Occult Hepatitis B Virus Infection in Patients With Chronic Hepatitis C Treated With Antiviral Therapy

Background

Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver and/or in the serum of patients with negative results of hepatitis B s antigen (HBsAg) test with or without serological markers of previous viral exposure. The impact of OBI in patients with chronic hepatitis C (CHC) is still unclear.

Objectives

The Aim of this study was to assess OBI prevalence and its potential implications on treatment outcome in a cohort of patients with CHC underwent standard antiviral therapy.

Patients and Methods

Baseline serum samples from 137 HBsAg-negative CHC patients treated with pegylated-interferon and ribavirin (73 Responders/74 Non Responders),were retrospectively analyzed for HBV status.

Results

Seventy-three patients (53.3%) showed markers of previous exposure to HBV. HBV DNA was detected in 2 of 137 serum samples (1.5%), both carrying HBV antibodies. Liver biopsies and post-therapy sera were available for 35 patients (12 Responders/23 Non Responders). HBV DNA sequences were found in 13 of 35 specimens (37.1%), all of patients with HBV DNA negativity in basal and post-therapy serum samples. Among OBI-positive patients, 5 (38.5%) carried serological markers of HBV infection. Regarding therapy outcome, in the OBI-positive group there were 5 of 13 (38.5%) sustained virological responders (SVR) compared to 7 of 22 (31.8%) in the OBI-negative one.

Conclusions

Despite the high prevalence rate of liver HBV DNA in patients with CHC, SVR was not affected by occult HBV infection.     

湖北省维持性血液透析患者丙型肝炎病毒感染调查

目的：调查维持性血液透析患者丙型肝炎病毒（HCV）感染情况,并探讨其相关危险因素。方法;对湖北省84所医院3608例维持性血液透析（MHD）患者,采用ELISA法检测血清标志物HCV抗体。同时调查其输血史和透析史,进行相关性分析。结果：3608例MHD患者中,HCV感染率5．88％。有输血史HCV感染率（7．12％）显著高于无输血史者（2．13％,P〈0．01）。HCV阳转率透析时间小于1年为0．98％,透析1～2年为4．19％,透析2～3年为4．59％,透析3年以上为13．06％（P〈0．01）。且随着每周透析次数的增加,HCV的阳转率也明显上升（P〈0．05）。接受过1所医院透析的患者,HCV阳转率为3．09％,接受过2所为5．84％,接受过3所为7．44％,接受4所及以上为11．29％（P〈0．01）。结论：反复输血、透析时间长、透析次数多、接受多家医院透析是MHD患者感染HCV高的重要因素。减少输血、加强透析治疗环节院内感染的质量控制对预防HCV感染有重要意义。     

Hepatitis B Virus Vaccine for Patients with Hepatitis C Virus Infection

Summary Hepatitis C is a disease with varying rates of progression. The role of hepatitis B virus (HBV) as a cofactor in the development of hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC) has been suggested and the use of HBV vaccine in all HCV-infected patients has been advocated. This review presents the implications of HBV and HCV coinfection and addresses the issues of HBV vaccine immunogenicity and safety in patients with chronic HCV infection. Received: December, 1999 · Revision accepted: July 1, 2000     

Occult Hepatitis B Virus Infection in Hemodialysis Patients in Japan

Hepatitis B surface antigen is widely used in hepatitis B virus surveillance; patients who test negative for the antigen are judged to be uninfected. However, occult hepatitis B virus infection has been confirmed with hepatitis B virus DNA at low levels in the liver and peripheral blood in patients positive for hepatitis B core antibody or hepatitis B surface antibody, even if they test negative for hepatitis B surface antigen. To investigate the prevalence of occult hepatitis B virus in hemodialysis patients, we performed cross‐sectional analysis of 161 hemodialysis patients in two related institutions for hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody. Hepatitis B surface antigen, hepatitis B core antibody, or hepatitis B surface antibody was present in 45 patients (28.0%). Hepatitis B virus DNA was present in six patients (3.7%), all of whom also tested positive for hepatitis B core antibody. Hepatitis B surface antibody positivity was unrelated in only one of the six patients. Four of the six patients were positive for hepatitis B surface antigen; however, two (1.3%) of these with occult hepatitis B virus infection were found to be hepatitis B surface antigen negative. Occult hepatitis B virus infection may be missed in hepatitis B virus surveillance using hepatitis B surface antigen alone; therefore, routine hepatitis B core antibody screening is necessary. Patients who test positive for hepatitis B core antibody should undergo further hepatitis B virus DNA testing to enable accurate hepatitis B virus screening.     

Occult Hepatitis B Virus Infection in Japanese Chronic Hemodialysis Patients

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti‐HBc) was determined by various chemiluminescent immunoassays. HBV‐DNA was quantified in patients positive for anti‐HBc using quantitative real‐time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg‐positive and 218 (20.9%) were anti‐HBc‐positive. All HBsAg‐positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg‐negative and anti‐HBc‐positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.     

Prevalence of Occult Hepatitis B Virus in Plasma and Peripheral Blood Mononuclear Cell Compartments of Patients With Chronic Hepatitis C Infection in Tehran-Iran

Background

Occult hepatitis B virus (HBV) infection (OBI) is frequently reported in patients with chronic hepatitis C virus (HCV) infection. An association between OBI and more liver damage, cirrhosis, hepatocellular carcinoma, and reduced response to interferon therapy in patients with HCV infection is suggested.

Objectives

The aim of this study was to determine the prevalence of occult HBV, and evaluate its clinical influence on patients with chronic HCV.

Patients and Methods

A cohort study including50 patients with positive results for HCV, and negative results for HBsAg tests was performed. The patients were divided into two groups: one group had positive results for both HCV and occult HBV tests (n = 18), and the other had positive results for HCV, but negative findings for occult HBV (n = 32). All were treated with PEG-IFN alpha-2a and Ribavirin. Presence of HCV RNA was followed in these patients.

Results

HBV-DNA was detected using nested-PCR in 20% of plasma and 32.6% of peripheral blood mononuclear cell (PBMC) compartments. No significant differences were observed between patients with and without occult HBV for sex, age, duration of HCV infection, histological markers, presence of anti-HBc, HCV viral load, and HCV genotype. The response rate was significantly higher in patients with positive results for HBV-DNA test compared to those with negative findings (100% vs. 71.9 %, P < 0.05).

Conclusions

In conclusion, occult HBV was found in 36% of patients with negative results for HBsAg, but positive results for HCV. Detection of HBV-DNA in both PBMCs and plasma together in comparison with plasma alone provided more true identification of OBI.The SVR rate was significantly higher in coinfected patients than mono-infected ones.     

Occult Hepatitis B Infection and its Possible Impact on Chronic Hepatitis C Virus Infection

As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV) replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV) related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease.     

Phylogenetic Analysis of Torque Teno Virus in Hepatitis C Virus Infected Patients in Shiraz

Background

Torque teno virus (TTV) was the first human Circoviridae detected in a Japanese patient with unknown hepatitis in 1997. Subsequently, several studies performed to evaluate different aspects of Torque teno virus pathogenesis.

Objectives

The present study aimed to determine dominant genotype of Torque teno virus in chronic hepatitis disease using 5΄-UTR sequence among patients infected by hepatitis C virus in Shiraz – Iran.

Patients and Methods

The study conducted in 240 patients with chronic hepatitis C from Prof. Alborzi Clinical Microbiology Research Center. The presence of Torque teno virus DNA and its genotype in plasma was assessed by nested polymerase chain reaction using two primer sets for 5΄-UTR and N22 regions. Phylogenetic analysis was performed based on 5΄-UTR region.

Results

DNA of Torque teno virus was detected in 220 out of 240 (92 %) patients with chronic hepatitis C by the use of 5΄-UTR primer based PCR method and in 12 out of 240 (5%) by the use of N22 primer. Based on phylogenetic analysis it was shown that the Dominant genotype in this study was 11. Genotypes 1, 3, 17, and 22 were also detected. Some sequences could not be classified to a specific genotype.

Conclusions

The prevalence of Torque teno virus DNA in patients with chronic hepatitis C disease by the use of 5΄-UTR primer appeared to be higher compared to that revealed by N22 primer. We observed five genotypes among hepatitis C chronic patients in our study.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients: A Concept for Consideration

Hemodialysis patients potentially have an increased risk of infection with parenterally transmitted viral agents due to an impaired host immune response and multiple transfusion requirements. Viral hepatitis is considered as a problem for hemodialysis patients because 1.9% of all deaths among this population are related to the consequence of viral hepatitis. Hepatitis B virus (HBV) is one of the most important causes of transmitted infections by the parenteral route in hemodialysis patients. Occult HBV infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg), which harbors potential risk of HBV transmission through hemodialysis. There are conflicting reports on the prevalence of occult HBV infection (OBI) in hemodialysis patients. Considering the importance of occult HBV infection in hemodialysis patients and the growing evidence on this subject, the purpose of this review is to provide comprehensive information on OBI prevalence in hemodialysis patients and highlight the most important points in this issue.     

GB Virus C infection in Patients With HIV/Hepatitis C Virus Coinfection: Improvement of the Liver Function in Chronic Hepatitis C

Background:

Previous studies in patients with hepatitis C virus (HCV)/HIV coinfection have shown that the presence of GBV-C is associated with significantly less compensated and decompensated cirrhosis, and an improvement in cirrhosis-free survival.

Objectives:

This study aimed to describe the effect of GBV-C in patients with chronic hepatitis C and HIV coinfection.

Patients and Methods:

We retrospectively studied 105 injecting drug users with chronic hepatitis C and HIV coinfection and 72 patients with chronic HCV mono-infections. Plasma samples were tested for GBV-C RNA with primers to the 5’untranslated region gene. HIV and HCV viral load, CD4⁺ and CD8⁺ cell count, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested in all patients.

Results:

GBV-C RNA was identified in 34 (32.38%) of the patients with HIV/HCV coinfection, and in 24 (33.33%) of the patients with HCV mono-infection. GBV-C infection was associated with significantly lower ALT and AST levels in patients with chronic hepatitis C and HIV coinfection, but not in those HCV mono-infections. The presence of GBV-C infection was not correlated with CD4⁺ and CD8⁺ cell count, gender, age, HIV load, HCV load, and HCV genotype.

Conclusions:

This study found that GBV-C infection has a high frequency among injecting drug users with HIV/HCV coinfection and HCV mono-infection in Yunnan, China. In patients with chronic hepatitis C and HIV coinfection, GBV-C RNA was associated with significantly lower ALT and AST levels, suggesting a beneficial effect of GBV-C infection on chronic hepatitis C.     

乙、丙型肝炎病毒单纯和重叠感染——附503例临床对比分析

503例病毒性肝炎分为乙型肝炎(HB)、丙型肝炎(HC)、乙丙型肝炎(HBC)三组进行临床对比分析,以探讨双重病毒感染对病情的影响。结果:HBC组肝硬变比率和血清透明质酸(HA)异常率显著高于HB(P<0.05)和HC(P<0.001和P<0.05);重型肝炎比率和病死率与HB和HC相似;无症状病毒携带比率与HB相似而显著低于HC;血清谷丙转氨酶(ALT)和血清胞红素(SB)异常率与HC相近,较HB为低(P均<0.01)。HB与HC相比,HB肝硬变比率和SB异常率显著高于HC(P均<0.001);无症状病毒携带比率显著低于HC。HBV单纯感染较HCV单纯感染病情重;HBV与HCV双重感染者肝硬变比率增高,但并不一定加重肝损害的严重程度。     

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

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.     

Hepatitis C Virus Infection in Institutionalized Psychiatric Patients

The objective of this study was to determine if HCV can be transmitted from patient to patient in psychiatric institutions and to determine possible routes of infection. We did a cross-sectional survey of 196 Japanese psychiatric patients tested for HCV and HBV markers and 400 age- and sex-matched controls. Anti-HCV was detected in 10.2% and antibody to hepatitis B core antigen was detected in 44.4% of the patients, a significantly higher prevalence than found among matched controls. A multiple regression logistic analysis was used to identify risk factors that could indicate the route of infection by HCV. Duration of hospitalization, age, razor sharing, and history of surgery proved to be statistically significant independent risk factors associated with positive anti-HCV results [odds ratio (OR), 4.00; 95% confidence interval (CI), CI, 1.74–9.19; OR, 2.19; 95% CI, 1.27–1.3.77; OR, 4.90; 95% CI, 1.29–18.86; OR, 3.35; 95% CI, 0.997–11.3, respectively]. These observations suggest that razor sharing played an important role in the spread of the HCV infection in the institutionalized psychiatric patients we studied.     

Distribution of Hepatitis C Virus Genotypes Among Azerbaijani Patients in Capital City of Iran-Tehran

Background

Determination of the Hepatitis C virus (HCV) genotype distributed in a particular area has an important role on public health throughout the world.

Objectives

The aim of this study was to determine the frequency of HCV genotypes in Azerbaijani patients.

Patients and Methods

From March 2010 until March 2012, 235 Azerbaijani patients with established chronic hepatitis C, referred to Hospitals related to Iran University of Medical Sciences and Tehran Hepatitis Center, Clinical department of Baqiyatallah Research Center for Gastroeneterology and Liver Disease, were enrolled in this cross sectional study. About 5 mL of peripheral blood was collected from patients and after separation of plasma, viral RNA extracted. HCV-RNA were amplified by RT-nested PCR using primers from the 5´-UTR and genotyped by RFLP assay, and then HCV genotypes were confirmed using sequencing of cloned PCR products into pJET1.2/blunt cloning vector.

Results

HCV genotyping of positive plasma samples demonstrated that predominant HCV subtype was noted for 1b (71.1%) followed by subtype 3a (17.0%), genotype 2 (6.8%), 1a (1.7%), and mixed infection (3.4%). The mean ± SD age of patients was 37.3 ± 11.8 (range: 2-63) years. Out of 235 patients, 139 (59.1%) were male. The frequency of HCV subtype 3a was higher in patients under 40 years old (3a: 18.1% vs. 15.0%), and subtype 3a was higher in male patients (3a: 18.7% vs. 14.6%).

Conclusions

The current study shows that the predominant HCV genotype among Azerbaijani patients with established chronic hepatitis C is subtype 1b (71.1%) followed by subtype 3a (17.0%).     

Persistent Hepatitis E Virus Genotype 4 Infection in a Child With Acute Lymphoblastic Leukemia

Introduction:

In general, the hepatitis E virus (HEV) causes acute, self-limiting hepatitis. Prolonged and chronic infections caused by HEV genotype 3 have been found in some immunosuppressed patients in developed countries.

Case Presentation:

Here we report a Chinese boy with acute lymphoblastic leukemia, who developed hepatitis E during a period of intensive chemotherapy. Twenty months after the initial infection, HEV viremia was reappeared in the patient, with detectable anti-HEV IgM and IgG and modestly elevated serum transaminases. Sequence analysis of the viral RNAs revealed the reactivation of the HEV genotype 4d strain, indicating viral persistence in the patient.

Conclusions:

To our knowledge, this is the first chronic case confirmed by the prolonged presence of HEV RNA in china. It is also the first reported persistent hepatitis E infection caused by HEV genotype 4.