Risk Factors of HCV Seroconversion in Hemodialysis Patients in Tabriz,Iran

Background:

Hepatitis C virus (HCV) infection is a significant health concern in patients with end-stage renal disease under dialysis. Epidemiological studies have reported a prevalence rate of 5.5-55.9% for this condition in Iran.

Objectives:

We evaluated the risk factors for HCV infection and seroconversion in hemodialysis patients.

Patients and Methods:

A retrospective analysis was performed on 455 hemodialysis patients from each of the five dialysis units in Tabriz, northwest Iran. Possible risk factors for HCV infection and seroconversion were evaluated.

Results:

A total of 37 patients were HCV positive (8.1% of the study population) and seroconversion occurred in 18 of them during the dialysis treatment (3.95% of the study population). History of renal transplantation (44.4%, P < 0.0001), surgical intervention (except for renal transplantation and AV fistula placement) (94.4%, P = 0.03), and mean duration of dialysis (106.06 ± 55.519, P < 0.0001) had strong statistically significant associations with the seroconversion.

Conclusions:

The current study indicates increased risk for HCV infection in patients under dialysis and its relation with the mean duration of hemodialysis, history of renal transplantation and surgical intervention. Considering the immune deficiency in these patients, intense education to both patients and medical staff will be beneficial.     

Serum Iron Markers in Patients With Chronic Hepatitis C Infection

Background

Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.

Objectives

The aim of this study was to investigate the possible correlations between iron metabolism serum markers, HCV viral load, and liver disease severity in treatment-naive patients with chronic hepatitis C infection.

Patients and Methods

Eighty five patients with untreated hepatitis C chronic infection were investigated.

Results

Twenty one patients (24.7%) had elevated serum iron levels, and 29 subjects (34.1%) had severe liver fibrosis. Significantly elevated levels of serum iron (P < 0.05) and ferritin (P < 0.001), associated with lower levels of TIBC (P < 0.05) were detected in patients with severe fibrosis compared to no/mild fibrosis. Severe necroinflammatory activity was also significantly correlated with serum iron (P < 0.001), TIBC (P < 0.05), and ferritin levels (P < 0.001). Using multiple linear regression analysis, serum levels of ferritin and transferrin were the independent variables selected as being good predictors for advanced fibrosis and severe necroinflammatory activity. No significant correlations were detected between HCV viral load and iron markers.

Conclusions

This study revealed that serum iron markers (especially ferritin and transferrin) might be used as surrogate markers for both liver fibrosis and necroinflammatory activity.Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.     

Estrogen Receptor Alpha Expression and Liver Fibrosis in Chronic Hepatitis C Virus Genotype 1b: A Clinicopathological Study

Background:

Hepatic damage due to chronic hepatitis C virus (HCV) genotype 1b infection varies widely.

Objectives:

We aimed to investigate whether estrogen receptor alpha (ERα) plays a role in liver fibrosis in patients infected with HCV genotype 1b.

Patients and Methods:

All the consecutive patients who received the same standard treatment protocol for HCV genotype 1b were subdivided into two subgroups according to their fibrosis scores as fibrotic stages < 2 in mild fibrosis group and fibrotic stages ≥ 2 in advanced fibrosis group, depending on the presence of septal fibrosis. ERα was stained in liver biopsy specimens. Demographics and clinical properties were compared between the groups. Multivariate logistic regression analysis was performed to predict advanced fibrosis.

Results:

There were 66 patients in the mild fibrosis group and 24 in the advanced fibrosis group. Among the mild and advanced fibrosis groups, 65.1% and 50%were female, respectively (P = 0.19). There was an inverse correlation between ERα and fibrotic stage (r: -0.413; P < 0.001). Age, platelet counts, neutrophil counts, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transferase (GGT) and ERα were statistically significant in the univariate analysis. In multivariate logistic regression analyses, ERα expression continued to be an independent predicting factor of liver fibrosis in patients infected with chronic HCV genotype 1b (OR: 0.10; 95% CI: 0.018-0.586; P < 0.001).

Conclusions:

ERα expression in liver was inversely correlated with liver fibrosis among patients infected with chronic HCV genotype 1b.     

Assessment of Myocardial Ischemia in Obese Individuals Undergoing Physical Stress Echocardiography (PSE)

Background

Physical stress echocardiography is an established methodology for diagnosis and risk stratification of coronary artery disease in patients with physical capacity. In obese (body mass index ≥ 30 kg/m²) the usefulness of pharmacological stress echocardiography has been demonstrated; however, has not been reported the use of physical stress echocardiography in this growing population group.

Objective

To assess the frequency of myocardial ischemia in obese and non-obese patients undergoing physical stress echocardiography and compare their clinical and echocardiographic differences.

Methods

4,050 patients who underwent treadmill physical stress echocardiography were studied according to the Bruce protocol, divided into two groups: obese (n = 945; 23.3%) and non-obese (n = 3,105; 76.6%).

Results

There was no difference regarding gender. Obese patients were younger (55.4 ± 10.9 vs. 57.56 ± 11.67) and had a higher frequency of hypertension (75.2% vs. 57, 2%; p < 0.0001), diabetis mellitus (15.2% vs. 10.9%; p < 0.0001), dyslipidemia (59.5% vs 51.9%; p < 0.0001), family history of coronary artery disease (59.3% vs. 55.1%; p = 0.023) and physical inactivity (71.4% vs. 52.9%, p < 0.0001). The obese had greater aortic dimensions (3.27 vs. 3.14 cm; p < 0.0001), left atrium (3.97 vs. 3.72 cm; p < 0.0001) and the relative thickness of the ventricule (33.7 vs. 32.8 cm; p < 0.0001). Regarding the presence of myocardial ischemia, there was no difference between groups (19% vs. 17.9%; p = 0.41). In adjusted logistic regression, the presence of myocardial ischemia remained independently associated with age, female gender, diabetes and hypertension.

Conclusion

Obesity did not behave as a predictor of the presence of ischemia and the physical stress echocardiography. The application of this assessment tool in large scale sample demonstrates the feasibility of the methodology, also in obese.     

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.     

Low Prevalence of Hepatitis C Virus Infection Among HIV-Positive Patients: Data From a Large-Scale Cohort Study in Istanbul,Turkey

Background:

Rate of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) varies in different countries. This may be attributable to common transmission routes as well as social, economic, and cultural factors.

Objectives:

The purpose of this study was to investigate the prevalence and risk factors of HCV infection among HIV-positive patients in Istanbul, Turkey.

Patients and Methods:

Since January 2006 to November 2013, 949 HIV-positive patients that were enrolled in this study by ACTHIV-IST (Action Against HIV in Istanbul) Study Group, which consists of five centers to follow up HIV-positive patients in Istanbul. Epidemiologic and clinical data were collected retrospectively from medical records and were transferred to an HIV database system.

Results:

Among 949 patients, 84% were men and the mean age was 37.92 ± 11.54 years (range, 17-79). The most frequent route of transmission was heterosexual intercourse (48.8%), followed by men having sex with men (30.5%). Only nine patients (0.9%) had history of injection drug use (IDU). The prevalence of HIV/HCV coinfection was 0.9% (9:949). The IDU rate was 44.4% (4:9) in patients with HIV/HCV coinfection (three of them were not Turkish citizens), whereas this rate was only 0.6% (5:881) in patients with only HIV infection (P < 0.01). Genotypes 1b, 2a/2c, and 3 were determined in five, one, and two patients, respectively. Genotype could not be determined in one patient. History of residence in a foreign country (P < 0.01) and imprisonment (P < 0.01) were also considered as risk factors in terms of HIV/HCV coinfection.

Conclusions:

Prevalence of HIV/HCV coinfection is considerably low in Turkey. The extremely rare prevalence of IDU might have a role in this low prevalence.     

Predictors of Pegylated Interferon Alpha and Ribavirin Efficacy and Long-Term Assessment of Relapse in Patients With Chronic Hepatitis C: A One-Center Experience From China

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.     

Predictors of survival and incidence of hepatoblastoma in the paediatric population

Objectives

This study evaluates current trends in incidence, clinical outcomes and factors predictive of survival in children with hepatoblastoma (HB).

Methods

The Surveillance, Epidemiology and End Results (SEER) database was queried for the period 1973–2009 for all patients aged <20 years with HB.

Results

A total of 606 patients were identified. The age-adjusted incidence was 0.13 patients per 100 000 in 2009. An annual percentage change of 2.18% (95% confidence interval (CI) 1.10–3.27; P < 0.05) was seen over the study period. Overall survival rates at 5, 10 and 20 years were 63%, 61% and 59%, respectively. Ten-year survival rates significantly improved in patients with resectable disease who underwent operative treatment in comparison with those with non-resectable HB (86% versus 39%; P < 0.0001). Multivariate analysis showed surgical treatment (hazard ratio (HR) = 0.23, 95% CI 0.17–0.31; P < 0.0001), Hispanic ethnicity (HR = 0.61, 95% CI 0.43–0.89; P = 0.01), local disease at presentation (HR = 0.43, 95% CI 0.29–0.63; P < 0.0001) and age < 5 years (HR = 0.63, 95% CI 0.41–0.95; P < 0.03) to be independent prognostic factors of survival.

Conclusions

The incidence of paediatric HB has increased over time. Hepatoblastoma is almost exclusively seen in children aged < 5 years. When HB presents after the age of 5 years, the prognosis is most unfavourable. Tumour extirpation markedly improves survival in paediatric patients with local disease.     

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.     

Differentially Expressed Proteins in Chronic Active Hepatitis,Cirrhosis, and HCC Related to HCV Infection in Comparison With HBV Infection: A proteomics study

Background

Hepatocellular carcinoma is a highly progressive cancer in the case of late diagnosis which is frequently associated with HBV and HCV viral infections.

Objectives

To identify differentially expressed serum proteins among three main stages of HCV infection and healthy individuals, and their comparisons with sera from patients with the same stage of HBV infection.

Patients and Methods

Two-dimensional polyacrylamide gel electrophoresis combined with liquid chromatography-tandem mass spectrometry was performed on 47 sera from healthy volunteers, those with chronic active hepatitis, cirrhosis and HCC patients associated with HBV and HCV infections.

Results

Among these, 62 spots were differentially expressed (≥ 1.5 fold; P < 0.05), of which 42 spots that corresponded to 15 proteins were identified by liquid chromatography-tandem mass spectrometry. CD5-like antigen (CD5L) was differentially expressed between cirrhosis and HCC patients with HCV infection. Leucine-rich α2-glycoprotein (LRG) and haptoglobin (HP) α2 isoforms differed in the HCC that was associated with either HCV or HBV infections.

Conclusions

CD5L might be a useful biomarker for early diagnosis of HCC in HCV cirrhotic patients. LRG and HP α2 isoforms could be potential markers for distinguishing viral HCC. Our results also further support the presence of varying molecules involved in hepatocarcinogenesis in HBV when compared with HCV infection.     

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.     

Smoking in Saudi Arabia and its relation to coronary artery disease

Objectives

The health hazards related to smoking are well known. Smoking is a recognized risk factor for coronary artery disease (CAD). Despite rejection of smoking by the Saudi community, we are still seeing smokers in our population. This study is designed to determine the prevalence of smoking in the Kingdom of Saudi Arabia (KSA), and to find out its relation to CAD. This study is part of the Coronary Artery Disease In Saudis (CADIS) study.

Methods

This health survey was conducted by collecting data regarding smoking status among adult Saudis aged between 30 and 70 years of both sexes in KSA over a five year period from 1995 up to 2000. The study sample was of normal distribution and representative of all regions of KSA. The data were analyzed to provide the prevalence of smoking and its relation with CAD.

Results

The total number of subjects was 17,350, and current smokers were 2217; accordingly the overall prevalence of smoking among Saudis was 12.8%. Males (1555) were significantly smoking more than females (662) with a prevalence of 18.7% and 7.3%, respectively (P < 0.0001). Smoking is more prevalent among Saudis living in urban, northern, western, and eastern regions compared to other regions of KSA. Smokers are more likely to develop CAD compared to non-smokers (P < 0.0001).

Conclusions

Smoking is a prevalent health problem among Saudis that requires intervention for eradication. We found clear association between cigarettes smoking and CAD particularly among males. Persistent education of the health hazards related to smoking is recommended particularly at early age in-order to prevent initiation of smoking.     

Continuous Long-Term Entecavir Therapy in Na?ve Chronic Hepatitis B Patients Showing Partial Virologic Response

Background/Aims

We investigated the efficacy of continuous long-term entecavir 0.5 mg treatment in naïve chronic hepatitis B patients showing a partial virologic response (PVR).

Methods

A total of 227 patients were included. PVR was defined as a more than 1 log₁₀ IU/mL decline in detectable serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR; ≥20 IU/mL) at week 48. A complete virologic response (CVR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL) at week 48.

Results

At week 48, the rate of the PVR was 64/227 (28.2%). Among patients with PVR, the cumulative rates of virologic response (serum HBV DNA <20 IU/mL) at weeks 96 and 144 were 45.2% and 73.8%, respectively. The cumulative rates of genotypic resistance were not significantly different between patients with a PVR and patients with a CVR (p=0.057). However, the cumulative rates of virologic breakthrough were higher in patients with PVR than in patients with CVR (4% vs 0% and 11.2% vs 0% at weeks 96 and 144, respectively; p<0.001).

Conclusions

Long-term continuous entecavir 0.5 mg treatment in patients with a PVR resulted in an additional virologic response without a significant increase in genotypic resistance. However, the rate of virologic breakthrough was higher in the partial responders.     

Increased QT dispersion and P wave dispersion in major depressive disorder

BACKGROUND:

QT and P wave dispersion parameters can indicate abnormalities in autonomic nervous system and cardiac functioning.

OBJECTIVES:

To determine QT and P wave dispersion in patients with major depressive disorder compared with healthy volunteers.

METHODS:

Fifty newly diagnosed patients with major depressive disorder and 50 age- and sex-matched healthy volunteers underwent 12-lead electrocardiography. QT interval, QT dispersion, heart rate-corrected QT dispersion and P wave dispersions were calculated manually by a blinded specialist.

RESULTS:

Groups were comparable in terms of age, sex, body mass index, smoking status, metabolic diseases and left ventricular ejection fraction. The major depressive disorder group had significantly higher QT dispersion (58.5±9.9 versus 41.7±3.8; P<0.001), heart rate-corrected QT dispersion (62.5±10.0 versus 45.2±4.3; P<0.001) and P wave dispersion (46.9±4.8 versus 41.5±5.1; P<0.001).

CONCLUSION:

Increased QT dispersion, heart-rate corrected QT dispersion and P wave dispersion in major depressive disorder patients may be indicative of autonomic imbalance and increased risk of cardiac morbidity and mortality.     

Disease Progression in Chronic Hepatitis B Patients under Long-Term Antiviral Therapy

Background/Aims

We investigated factors associated with the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients during long-term oral nucleos(t)ide analog (NA) therapy.

Methods

This retrospective study included 524 naive CHB patients who received oral NA therapy for more than 48 weeks between January 2003 and December 2007. The primary outcome was 5-year cumulative probability of disease progression and HCC development. Disease progression was defined as cirrhosis development, cirrhotic complications, HCC or liver-related mortality.

Results

For the 524 patients, the cumulative probabilities of disease progression and HCC development at 1, 2, 3, 4 and 5 years were 1.1%, 6.3%, 9.0%, 11.6%, and 16.2% and 0.2%, 1.8%, 3.6%, 5.8%, and 9.3%, respectively. In multivariate analysis, age >50 years (hazard ratio [HR], 1.05) and cirrhosis (HR, 2.95) were significant factors for disease progression. Similarly, age >50 years (HR, 1.05), family history of HCC (HR, 5.48), and cirrhosis (HR, 17.16) were significant factors for HCC development. Importantly, longer duration (>12 months) of maintained virological response (<20 IU/mL) reduced the risks of disease progression (HR, 0.19) and HCC development (HR, 0.09).

Conclusions

Longer duration of maintained virological response significantly reduces the risk of disease progression or HCC development in CHB patients undergoing long-term oral NA therapy.     

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.     

Prophylactic Lamivudine to Improve the Outcome of Breast Cancer Patients With HBsAg Positive During Chemotherapy: A Meta-Analysis

Context

Raising the chemotherapy-induced HBV reactivation is parallel to the increment of chemotherapy treatments in breast cancer patients. This meta-analysis aims to evaluate the efficacy of prophylactic use of lamivudine in breast cancer patients with HBsAg positive during chemotherapy.

Evidence Acquisition

MEDLINE, Pubmed, Ovid and Embase were used to search for clinical studies comparing with or without prophylactic use of lamivudine for HBV reactivation in breast cancer patients receiving chemotherapy. Outcomes of interest were the rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis attributable to HBV reactivation, severity of hepatitis and severity of hepatitis attributable to HBV reactivation, the rate of chemotherapy disruption, and the rate of chemotherapy disruption attributable to HBV reactivation, overall mortality, and mortality attributable to HBV reactivation.

Results

Four studies with 285 patients were included in this meta-analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis related to HBV reactivation were reduced by use of prophylactic lamivudine compared to control group. Pooled Odds Ratios (ORs) were 0.09 (95% confidence intervals [CI] 0.03-0.26; P < 0.0001), 0.23 (95% CI 0.06-0.92; P = 0.04), and 0.10 (95% CI 0.03-0.32; P < 0.0001) respectively. There was a reduction in chemotherapy disruption related to HBV reactivation by use of prophylactic lamivudine (pooled OR = 0.11; 95% CI 0.02-0.58; P = 0.01). Chemotherapy disruption, overall mortality, and mortality attributable to HBV reactivation were not significantly different between two groups. Pooled ORs were 0.42 (95% CI 0.11-1.58; P = 0.20), 0.37 (95% CI 0.07-2.04; P = 0.25), and 0.25 (95% CI 0.01-6.82; P = 0.41) respectively. Lamivudine was well-tolerated, and no additional toxicity was observed.

Conclusions

Use of prophylactic lamivudine may have positive effect on the outcome of breast cancer patients with HBsAg positive during chemotherapy.     

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

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. {"type":"entrez-nucleotide-range","attrs":{"text":"JN257148-JN257217","start_term":"JN257148","end_term":"JN257217","start_term_id":"364505024","end_term_id":"364505559"}}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.     

Clinical Values of Elevated Serum Cytokeratin-18 Levels in Hepatitis: A Meta-Analysis

Background:

As an important intermediate filament protein within liver cells, cytokeratin-18 (CK-18) has been confirmed as a potential indicator in various hepatitis progressions.

Objectives:

We sought to clarify the connection between serum CK-18 levels and hepatitis pathogenesis in the present meta-analysis.

Materials and Methods:

With the application of various computerized databases, including PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, China BioMedicine (CBM), China National Knowledge Infrastructure (CNKI), published papers that assessed the relationship between serum CK-18 levels and hepatitis were obtained. The main key words used are “Hepatitis”, “hepatitides”, “Cytokeratin-18”, “Keratin-18” and “CK-18”. Statistical analysis was conducted using the STATA software (version 12.0).

Results:

Eight case-control studies published between 2010 and 2014 were confirmed eligible, according to our selection criteria. The results of the meta-analysis showed that serum levels of CK-18 in hepatitis patients were higher compared to healthy controls (standardized mean difference (SMD) = 3.71, 95%CI: 2.27-5.14, P < 0.001). Subgroup analysis by ethnicity and disease implicated that high serum CK-18 levels might be a risk factor for non-alcoholic steatohepatitis (NASH), chronic hepatitis C (CHC), and chronic hepatitis B (CHB) (all P < 0.05) among Asians (SMD = 2.89, 95%CI: 2.35-3.43, P < 0.001), Africans (SMD = 0.69, 95%CI: 0.12-1.26, P = 0.017), and Caucasians (SMD = 4.86, 95%CI: 1.82-7.89, P = 0.002).

Conclusions:

Serum CK-18 levels in hepatitis patients were higher, compared with healthy controls. Our results revealed the clinical values of CK-18, in combination with other apoptosis markers, in identifying the development of hepatitis.     

Evaluating Liver Fibrosis by Transient Elastometry in Patients With HIV-HCV Coinfection and Monoinfection

Background:

Due to the high efficacy of combination antiretroviral therapy (cART), the number of patients living with HIV is increasing. Chronic HCV infection has become a leading cause of non-AIDS related morbidity and mortality in patients with HIV infection.

Objectives:

The aim of this cross-sectional study was to identify factors associated with liver fibrosis (LF) in patients with HIV monoinfection and HIV-HCV coinfection.

Patients and Methods:

We analyzed LF by transient elastometry ([TE], Fibroscan) in three groups of patients (HIV, HIV-HCV and HCV) followed at the Infectious Diseases Department of University of Ancona, Italy, between October 2009 and November 2012.

Results:

In total, 354 adults including 98 HIV, 70 HIV-HCV and 186 HCV patients were studied. HIV-HCV patients had a longer duration of HIV (P < 0.006) and HCV (P < 0.001) infections. Additionally, they were receiving cART therapy for a longer period (P < 0.001); they had higher prevalence of lipodystrophy (P < 0.001) and higher HCV load (P = 0.004). LF was significantly more pronounced in HCV and HIV-HCV compared to HIV patients (P < 0.001). A total of 13.3%, 39.2% and 51.4% of HIV, HCV and HIV-HCV, respectively, showed a LF ≥ F2. Additionally, a severe LF (F = 4) was significantly more frequent among HIV-HCV compared to other groups. A longer exposure to didanosine, stavudine, lopinavir/ritonavir and fosamprenavir resulted in increased LF by univariate analysis (P ranging from < 0.001 to 0.007). By logistic regression analysis, the only variables significantly associated with increased LF were HCV coinfection, older age, and high AST values (P ranging from < 0.001 to 0.036).

Conclusions:

HCV coinfection, older age and AST were associated with LF in patients with HIV infection.