated by a number of hemodynamic and metabolic aberrations. These include catecholamine refractoriness and altered glucose metabolism. Recently, a nonshock rat model of continuous endotoxin infusion via an implanted osmotic pump was developed that reproduces some of the metabolic and cardiovascular findings of human sepsis. By using this model, we have found a decreased number of hepatic plasma membrane alpha 1-adrenergic and (Arg8)vasopressin receptors in rats continuously infused with endotoxin. There was a significant decrease in (/sup 3/H)prazosin (35 +/- 7%) and (/sup 3/H) (Arg8)vasopressin (43 +/- 8%) receptors after 30 h of continuous endotoxin infusion with no change in affinity. The ability of norepinephrine to form the high-affinity complex with alpha 1-adrenergic receptors was not altered after chronic endotoxin infusion. The results are consistent with the concept that alterations in receptor number might underlie certain of the metabolic consequences of chronic sepsis.

  6. Chronic Hepatitis C Virus Infection: A Review of Current Direct-Acting Antiviral Treatment Strategies

    PubMed Central

    Zhang, Johnathan; Nguyen, Douglas; Hu, Ke-Qin

    2016-01-01

    Chronic Hepatitis C virus (HCV) infection carries a significant clinical burden in the United States, affecting more than 4.6 million Americans. Untreated chronic HCV infection can result in cirrhosis, portal hypertension, and hepatocellular carcinoma. Previous interferon based treatment carried low rates of success and significant adverse effects. The advent of new generation oral antiviral therapy has led to major improvements in efficacy and tolerability but has also resulted in an explosion of data with increased treatment choice complexity. Treatment guidelines are constantly evolving due to emerging regimens and real world treatment data. There also still remain subpopulations for whom current treatments are lacking or unclearly defined. Thus, the race for development of HCV treatment regimens still continues. This review of the current literature will discuss the current recommended treatment strategies and briefly overview next generation agents. PMID:27293521

  7. Complement fixing hepatitis B core antigen immune complexes in the liver of patients with HBs antigen positive chronic disease.

    PubMed Central

    Rizzetto, M; Bonino, F; Crivelli, O; Canese, M G; Verme, G

    1976-01-01

    One hundred and fifty-two biopsies from serologically HBsAg positive and negative patients with liver disease were studied in immunofluorescence: for the presence of the surface (HBs) and the core (HBc) antigenic determinants foeterminants of the hepatitis B virus, of immunoglobulins and complement (C) deposits, and for the capacity to fix human C. Circumstantial evidence is presented suggesting that HBc immune-complexes are a relevant feature in the establishment and progression of chronic HBSAg liver disease. C fixation by liver cells was shown in all HBC positive patients with chronic hepatitis; an active form was present in every case, except two with a persistent hepatitis, an inverse ratio of HBc to C binding fluorescence being noted between active chronic hepatitis and cirrhotic patients. HBc without C fixation was observed in only three patients in the incubation phase of infectious hepatitis. IgG deposits were often found in HBc containing, C fixing nuclei. No C binding or IgG deposits were observed in acute self-limited type B hepatitis, in serologically positive patients with normal liver or minimal histological lesions, with and without HBs cytoplasmic fluorescence in their biopsy, or in serologically negative individuals. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1001973

  8. Simulation Shows That Early Treatment of Chronic Hepatitis B Infection Can Cut Deaths and Be Cost-Effective

    PubMed Central

    Post, Sarah E.; Sodhi, Neetu Khurana; Peng, Chia-hui; Wan, Kejia; Pollack, Henry J.

    2014-01-01

    Chronic hepatitis B affects more than a million people in the U.S. and causes 4,000 deaths each year, yet the costs and benefits of treatment have not been fully evaluated. Using a model that simulates disease progression, we compare treatment programs for hepatitis B that start at an early versus late stage of disease. Early care is shown to improve health, reduce premature deaths, and prevent expensive complications, making it highly cost-effective. Our results demonstrate the importance of linking hepatitis B screening to treatment, and illustrate how predictive models can be used to evaluate strategies for improving access to care. PMID:21289356

  9. Monocyte Adhesion Molecules Expression in Patients with Chronic Hepatitis C Liver Disease

    PubMed Central

    El-Bassiouni, Nora E.I.; Mahmoud, Ola M.; El Ahwani, Eman G; Ibrahim, Raafat A.; El Bassiouny, Azza E.I.

    2013-01-01

    Background Chronic viral hepatitis is histologically characterized by predominantly periportal infiltration of mononuclear cells, including lymphocytes and monocytes/macrophages. Intralobular infiltration of these inflammatory cells is an ominous sign of deterioration and a criterion for disease activity. Objective To assess the monocyte inflammatory milieu, monocytes adhesion molecules, their endothelial receptors, cytokines and chemokines in patients with HCV induced chronic liver disease, in an attempt to clarify the role of blood monocytes in induction of inflammation and fibrogenesis in chronic hepatitis C liver disease. Subjects and Methods The current study included 60 patients with chronic liver disease categorized into 2groups: Patients chronic hepatitis C (CHC) and patients with liver cirrhosis (LC), 15 patients each; 15 healthy subjects were included as normal controls. Immunophenotype characterization was carried out by flowcytometric analysis for identification of CD11a, CD11b and CD49d monocyte surface antigen expression in different groups studied. The circulating levels of the soluble adhesion molecules (sE-selectin, sICAM-1 and sVCAM-1), cytokines (TNF-α and IL-1) and chemokines (MCP-1) were also assessed by immunoassays. Results Data demonstrated a significant increase (p<0.01) in the surface expression of CD11a on peripheral blood monocytes and in the circulating levels sE-selectins, sICAM-1, sVCAM-1 and TNF-α in both groups of patients compared to healthy subjects. Data also revealed a significant increase (p<0.01) in the surface expression of each of CD11b and CD49d on peripheral blood monocytes and in the circulating levels sICAM-1, sVCAM-1 and TNF-α in patients with LC compared to those with CHC. Moreover, data demonstrated that the increase in surface antigen expression of each CD11a (p<0.01), CD11b (p<0.05) and CD49d (p<0.01) on circulating peripheral blood monocytes is positively correlated with the increase in the circulating levels of

  10. DEPDC5 variants increase fibrosis progression in Europeans with chronic hepatitis C virus infection

    PubMed Central

    Burza, Maria Antonella; Motta, Benedetta Maria; Mancina, Rosellina Margherita; Pingitore, Piero; Pirazzi, Carlo; Lepore, Saverio Massimo; Spagnuolo, Rocco; Doldo, Patrizia; Russo, Cristina; Lazzaro, Veronica; Fischer, Janett; Berg, Thomas; Aghemo, Alessio; Cheroni, Cristina; De Francesco, Raffaele; Fargion, Silvia; Colombo, Massimo; Datz, Christian; Stickel, Felix

    2015-01-01

    Chronic hepatitis C virus (HCV) infection may progress to cirrhosis and hepatocellular carcinoma (HCC). Recently, two genetic variants, DEPDC5 rs1012068 and MICA rs2596542, were associated with the onset of HCC in Asian subjects with chronic HCV infection. The aim of the present study was to analyze whether DEPDC5 and MICA genetic variants were associated with liver disease progression in European subjects with chronic HCV infection. In a Northern Italian discovery cohort (n = 477), neither DEPDC5 rs1012068 nor MICA rs2596542 were associated with HCC (n = 150). However, DEPDC5 rs1012068 was independently associated with cirrhosis (n = 300; P = 0.049). The association of rs1012068 with moderate to severe fibrosis was confirmed in an independent cross‐sectional German cohort (n = 415; P = 0.006). Furthermore, DEPDC5 rs1012068 predicted faster fibrosis progression in a prospective cohort (n = 247; P = 0.027). Next, we examined the distribution of nonsynonymous DEPDC5 variants in the overall cross‐sectional cohort (n = 912). The presence of at least one variant increased the risk of moderate/severe fibrosis by 54% (P = 0.040). To understand the molecular mechanism underlying the genetic association of DEPDC5 variants with fibrosis progression, we performed in vitro studies on immortalized hepatic stellate cells (LX‐2). In these cells, down‐regulation of DEPDC5 resulted in increased expression of β‐catenin and production of its target matrix metallopeptidase 2 (MMP2), a secreted enzyme involved in fibrosis progression. Conclusion: DEPDC5 variants increase fibrosis progression in European subjects with chronic HCV infection. Our findings suggest that DEPDC5 down‐regulation may contribute to HCV‐related fibrosis by increasing MMP2 synthesis through the β‐catenin pathway. (Hepatology 2016;63:418–427) PMID:26517016

  11. Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

    PubMed Central

    Peters, D. N.; Steinberg, H.; Anderson, W. I.; Hornbuckle, W. E.; Cote, P. J.; Gerin, J. L.; Lewis, R. M.; Tennant, B. C.

    1992-01-01

    Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1632459

  12. Hepatitis B vaccination in chronic kidney disease patients: a call for novel vaccines.

    PubMed

    Grzegorzewska, Alicja E

    2014-11-01

    The protective immunization rates in response to hepatitis B vaccination in chronic kidney disease (CKD) patients are lower than response rates in the general population because of genetic and CKD-related factors as well as logistic problems with a proper providing of the recommended vaccination schedules. This review focuses on third-generation vaccines and adjuvanted vaccines commercially introduced in some countries, investigated in clinical trials, especially involving CKD patients or used only in the experimental studies. In order to improve the immunization rate, the use of third-generation vaccines (yeast-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S1/pre-S2/S HBV vaccines), novel adjuvants (AS04, AS02, phosphorothioate oligodeoxyribonucleotide, hemokinin-1, a polysaccharide based on delta inulin, nano-complex Hep-c, cyclic diguanylate) or immunostimulants for enhancement of immunogenicity of existing recombinant hepatitis B vaccines is tried to improve results of hepatitis B vaccination prior to dialysis commencement or already on renal replacement therapy.

  13. Animal Models of Chronic Hepatitis Delta Virus Infection Host–Virus Immunologic Interactions

    PubMed Central

    Aldabe, Rafael; Suárez-Amarán, Lester; Usai, Carla; González-Aseguinolaza, Gloria

    2015-01-01

    Hepatitis delta virus (HDV) is a defective RNA virus that has an absolute requirement for a virus belonging to the hepadnaviridae family like hepatitis B virus (HBV) for its replication and formation of new virions. HDV infection is usually associated with a worsening of HBV-induced liver pathogenesis, which leads to more frequent cirrhosis, increased risk of hepatocellular carcinoma (HCC), and fulminant hepatitis. Importantly, no selective therapies are available for HDV infection. The mainstay of treatment for HDV infection is pegylated interferon alpha; however, response rates to this therapy are poor. A better knowledge of HDV–host cell interaction will help with the identification of novel therapeutic targets, which are urgently needed. Animal models like hepadnavirus-infected chimpanzees or the eastern woodchuck have been of great value for the characterization of HDV chronic infection. Recently, more practical animal models in which to perform a deeper study of host virus interactions and to evaluate new therapeutic strategies have been developed. Therefore, the main focus of this review is to discuss the current knowledge about HDV host interactions obtained from cell culture and animal models. PMID:25686091

  14. Non-invasive assessment of liver fibrosis in chronic hepatitis B

    PubMed Central

    Branchi, Federica; Conti, Clara Benedetta; Baccarin, Alessandra; Lampertico, Pietro; Conte, Dario; Fraquelli, Mirella

    2014-01-01

    The goal of this review is to provide a comprehensive picture of the role, clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus (HBV) infection. During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility, poor acceptance by patients. Elastographic techniques conceived to assess liver stiffness, in particular transient elastography, and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis. Recent evidence highlights that both liver stiffness and some bio-chemical markers correlate with survival and major clinical end-points such as liver decompensation, development of hepatocellular carcinoma and portal hypertension. Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis. Given their prognostic value, transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes. Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development. PMID:25356021

  15. Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome.

    PubMed

    Sousa, Vanessa C S D; Carmo, Rodrigo F; Vasconcelos, Luydson R S; Aroucha, Dayse C B L; Pereira, Leila M M B; Moura, Patrícia; Cavalcanti, Maria S M

    2016-05-01

    The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C-262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C-262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0-F1), 200 had moderate/severe fibrosis (F2-F4), and 106 had HCC. Genotyping of SNPs was performed by real-time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.

  16. A Retrospective Study on the Significance of Liver Biopsy and Hepatitis B Surface Antigen in Chronic Hepatitis B Infection

    PubMed Central

    Zeng, Da-Wu; Zhang, Jie-Min; Liu, Yu-Rui; Dong, Jing; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-01-01

    Abstract To investigate changes in the HBV replication level along with the natural course of chronic HBV infection and to examine the accuracy of the immune tolerant phase defined by the serological profile. A total of 390 chronic HBV-infected patients were retrospectively recruited for this study. They were classified into immune-tolerance (IT), immune-clearance (IC), low-replicative (LR), and HBeAg-negative hepatitis (ENH) phases according to serological profiles (single-standard, SS) or dual-standard (DS) with the inclusion of liver histology. Serum HBV DNA and HBsAg were quantitatively measured, and liver histology was quantitatively analyzed. The accuracy of the SS-defined IT phase was low, and active pathological changes were detected in 56 of 112 SS-defined IT patients. DS-defined IT patients had higher HBsAg levels (P = 0.0002) than the SS-defined patients. The quantitative HBsAg level can help identify SS-defined IT patients with potential liver injury. The area under the received operating characteristic curve for predicting the DS-defined IT phase was 0.831 (HBsAg 4.398 log IU/mL; sensitivity 87.5%; specificity 73.2%). HBV DNA was reduced by 4 logs, whereas HBsAg was only decreased by 2 logs with HBeAg positive to negative phase conversion. Approximately half of IT patients defined by SS may have medium or severe liver injury. Quantitative measurement of the HBsAg level can help identify SS-defined IT patients with potential liver injury. PMID:26937895

  17. Comparison of collagen proportionate areas in liver fibrosis quantification between chronic hepatitis B and C

    PubMed Central

    Chen, Sheng-Hung; Peng, Cheng-Yuan; Chiang, I-Ping; Lai, Hsueh-Chou; Lee, Chiung-Ju; Su, Wen-Pang; Kao, Jung-Ta; Chuang, Po-Heng

    2016-01-01

    Abstract Few studies have compared the distinct hepatic collagen morphometrics of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). This study compared the discrepancies between CHB and CHC in liver fibrosis (F) quantification by using the collagen proportionate area (CPA) and liver stiffness (LS) measured with shear wave velocity (SWV). This study enrolled 274 eligible consecutive patients diagnosed with CHB (n = 137) or CHC (n = 137). Their ages ranged from 20 to 80 years (median = 50). In total, 154 patients (56.2%) were male. Participant LS was measured by using acoustic radiation force impulse elastography preceding an immediate percutaneous liver biopsy. The total proportion of the collagen stained with picrosirius red to the total tissue area was expressed as the CPA percentage, which was stratified into portal–bridging (PB) and perisinusoidal (PS) proportionate areas (PAs). Based on the METAVIR F staging system, 36 (26.3%), 36 (26.3%), 28 (20.4%), and 37 (27.0%) participants in the CHB group and 34 (24.8%), 45 (32.9%), 34 (24.8%), and 24 (17.5%) participants in the CHC group were staged as F1, F2, F3, and F4, respectively. Both the total CPAs and PBPAs were significantly (P < 0.05) higher in the CHC group than in the CHB group within all F-stratified subgroups. The SWVs were significantly (P < 0.05) higher in the CHC group than in the CHB group only within the F2, F3, and F4 subgroups. However, the PSPAs did not differ significantly between the CHC and CHB groups within all subgroups. Multiple regression analysis revealed that viral hepatitis etiology (P < 0.001), METAVIR F stages (P < 0.001), and platelet count (P = 0.007) were independent factors correlated with the CPA (R2 = 0.543, P < 0.001). In conclusion, both the F stage-stratified CPAs and SWVs tended to be higher in cases of CHC than in those of CHB. The type of viral hepatitis significantly affected both the CPA and SWV values. The PBPAs were more

  18. Comparison of collagen proportionate areas in liver fibrosis quantification between chronic hepatitis B and C.

    PubMed

    Chen, Sheng-Hung; Peng, Cheng-Yuan; Chiang, I-Ping; Lai, Hsueh-Chou; Lee, Chiung-Ju; Su, Wen-Pang; Kao, Jung-Ta; Chuang, Po-Heng

    2016-08-01

    Few studies have compared the distinct hepatic collagen morphometrics of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). This study compared the discrepancies between CHB and CHC in liver fibrosis (F) quantification by using the collagen proportionate area (CPA) and liver stiffness (LS) measured with shear wave velocity (SWV).This study enrolled 274 eligible consecutive patients diagnosed with CHB (n = 137) or CHC (n = 137). Their ages ranged from 20 to 80 years (median = 50). In total, 154 patients (56.2%) were male. Participant LS was measured by using acoustic radiation force impulse elastography preceding an immediate percutaneous liver biopsy. The total proportion of the collagen stained with picrosirius red to the total tissue area was expressed as the CPA percentage, which was stratified into portal-bridging (PB) and perisinusoidal (PS) proportionate areas (PAs).Based on the METAVIR F staging system, 36 (26.3%), 36 (26.3%), 28 (20.4%), and 37 (27.0%) participants in the CHB group and 34 (24.8%), 45 (32.9%), 34 (24.8%), and 24 (17.5%) participants in the CHC group were staged as F1, F2, F3, and F4, respectively. Both the total CPAs and PBPAs were significantly (P < 0.05) higher in the CHC group than in the CHB group within all F-stratified subgroups. The SWVs were significantly (P < 0.05) higher in the CHC group than in the CHB group only within the F2, F3, and F4 subgroups. However, the PSPAs did not differ significantly between the CHC and CHB groups within all subgroups. Multiple regression analysis revealed that viral hepatitis etiology (P < 0.001), METAVIR F stages (P < 0.001), and platelet count (P = 0.007) were independent factors correlated with the CPA (R = 0.543, P < 0.001).In conclusion, both the F stage-stratified CPAs and SWVs tended to be higher in cases of CHC than in those of CHB. The type of viral hepatitis significantly affected both the CPA and SWV values. The PBPAs were more closely

  19. Comparison of Quasispecies Diversity of HCV between Chronic Hepatitis C and Hepatocellular Carcinoma by Ultradeep Pyrosequencing

    PubMed Central

    Park, Chang-Wook; Hwang, Keumrock; Oh, Heung-Bum; Lee, Han Chu

    2014-01-01

    Backgrounds. Hepatitis C virus (HCV) exists as population of closely related genetic variants known as quasispecies. HCV quasispecies diversity is strongly influenced by host immune pressure on virus. Quasispecies diversity is expected to decline as host immune response to HCV decreases over natural course of progressing from chronic hepatitis C (CHC) to hepatocellular carcinoma (HCC). Methods. Ultradeep pyrosequencing (UDPS) was used to evaluate degree of quasispecies diversity in 49 patients infected with HCV including 26 with CHC and 23 with HCC. Whole structural protein of HCV genome was subjected to UDPS. Results. Shannon's indices for quasispecies diversity in HCV E1 were significantly lower in patients with HCC than in those with CHC. 14 amino acid positions differed significantly between two groups. Area under curve of ROC analysis for differentiating HCC from CHC was >0.8 for all of 14 amino acid positions. Conclusion. HCV quasispecies diversity as indicator of declining host immune functions was easily assessed by UDPS technology. Shannon's indices in 14 amino acid positions were found to differentiate between patients with CHC and those with HCC. Our data propose that degree of HCV quasispecies measured by UDPS might be useful to predict progression of HCC in chronic HCV patients. PMID:24999482

  20. Virus evolution during chronic hepatitis B virus infection as revealed by ultradeep sequencing data.

    PubMed

    Jones, Leandro R; Sede, Mariano; Manrique, Julieta M; Quarleri, Jorge

    2016-02-01

    Despite chronic hepatitis B virus (HBV) infection (CHB) being a leading cause of liver cirrhosis and cancer, HBV evolution during CHB is not fully understood. Recent studies have indicated that virus diversity progressively increases along the course of CHB and that some virus mutations correlate with severe liver conditions such as chronic hepatitis, cirrhosis and hepatocellular carcinoma. Using ultradeep sequencing (UDS) data from an intrafamilial case, we detected such mutations at low frequencies among three immunotolerant patients and at high frequencies in an inactive carrier. Furthermore, our analyses indicated that the HBV population from the seroconverter patient underwent many genetic changes in response to virus clearance. Together, these data indicate a potential use of UDS for developing non-invasive biomarkers for monitoring disease changes over time or in response to specific therapies. In addition, our analyses revealed that virus clearance seemed not to require the virus effective population size to decline. A detailed genetic analysis of the viral lineages arising during and after the clearance suggested that mutations at or close to critical elements of the core promoter (enhancer II, epsilon encapsidation signal, TA2, TA3 and direct repeat 1-hormone response element) might be responsible for a sustained replication. This hypothesis requires the decline in virus load to be explained by constant clearance of virus-producing hepatocytes, consistent with the sustained progress towards serious liver conditions experienced by many CHB patients. PMID:26581478

  1. Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure

    PubMed Central

    Chen, En-Qiang; Zeng, Fan; Zhou, Ling-Yun; Tang, Hong

    2015-01-01

    Hepatitis B virus (HBV) associated acute-on-chronic liver failure (ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B (CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field. PMID:26576085

  2. Behavioral and Healthcare-Associated Risk Factors for Chronic Hepatitis C Virus Infection in Korea

    PubMed Central

    Kim, Jong Yeop; Cho, Juhee; Hwang, Sung Ho; Kil, Ho; Bae, Si Hyun; Kim, Young Seok; Lee, Han Chu

    2012-01-01

    The risk factors related to hepatitis C virus (HCV) infection showed geographic and temporal differences. We investigated HCV-related risk factors in Korea where intravenous drug use (IVDU) is uncommon. The HCV-related risk factors were investigated in a prospective, multicenter chronic HCV cohort (n = 711) using a standardized questionnaire in four university hospitals. The results were compared with those of 206 patients with chronic liver diseases not related to either of HCV or hepatitis B virus infection (comparison group). The IVDU was found in 3.9% and remote blood transfusion (≥ 20 yr ago) in 18.3% in HCV cohort group, while that in comparison group was in none and 5.3%, respectively. In a multivariate logistic analysis, transfusion in the remote past (odds ratio [OR], 2.99), needle stick injury (OR, 4.72), surgery (OR, 1.89), dental procedures (OR, 2.96), tattooing (OR, 2.07), and multiple sexual partners (2-3 persons; OR, 2.14, ≥ 4 persons; OR, 3.19), were independent risk factors for HCV infection. In conclusion, the major risk factors for HCV infection in Korea are mostly related to conventional or alterative healthcare procedures such as blood transfusion in the remote past, needle stick injury, surgery, dental procedure, and tattooing although multiple sex partners or IVDU plays a minor role. PMID:23166420

  3. Could the depression of obese patients suffering from chronic hepatitis C be temporarily improved?

    PubMed

    Tarantino, G; Basile, V; Conca, P; Ariello, M; Di Minno, M N D; Romano, A; Gentile, A; Capone, D

    2008-09-01

    Depression is an usual finding in patients suffering from chronic hepatitis C. Development of moderate to severe depressive symptoms occurs frequently during pegylated interferon/ribavirin treatment and is generally predicted by baseline depression scores. Furthermore, the obese patients have been found to be twice as likely to suffer from anxiety, impaired social interaction, and depression when compared with the no obese population. In order to evaluate the efficacy of a pharmacological treatment of depression, 68 obese patients with chronic hepatitis C, under or not antiviral therapy, were selected and enrolled into this open, controlled pilot study. Our population was divided in two groups: 'on Selective Serotonin Reuptake Inhibitors plus support', with individual titration of medication to adequate side-effects, including thirty seven patients, and 'on only support', involving thirty one patients. Both groups were well balanced for gender, age and antiviral treatment. The selected patients had, at entry, a Beck Depression Inventory score of 24.5 +/- 8.1 (mean +/- SD). Therapeutic successful outcomes (a decreased score of >or= 10 units compared to the baseline) were statistically more frequent in antidepressant drug-treated group (P = 0.005); they were well predicted by dose of Selective Serotonin Reuptake Inhibitors. Thirty five percent of patients were non-responder to Selective Serotonin Reuptake Inhibitors. The drug tolerability was good. Nearly twenty percent of patients were responder to only support.

  4. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection.

    PubMed

    Zeng, Da-Wu; Dong, Jing; Liu, Yu-Rui; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-08-01

    There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the "gold standard" for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians. PMID:27547009

  5. Differences in Metabolites of Different Tongue Coatings in Patients with Chronic Hepatitis B

    PubMed Central

    Zhao, Yu; Gou, Xiao-jun; Dai, Jian-ye; Peng, Jing-hua; Feng, Qin; Sun, Shu-jun; Cao, Hui-juan; Zheng, Ning-ning; Fang, Jun-wei; Jiang, Jian; Su, Shi-bing; Liu, Ping; Hu, Yi-yang; Zhang, Yong-yu

    2013-01-01

    Tongue coating is one of the important foundations of tongue diagnosis in traditional Chinese medicine (TCM) and plays an important role in reflecting the occurrence, development, and prognosis of the disease. However, its material basis is still poorly understood. In this study, a urinary metabonomic method based on gas chromatography coupled to mass spectrometry (GC/MS) was developed. The distinct clustering in metabolic profile was observed from Group A (thick yellow coating in patients with chronic hepatitis B), Group B (thick white coating in patients with chronic hepatitis B), and Group C (thin white coating with healthy humans) using orthogonal projections to latent structures (OPLS). Based on the variable of importance in the project (VIP) values, some significantly changed metabolites have been identified. These changes were related to the disturbance in energy metabolism, amino acid metabolism, nucleotide metabolism, and gut microflora, which were helpful to understand the material basis leading to the formation of tongue coating. This study demonstrated that tongue coating may have an objective material basis. PMID:23690837

  6. Interstitial pneumonitis associated with pegylated interferon alpha-2b therapy for chronic hepatitis C: case report.

    PubMed

    Carrillo-Esper, Raúl; González-Avila, Daniela; Uribe-Ríos, Marittza; Méndez-Sánchez, Nahum

    2008-01-01

    Since 2004, pegylated interferon (P-IFN) in combination with ribavirin has become the optimal choice of therapy for chronic hepatitis C virus (HCV) infection. IFN a-2b suppresses HCV replication and restores elevated serum aminotransferase levels, leading to improvements in the histological changes in the livers of patients with chronic hepatitis C. Unfortunately, P-IFN has several adverse effects, including pneumonitis. This complication has been reported in the treatment of malignant diseases and CHC. We report a patient with interstitial pneumonitis thought to be caused by an IFN-based treatment in an unusual scenario of a patient with HCV-related Child-Pugh stage A cirrhosis, who experienced dyspnea, fever, and cough after 12 months of treatment with P-IFN a-2b. Her lung injury and pulmonary symptoms did not disappear despite discontinuation of IFN and the administration of corticosteroid. We concluded that the patient developed a fatal interstitial pneumonitis associated with P-INF a-2b therapy. PMID:18376374

  7. Personality, Coping, and Well-Being for People Living with Chronic Hepatitis C.

    PubMed

    Cellar, Douglas F; Voster, Devon; Fetters, Rachel; Twitchell, Emily; Harper, Gary W; Scott, Cotler

    2016-04-01

    The present study examined the relationships between personality, coping strategies, and health ratings to extend past research to people living with chronic hepatitis C (HCV). Participants were 35 people (11 men, 24 women; M age = 49.6 yr., SD = 10.6) living with chronic hepatitis C for an average of 9.0 yr. (SD = 6.0) since diagnosis. Participants provided descriptions of stressful situations and responded to a personality inventory, Ways of Coping Questionnaire scales (planful problem solving and escape-avoidance) and SF36 Health Survey scales measuring physical functioning and mental health. The stressful situations were judgmentally clustered into seven dimensions (diagnosis/mortality, disclosure, stigma, social and work role functioning, compounding problems, and no stress). Correlational analyses indicated strong negative relationships between escape-avoidance coping and health measures. Emotional Stability and Extraversion were positively related to both health variables, and Extraversion was negatively related to escape-avoidance coping. The results suggest that research from other contexts that has examined these relationships tended to generalize to people living with HCV.

  8. Impact of host gene polymorphisms on susceptibility to chronic hepatitis B virus infection.

    PubMed

    Moudi, Bita; Heidari, Zahra; Mahmoudzadeh-Sagheb, Hamidreza

    2016-10-01

    Hepatitis B virus (HBV) infection can result in a number of different clinical conditions, including asymptomatic HBV carriers to chronic hepatitis and primary hepatocellular carcinoma. Variations in cytokine genes have been discussed to affect the natural history of HBV infection. These cytokines may involve in the viral binding to the cells, modulating the host immune response to infection and pathological changes in the liver, and affecting the antiviral therapies. Various studies reveal that SNPs play an important role in pathogenesis of HBV. On the other hand, various outcomes of infection cannot be completely shown by genetic factors because these studies have inconsistent results with regard to the possible impacts of host genetic polymorphisms on susceptibility to infection. Therefore, to identify the real effects of host genetic factors in HBV susceptibility and natural history of the disease, studies with large sample size will be needed. In addition, due to the complex interactions of genetic factors it is better to identify synergies of several SNPs. Such studies can provide better insights into the novel methods of diagnosis and treatment. Current review will discuss significant genetic variations in cytokine genes that may affect the susceptibility to the chronic HBV infection. PMID:27346643

  9. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

    PubMed Central

    Zeng, Da-Wu; Dong, Jing; Liu, Yu-Rui; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-01-01

    There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the “gold standard” for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians. PMID:27547009

  10. Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

    PubMed Central

    Amador-Cañizares, Yalena; Alvarez-Lajonchere, Liz; Guerra, Ivis; Rodríguez-Alonso, Ingrid; Martínez-Donato, Gillian; Triana, Julián; González-Horta, Eddy E; Pérez, Angel; Dueñas-Carrera, Santiago

    2008-01-01

    AIM: In the present study, antibody and peripheral blood mononuclear cells (PBMC) proliferative responses against hepatitis C virus (HCV) antigens were evaluated in HCV chronically infected patients. METHODS: Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay (ELISA) and carboxyfluorescein succinimidyl ester staining. RESULTS: Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM (P = 0.027) and IgG (P = 0.0006) was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid (P = 0.017) and NS3 (P = 0.005) after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage (P = 0.036). IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4+ or CD8+ T cells, being the capsid poorly recognized. CONCLUSION: These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation. PMID:19058312

  11. Assessment of indicators of vitamin A status in non-cirrhotic chronic hepatitis C patients

    PubMed Central

    Santana, R.C.; Machado, A.A.; Martinelli, A.L.C.; Jordão, A.A.; Ramalho, L.N.Z.; Vannucchi, H.

    2015-01-01

    Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels. PMID:26577844

  12. Manipulation of Regulatory Cells’ Responses to Treatments for Chronic Hepatitis B Virus Infection

    PubMed Central

    Tavakolpour, Soheil; Alavian, Seyed Moayed; Sali, Shahnaz

    2016-01-01

    Background Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease’s progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. Objectives In this study, we focused on treating CHB infection via the manipulation of T cells’ responses to identify possible approaches to cure CHB. Materials and Methods All studies relevant to the role of cellular and humoral responses in HBV infection (especially regulatory cells) were investigated via a systematic search of different databases, including PubMed, Scopus, and Google Scholar. Considering extracted data and also our unpublished data regarding the association between regulatory cytokines and CHB, we introduced a novel approach for the induction of seroclearance. Results Considering the increased levels of regulatory cytokines and also regulatory T cells (Tregs) during CHB, it seems that these cells are deeply involved in CHB infection. The inhibition of regulatory T cells may reverse the dysfunction of effector T cells in patients with CHB infection. In order to inhibit Tregs’ responses, different types of approaches could be employed to restore the impaired function of effector T cells. The blockade of IL-10, IL-35, CTLA-4, PD-1, and TIM-3 were discussed throughout this study. Regardless of the efficacy of these methods, CHB patients may experience serious liver injuries due to the cytotoxic action of CD8+ T cells. Antiviral therapy and a decrease in HBV DNA to undetectable levels could also significantly reduce the risk of the hepatitis B flare. Conclusions The inhibition of Tregs is a novel therapeutic approach to cure chronically HBV infected patients. However, further studies are

  13. Manipulation of Regulatory Cells’ Responses to Treatments for Chronic Hepatitis B Virus Infection

    PubMed Central

    Tavakolpour, Soheil; Alavian, Seyed Moayed; Sali, Shahnaz

    2016-01-01

    Background Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease’s progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. Objectives In this study, we focused on treating CHB infection via the manipulation of T cells’ responses to identify possible approaches to cure CHB. Materials and Methods All studies relevant to the role of cellular and humoral responses in HBV infection (especially regulatory cells) were investigated via a systematic search of different databases, including PubMed, Scopus, and Google Scholar. Considering extracted data and also our unpublished data regarding the association between regulatory cytokines and CHB, we introduced a novel approach for the induction of seroclearance. Results Considering the increased levels of regulatory cytokines and also regulatory T cells (Tregs) during CHB, it seems that these cells are deeply involved in CHB infection. The inhibition of regulatory T cells may reverse the dysfunction of effector T cells in patients with CHB infection. In order to inhibit Tregs’ responses, different types of approaches could be employed to restore the impaired function of effector T cells. The blockade of IL-10, IL-35, CTLA-4, PD-1, and TIM-3 were discussed throughout this study. Regardless of the efficacy of these methods, CHB patients may experience serious liver injuries due to the cytotoxic action of CD8+ T cells. Antiviral therapy and a decrease in HBV DNA to undetectable levels could also significantly reduce the risk of the hepatitis B flare. Conclusions The inhibition of Tregs is a novel therapeutic approach to cure chronically HBV infected patients. However, further studies are

  14. Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and Inositol 1,4,5–trisphosphate receptor

    PubMed Central

    de Bartolomeis, Andrea; Tomasetti, Carmine; Cicale, Maria; Yuan, Pei-Xiong; Manji, Husseini K.

    2012-01-01

    Homer proteins are associated with both dopaminergic and glutamatergic function. In addition, these proteins are implicated in many signal transduction pathways that are also putative targets of the mood stabilizers lithium and valproate (VPA). This study investigated the effect of in vivo chronic administration of therapeutically-relevant doses of lithium and VPA on the expression of the inducible (Homer1a and ania-3) and constitutive (Homer1b/c) isoforms of the Homer1 gene in rat brain, and of two other Homer-related genes: Inositol 1,4,5 trisphosphate receptor (IP3R) and Shank. Homer1b/c was significantly decreased in cortex by VPA, and in striatal and accumbal subregions by both lithium and VPA. Both mood stabilizers reduced Homer1b/c expressionin the dorsolateral caudate-putamen, while only VPA decreased gene expression in all other striatal subregions. Shank and IP3R were downregulated by both mood stabilizers in the cortex. Neither chronic lithium nor VPA affected Homer immediate-early genes. These results suggest that lithium and VPA similarly modulate the expression of structural postsynaptic genes with topographic specificity in cortical and subcortical regions. Thus, Homer may represent an additional molecular substrate for mood stabilizers, and a potential link with dopaminergic function. PMID:22245542

  15. Perceptions about preventing hepatocellular carcinoma among patients with chronic hepatitis in Taiwan

    PubMed Central

    Chen, Ya-Wen; Liu, Chien-Cheng; Perng, Daw-Shyong

    2013-01-01

    AIM: To measure patient perceptions about preventing hepatocellular carcinoma (HCC) and to predict the factors that influence patient willingness to receive therapy. METHODS: A cross-sectional descriptive study was conducted at an outpatient clinic of a medical institution in southern Taiwan. Four hundred patients with chronic hepatitis B/C were recruited as participants. Two structured questionnaires based on the health belief model were utilized in this study, including the scales of perceptions about preventing HCC and knowledge of hepatitis B/C. RESULTS: The statistical results demonstrated that the participants’ perceived susceptibility (r = -0.22, P < 0.001), benefits (r = -0.11, P = 0.028) and cues to action (r = -0.12, P = 0.014) about the prevention of HCC was significantly correlated with their age. The participants’ perceptions were also associated with their educational levels, household incomes and knowledge of hepatitis. Older patients and those with a lower socioeconomic status tended to have negative perceptions and less knowledge of hepatitis. Multivariate logistic regression further indicated that the participants’ age (B = -0.044, SE = 0.017, odds ratio = 0.957, P = 0.008, 95%CI: 0.926-0.989) and perceived barriers (B = -0.111, SE = 0.030, odds ratio = 0.895, P < 0.001, 95%CI: 0.845-0.949) were correlated with their willingness to receive antiviral therapy. CONCLUSION: Healthcare professionals should provide appropriate and effective guidance to increase their patients’ awareness and to decrease the perceived barriers for continuing surveillance and antiviral therapy. PMID:23801839

  16. Effect of chronic renal insufficiency on hepatic and renal udp-glucuronyltransferases in rats.

    PubMed

    Yu, Chuanhui; Ritter, Joseph K; Krieg, Richard J; Rege, Bhaskar; Karnes, Thomas H; Sarkar, Mohamadi A

    2006-04-01

    Significant evidence exists regarding altered CYP450 enzymes in chronic renal insufficiency (CRI), although none exists for the phase II enzymes. The objective of this study was to investigate the effect of CRI on hepatic and renal UDP-glucuronyltransferase (UGT) enzymes. Three groups of rats were included: CRI induced by the 5/6th nephrectomy model, control, and control pair-fed (CPF) rats. UGT activities were determined in liver and kidney microsomes by the 3- and 17-glucuronidation of beta-estradiol (E2-3G and E2-17G), glucuronidation of 4-methylumbelliferone (4-MUG), and 3-glucuronidation of morphine (M3G). UGT isoforms responsible for these catalytic activities were screened using recombinant rat UGT1A1, UGT1A2, UGT1A3, UGT1A7, UGT2B2, UGT2B3, and UGT2B8. UGT protein levels were examined by Western blot analysis using polyclonal antibodies. There was no significant difference between CRI and CPF rats in hepatic and/or renal E2-3G (UGT1A1), E2-17G (UGT2B3), 4-MUG (UGT1A6), and M3G (UGT2B1) formation. Formation of E2-17G and 4-MUG in the liver and E2-3G and 4-MUG in the kidney was significantly reduced (p < 0.05) in CPF and CRI rats compared with control rats. The down-regulated glucuronidation activities were accompanied by corresponding reductions in protein content of specific UGT isoforms. These results suggest that CRI does not seem to influence the protein levels or catalytic activity of most of the major hepatic or renal UGT enzymes. The observed down-regulation of hepatic and renal UGTs in CRI and CPF rats could be caused by restricted food intake in these groups of rats.

  17. Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C

    PubMed Central

    Svegliati-Baroni, Gianluca; Faraci, Graziella; Fabris, Luca; Saccomanno, Stefania; Cadamuro, Massimiliano; Pierantonelli, Irene; Trozzi, Luciano; Bugianesi, Elisabetta; Guido, Maria; Strazzabosco, Mario; Benedetti, Antonio; Marchesini, Giulio

    2013-01-01

    Objective To study the mechanism(s) linking insulin resistance (IR) to hepatic fibrosis and the role of the epithelial component in tissue repair and fibrosis in chronic hepatitis C (CHC). Design Prospective observational study. Setting Tertiary care academic centre. Patients 78 consecutive patients with CHC. Main outcome measures IR, calculated by the oral glucose insulin sensitivity during oral glucose tolerance test; necroinflammatory activity and fibrosis, defined according to Ishak’s score; steatosis, graded as 0 (<5% of hepatocytes), 1 (5–33%), 2 (33–66%) and 3 (>66%). To evaluate the role of the epithelial component in tissue repair and fibrosis, the expansion of the ductular reaction (DR) was calculated by keratin-7 (CK7) morphometry. Nuclear expression of Snail, downregulation of E-cadherin and expression of fibroblast specific protein-1 (FSP1) and vimentin by CK7-positive cells were used as markers of epithelial-mesenchymal transition in DR elements. Results IR, the degree of necroinflammation and expansion of the DR (stratified as reactive ductular cells (RDCs), hepatic progenitor cells and intermediate hepatobiliary cells according to morphological criteria) were all associated with the stage of fibrosis. Nuclear Snail expression, E-cadherin downregulation and vimentin upregulation were observed in RDCs. By dual immunofluorescence for CK7 and FSP1, the number of RDCs undergoing epithelial-mesenchymal transition progressively increased together with the necroinflammatory score. By multivariate analysis, total inflammation and insulin resistance were the only factors significantly predicting the presence of advanced fibrosis (Ishak score ≥3) and the expansion of RDCs. Conclusion This study indicates that IR is associated with the degree of necroinflammatory injury in CHC and contributes to hepatic fibrosis by stimulating the expansion of RDCs that express epithelial-mesenchymal transition markers. PMID:20966027

  18. Differential expression of stress-inducible proteins in chronic hepatic iron overload

    SciTech Connect

    Brown, Kyle E. Broadhurst, Kimberly A.; Mathahs, M. Meleah; Weydert, Jamie

    2007-09-01

    Introduction:: Oxidative stress can trigger a cellular stress response characterized by induction of antioxidants, acute phase reactants (APRs) and heat shock proteins (HSPs), which are presumed to play a role in limiting tissue damage. In rodents, hepatic iron overload causes oxidative stress that results in upregulation of antioxidant defenses with minimal progressive liver injury. The aim of this study was to determine whether iron overload modulates expression of other stress-responsive proteins such as APRs and HSPs that may confer protection against iron-induced damage in rodent liver. Methods:: Male rats received repeated injections of iron dextran or dextran alone over a 6-month period. Hepatic transcript levels for a panel of APRs and HSPs were quantitated by real-time PCR and protein expression was evaluated by Western blot and immunohistochemistry. Results:: Hepatic iron concentrations were increased > 50-fold in the iron-loaded rats compared to controls. Iron loading resulted in striking increases in mRNAs for Hsp32 (heme oxygenase-1; 12-fold increase vs. controls) and metallothionein-1 and -2 (both increased {approx} 6-fold). Transcripts for {alpha}1-acid glycoprotein, the major rat APR, were increased {approx} 3-fold, while expression of other classical APRs was unaltered. Surprisingly, although mRNA levels for the HSPs were not altered by iron, the abundance of Hsp25, Hsp70 and Hsp90 proteins was uniformly reduced in the iron-loaded livers, as were levels of NAD(P)H:quinone oxidoreductase 1, an Hsp70 client protein. Conclusions:: Chronic iron administration elicits a unique pattern of stress protein expression. These alterations may modulate hepatic responses to iron overload, as well as other injury processes.

  19. Soluble Serum CD81 Is Elevated in Patients with Chronic Hepatitis C and Correlates with Alanine Aminotransferase Serum Activity

    PubMed Central

    Welker, Martin-Walter; Reichert, David; Susser, Simone; Sarrazin, Christoph; Martinez, Yolanda; Herrmann, Eva; Zeuzem, Stefan; Piiper, Albrecht; Kronenberger, Bernd

    2012-01-01

    Aim Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity. Patients and Methods Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry. Results Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027). Conclusion CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis. PMID:22355327

  20. Hepatitis B e Antigen Status and Hepatitis B DNA Levels in Women of Childbearing Age with Chronic Hepatitis B Infection Screening for Clinical Trials

    PubMed Central

    Tran, Tram T.; Gordon, Stuart C.; Fung, Scott; Dinh, Phillip; Yee, Leland; Martins, Eduardo Bruno; Buti, Maria; Marcellin, Patrick

    2015-01-01

    Background Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load. Aim To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials. Methods Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18–69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive. Results Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load. Conclusions Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load. PMID:25789483

  1. Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection.

    PubMed

    Smith, Michael A; Lim, Alice

    2015-01-01

    Over the last several years, many advances have been made in the treatment of chronic hepatitis C virus (HCV) infection with the development of direct-acting antivirals. Paritaprevir/ritonavir/ombitasvir with dasabuvir (PrOD) is a novel combination of a nonstructural (NS) 3/4A protein inhibitor boosted by ritonavir, an NS5A protein inhibitor, and an NS5B nonnucleoside polymerase inhibitor. This review aims to discuss the pharmacology, efficacy, safety, drug interactions, and viral drug resistance of PrOD in the treatment of HCV genotype 1 infections. Phase I, II, and III human and animal studies that describe the pharmacology, pharmacokinetics, efficacy, and safety of PrOD for HCV were identified and included. Studies that evaluated patients without cirrhosis (n=2,249) and with cirrhosis (n=422) demonstrated that PrOD for 12 or 24 weeks was effective at achieving sustained virologic response rates (>90%) in patients with genotype 1a or 1b HCV infection. Although indicated for the treatment of HCV genotype 1 infection, PrOD is also recommended for the treatment of HCV in patients coinfected with HIV. Additionally, promising data exist for the use of PrOD in liver-transplant recipients. The most common adverse drug events associated with PrOD included nausea, pruritus, insomnia, diarrhea, asthenia, dry skin, vomiting, and anemia. The high efficacy rates seen coupled with a favorable side effect profile seen with PrOD with or without ribavirin have led to its addition as a recommended treatment regimen for HCV genotype 1 infection. PMID:26622169

  2. New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a.

    PubMed Central

    Ohno, O; Mizokami, M; Wu, R R; Saleh, M G; Ohba, K; Orito, E; Mukaide, M; Williams, R; Lau, J Y

    1997-01-01

    Recent studies have focused on whether different hepatitis C virus (HCV) genotypes are associated with different profiles of pathogenicity, infectivity, and response to antiviral therapy. The establishment of a simple and precise genotyping system for HCV is essential to address these issues. A new genotyping system based on PCR of the core region with genotype-specific PCR primers for the determination of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a was developed. A total of 607 samples (379 from Japan, 63 from the United States, 53 from Korea, 35 from Taiwan, 32 from China, 20 from Hong Kong, 15 from Australia, 6 from Egypt, 3 from Bangladesh, and 1 from South Africa) were tested by both the assay of Okamoto et al. (H. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyamura, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) and this new genotyping system. Comparison of the results showed concordant results for 539 samples (88.8%). Of the 68 samples with discordant results, the nucleotide sequences of the HCV isolates were determined in 23, and their genotypes were determined by molecular evolutionary analysis. In all 23 samples, the assignment of genotype by our new genotyping system was correct. This genotyping system may be useful for large-scale determination of HCV genotypes in clinical studies. PMID:8968908

  3. Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients.

    PubMed

    Enooku, Kenichiro; Nakagawa, Hayato; Soroida, Yoko; Ohkawa, Ryunosuke; Kageyama, Yuko; Uranbileg, Baasanjav; Watanabe, Naoko; Tateishi, Ryosuke; Yoshida, Haruhiko; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

    2014-08-15

    Serum mitochondrial creatine kinase (MtCK) activity was reportedly increased in cirrhotic patients although less prominent than that in hepatocellular carcinoma (HCC) patients. To elucidate the clinical significance of serum MtCK activity in chronic liver disease, 171 chronic hepatitis C patients were enrolled. Serum MtCK activity in study subjects was correlated with serum albumin, platelet counts, liver stiffness values and serum aspartate and alanine aminotransferase. In mouse fibrotic liver induced by bile duct ligation, ubiquitous MtCK mRNA and protein expressions were significantly enhanced and its immunoreactivity was increased, predominantly in hepatocytes. During the mean follow-up period of 2.7 years, HCC developed in 21 patients, in whom serum MtCK activity was significantly higher than that in patients without HCC development. Multivariate Cox regression analysis revealed that higher serum MtCK activity was a risk for HCC development. A cutoff value of MtCK for the prediction of HCC development was determined as 9.0 U/L on receiver operating characteristics analysis, where area under receiver operating characteristics curve was 0.754, with a sensitivity of 61.9%, a specificity of 92.8% and a high negative predictive value of 94.2%. Cumulative incidence of HCC was significantly higher in patients with serum MtCK activity of >9.0 U/L compared to those with serum MtCK activity of ≤ 9.0 U/L even in patients with elevated liver stiffness value, >15 kPa. In conclusion, serum MtCK activity may be increased correlatively with the stage of liver fibrosis and hepatocellular damage. Increased serum MtCK activity is an independent risk for hepatocarcinogenesis in chronic hepatitis C patients. PMID:24420733

  4. The Effect of Chronic Hepatitis B Virus Infection on BDCA3+ Dendritic Cell Frequency and Function

    PubMed Central

    van der Aa, Evelyn; Buschow, Sonja I.; Biesta, Paula J.; Janssen, Harry L. A.; Woltman, Andrea M.

    2016-01-01

    Chronic hepatitis B virus (HBV) infection results from inadequate HBV-specific immunity. BDCA3+ dendritic cells (DCs) are professional antigen presenting cells considered to be important for antiviral responses because of specific characteristics, including high interferon-λ production. BDCA3+ DCs may thus also have a role in the immune response against HBV, and immunotherapeutic strategies aiming to activate DCs, including BDCA3+ DCs, in patient livers may represent an interesting treatment option for chronic HBV. However, neither the effect of chronic hepatitis B (CHB) infection on the frequency and function of BDCA3+ DCs in liver and blood, nor the effect of the viral surface protein (HBsAg) that is abundantly present in blood of infected individuals are known. Here, we provide an overview of BDCA3+ DC frequency and functional capacity in CHB patients. We find that intrahepatic BDCA3+ DC numbers are increased in CHB patients. BDCA3+ DCs from patient blood are not more mature at steady state, but display an impaired capacity to mature and to produce interferon-λ upon polyI:C stimulation. Furthermore, in vitro experiments exposing blood and intrahepatic BDCA3+ DCs to the viral envelope protein HBsAg demonstrate that HBsAg does not directly induce phenotypical maturation of BDCA3+ DCs, but may reduce IFN-λ production via an indirect unknown mechanism. These results suggest that BDCA3+ DCs are available in the blood and on site in HBV infected livers, but measures may need to be taken to revive their function for DC-targeted therapy. PMID:27529176

  5. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  6. Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection

    PubMed Central

    ZHANG, QINGQING; XU, MINGYI; QU, YING; LI, ZHENGHONG; ZHANG, QIDI; CAI, XIAOBO; LU, LUNGEN

    2015-01-01

    Considering the limitations of liver biopsy, reliable non-invasive serum biomarkers of liver fibrosis are required for early diagnosis. The present study analyzed the expression profile of circulating micro (mi)RNAs during the development and progression of hepatic fibrosis in patients with chronic hepatitis B virus (HBV) infection, aiming to identify novel earlier diagnostic biomarkers. Fresh plasma samples were collected from 50 patients diagnosed with chronic HBV infection and hepatic fibrosis. These patients were classified into five groups (S0, S1, S2, S3 and S4; n=10 per group) based on Scheuer's staging criteria. The differential expression of the circulating miRNAs was determined by performing miRNA microarray hybridization. Finally, the target genes of the miRNAs were predicted and classified using gene ontology analysis. A total of 140 miRNAs were detected in the S1–S4 patient groups, and their expression levels were >2-fold higher compared with those in the S0 group. The numbers of miRNAs differentially expressed in the S1–S4 patient groups were 48, 97, 84 and 56, respectively, with 12 miRNAs differentially expressed at all stages, 10 of which were upregulated and two of which were downregulated. The target genes of the miRNAs identified were found to be involved in 100 signal transduction pathways, the majority of which affected hepatic fibrosis via the TGF-/Smad, Wnt, MAPK, Jak/STAT and VEGF pathways. The differential expression levels of miRNAs were closely associated with the staging of hepatic fibrosis. The results of the present study provide evidence to facilitate the development and application of non-invasive biomarkers for earlier diagnosis of hepatic fibrosis. PMID:26299203

  7. AIC649 Induces a Bi-Phasic Treatment Response in the Woodchuck Model of Chronic Hepatitis B.

    PubMed

    Paulsen, Daniela; Weber, Olaf; Ruebsamen-Schaeff, Helga; Tennant, Bud C; Menne, Stephan

    2015-01-01

    AIC649 has been shown to directly address the antigen presenting cell arm of the host immune defense leading to a regulated cytokine release and activation of T cell responses. In the present study we analyzed the antiviral efficacy of AIC649 as well as its potential to induce functional cure in animal models for chronic hepatitis B. Hepatitis B virus transgenic mice and chronically woodchuck hepatitis virus (WHV) infected woodchucks were treated with AIC649, respectively. In the mouse system AIC649 decreased the hepatitis B virus titer as effective as the "gold standard", Tenofovir. Interestingly, AIC649-treated chronically WHV infected woodchucks displayed a bi-phasic pattern of response: The marker for functional cure--hepatitis surface antigen--first increased but subsequently decreased even after cessation of treatment to significantly reduced levels. We hypothesize that the observed bi-phasic response pattern to AIC649 treatment reflects a physiologically "concerted", reconstituted immune response against WHV and therefore may indicate a potential for inducing functional cure in HBV-infected patients. PMID:26656974

  8. [Epidemiology and clinical aspects of chronic hepatitis B and non-A, non-B virus infections].

    PubMed

    Stremmel, W; Strohmeyer, G

    1989-09-01

    Hepatitis B and Non-A-non-B infections often become chronic and proceed to cirrhosis associated with a shortened life expectancy. Both infections are transmitted by parenteral or sexual routes. New insights in the structure of the hepatitis B virus (HBV) as well as in the immune response mechanism of the organism permit by serological testing a clear definition of the replicative state of the virus. Together with the parameters of inflammation (e.g. transaminases, liver histology) it is possible to determine the activity of the hepatitis. The most effective treatment of chronic HBV-infection today is the therapy with alpha- or beta-interferon. The aim of this treatment is the inhibition of HBV replication and accellerated elimination of the virus, indicated by seroconversion of HBEAg to anti-HBEAg. The most significant advance in the knowledge of percutaneous Non-A-non-B hepatitis is the identification of the responsible virus and the development of a diagnostic test for its serological detection. Since this type of hepatitis becomes chronic in 50-60% of the cases, therapy is urgently required. Clinical studies showed that also for Non-A-non-B virus infection alpha-interferon is most effective. Currently the optimal dosage, duration and point in time for interferon treatment is being evaluated.

  9. Aflatoxin levels in chronic hepatitis B patients with cirrhosis or hepatocellular carcinoma in Balıkesir, Turkey.

    PubMed

    Aydın, M; Aydın, S; Bacanlı, M; Başaran, N

    2015-11-01

    Aflatoxins, the secondary metabolites produced by species of naturally occurring Aspergilli, are commonly found in food such as cereals, dried fruits and juice, wine, beer and spices. They are hepatotoxic and are well known human carcinogens based on evidence from human studies. Aflatoxins are an environmental risk factor for the development of hepatocellular carcinoma (HCC). Chronic hepatitis B-infected patients are at increased risk of cirrhosis, hepatic failure and liver cancer. This study was designed to determine the serum aflatoxin B1 (AFB1 ), aflatoxin B2 (AFB2 ), aflatoxin G1 (AFG1 ) and aflatoxin G2 (AFG2 ) concentrations using high-pressure liquid chromatography (HPLC) in hepatitis B-infected patients with or without cirrhosis and liver cancer, alongside healthy controls in Balıkesir, Turkey. The mean AFB1 and total AF levels in patients without liver cancer and cirrhosis were significantly higher than healthy controls. The mean AFB1 and total AF levels in patients with chronic hepatitis B and HCC were significantly higher than infected patients with or without cirrhosis. These results suggest that patients with chronic hepatitis B who are exposed to AFs are at increased risk for developing HCC, which might be prevented by reducing consumption of contaminated foods.

  10. Delayed type hypersensitivity (DTH) skin reaction to hepatitis B surface antigen (HBsAg) in patients with type B acute and chronic hepatitis.

    PubMed Central

    Nagafuchi, S; Kashiwagi, S; Hayashi, S; Inoue, T; Imayama, S; Takeshita, M; Kikuchi, M

    1985-01-01

    Skin reactivity to HBsAg was studied in patients with type B acute and chronic hepatitis and in healthy controls. HBsAg preparations containing 50 micrograms/ml of antigen both with and without alum elicited positive skin reactions in all seven anti-HBs+ persons. Histological examination of skin tissue from the reactive area using monoclonal antibodies to the cell surface of lymphocytes revealed accumulation of Leu-3a positive lymphocytes, showing that the inflammation was a typical delayed type hypersensitivity (DTH) reaction. Irrespective of the presence of HBeAg and anti-HBe, patients with chronic type B hepatitis responded clearly to PPD and SK/SD antigens, whereas they did not exhibit DTH skin reactivity to HBsAg. In contrast, although patients with acute type B hepatitis did not exhibit specific DTH a reaction to HBsAg in the acute period, they began to develop DTH skin reactivity to HBsAg in the convalescent phase of the disease preceding the appearance of anti-HBs antibody. It is suggested that DTH reaction to HBsAg might play an important role in the pathogenesis of type B viral hepatitis. Images Fig. 2 PMID:4075587

  11. Effect of chronic ethanol on hepatic apolipoprotein (Apo)E glycosylation

    SciTech Connect

    Ghosh, P.; Okoh, C.; Chirtel, S.J.; Liu, Q.H.; Lakshman, M.R. George Washington Univ., Washington, DC )

    1991-03-15

    The authors have previously shown that chronic ethanol feeding significantly inhibits the secretion of ApoE in rats. Since many carbohydrate precursors are essential for the synthesis of mature ApoE before it is secreted, the authors have investigated the effects of chronic ethanol on the incorporation of these precursors into ApoE. Male Wistar rats were divided into groups and were pair-fed with Control and Ethanol liquid diets for a period of 8 weeks. At the end, hepatocytes were isolated from each group and {approximately}400 mg cells were incubated in 8 ml final volume of Krebs bicarbonate buffer, pH 7.4 for 30 min. at 37C with the following labeled precursors individually: (2-{sup 3}H)mannose, (6-{sup 3}H)N-acetyl mannosamine, (4,5-{sup 3}H)galactose, (5,6-{sup 3}H)fucose, and (4,5-{sup 3}H)leucine. The incorporation of each precursor into immunoprecipitable ApoE was measured in cell homogenate, microsome and the Golgi fractions. The results showed that chronic ethanol treatment did not significantly inhibit the incorporation of leucine, fucose and galactose into ApoE at any of the subcellular levels. In contrast, chronic ethanol inhibited the incorporation of: (a) mannose into ApoE by 38% both at whole cell and at microsomal level and (b) N-acetyl mannosamine by 26% at the whole cell level and at the Golgi level. Based on these results, it is concluded that chronic ethanol feeding impairs the mannosylation and sialylation of ApoE in rat liver probably by altering the structure and functions of hepatic microsome and Golgi.

  12. Effect of branched-chain amino acid-enriched nutritional supplementation on interferon therapy in Japanese patients with chronic hepatitis C virus infection: a retrospective study

    PubMed Central

    2012-01-01

    Background The aims of this study were to evaluate the effects of nutritional supplementation with branched-chain amino acids (BCAA) with zinc component (Aminofeel®) on adherence to and outcome of therapy in patients treated with interferon (IFN) for chronic hepatitis C and cirrhosis and to determine whether to recommend the supplement. Methods In this retrospective study, 51 patients who received IFN therapy were investigated among 203 consecutive patients who visited our hospital and were advised regarding the potential benefit of taking Aminofeel®. Each patient was free to choose whether to purchase and take Aminofeel®. Results Twenty four patients (group 1-A) took Aminofeel® during standard IFN therapy and 13 (group 1-B) did not. Low-dose, long-term IFN (maintenance) therapy, mainly peglated (Peg)-IFN alpha 2a, was administered to 14 patients who were difficult to treat, because of no effect or harmful side effects with standard IFN therapy, and who had advanced liver fibrosis. Among the 14, 11 patients (group 2-A) took Aminofeel® and 3 (group 2-B) did not. The prevalence of obesity was significantly higher (P=0.04) in group 1-A than in group 1-B. The rate of adherence to IFN therapy was higher in group 1-A (83.3%) than in group 1-B (53.8%, P=0.05). There were no significant differences between the two groups in the rates of sustained virological response (SVR) to IFN therapy. According to multivariate analysis, two factors, SVR and intake of Aminofeel®, were associated with successful adherence to IFN therapy. The adjusted odds ratios for these two factors were 13.25 and 12.59, respectively, and each was statistically significant. The SVR rate of maintenance IFN therapy was in 18.2% group 2-A and 0% in group 2-B. Conclusion Our data show that BCAA intake is useful for adherence to and effect of IFN therapy for patients with chronic hepatitis C. Nutritional supplementation with BCAA seems to be useful for HCV-infected patients receiving IFN therapy

  13. Graft loss following liver transplantation in patients with chronic hepatitis C.

    PubMed

    Rosen, H R; O'Reilly, P M; Shackleton, C R; McDiarmid, S; Holt, C; Busuttil, R W; Martin, P

    1996-12-27

    Liver disease due to hepatitis C (HCV) is an increasingly frequent indication for orthotopic liver transplantation (OLT). The aim of the current study was to analyze the causes of graft loss following OLT for chronic hepatitis C and the longterm outcome following retransplantation in a large university program. Between January 1990 and December 1995, 1183 patients underwent primary OLT at our center. In 304 patients, HCV was diagnosed by seropositivity and/or polymerase chain reaction. Fifty-six (18.4%) of these patients underwent retransplantation. The 36 patients retransplanted for primary non-function were excluded from further analysis. The other indications for regrafting (>30 days following primary transplant) included hepatic artery thrombosis (5), chronic rejection (4), severe HCV recurrence (5), and other etiologies (6). The cumulative survival rates for the 248 patients who received 1 OLT (group 1) were 84% after one year and 75% after three years. The corresponding rates for the 20 non-PNF patients who were retransplanted (group 2) were 60% and 43%, respectively (P<.0001). Moreover, logistic regression analysis confirmed that patients in group 2 were more than 4 times likely to die than patients in group 1 (P<.0034; risk ratio, 4.2; 95% confidence interval 1.61 to 11.37). Patients undergoing retransplantation had a high incidence of serious infectious complications leading to mortality. Two additional patients with severe recurrent HCV died awaiting liver retransplantation. Eight of the 304 total patients (2.6%) transplanted for chronic HCV developed graft failure secondary to HCV recurrence and 6 of the 8 were retransplanted; 3 of the 6 patients retransplanted are alive without evidence of histologic recurrence (mean follow-up less than 1 year). In summary, despite the high frequency of recurrent histologic evidence of HCV following primary OLT (70% at 3 years), graft loss attributable solely to HCV is an infrequent finding. Retransplantation per se is

  14. [Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C].

    PubMed

    Rammeh, Soumaya; Khadra, Hajer Ben; Znaidi, Nadia Sabbegh; Romdhane, Neila Attia; Najjar, Taoufik; Bouzaidi, Slim; Zermani, Rachida

    2014-01-01

    Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

  15. Clinical outcome of acute and chronic hepatitis delta over time: a long-term follow-up study.

    PubMed

    Buti, M; Homs, M; Rodriguez-Frias, F; Funalleras, G; Jardí, R; Sauleda, S; Tabernero, D; Schaper, M; Esteban, R

    2011-06-01

    Long-term changes in the frequency and outcome of hepatitis delta virus (HDV) infection have seldom been analysed. This retrospective, longitudinal study includes 398 consecutive hepatitis B surface antigen (HBsAg)-positive patients with anti-HDV antibodies who attended our institution between 1983 and 2008. At enrolment, 182 patients had acute and 216 chronic hepatitis. Patients were grouped into two periods. Those who attended between 1983 and 1995 and those between 1996 and 2008. The former group was significantly younger, mainly intravenous drugs users, and had a greater incidence of acute HDV and HIV and HCV coinfection. Patients with acute HBV/HDV coinfection cleared both infections in 90% of cases, while all patients with HDV superinfection evolved to chronic disease. One hundred and fifty-eight patients with chronic HDV were followed for a median period of 158months. Seventy-two per cent of the patients remained stable, 18% had hepatic decompensation, 3% developed hepatocellular carcinoma, and 8% cleared HBsAg. Liver-related death was observed in 13% of patients and mainly occurred in patients from the first period (P=0.012). These results indicate an outbreak of HDV at the end of the 1980s and the beginning of the 1990s, with a large number of acute HDV cases affecting predominately young, male intravenous drug users. Currently, patients with chronic HDV disease are older, and factors associated with worse prognosis include the presence of cirrhosis and age at the time of diagnosis.

  16. New horizon for radical cure of chronic hepatitis B virus infection.

    PubMed

    Tajiri, Kazuto; Shimizu, Yukihiro

    2016-07-28

    About 250 to 350 million people worldwide are chronically infected with hepatitis B virus (HBV), and about 700000 patients per year die of HBV-related cirrhosis or hepatocellular carcinoma (HCC). Several anti-viral agents, such as interferon and nucleos(t)ide analogues (NAs), have been used to treat this disease. NAs especially have been shown to strongly suppress HBV replication, slowing the progression to cirrhosis and the development of HCC. However, reactivation of HBV replication often occurs after cessation of treatment, because NAs alone cannot completely remove covalently-closed circular DNA (cccDNA), the template of HBV replication, from the nuclei of hepatocytes. Anti-HBV immune responses, in conjunction with interferon-γ and tumor necrosis factor-α, were found to eliminate cccDNA, but complete eradication of cccDNA by immune response alone is difficult, as shown in patients who recover from acute HBV infection but often show long-term persistence of small amounts of HBV-DNA in the blood. Several new drugs interfering with the life cycle of HBV in hepatocytes have been developed, with drugs targeting cccDNA theoretically the most effective for radical cure of chronic HBV infection. However, the safety of these drugs should be extensively examined before application to patients, and combinations of several approaches may be necessary for radical cure of chronic HBV infection. PMID:27478536

  17. Current and future antiviral drug therapies of hepatitis B chronic infection

    PubMed Central

    Koumbi, Lemonica

    2015-01-01

    Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host’s immune system. Currently the approved therapeutic regimens include pegylated-interferon (IFN)-α and monotherapy with five nucleos(t)ide analogues (NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection. PMID:26052392

  18. New horizon for radical cure of chronic hepatitis B virus infection

    PubMed Central

    Tajiri, Kazuto; Shimizu, Yukihiro

    2016-01-01

    About 250 to 350 million people worldwide are chronically infected with hepatitis B virus (HBV), and about 700000 patients per year die of HBV-related cirrhosis or hepatocellular carcinoma (HCC). Several anti-viral agents, such as interferon and nucleos(t)ide analogues (NAs), have been used to treat this disease. NAs especially have been shown to strongly suppress HBV replication, slowing the progression to cirrhosis and the development of HCC. However, reactivation of HBV replication often occurs after cessation of treatment, because NAs alone cannot completely remove covalently-closed circular DNA (cccDNA), the template of HBV replication, from the nuclei of hepatocytes. Anti-HBV immune responses, in conjunction with interferon-γ and tumor necrosis factor-α, were found to eliminate cccDNA, but complete eradication of cccDNA by immune response alone is difficult, as shown in patients who recover from acute HBV infection but often show long-term persistence of small amounts of HBV-DNA in the blood. Several new drugs interfering with the life cycle of HBV in hepatocytes have been developed, with drugs targeting cccDNA theoretically the most effective for radical cure of chronic HBV infection. However, the safety of these drugs should be extensively examined before application to patients, and combinations of several approaches may be necessary for radical cure of chronic HBV infection. PMID:27478536

  19. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C.

    PubMed

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L; Berg, Thomas; Dore, Gregory J; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  20. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    PubMed Central

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  1. Treatment of chronic hepatitis B with nucleos(t)ide analogues.

    PubMed

    Ohishi, Waka; Chayama, Kazuaki

    2012-03-01

    Recently antiviral therapies for chronic hepatitis B using nucleos(t)ide analogues have become standard treatment modalities on the basis of several independent guidelines, starting with those of the American Association for the Study of Liver Diseases (AASLD) and other such organizations and bodies, including the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver (APASL), and the Japanese Ministry of Health, Labour and Welfare (MHLW)'s research team. The philosophies underlying such treatment strategies are considered basically equivalent. MHLW's guidelines define subjects for medical intervention to be cases measuring alanine aminotransferase (ALT) ≥31 IU/L, with serological hepatitis B virus (HBV) DNA level ≥5 log copies/mL for hepatitis B e antigen (HBeAg)-positive cases, and serological HBV DNA level ≥4 log copies/mL for HBeAg-negative cases. These Japanese guidelines advocate entecavir as the first-line treatment option for nucleos(t)ide-naïve patients, and combination treatment of lamivudine and adefovir as the basis of treatment for patients with lamivudine- and/or entecavir-resistant viruses. Of particular note for patients undergoing lamivudine treatment with persistent HBV DNA level < 2.1 log copies/mL is the recommendation of a switch to entecavir. Early detection of drug-resistant virus is desirable after initiation of nucleos(t)ide analogue treatment, but such a procedure is not uniformly available at all medical institutions. Nevertheless, timely estimation of potential early-stage drug-resistant virus development is crucial for getting a head start on treatment. HBV core-related antigen (HBcrAg) level or HBV DNA level are considered useful markers for the appearance of such drug-resistant viruses.

  2. Racial differences in responses to therapy with interferon in chronic hepatitis C. Consensus Interferon Study Group.

    PubMed

    Reddy, K R; Hoofnagle, J H; Tong, M J; Lee, W M; Pockros, P; Heathcote, E J; Albert, D; Joh, T

    1999-09-01

    The likelihood of a sustained response to a course of interferon in patients with chronic hepatitis C correlates with several clinical and viral factors, including age, viral genotype and initial levels of hepatitis C virus (HCV) RNA in serum. The role of race and ethnicity has not been assessed. We evaluated the association of race with response to interferon in a large randomized, controlled trial using either consensus interferon (9 microg) or interferon alfa-2b (3 million units) given three times weekly for 24 weeks. African-American patients participating in the study were similar to white patients in mean age (43 vs. 42 years) and baseline levels of HCV RNA (3.6 vs. 3.0 million copies/mL) but had lower rates of cirrhosis (5% vs. 12%) and more frequently had viral genotype 1 (88% vs. 66%: P =.004). Most strikingly, the rates of end-of-treatment and sustained virological responses were lower among the 40 African-American patients (5% and 2%) than among the 380 white patients (33% and 12%) (P =.04 and.07). Rates of response among Hispanic and Asian-American patients were not statistically different than non-Hispanic white patients. Median viral levels decreased by week 24 of therapy by 2.5 logs in white patients (from 3.0 to 0.012 million copies/mL) but by only 0.5 logs among African- American patients (from 3.6 to 1.8 million copies/mL). Thus, there are marked racial differences in virological responses to interferon in hepatitis C that must be considered in assessing trials of interferon therapy and in counseling patients regarding treatment. The differences in response rates are as yet unexplained. PMID:10462387

  3. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver.

    PubMed

    Savransky, Vladimir; Bevans, Shannon; Nanayakkara, Ashika; Li, Jianguo; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

    2007-10-01

    Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P < 0.01) and AST (637 +/- 37 U/l vs. 175 +/- 13 U/l in the control group; P < 0.001), whereas alkaline phosphatase and total bilirubin levels were unchanged. Histology revealed hepatic steatosis in both groups, with mild accentuation of fat staining in the zone 3 hepatocytes in mice exposed to CIH. Animals exposed to CIH exhibited lobular inflammation and fibrosis in the liver, which were not evident in control mice. CIH caused significant increases in lipid peroxidation in serum and liver tissue; significant increases in hepatic levels of myeloperoxidase and proinflammatory cytokines IL-1beta, IL-6, and CXC chemokine MIP-2; a trend toward an increase in TNF-alpha; and an increase in alpha1(I)-collagen mRNA. We conclude that CIH induces lipid peroxidation and inflammation in the livers of mice on a high-fat, high-cholesterol diet.

  4. Retreatment of patients who do not respond to initial therapy for chronic hepatitis C.

    PubMed

    Shiffman, Mitchell L

    2004-05-01

    Despite improvements in the treatment of chronic hepatitis C virus (HCV) infection, nearly half of all patients do not respond to initial therapy. Retreatment of these patients with pegylated interferon and ribavirin has been successful in only a limited percentage of cases. Factors associated with sustained virologic response (SVR) following retreatment include prior treatment with interferon monotherapy, HCV genotype 2 or 3, a low serum HCV RNA level, and the absence of cirrhosis. Fewer than 6% of nonresponders who were previously treated with interferon and ribavirin and who have cirrhosis, genotype 1, and a high viral load achieve SVR following retreatment with pegylated interferon and ribavirin. No therapy has been shown to yield SVR in patients who do not respond to pegylated interferon and ribavirin. Long-term maintenance therapy with pegylated interferon is currently being evaluated in nonresponders with advanced fibrosis and cirrhosis. Its use should be considered investigational at this time. PMID:15468612

  5. [Cytokine regulation of immune response in patients with chronic hepatitis C].

    PubMed

    Korochkina, O V; Sobchak, D M; Mikhaĭlova, E A; Monakova, E A

    2003-01-01

    To evaluate content of interleukines (IL-1, IL-2, IL-4 and IL-6) and tumor necrosis factor (TNF) in patients with chronic hepatitis C (CHC), 72 CHC patients (37 males and 35 females, mean age 37.2 +/- 4.8 years) were examined. The control group consisted of 20 healthy donors (mean age 25.5 +/- 2.3 years). It was found that low levels of IL-1, IL-2, IL-6, TNF evidence for weak immune response which means long-term virus circulation and active replication. The highest concentrations of the above cytokines correspond to low replicative activity while high IL-4 levels point to active virus replication. IL-1, IL-2, IL-4, IL-6, TNF were high in patients with high cytolysis. Cytokine regulation of immune response can be used for assessment of the effectiveness of antiviral and immunocorrective therapy.

  6. Tenofovir-associated nephrotoxicity in patients with chronic hepatitis B: two cases

    PubMed Central

    Cho, Hyeki; Cho, Yuri; Cho, Eun Ju; Lee, Jeong-Hoon; Yu, Su Jong; Oh, Kook-Hwan; Lee, Kyoungbun; Mustika, Syifa; Yoon, Jung-Hwan; Kim, Yoon Jun

    2016-01-01

    Tenofovir disoproxil fumarate (TDF) is effective against chronic hepatitis B (CHB) infection and its use is increasing rapidly worldwide. However, it has been established that TDF is associated with renal toxicity in human immunodeficiency virus-infected patients, while severe or symptomatic TDF-associated nephrotoxicity has rarely been reported in patients with CHB. Here we present two patients with TDF-associated nephrotoxicity who were being treated for CHB infection. The first patient was found to have clinical manifestations of proximal renal tubular dysfunction and histopathologic evidence of acute tubular necrosis at 5 months after starting TDF treatment. The second patient developed acute kidney injury at 17 days after commencing TDF, and he was found to have membranoproliferative glomerulonephritis with acute tubular injury. The renal function improved in both patients after discontinuing TDF. We discuss the risk factors for TDF-associated renal toxicity and present recommendations for monitoring renal function during TDF therapy. PMID:27377911

  7. Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection

    PubMed Central

    FakhriRavari, Alireza; Malakouti, Mazyar; Brady, Rebecca

    2016-01-01

    Abstract Hepatitis C virus (HCV) infection affects as many as 185 million people globally, many of whom are chronically infected and progress over time to cirrhosis, decompensated liver disease, hepatocellular carcinoma, and eventually death without a liver transplant. In the United States, HCV genotype 1 constitutes about 75% of all infections. While interferon and ribavirin therapy was the cornerstone of treatment for many years, interferon-free treatments have become the standard of care with the emergence of new direct-acting agents, resulting in more effective treatment, shorter duration of therapy, better tolerability, lower pill burden, and ultimately better adherence. This review will summarize the evidence for the currently available combination therapies as well as emerging therapies in phase 3 trials for treatment of HCV genotype 1. PMID:27350940

  8. New Direct-Acting Antiviral Therapies for Treatment of Chronic Hepatitis C Virus Infection

    PubMed Central

    Ara, A. Kardashian

    2015-01-01

    The treatment of hepatitis C virus infection has been advancing at breakneck speeds over the past few years. This article provides an update on the newest drugs available and those currently in development, including newer-generation protease inhibitors, RNA-dependent RNA polymerase, and nonstructural component inhibitors. Also discussed in this article are the regimens developed and the genotypes they target. Treatment of cirrhotic patients and patients who have failed prior therapy is also addressed, as are special populations, such as patients with harder-to-treat genotypes, patients with HIV coinfection, patients who have undergone liver transplantation, and patients with chronic kidney disease. Future developments and economic considerations are also mentioned. PMID:27118941

  9. Successful Treatment of Chronic Hepatitis C with Triple Therapy in an Opioid Agonist Treatment Program

    PubMed Central

    Litwin, Alain H.; Soloway, Irene J.; Cockerham-Colas, Lauren; Reynoso, Sheila; Heo, Moonseong; Tenore, Christopher; Roose, Robert J.

    2015-01-01

    Background People who inject drugs (PWID) constitute 10 million people globally with hepatitis C virus, including many opioid agonist treatment patients. Little data exist describing clinical outcomes for patients receiving HCV treatment with direct-acting antiviral agents (DAAs) in opioid agonist treatment settings. Methods In this retrospective observational study, we describe clinical outcomes for 50 genotype-1 patients receiving HCV treatment with triple therapy: telaprevir (n = 42) or boceprevir (n = 8) in combination with pegylated interferon and ribavirin on-site in an opioid agonist treatment program. Results Overall, 70% achieved an end of treatment response (ETR) and 62% achieved a sustained virological response (SVR). These treatment outcomes are nearly equivalent to previously published HCV outcomes shown in registration trials, despite high percentages of recent drug use prior to treatment (52%), ongoing drug use during treatment (45%) and psychiatric comorbidity (86%). Only 12% (n=6) discontinued antiviral treatment early for non-virological reasons. Four patients received a blood transfusion, and one discontinued telaprevir due to severe rash. Conclusions These data demonstrate that on-site HCV treatment with direct-acting antiviral agents is effective in opioid agonist treatment patients including patients who are actively using drugs. Future interferon-free regimens will likely be even more effective. Opioid agonist treatment programs represent an opportunity to safely and effectively treat chronic hepatitis C, and PWID should have unrestricted access to DAAs. PMID:26341685

  10. The case of chronic hepatitis B treatment with tenofovir: an update for nephrologists.

    PubMed

    Coppolino, Giuseppe; Simeoni, Mariadelina; Summaria, Chiara; Postorino, Maria Concetta; Rivoli, Laura; Strazzulla, Alessio; Torti, Carlo; Fuiano, Giorgio

    2015-08-01

    Tenofovir is a nucleotide acting both as an inhibitor of human immunodeficiency (HIV) reverse transcriptase and as a competitor for hepatitis B virus (HBV) RNA-directed DNA polymerase. Approved worldwide in 2001, tenofovir is used as a component of highly active antiretroviral therapy (HAART) in patients with HIV infection. Since 2008, it has also been indicated for treatment of chronic HBV infection or HIV/HBV co-infection. The aim of the treatment consists in suppressing viral replication, thus reducing hepatic complications and improving patient survival. Furthermore, tenofovir could represent an effective therapeutic option in lamivudine-resistant HBV patients. Tenofovir is eliminated unchanged through urine via glomerular filtration (80%) and proximal tubular secretion (20%). Thus, alterations in renal clearance may interfere with tenofovir pharmacokinetics and systemic drug concentrations, modifying the therapeutic response. Hence, a renal overload of tenofovir in patients with a pre-existing kidney impairment could result in a worsening of renal function. Following a brief introduction on HBV infection and its therapeutic options, we review the latest evidence, to our knowledge, on renal toxicity of tenofovir in HBV patients and on drug management. PMID:26054819

  11. Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with the Combined Pegylated Interferon-Ribavirin Therapy.

    PubMed

    Hamza, Iman; Eid, Yara; El-Sayed, Mohammad; Marzaban, Raghda; Abdul-Kareem, Shaimaa

    2016-09-01

    Hepatitis C virus (HCV) is an Egyptian serious national health problem. The combination of pegylated interferon (PEG-IFN) with ribavirin (RIB) was considered the established therapy for chronic hepatitis C (CHC), and it was associated with several adverse effects, including thyroid dysfunction (TD). The aim of this work was to study TD in CHC patients receiving PEG-IFN+ RIB therapy. This retrospective study included 100 adult patients attending the outpatient clinics at AL-Kahera Al-Fatemya hospital and were eligible candidates for PEG-IFN+ RIB therapy. Thyroid hormonal profile (thyroid-stimulating hormone, free triiodothyronine, and free thyroxine) was done before initiation of treatment (week 0) and at weeks 12, 24, 48, and 72. The incidence of TD was more evident by the end of treatment (week 48); it was found to be 35%, mostly in the form of hypothyroidism, while the least incidence was detected by week 12 (2%), all in the form of hyperthyroidism. Generally, hypothyroidism was higher than hyperthyroidism in multiple folds. Thyroid profile was not significantly related to viral load. PMID:27333271

  12. Altered effector functions of NK cells in chronic hepatitis C are associated with IFNL3 polymorphism.

    PubMed

    Rogalska-Taranta, Magdalena; Markova, Antoaneta A; Taranta, Andrzej; Lunemann, Sebastian; Schlaphoff, Verena; Flisiak, Robert; Manns, Michael P; Cornberg, Markus; Kraft, Anke R M; Wedemeyer, Heiner

    2015-08-01

    Interferon α-mediated effector functions of NK cells may contribute to the control of HCV replication and the pathogenesis of liver disease. The single-nucleotide polymorphism rs12979860 near IFNL3 (previously known as IL28B) is important in response to IFN-α treatment and in spontaneous resolution of acute hepatitis C. The role of the IFNL3 polymorphism in NK cell function is unclear. Thus, we investigated the role of IFNL3 polymorphism in type I IFN-dependent regulation of NK cell functions in patients with cHC and healthy control subjects. We demonstrated a marked polarization of NK cells toward cytotoxicity in response to IFN-α stimulation in patients with hepatitis C. That TRAIL up-regulation was present, particularly in patients with the IFNL3-TT allele, was supported by a shift in the pSTAT-1:pSTAT-4 ratios toward pSTAT-1. In patients bearing the IFNL3-TT allele, NK cell effector function correlated with liver disease activity. In contrast, higher cytokine production of NK cells was observed in healthy individuals with the IFNL3-CC genotype, which may support spontaneous HCV clearance in acute infection. Overall, these findings show that the role of NK cells may differ in chronic infection vs. early antiviral defense and that the IFNL3 genotype differentially influences NK cell function. PMID:26034208

  13. Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; España Contreras, Pilar; Pinazo Martínez, Isabel; de la Cruz Lombardo, Jesús; Olmedo Martín, Raúl

    2016-01-01

    The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined. PMID:27547001

  14. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    PubMed Central

    Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

    2010-01-01

    AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

  15. Hepatitis C virus quasispecies in chronically infected children subjected to interferon–ribavirin therapy

    PubMed Central

    Figlerowicz, Magdalena; Jackowiak, Paulina; Formanowicz, Piotr; Kędziora, Paweł; Alejska, Magdalena; Malinowska, Nelli; Błażewicz, Jacek

    2010-01-01

    Accumulating evidence suggests that certain features of hepatitis C virus (HCV), especially its high genetic variability, might be responsible for the low efficiency of anti-HCV treatment. Here, we present a bioinformatic analysis of HCV-1a populations isolated from 23 children with chronic hepatitis C (CHC) subjected to interferon–ribavirin therapy. The structures of the viral quasispecies were established based on a 132-amino-acid sequence derived from E1/E2 protein, including hypervariable region 1 (HVR1). Two types of HCV populations were identified. The first type, found in non-responders, contained a small number of closely related variants. The second type, characteristic for sustained responders, was composed of a large number of distantly associated equal-rank variants. Comparison of 445 HVR1 sequences showed that a significant number of variants present in non-responding patients are closely related, suggesting that certain, still unidentified properties of the pathogen may be key factors determining the result of CHC treatment. Electronic supplementary material The online version of this article (doi:10.1007/s00705-010-0789-7) contains supplementary material, which is available to authorized users. PMID:20842394

  16. Natural interferon-beta treatment for patients with chronic hepatitis C in Japan.

    PubMed

    Sasaki, Reina; Kanda, Tatsuo; Nakamoto, Shingo; Haga, Yuki; Nakamura, Masato; Yasui, Shin; Jiang, Xia; Wu, Shuang; Arai, Makoto; Yokosuka, Osamu

    2015-05-18

    Chronic hepatitis C virus (HCV) infection can cause liver cirrhosis and hepatocellular carcinoma (HCC). Several studies have demonstrated that the eradication of HCV reduces the occurrence of HCC. In Japan, as many people live to an advanced age, HCV-infected patients are also getting older, and the age at HCC diagnosis has also increased. Although older HCV-infected patients have a risk of developing HCC, the treatment response to peginterferon-alpha plus ribavirin therapy is relatively poor in these patients because of drop-out or discontinuation of this treatment due to adverse events. It is established that the mechanism of action between interferon-alpha and interferon-beta is slightly different. Short-term natural interferon-beta monotherapy is effective for patients with acute hepatitis C and patients infected with HCV genotype 2 and low viral loads. Natural interferon-beta plus ribavirin for 48 wk or for 24 wk are also effective for some patients with HCV genotype 1 or HCV genotype 2. Natural interferon-beta plus ribavirin has been used for certain "difficult-to-treat" HCV-infected patients. In the era of direct-acting anti-virals, natural interferon-beta plus ribavirin may be one of the therapeutic options for special groups of HCV-infected patients. In the near future, signal transduction pathways of interferon-beta will inform further directions. PMID:26052401

  17. Embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy

    SciTech Connect

    Sakurabayashi, Shin; Sezai, Shuichi; Yamamoto, Yoshihiro; Hirano, Masanori; Oka, Hiroshi

    1997-03-15

    Purpose. To evaluate the efficacy of embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). Methods. Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4 women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1 had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein shunt. Shunt embolization was performed using stainless steel coils, with a percutaneous transhepatic portal vein approach in 4 patients and a transrenal vein approach in 3 patients. Results. After embolization, the shunt disappeared in 4 patients on either ultrasound pulsed Doppler monitoring or portography. Complications observed in the 7 patients were fever, transient pleural effusion, ascites, and mild esophageal varices. For 3-6 months after embolization, the 4 patients whose shunts disappeared showed minimal or no reappearance of a shunt, and had no recurrence of encephalopathy. The serum ammonia levels decreased and electroencephalograms also improved. One of the 4 patients, who developed mild esophageal varices, required no treatment. Treatment was effective in 3 of the 4 patients (75%) who underwent embolization via a transhepatic portal vein. Conclusion. Transvascular embolization of shunts improved the outcome in 4 of 7 patients. The most effective embolization was achieved via the percutaneous transhepatic portal vein approach.

  18. Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression

    PubMed Central

    Jia, Hong-mei; Li, Qi; Zhou, Chao; Yu, Meng; Yang, Yong; Zhang, Hong-wu; Ding, Gang; Shang, Hai; Zou, Zhong-mei

    2016-01-01

    Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury. PMID:27006086

  19. Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance.

    PubMed

    Jiménez-Pérez, Miguel; González-Grande, Rocío; España Contreras, Pilar; Pinazo Martínez, Isabel; de la Cruz Lombardo, Jesús; Olmedo Martín, Raúl

    2016-08-01

    The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined. PMID:27547001

  20. Interferon therapy in hepatitis C leading to chronic type 1 diabetes

    PubMed Central

    Zornitzki, Taiba; Malnick, Stephen; Lysyy, Lyudmila; Knobler, Hilla

    2015-01-01

    AIM: To review the prevalence, clinical data and course of interferon- associated type 1 diabetes in chronic hepatitis C virus (HCV) infection. METHODS: Search of all interferon (INF)-related type 1 diabetes mellitus (T1DM) cases published in the English literature from 1992 to December 2013 according to the key words: chronic hepatitis C infection, diabetes mellitus type 1, insulin dependent diabetes mellitus, and interferon treatment. We found 107 cases and analyzed their clinical and laboratory data and long-term follow-up. Due to the predominance of cases described in Japanese literature, we analyzed separately cases of Caucasian and Japanese origin. In addition we describe a representative case with HCV who developed INF-related T1DM. RESULTS: Our data show that INF treatment increases the risk of developing T1DM by 10-18 fold compared with the corresponding general population and the median age of onset was 43 years (range: 24-66 years) in Caucasians and 52 years (range: 45-63 years) in Japanese. Most patients developed T1DM during INF treatment, after a median time-period of 4.2 and 5.7 mo in Caucasian and Japanese groups, respectively. The clinical course was characterized by a fulminant course with abrupt severe hyperglycemia or ketoacidosis, a high titer of anti-islet autoantibodies and almost all patients (105/107) permanently required insulin therapy with a follow-up of up to 4 years. A substantial number of patients had evidence for other autoimmune disorders mainly thyroid diseases (25% and 31% in Caucasian and Japanese groups, respectively). CONCLUSION: INF-associated T1DM in HCV has a fulminant course, often associated with other autoimmune diseases, and results almost inevitably in permanent insulin therapy requirement. PMID:25574096

  1. Hepatocellular carcinoma surveillance rates in commercially insured patients with noncirrhotic chronic hepatitis B.

    PubMed

    Goldberg, D S; Valderrama, A; Kamalakar, R; Sansgiry, S S; Babajanyan, S; Lewis, J D

    2015-09-01

    American association for the study of liver diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines recommend biannual hepatocellular carcinoma (HCC) screening for noncirrhotic patients with chronic hepatitis B infection (HBV), yet there are no data estimating surveillance rates or factors associated with surveillance. We performed a retrospective cohort study of US patients using the Truven Health Analytics databases from 2006 to 2010 and identified patients with noncirrhotic chronic HBV. Surveillance patterns were characterized using categorical and continuous outcomes, with the continuous measure of the proportion of time 'up to date' with surveillance (PUTDS), with the 6-month interval following each ultrasound categorized as 'up to date'. During a median follow-up of 26.0 (IQR: 16.2-40.0) months among 4576 noncirrhotic patients with chronic HBV (median age: 44 years, IQR: 36-52), only 306 (6.7%) had complete surveillance (one ultrasound every 6-month interval), 2727 (59.6%) incomplete (≥1 ultrasound) and 1543 (33.7%) none. The mean PUTDS was 0.34 ± 0.29, and the median was 0.32 (IQR: 0.03-0.52). In multinomial logistic regression models, patients diagnosed by a nongastroenterologist were significantly less likely to have complete surveillance (P < 0.001), as were those coinfected with HBV/HIV (P < 0.001). In linear regression models, nongastroenterologist provider, health insurance subtype, HBV/HIV coinfection, rural status and metabolic syndrome were independently associated with decreased surveillance. Patients with HIV had an absolute decrease in the PUTDS of 0.24, while patients in less populated rural areas had an absolute decrease of 0.10. HCC surveillance rates in noncirrhotic patients with chronic HBV in the United States are poor and lower than reported rates of HCC surveillance in cirrhotic patients.

  2. Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review.

    PubMed

    Wu, Fa-Ling; Shi, Ke-Qing; Chen, Yong-Ping; Braddock, Martin; Zou, Hai; Zheng, Ming-Hua

    2014-08-01

    Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems. PMID:24762209

  3. Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity.

    PubMed

    Chook, Jack Bee; Ngeow, Yun Fong; Khang, Tsung Fei; Ng, Kee Peng; Tiang, Yee Peng; Mohamed, Rosmawati

    2013-03-01

    Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis. PMID:23297244

  4. Detection of Hepatitis B Virus Covalently Closed Circular DNA in the Plasma of Iranian HBeAg-Negative Patients With Chronic Hepatitis B

    PubMed Central

    Tajik, Zahra; Keyvani, Hossein; Bokharaei-Salim, Farah; Zolfaghari, Mohammad Reza; Fakhim, Shahin; Keshvari, Maryam; Alavian, Seyed Moayed

    2015-01-01

    Background: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a marker of HBV replication in the liver of patients infected with HBV. Objectives: This study aimed to investigate the association between the presence of cccDNA in the plasma samples of Iranian treatment-naive patients with chronic hepatitis B infection and HBV viral load and HBsAg levels. Patients and Methods: From April 2012 to May 2015, 106 treatment-naive patients with chronic