Prevalence of Hepatitis D Virus Infection Among Patients With Chronic Hepatitis B Attending Birjand Hepatitis Clinic (East of Iran) in 2012

Background

Hepatitis delta virus (HDV) is a defective RNA virus dependent on Hepatitis B virus (HBV) infection for its replication and expression. All patients with HBV infection should be tested for the presence of HDV infection. It is estimated that approximately 5% of hepatitis B surface antigen (HbsAg) carriers in the world are HDV infected patients. HBV-HDV co-infection may lead to more severe acute disease and higher risks of fulminant hepatitis, cirrhosis, and hepatocellular carcinoma than those having HBV infection alone. Also, HBV infected patients with HDV super-infection have a higher rate of progression to chronic disease and serious complications.

Objectives

Our aim was to determine the prevalence of HDV infection among chronic hepatitis B (CHB) patients attending Birjand Hepatitis Clinic, East of Iran.

Materials and Methods

A cross-sectional analytical study was conducted on 413 CHB patients in 2012. Serology test for anti-HDV was measured by ELISA in these patients. CHB patients had positive hepatitis B surface antigen for at least 6 months before the study entrance.

Results

The mean age of CHB patients was 38.5± 11.9 years and 55.9% of them (231 patients) were male. There were 13 cases (3.1%) with HDV infection. There was no association between positive anti-HDV serology and factors such as age, gender, carrier state, liver enzymes, and positive hepatitis B e antigen (HBeAg) serology.

Conclusions

Although HDV had a low prevalence in our area, it is important for healthcare providers and policy makers to plan preventive strategies for HDV spread as well as HBV prevention programs among high risk population.     

Low Serum Hepatitis B Surface Antigen Level Predicts Compensated Cirrhosis Caused by Chronic Hepatitis B in HBeAg Positive Patients in East China

Backgrounds:

Serum hepatitis B surface antigen (HBsAg) levels are associated with fibrosis in patients with chronic hepatitis B (CHB) infection.

Objectives:

The aim of our study was to evaluate serum HBsAg level as a biomarker for compensated cirrhosis in hepatitis B e antigen (HBeAg) positive CHB patients.

Patients and Methods:

Two-hundred and one HBeAg-positive Chinese CHB patients with or without cirrhosis were enrolled in this retrospective study. Cirrhosis was diagnosed based on liver biopsy. Furthermore, patients with decompensated cirrhosis were excluded. A statistical analysis was performed regarding the association between serum HBsAg level and compensated cirrhosis.

Results:

Patients with compensated cirrhosis had a significantly lower mean serum HBsAg level compared to those without cirrhosis (3.27 Log₁₀ IU/mL VS 4.17 Log₁₀ IU/mL, P < 0.001). Furthermore, examining the correlation with compensated cirrhosis revealed that lower level of serum HBsAg was a significant factor in multivariate analysis. The area under the receiver operating characteristics curve of serum HBsAg was 0.856 for compensated cirrhosis. A positive predictive value of 66.2% and negative predictive value of 90.7% were obtained with a cut-off value of < 3.60 Log₁₀ IU/mL (4000 IU/mL) of serum HBsAg. Moreover, the rate of compensated cirrhosis increased to 75.0% after combining with APRI > 2.

Conclusions:

In HBeAg positive CHB patients, low serum HBsAg level is a useful predictor of compensated cirrhosis.     

Prognostic Values of Fluctuations in Serum Levels of Alanine Transaminase in Inactive Carrier State of HBV Infection

Background:

Current guidelines introduce periodic monitoring of serum alanine transaminase (ALT) as the first-line modality in follow-up patients, with a hepatitis B virus (HBV) inactive carrier state.

Objectives:

This study aimed to determine the incidence rate and patterns of ALT fluctuations and prognostic values for the development of chronic HBV e antigen (HBeAg)-negative hepatitis B (CHB), HBV surface antigen (HBsAg) seroclearance, and liver-related complications.

Patients and Methods:

Treatment-naïve patients with a chronic HBV infection, HBeAg(-)/HBeAb(+), normal ALT levels, and HBV DNA < 2000 IU/mL, were followed-up every 6-12 months by assessing serum ALT levels. Serum HBV DNA was measured in cases of elevated ALT levels.

Results:

A total of 399 patients were followed-up for 8.9 years; ALT > upper limit of normal (ULN, i.e. 40 IU/L) was detected in 103 (25.8%) patients, with an annual incidence rate of 2.9%. ALT elevation was associated with; male gender, age, and higher serum ALT levels at study entry. Among the cases of ALT elevations, 16 (15.5%) patients had ALT levels > 2 × ULN. There were 38 (36.9%) patients who had ALT levels that remained > ULN over six months, and 21 (20.4%) patients experienced at least two episodes of ALT elevations. In 15 (14.6%) patients, elevated ALT levels were associated with increased HBV replication (i.e. HBV DNA > 2 000 IU/mL) and these were considered as CHB. However, elevation of ALT levels, even in the absence of HBV replication, increased the risk for the development of CHB up to 8-fold in prospective follow-ups. HBsAg seroclearance, cirrhosis, and hepatocellular carcinoma were detected in 43 (10.8%), 4 (1%), and 1 (0.25%) patients, respectively.

Conclusions:

Fluctuations in serum ALT levels may change the prognosis of a HBV inactive carrier state.     

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.     

HLA-DPB1 Variant Effect on Hepatitis B Virus Clearance and Liver Cirrhosis Development Among Southwest Chinese Population

Background:

Previous studies have shown that genetic variants in HLA-DP genes affect disease progression in hepatitis B virus (HBV) infection.

Objectives:

We aimed to evaluate possible association between HLA-DPB1 rs9277534 polymorphism and different clinical complications of hepatitis B virus (HBV) infection.

Materials and Methods:

Snapshot assay was used to investigate the association of rs9277534 polymorphism in 342 patients with persistent HBV infection and 342 age and gender-matched HBV spontaneous clearance controls. Patients were categorized into asymptomatic HBV carriers (AsC, n = 104), chronic hepatitis B (CHB, n = 116), and liver cirrhosis (LC, n = 122) subgroups.

Results:

There was a significantly higher proportion of the rs9277534 minor allele A in HBV spontaneous clearance control than that in HBV persistent infection group (OR = 0.58, 95%CI = 0.46-0.73, P < 0.0001). Genotypic analysis showed that GA and AA genotypes were associated with HBV spontaneous clearance (GA: OR = 0.56, 95%CI = 0.40-0.79, P = 0.019; AA: OR = 0.24, 95%CI = 0.14-0.44, P < 0.0001). A significant difference was found between AsC and LC groups in the distribution of AA genotype (OR = 9.32, 95%CI = 1.293-67.14, P = 0.027).

Conclusions:

Variant at rs9277534 could affect both the spontaneous clearance of HBV infection and progression from asymptomatic HBV carriers to HBV-related liver cirrhosis in Southwest Han Chinese population.     

Identification of acute vaccine-preventable hepatitis in individuals with chronic hepatitis in British Columbia between 1991 and 2007

BACKGROUND:

In British Columbia (BC), hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccines are provincially funded for persons with chronic hepatitis infections.

PURPOSE:

To assess the effectiveness of BC public health follow-up of HBV and hepatitis C virus (HCV) cases and immunization policy by determining the number of vaccine-preventable acute hepatitis infections reported following a chronic HBV or HCV diagnosis, by examining demographic characteristics and by observing temporal trends.

METHODS:

All newly identified cases of HAV, HBV and HCV between 1991 and October 2007 were extracted from the BC integrated Public Health Information System and linked to ascertain cases of hepatitis suprainfection.

RESULTS:

Between 1991 and October 2007, 30 BC residents with chronic HBV and 104 with HCV were subsequently diagnosed with HAV. Acute HBV was identified in 162 persons previously diagnosed with HCV. Significantly more men than women developed hepatitis suprainfection (P<0.0001), but women were of a younger age when they were diagnosed with HAV (P=0.02) and acute HBV (P=0.0002). HAV suprainfection cases among those with HCV peaked in 1998 at 33 cases and declined to zero cases in 2007. In comparison, HBV suprainfection among individuals with chronic HCV peaked in 1996 at 26 cases and declined to two cases in 2007.

DISCUSSION:

Cases of HAV and acute HBV have declined among HCV-infected individuals. However, despite the availability of publicly funded vaccines for high-risk groups, a substantial number of acute HBV infections post-HCV identification are still identified, indicating that follow-up and vaccination coverage should be improved in these populations.     

慢性乙型肝炎重叠戊型肝炎病毒感染的研究

目的了解慢性乙型肝炎重叠戊型肝炎病毒(HEV)感染的临床特点、乙型肝炎病毒(HBV)复制指标、肝功能损伤程度及预后。方法收集慢性乙型肝炎患者和慢性乙型肝炎重叠HEV感染(重叠感染组)各115例,两组病情(轻、中、重度)和HBV DNA定量相同,对两组患者进行临床分析,慢性乙型肝炎组中74例和重叠感染组中的51例患者,在B超引导下做肝活组织检查；应用酶联免疫吸附试验和聚合酶链反应分别检测两组患者HBV标志物,HBV DNA及抗HEV lgM。结果重叠感染组重型肝炎57例,发生率49．6%,死亡29例,病死率25．2%；慢性乙型肝炎组重型肝炎5例,发生率4．4%,死亡2例,病死率1．7%,两组比较,x~2值分别为58．80和27．01,P值均＜0．01,差异有统计学意义。血清HBV DNA≥10~4患者：重叠感染组占83．7%(36/43),单纯慢性乙型肝炎组占97．1%(67/69),x~2=4．73,P＜0．05；重叠感染组总胆红素平均(495．0±217．0)μmol/L、丙氨酸氨基转移酶平均(967．0±395．0) U/L,单纯慢性乙型肝炎组总胆红素平均(216．0±195．0)μmol/L和丙氨酸氨基转移酶平均(373．0±212．0)U/L,两组比较,t值分别为10．20和14．52,P值均＜0．01,差异有统计学意义；肝组织炎症G3和G4重叠感染组33例,占64．7%,单纯慢性乙型肝炎组25例,占33．8%,x~2=12．46,P＜0．01,差异有统计学意义。结论重叠感染组肝功能损害严重,肝组织炎症程度高,HBV DNA水平低,病死率高,预后差。     

Efficacy of Tenofovir Disoproxil Fumarate Therapy in Nucleoside-Analogue Naive Iranian Patients Treated for Chronic Hepatitis B

Background:

Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB).

Objectives:

To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB.

Patients and Methods:

The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability.

Results:

In all, 93 patients (64.5% hepatitis B e antigen [HBeAg]-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia.

Conclusions:

The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF.     

Relationship Between HBV Genotypes B,C and Follicular Helper T Cells in Patients with Chronic Hepatitis B and its Significance

Background

Clinical observations have shown that patients infected with chronic hepatitis B virus (HBV) genotype C versus genotype B had a higher load of the virus, more serious illness, and poorer responses to antiviral therapy and prognosis. However, the disparity between the two has not been clarified.

Objectives

To explore possible relationship between HBV genotypes B and C and peripheral blood follicular helper T cells (Tfh) and its significance in treating chronic hepatitis B (CHB) patients.

Patients and Methods

One hundred and fifty CHB patients were enrolled into this study, including 70 cases infected with HBV genotype C and 79 cases with genotype B. One patient had suffered from both genotypes B and C. The levels of Tfh, also known as interleukin-21 (IL-21), HBV specific cytotoxic T lymphocytes (CTL), HBV DNA and alanine transaminase (ALT) were evaluated and compared in patients infected with genotype B and C.

Results

Levels of Tfh, IL-21 and HBV specific CTL of patients infected with HBV genotype C were significantly lower than those of patients infected with HBV genotype B, P < 0.01. Levels of HBV DNA and ALT of patients infected with genotype C were significantly higher than those of the patients infected with HBV genotype B, P < 0.01.

Conclusions

Compared with chronic hepatitis B (CHB) patients infected with genotype B, higher levels of serum HBV DNA, ALT and TBil of patients infected with HBV genotype C may be related to their lower level of peripheral blood Tfh, which may result in lower IL-21, and it may result in lower HBV specific CTL.     

The impact of hepatitis B knowledge and stigma on screening in Canadian Chinese persons

BACKGROUND

Chronic hepatitis B (CHB) infection is endemic in East Asia, and those who emigrate to North America have higher rates of CHB infection when compared with the general population. To date, Chinese persons residing in Canada have not been mandated to be screened for CHB infection.

OBJECTIVE:

To understand factors that influence hepatitis B screening behaviour among the Chinese community in Toronto, Ontario, and to determine whether stigma acts as a barrier to screening.

METHODS:

Self-identified Chinese individuals at a family physician’s office and at English as a second language (ESL) classes in Toronto completed a questionnaire with demographic questions, a hepatitis B virus (HBV) stigma scale and an HBV knowledge scale. Pearson product moment correlation and multiple regression techniques were used to analyze the data.

RESULTS:

The study group included 343 individuals. Their mean (± SD) age was 48.76±17.49 years and the majority were born in China (n=229 [68%]). The mean score on the HBV knowledge scale was 10.13±1.76 (range 0 to 15), with higher scores indicating greater HBV knowledge. The mean score on the stigma scale was 54.60±14.18 (range 20 to 100), with higher scores indicating more stigma. Being an immigrant, having a family physician and having greater knowledge of HBV were associated with increased rates of screening for this infection. In contrast, greater levels of HBV stigma were associated with decreased likelihood of screening for HBV infection.

CONCLUSIONS:

HBV stigma is associated with reduced rates of screening for this infection.     

Occult Hepatitis B (OBH) in Clinical Settings

Context

Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings.

Evidence Acquisition

OHB could be found in different population and clinical backgrounds including: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters.

Results

The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown.

Conclusions

Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.     

Missed opportunities for prevention of perinatal transmission of hepatitis B: A retrospective cohort study

BACKGROUND:

Perinatal transmission of hepatitis B virus (HBV) can occur despite postexposure prophylaxis (PEP). Recent literature suggests that antiviral treatment during pregnancy when maternal HBV DNA levels are elevated can further decrease vertical transmission. However, HBV DNA screening is not routinely performed antenatally.

OBJECTIVE:

To determine the rates of HBV prevalence and perinatal transmission in an antenatal cohort.

METHODS:

A retrospective review of public health records (December 2008 to December 2010) was performed for both mothers and newborns.

RESULTS:

A total of 725 mother-infant pairs were included. Of these, 574 of 715 (80%) women had antenatal hepatitis B e antigen (HBeAg) testing performed, and 127 of 574 (22%) were HBeAg positive (HBeAg+). Of babies born to hepatitis B surface antigen-positive (HBsAg+) mothers, only 573 of 725 (79%) received complete PEP. In addition, 172 of 725 (24%) infants did not receive post-PEP blood testing or were lost to follow-up. Of the 552 infants with results available, seven cases (1.3%) of mother-to-child HBV transmission were observed, six of which involved infants born to HBeAg+ women.

CONCLUSIONS:

Our findings suggest that routine HBeAg screening could identify a subset of mother-infant pairs among HBsAg+ pregnant women who are at higher risk for vertical HBV transmission. Determination of viral load in expectant HBeAg+ mothers may provide more precise insight into HBV transmission to their infants.     

慢性乙型肝炎患者重叠戊型肝炎病毒感染的临床与病理学研究

目的：观察重叠戊型肝炎病毒（HEV）感染对慢性乙型肝炎（CHB）肝脏损害及HBV复制的影响。方法：应用ELISA法对122例CHB患者血清进行了抗－HEV IgkM,IgG检测,同时应用肝穿刺活检、荧光定量PCR及免疫组化等技术对重叠与未重叠HEV感染者分别进行了ALT、总胆红素（TBil)、凝血酶原活动度（PTA）、白蛋白／球蛋白（A／G）、电泳γ球蛋白（γ－EP）水平、肝脏病理学、血清HBeAg及肝组织HBcAg阳性率、血清及肝组织中HBV DNA含量对比。具有可比性的重叠（7例）与未重叠HEV感染者（14例）1年后做第2次肝穿活检并做病理学比较;HBeAg阴性重叠HEV感染者8例做HEV感染急性期、恢复期血清HBeAg定性、HBV DNA含量对比。结果：重叠HEV感染者21例（17．2％）。重叠HEV感染者较未重叠感染者ALT、TBil增高,PTA降低（P＜0．05）,但A／G、γ－EP水平未见显著差别（P＞0．05）;血清HBeAg及肝组织HBcAg阳性率、血清及肝组织HBV DNA含量低（P＜0．05）;肝组织炎症活动度重（P＜0．05）,但纤维化程度未见明显差别（P＞0．05）。两组患者1年前肝组织炎症活动度及纤维化程度无显著差别,1年后仍无显著差别（P＞0．05）。HEV感染恢复期血清HBeAg阳性率、HBV DNA含量高于急性期（P＜0．05）。结论：重叠HEV感染可加重CHB肝组织炎症活动度;对HBV复制具有短暂抑制作用。     

戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染的临床特征比较

目的分析比较戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床特征,并初步探索戊型肝炎慢性化问题。方法对66例戊型肝炎与37例慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床资料进行回顾性分析比较及统计。结果慢性乙型肝炎重叠戊型肝炎病毒感染患者较戊型肝炎患者丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)升高水平及发生率无显著差异,而在白蛋白(A)、白蛋白/球蛋白(A/G)及凝血酶原活动度(PTA)降低与肝纤维化系列各项指标增高方面更突出,消化道症状更重。结论慢性乙型肝炎重叠戊型肝炎病毒感染后肝功能损害更严重,凝血酶原时间长,慢性肝病特征常见,但单纯戊型肝炎患者慢性化问题也值得重视。     

Detection of Hepatitis B Virus Covalently Closed Circular DNA in the Plasma of Iranian HBeAg-Negative Patients With Chronic Hepatitis B

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 hepatitis B infection were enrolled in this cross-sectional study. The HBsAg titer was measured by the Roche HBsAg II assay on the Cobas e411 system, and HBV DNA quantitation was performed using the COBAS TaqMan 48 kit. Real-time polymerase chain reaction was performed for the detection of HBV cccDNA.

Results:

The mean (SD) age of the patients was 41.1 ± 12.4 years (range, 20 - 62 years). From a total of 106 study participants, 67 (63.2%) were males. The HBV cccDNA was detected in plasma specimens in 19 (17.9%) out of the total 106 patients, and a significant relationship was found between the presence of cccDNA in plasma sample of males (23.9%) and females (7.7%) (P = 0.039). Also, a significant correlation was found between the presence of cccDNA in plasma sample of the patients and HBV viral load level (P < 0.0001) and HBsAg titer (P = 0.0043).

Conclusions:

This study showed that cccDNA can be detected in the plasma specimen of 17.9% of Iranian treatment-naive patients with chronic hepatitis B infection. Therefore, designing prospective studies focusing on the detection of cccDNA in these patients would provide more information.     

Association of Mutations in the Basal Core Promoter and Pre-core Regions of the Hepatitis B Viral Genome and Longitudinal Changes in HBV Level in HBeAg Negative Individuals: Results From a Cohort Study in Northern Iran

Background:

Although certain HBV mutations are known to affect the expression of Hepatitis e antigen, their association with HBV viral level or clinical outcomes is less clear.

Objectives:

We evaluated associations between different mutations in the Basal Core promoter (BCP) and Pre-core (PC) regions of HBV genome and subsequent changes in HBV viral DNA level over seven years in a population of untreated HBeAg negative chronic hepatitis B (CHB) participants in Northeast of Iran.

Materials and Methods:

Participants in the current study were drawn from the Golestan Hepatitis B Cohort Study (GHBCS), a cohort of approximately 2590 HBsAg positive subjects (living in Gonbad city) embedded in the Golestan Cohort Study (GCS). At baseline, HBsAg was measured in all participants and revealed 2590 HBsAg positive cases. We randomly selected 304 participants who their blood sample were taken at both baseline and seven years later in follow-up and had not been treated for HBV during this time. HBV viral load were assessed at baseline and at year 7. The BCP and PC regions of the HBV DNA, at baseline, were amplified via hemi-nested PCR and sequenced by cycle sequencing. At year 7, liver stiffness was assessed by fibroscan; also, other parameters of liver disease were assessed following standard clinical protocols. Associations were assessed via tabulation, chi-square, t-tests and logistic regression. P values < 0.05 were considered statistically significant and all tests were two-sided.

Results:

Among 304 HBsAg positive participants, 99 had detectable HBV DNA at study baseline. Of these, 61.6% had PC mutations (48.5% A1896 and 25.2% G1899). In contrast to other mutations, A1896 was associated with a higher proportion of detectable HBV DNA at year 7 (39.6%) compared to patients with the wild type (13.7%) (OR: 4.36, CI95% = 1.63-11.70; P Value = 0.002). Although participants with the A1896 mutation had higher year-7 HBV viral load than participants with G1896 (2.30 ± 1.66 IU/mL vs. 1.76 ± 1 IU/mL among patients with detectable HBV; P value = 0.052), no association was observed with either serum level ALT or liver stiffness. Interestingly, mutations in the basal core promoter (BCP) region had no significant effect on virus DNA detection.

Conclusions:

In this population with chronic HBeAg negative hepatitis B, an association was observed between the G1896A mutation in the Pre-core region of HBV and subsequent level of HBV DNA seven years later, which indicated that mutations in this region of HBV genome may contribute to disease progression in these patients and play an important role in HBV natural course of disease.     

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.     

The Expression of Programmed Death-1 in Circulating CD4+ and CD8+ T Cells during Hepatitis B Virus Infection Progression and Its Correlation with Clinical Baseline Characteristics

Background/Aims

Programmed death-1 (PD-1) expression was investigated in CD4⁺ and CD8⁺ T cells from hepatitis B virus (HBV)-infected patients at the chronic hepatitis B (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) stages.

Methods

PD-1 expression in circulating CD4⁺ and CD8⁺ T cells was detected by flow cytometry. The correlations between PD-1 expression and HBV viral load, alanine aminotransaminase (ALT) levels and aspartate aminotransferase (AST) levels were analyzed using GraphPad Prism 5.0.

Results

PD-1 expression in CD4⁺ and CD8⁺ T cells was significantly increased in both the CHB group and advanced-stage group (LC plus HCC). In the CHB group, PD-1 expression in both CD4⁺ and CD8⁺ T cells was positively correlated with the HBV viral load, ALT, and AST levels. However, in the LC plus HCC group, significant correlations between PD-1 expression and the clinical parameters were nearly absent.

Conclusions

PD-1 expression in peripheral CD4⁺ and CD8⁺ T cells is dynamic, changes with HBV infection progression, and is related to HBV viral load and liver function, especially in CHB. PD-1 expression could be utilized as a potential clinical indicator to determine the extent of virus replication and liver injury.     

Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

Background

Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone.

Objectives

The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates.

Patients and Methods

81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations.

Results

12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients.

Conclusions

HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.     

Adiponectin and Its Receptors in Chronic Hepatitis B Patients With Steatosis in China

Background

HBV infection is a serious public health problem worldwide, which can contribute to the incidence of chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC).

Objectives

In the present report, we assessed the association between adiponectin, its receptors and hepatic steatosis, fibrosis, and inflammation with hepatitis B virus.

Patients and Methods

Liver biopsies from 89 patients with untreated chronic hepatitis B (34 steatosis vs. 55 without steatosis) were analyzed; liver biopsies from 50 healthy adults were used as control. The liver biopsies were subjected to routine histological examination, and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2).

Results

The two groups were found to be comparable with respect to demographic, biochemical, metabolic, histological, and viral characteristics. BMI, γ-GT, FPG, insulin, and insulin sensitivity estimated by the HOMA index were significantly higher in patients with steatosis. The viral load of HBV and HBeAg positivity was higher in patients with steatosis than those without steatosis. High serum adiponectin levels were significantly correlated with abnormal serum ALT level (vs. normal ALT, P = 0.000), and HBV genotype C (vs. genotype B, P = 0.018). In patients with chronic HBV, the insulin sensitizing adipokine adiponectin, and its receptor AdipoR2were associated with steatosis. While adiponectin may becorrelated with inflammation, adiponectin, and its receptors were not associated with viral factors.

Conclusions

Our results suggest that the role of adiponectin might be impaired in chronic hepatitis B with steatosis. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with steatosis. These findings indicated that reduced liver adiponectin expression may play an important role in the pathogenesis, and progression of CHB patients with steatosis. However, hepatic expression of adiponectin, and adipoR2 was not associated with various measures of HBV infection.