فهرست مطالب

Hepatitis Monthly
Volume:15 Issue: 6, Jun 2015

  • تاریخ انتشار: 1394/05/02
  • تعداد عناوین: 9
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  • Alessandro Federico*, Mario Masarone, Marco Romano, Marcello Dallio, Valerio Rosato, Marcello Persico Page 1
    Background
    Standard [i.e. pegylated interferon (Peg-IFN) + ribavirin] treatment of hepatitis C virus (HCV)-related chronic hepatitis is associated with a sustained virological response (SVR) in 50 - 90% of patients. A rapid virological response (RVR) (i.e. negative HCV-RNA after 4 weeks of treatment) predicts SVR in almost 90% of patients.
    Objectives
    The main aim of this study was to assess the strength of RVR, as a predictive factor of antiviral treatment response. Patients and
    Methods
    Using univariate and multivariate analysis, we retrospectively evaluated biochemical, metabolic, genetic and viral variables that might affect both RVR and SVR to Peg-IFN plus ribavirin, in 315 consecutive outpatients affected by HCV-related chronic hepatitis.
    Results
    At univariate analysis, staging, body mass index, RVR, genotype and viral load were significantly related to SVR (P < 0.001). At multivariate analysis, RVR and genotype remained significant (P < 0.00001). The RVR had a predictive value of 83%. At univariate and multivariate analyses, diabetes (P = 0.003), genotype 2 (P = 0.000) and HCV-RNA values (P = 0.016) were independent predictors of RVR, even though at multivariate analyses, only genotype 2 was significantly related to RVR. When we stratified patients, according to genotype, no laboratory or clinical factors were predictive of RVR in genotype 1 patients at either univariate or multivariate analysis. In genotype 2 patients, staging (P = 0.029) and diabetes (P = 0.001) were the only significant predictors of RVR at univariate analyses, whereas no factor was independently related to RVR, at multivariate analysis.
    Conclusions
    The RVR is the strongest factor of SVR and infection with HCV genotype 2 is significantly associated with RVR. Neither biochemical and/or metabolic factors seem to exert influence on RVR.
    Keywords: Antiviral Agents, Hepatitis C, Pegylated Interferon SA, Retrospective Studies, Ribavirin
  • Qin Wu, Feng Yu Zhan, En Qiang Chen, Cong Wang, Zhen Zhen Li, Xue Zhong Lei * Page 2
    Background
    Sustained virological response (SVR) and virological relapse maintain pivotal roles in the management of chronic hepatitis C (CHC); however, there is little data regarding the long-term outcomes of patients with CHC in China.
    Objectives
    We aimed to investigate the predictive factors of therapeutic effect and viral relapse in patients who achieved end-of-treatment response (ETR).Patients and
    Methods
    We retrospectively analyzed clinical, biochemical and virological data of 169 adult patients with CHC from China who were not treated with pegylated interferon-alpha (PEG IFN-α) and ribavirin, of which 142 achieved ETR and with a follow-up period ranging from six months to six years. Statistical analysis was performed by SPSS 20.0.
    Results
    Of the 169 patients, 124 (73.4%) achieved SVR and 23 (16.2%) experienced relapses post-therapy in cases of ETR patients. We considered sex, age, alanine aminotransferase, aspartate transaminase, baseline hepatitis C virus RNA level, HCV genotypes, IL28B rs12979860 genotype, rapid virological response (RVR), and early virological response (EVR). For antiviral effect in patients with CHC, HCV genotypes (2, 3) (χ2 = 11.285, P = 0.001), IL28B genotype (rs12979860 CC) (χ2 = 16.552, P < 0.001), RVR (χ2 = 37.339, P < 0.001), and EVR (χ2 = 70.265, P < 0.001) were significantly correlated with achieving SVR. For ETR patients with long-term follow-up, the relapse rate within six months was significantly higher than within other periods during six-year follow-up (χ2 = 7.792, P = 0.005). Relapse was virtually not observed after therapy ceased for 48 weeks. The IL28B genotype (rs12979860 CT/TT) (OR = 0.102; 95% CI, 0.031-0.339; P < 0.001), lower RVR (OR = 0.239; 95% CI, 0.078-0.738; P = 0.013), and EVR (OR = 0.102; 95% CI, 0.016-0.661; P = 0.017) were independent risk factors for relapse.
    Conclusions
    Our study comprehensively explored the predictive factors of therapeutic effect of administered drugs and analyzed viral relapse during a six-months to six-year follow-up period from China. The SVR may not be the perfect endpoint of HCV therapy in Chinese people; we recommend 48 weeks after treatment withdrawal as the suitable time point.
    Keywords: Hepatitis C, Chronic, Follow, Up Studies, Recurrence, Interferon
  • Abrar Hussain, Muhammad Idrees*, Muhammad Asif, Liaqat Ali, Mahmood Rasool Page 3
    Background
    The nonstructural protein NS4A of hepatitis C virus is composed of 54 amino acids. This small size protein has vital role in many cellular functions. The most important reported function is being a cofactor of viral enzymes serine protease and helicase.
    Objectives
    The objective of this study was to analyze the phylogenetic variation, its impact in terms of translation and any functional change in protein structure at primary 2D/3D structure using computational tools from Pakistani patients isolates.
    Material And Methods
    Patient sera infected with Hepatitis C virus, genotype 1A, were obtained from Molecular Diagnostics lab, CEMB, University of the Punjab Lahore by using BD Vacutainer collection tubes (Becton Dickenson).
    Results
    Phylogenetic analysis of the gene revealed that Pakistani 1a HCV strains are in the start of third cluster and there is a difference between inter Pakistani isolates at primary, secondary and tertiary levels.
    Conclusions
    Mutations were present in the central domain of NS4A (amino acids 21 - 34).
    Keywords: Hepatitis C Virus_Reverse Transcriptase Polymerase Chain Reaction_RNA
  • Naghi Dara, Farid Imanzadeh, Ali Akbar Sayyari, Peiman Nasri, Amir Hossein Hosseini* Page 4
    Introduction
    Coexistence of Wilson’s disease and autoimmune hepatitis has been rarely reported in English literature. In this group of patients, there exist features of both diseases and laboratory and histopathological studies may be misleading. Medical treatment for any of these entities, per se, may result in poor response. Therefore, by considering the acute hepatitis resembling Wilson’s disease and autoimmune hepatitis, simultaneous therapy with immunosuppressive and penicillamine may have a superior benefit.
    Case Presentation
    We present the case of a 10-year-old boy with nausea, vomiting, yellowish discoloration of skin and sclera, abdominal pain and tea-color urine. Physical examination showed mild hepatomegaly and right upper quadrant tenderness. Laboratory and histochemical studies and atomic absorption test were done and the results were highly suggestive of both Wilson’s disease and autoimmune hepatitis, in him.
    Conclusions
    This case study highlights, although rare, the coexistence of Wilson’s disease and autoimmune hepatitis and the need to maintain a high level of awareness of this problem. Therefore, it is reasonable to consider this type of hepatitis in rare patients, with dominant features of both diseases at the same time.
    Keywords: Hepatitis, Hepatolenticular Degeneration, Autoimmune
  • Alireza Hamidian Jahromi, David Hilton Ballard, Reza Bahrami, Horacio Ruben Vicente Dagostino* Page 5
    Background
    The quality of liver biopsy specimens obtained with different fine needle biopsy (FNB) techniques has not been compared.
    Objectives
    This study was performed to evaluate the diagnostic quality of three different liver FNB biopsy techniques.
    Materials And Methods
    Two sequential biopsy series were performed on piglets. Three biopsy techniques were compared: capillary-FNB, core-FNB (CFNB) and vacuum-assisted CFNB (VACFNB) in a swine model. Initially, 30 liver biopsies were performed (ten for each technique). The cellularity and quantity of blood in specimens were measured and compared. In the second series, 54 additional biopsies using CFNB and VACFNB techniques (27 each) in a separate piglet were evaluated in the same fashion.
    Results
    In the first series, cellularity and blood levels were significantly lower in capillary-FNB compared with CFNB (P < 0.001 and P = 0.011, respectively). There was no significant difference between CFNB and VACFNB in cellularity and blood (P = 0.15 and P = 0.1, respectively). In the second series, cellularity was significantly higher in CFNB compared with VACFNB (P < 0.001) with no significant difference in blood (P = 0.5).
    Conclusions
    Among these three different FNB techniques, CFNB technique provided the greatest cellularity. Capillary-FNB technique was inferior among all with the lowest quality of obtained material for cytopathological interpretation.
    Keywords: Fine Needle Biopsy, Fine, Needle Aspiration, Liver, Core Needle Biopsy
  • Ashraf Mohamadkhani, Faegh Bastani, Samaneh Khorrami, Reza Ghanbari, Sareh Eghtesad, Maryam Sharafkhah, Ghodratollah Montazeri, Hossein Poustchi* Page 6
    Background
    Chronic Hepatitis B (CHB) is accompanied by inflammation of liver because of infection with Hepatitis B Virus (HBV). Previous studies revealed an inverse association between vitamin D and HBV DNA levels.
    Objectives
    The current study aimed to investigate the levels of 25 (OH) D3 (the steady form of vitamin D), miR-378 and HBV DNA in the patients with CHB.Patients and
    Methods
    One hundred and seventy three patients with HBeAg negative CHB were recruited for the study. Plasma levels of HBVDNA and 25 (OH) D3 were quantified. The expression level of miR-378 in plasma was measured by a relative quantitative Real Time Polymerase Chain Reaction (qRT-PCR) assay.
    Results
    In the pathway regression analysis, the plasma level of 25 (OH) D3 showed a significant inverse correlation with plasma levels of HBV DNA (-0.198, P = 0.008) and direct correlation with miR-378 (0.188, P = 0.013). Similarly plasma level of miR-378 had inverse association with HBV DNA level (-0.177, P = 0.020).
    Conclusions
    These results suggest that vitamin D could involve in a miRNA- mediated regulatory pathway in control of HBV replication. Further studies are recommended to understand the effects of miR-378 and anti-infective action of vitamin D on Hepatitis B Virus.
    Keywords: Chronic Hepatitis B_Hepatitis B Virus_Vitamin D_miR_378
  • Thomas Mina, Samad Amini, Bavil, Olyaee, Frank Tacke, Piet Maes, Marc Van Ranst, Mahmoud Reza Pourkarim* Page 7
    Context: After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%.Evidence Acquisition: All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection.
    Results
    The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence.
    Conclusions
    Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity.
    Keywords: Hepatitis B Virus_Liver Failure_Acute_Human Genome Project
  • Hua Tian, Xingli Fu, Wang Li, Yuan Huang, Jiayao Sun, Gai Zhou, Chengli Zhou, Quan Shen, Shixing Yang, Wen Zhang* Page 8
    Background
    Hepatitis E Virus (HEV), a zoonotic pathogen, uses several species of animal as reservoirs. Swine is considered as the major reservoir for HEV infection in humans. Genotype 4 HEV is the dominant cause of hepatitis E disease in humans in China.
    Objectives
    Although many researches revealed that genotype 4 HEV is the main genotype that prevalent in eastern China, few researches have done to study the subtype of HEV in this area. Thus, this study aimed to investigate the subtype of HEV prevalent in eastern China.
    Materials And Methods
    A total of 125 anti-HEV IgM positive human serum and 290 swine fecal samples were subjected to reverse transcription polymerase chain reaction (RT-PCR) screening of HEV RNA. Positive PCR products were sequenced and phylogenetically analyzed.
    Results
    From a total of 125 human serum samples, 19.2% (24.125) were positive, while 9.66% (28.290) of the 290 swine fecal samples were positive for HEV RNA. Phylogenetic analysis based on partial capsid gene showed that the 51 HEV strains in the current study all belonged to genotype 4, clustering into 6 different subtypes. Our results also revealed that some of HEV isolates prevalent in the human and swine populations were classified into the same clusters.
    Conclusions
    Genotype 4 HEV in eastern China shows subtype diversity and some HEV isolates are involved in cross-species transmission.
    Keywords: Hepatitis E Virus_Genotype_Subtype_Genetic Diversity
  • Narges Shahbazi, Hayedeh Haeri, Mohsen Nasiri Toosi, Ali Jafarian, Reza Shahsiah, Monavar Talebian Moghadam, Sedigheh S. Poursaleh, Farid Azmoudeh-Ardalan * Page 9
    Background
    Early post-transplantation alterations in liver tests are caused by a variety of etiologies including rejection, biliary or vascular complications, and preservation/reperfusion injury (PRI).
    Objectives
    The aim of this study was to show the correlation between histopathologic changes of PRI and the alterations in liver tests in the early post-transplantation period.
    Materials And Methods
    Between April 2013 and August 2014, histopathologic findings of protocol, time-zero, Tru-Cut, liver needle biopsies were evaluated in 94 cases of cadaveric liver transplantation. The histopathologic changes included ballooning degeneration, micro- and macro-vesicular steatosis, bilirubinostasis, apoptotic cells, bile plugs and neutrophilic infiltration. These histopathologic changes were compared with the early (15 days) post-transplantation liver laboratory findings.
    Results
    Clinico-pathologic evaluation of all 94 cases was done by assessment of PRI findings in time-zero biopsies and possible causes of allograft injury were appraised. In 21 patients, a specific cause for allograft injury was found including rejection and/or surgical complications. In the remaining 73 cases, there was no specific cause for allograft injury and histopathologic findings of time-zero liver needle biopsies supported PRI. We classified liver laboratory tests alterations as: hepatocellular damage (elevation of transaminases and lactate dehydrogenase), cholestatic damage (elevation of alkaline phosphatase and total bilirubin) and mixed. Hepatocellular and cholestatic alterations in liver function tests were associated with the presence of marked apoptotic bodies and neutrophilic aggregates in time zero biopsies, respectively. On the other hand, macrovesicular steatosis was dominantly associated with mixed (hepatocellular and cholestatic) laboratory alterations of liver tests.
    Conclusions
    Any discrepancy between histopathologic changes in time-zero biopsies and pattern of early liver laboratory alterations may be considered as a warning for causes other than PRI.
    Keywords: Ischemia Reperfusion Injury, Liver Function Tests, Pathology, Liver Transplantation