Hepatitis D virus infection,cirrhosis and hepatocellular carcinoma in The Gambia

Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q‐MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case‐control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha‐foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q‐MAC, western blot and RNA assays. We evaluated separate cut‐offs of the Q‐MAC assay for predicting anti‐HDV and RNA positivity. Q‐MAC correctly identified 29/29 subjects who were western blot‐positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA‐positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA?; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV‐HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti‐HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74‐11.98) and HBV‐HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97‐134.95). In this Gambian population, HDV Q‐MAC had high sensitivity and specificity for both anti‐HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.     

Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections

In patients with multiple hepatotropic viral infections (B and C, or B, C and D), the reciprocal influence of each virus remains controversial. The aims of this study were twofold: first, to determine the impact of multiple infection on the replication status of B, C and D viruses and on histological features; and second, to compare patients with multiple infection to patients infected only with the hepatitis C virus (HCV). We retrospectively included 50 patients with multiple infection and 50 control HCV patients, who were matched on independent factors associated with fibrosis, such as age, gender, alcohol consumption and duration of infection. The replication status of hepatitis B virus (HBV), HCV and hepatitis D virus (HDV), and histological lesions, were determined. In patients with multiple infection, HCV RNA was present less frequently (44% vs 98%, P  < 0.001) and the prevalence of cirrhosis was higher (35% vs 8%, P  < 0.001). Among patients with triple infection ( n  = 16), HBV replication was observed in 25%, HCV RNA was detectable in only two ( P  < 0.0001) and HCV viremia was significantly lower than in the matched HCV patients (0 vs 54.7, P  < 0.0001). Among patients with dual infection ( n  = 34), HCV RNA was present less frequently in those with serological markers of active HBV infection than in those without (30% vs 79%, P  = 0.01). Hence, multiple infection is associated with a decrease of HCV replication. Cirrhosis seems to be more frequently observed in patients with multiple infection. In patients with triple infection, serum HCV RNA and markers of HBV replication were absent in 80%, suggesting that HDV acts as a dominant virus. In patients with dual infection, HBV and HCV exert an alternative, dominant replication.     

Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India

AIM: To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis in Indian population. METHODS: A total of 213 patients with HCC and 254 control subjects not affected with hepatic diseases or neoplasm were recruited. Odds ratios (ORs) were estimated for each risk factor and synergism among various risk factors was also studied. RESULTS: The ORs and 95% confidence intervals (CI) of HCC were 48.02 (25.06-91.98) for any HBV marker, 38.98 (19.55-77.71) for HBsAg positivity, 12.34 (2.84-53.61) for HBsAg negative and antibody positive (either of anti-HBe or total anti-HBc), 5.45 (2.02-14.71) for anti-HCV positive and HCV RNA positive, and 2.83 (1.51-5.28) for heavy alcohol use. No significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA negative. Synergism between alcohol and HCV infection in causing HCC was found, but not between alcohol and HBV. Overall, conclusive evidence of the presence or absence of cirrhosis was reached in 189 (88.73%) HCC patients; cirrhosis was present in 137 (72.48%) of them. ORs with 95% CI of HCC in the presence and absence of cirrhosis, respectively, for HBV were as follows: (i) 48.90 (24.61-97.19) and 35.03 (15.59-78.66) for any HBV marker; (ii) 39.88 (19.41-81.97) and 24.40 (10.60-56.18) for HBsAg positivity; and (iii) 12.10 (2.67-54.88) and 19.60 (3.94-97.39) for HBsAg negativity and antibody positivity. Significantly increased risk was found among cirrhotic patients for anti-HCV positivity and HCV RNA positivity [OR = 7.53 (2.73-20.78)] and for heavy alcohol use [OR = 3.32 (1.70-6.47)]; however, in the absence of cirrhosis, no significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA positive [OR = 0.97 (0.11-8.54)], or who had history of heavy alcohol use [OR = 1.58 (0.55-4.53)]. CONCLUSIONS: Infection with HBV and HCV are the major risk factors for the development of HCC in Indian patients. Presence of HBV antibodies even in the absence of HBsAg conferred increased risk for HCC in the presence or absence of cirrhosis. Anti-HCV positivity in the absence of HCV RNA conferred no increased risk. HCV RNA positivity and heavy alcohol use significantly increased the risk of HCC among cirrhotic patients, but not non-cirrhotic patients.     

Hepatitis B and C viruses are not risks for pancreatic adenocarcinoma

AIM:To investigate whether hepatitis B virus(HBV)and hepatitis C virus(HCV)increase risk of pancreatic ductal adenocarcinoma(PDAC).METHODS:We recruited 585 patients with cytological and/or pathologically confirmed PDAC in National Taiwan University Hospital from September 2000 to September 2013,and 1716 age-,sex-,and race-matched controls who received a screening program in a community located in Northern Taiwan.Blood samples were tested for the presence of HCV antibodies(anti-HCV),HBV surface antigen(HBsAg),antibodies against HBsAg(anti-HBs),and hepatitis B core antigen(anti-HBc)in all cases and controls.The odds ratio(OR)of PDAC was estimated by logistic regression analysis with adjustment diabetes mellitus(DM)and smoking.RESULTS:HBsAg was positive in 73 cases(12.5%)and 213 controls(12.4%).Anti-HCV was positive in22 cases(3.8%)and 45 controls(2.6%).Anti-HBs was positive in 338 cases(57.8%)and 1047 controls(61.0%).The estimated ORs of PDAC in multivariate analysis were as follows:DM,2.08(95%CI:1.56-2.76,P<0.001),smoking,1.36(95%CI:1.02-1.80,P=0.035),HBsAg+/anti-HBc+/anti-HBs-,0.89(95%CI:0.89-1.68,P=0.219),HBsAg-/anti-HBc+/anti-HBs+,1.03(95%CI:0.84-1.25,P=0.802).CONCLUSION:HBV and HCV infection are not associated with risk of PDCA after adjustment for age,sex,DM and smoking,which were independent risk factors of PDAC.     

Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

Influence of chronic HBV infection on superimposed acute hepatitis E

AIM:To investigate the influence of chronic hepatitis B virus(HBV)infection[based on the status of hepatitis B e antigen(HBeAg),HBV DNA,and cirrhosis]on superimposed acute hepatitis E.METHODS:A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital,Sun Yat-sen University,from January 2003 to January 2012.The patients were classified into two groups:an HBV+hepatitis E virus(HEV)group(a group with chronic HBV infection that was superinfected with acute hepatitis E,n=118)and an HEV group(a group with acute hepatitis E,n=176).We retrospectively analyzed and compared the clinical features of the two groups.Statistical analyses were performed using theχ2test or Fisher’s exact test for categorical variables and the Student’s t test forcontinuous variables.A P value<0.05 was considered statistically significant.RESULTS:The peak values of prothrombin time,serum total bilirubin,and Model for End-Stage Liver Disease scores were significantly higher in the HBV+HEV group.More patients in the HBV+HEV group had complications(39.8%vs 16.5%,P=0.000)and developed liver failure(35.6%vs 8.5%,P=0.000).Additionally,the mortality of the HBV+HEV group was significantly higher(20.3%vs 7.4%,P=0.002).Further analysis of the HBV+HEV group showed that there were no significant differences in complication occurrence,liver failure incidence,or mortality between patients with different HBeAg and HBV DNA statuses.However,in patients with underlying cirrhosis,complication occurrence and liver failure incidence significantly increased.In total,12.7%of the patients in the HBV+HEV group received anti-HBV treatment,but this therapy failed to reduce mortality in patients who developed liver failure.CONCLUSION:The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E.AntiHBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.     

Characteristics of Treatment Na?ve Chronic Hepatitis B in Bangladesh: Younger Populations are More Affected; HBeAg-negatives are More Advanced

Background/Aim:

Bangladesh is a densely populated country with intermediate endemicity for chronic hepatitis B (CHB). The aim of the present study was to evaluate the biochemical, virological and histological character of CHB patients and to examine the relationship between these indices.

Materials and Methods:

One thousand and twenty-two patients of CHB fulfilled our inclusion criteria. Inclusion criteria were (1) HBsAg positive for at least 6 months, (2) HBeAg-positive or negative and (3) hepatitis B virus (HBV) DNA positive. Patients with detectable antibodies to human immunodeficiency virus (HIV), hepatitis Delta virus (HDV) or hepatitis C virus (HCV), with previous antiviral treatment, overt cirrhosis and hepatocellular carcinoma, were excluded. Of these, 191 patients were randomly selected for liver biopsy and were evaluated for analysis.

Results:

In the 191 patients, male to female ratio was 4.6:1; age distribution was 26.5 ± 8.5 (mean ± standard deviation) years. One hundred and seventy-eight (93.2%) patients were under 40 years. Sixty-eight (35.6%) patients were HBeAg-negative, had less DNA load, and were significantly older, more fibrotic and cirrhotic (P < 0.001). Correlation was not found between DNA level and histological activity. Histological activity was not correlated with ALT level in HBeAg-positive patients (P < 0.001).

Conclusion:

CHB affects the younger population in Bangladesh. HBeAg-positive CHB was associated with more fibrosis and cirrhosis. Serum HBV DNA levels do not correlate with the severity of histological lesions in all patients. Evaluation by liver biopsy remains gold standard for taking decision of treatment.     

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study

BACKGROUNDAntiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy.AIMThe study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients.METHODSIn this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis.RESULTSUnivariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC.CONCLUSIONAge ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.     

Hepatocellular Carcinoma in Hepatitis D: Does it Differ from Hepatitis B Monoinfection?

Background/Aim:

Hepatitis D virus (HDV) superinfection in patients with chronic hepatitis B leads to accelerated liver injury, early cirrhosis, and decompensation. It may be speculated that hepatocellular carcinoma (HCC) may differ in these patients from hepatitis B virus (HBV) monoinfection. The aim of this study was to compare clinical aspects of hepatocellular carcinoma in patients of hepatitis D with HBV monoinfection.

Patients and Methods:

A total of 92 consecutive HCC cases seropositive for antibody against HDV antigen (HDV group) were compared with 92 HBsAg-positive and anti-HDV-negative cases (HBV group).

Results:

The features including sex, body mass index, presence of ascites, serum biochemistry, gross tumor appearance, child class, barcelona cancer liver clinic and okuda stages were not significantly different between the 2 groups. Decreased liver size was noticed more in cases of HDV compared with HBV group where the liver size was normal or increased (P=0.000). HDV patients had lower platelets (P=0.053) and larger varices on endoscopy (P=0.004). Multifocal tumors and elevated alpha-fetoprotein level >1000 IU/mL were more common in HBV group (P=0.040 and P= 0.061). TNM classification showed more stage III-IV disease in HBV group (P=0.000).

Conclusion:

Decreased liver size and indirect evidence of more severe portal hypertension and earlier TNM stage compared with HBV monoinfection indicate that HDV infection causes HCC in a different way, possibly indirectly by inducing inflammation and cirrhosis.     

Seroprevalence of HCV and its co-infection with HBV and HIV among liver disease patients of South Tamil Nadu

AIM: To determine the seroprevalence of hepatitis C virus (HCV) and its co-infection with hepatitis B virus (HBV), hepatitis delta agent (HDV) and human immunodeficiency virus (HIV) among liver disease patients of south Tamil Nadu.METHODS: A total of 1012 samples comprising 512 clinically diagnosed cases of liver disease patients and 500 apparently healthy age and sex matched individuals were screened for Hepatitis C virus (anti HCV and HCV RNA), Hepatitis B virus (HBsAg), Hepatitis delta agent (anti HDV) and Human immuno virus (antibodies to HIV-1 and HIV-2) using commercially available enzyme linked immunosorbent assay kits. HCV RNA was detected by RT-PCR. Liver function tests like ALT, AST, GGT, ALP, bilirubin and albumin were also studied.RESULTS: The seroprevalence of HCV was found to be 5.6% among liver disease patients by ELISA. 27/512, 49/512 and 12/512 patients were positive for HIV, HBV & HDV respectively. Co-infection of HCV & HBV was found in 8 patients, with 6 for HCV & HIV and 4 for HCV, HBV & HIV co-infections. Sex-wise analysis showed that HIV, HCV & HBV and HCV & HIV co-infection was high among females whereas for HBV it was high in males. The mean ALT and AST in HCV positive cases were 42.1 ± 8.3 and 49 ± 10.1. In people co-infected with HCV & HBV or HCV & HIV or HCV, HBV & HIV the mean ALT of 58.0 ± 03.16, 56.78 ± 4.401 and 64.37 ± 4.01 respectively.CONCLUSION: We strongly recommend routine test of the blood for HCV in addition to HBV and HIV. We also recommend individualized counseling to identify those at risk and testing for those who want it. Improved surveillance and periodic epidemiological studies will have to be undertaken to monitor and prevent these blood-borne viruses.     

Effectiveness of hepatitis B virus vaccination program in Egypt:Multicenter national project

AIM:To assess the effectiveness of hepatitis B virus(HBV) vaccination program among fully vaccinated children.METHODS:A national community based crosssectional study was carried out in 6 governorates representing Egypt. A total of 3600 children aged from 9 mo to 16 years who were fully vaccinated with HBV vaccine during infancy were recruited. Face to face interviews were carried out and sera were evaluated for hepatitis B surface antigen(HBsA g),anti-HBV core antibodies(total) and quantitative detection of hepatitis B surface antibody using enzyme linked immunoassays techniques. Samples positive to HBs Ag/anti-HBV core antibodies were subjected to quantitative HBV-DNA detection by real time polymerase chain reaction with 3.8 IU/L detection limit. RESULTS:Sero-protection was detected among 2059 children(57.2%) with geometric mean titers 75.4 ± 3.6 IU/L compared to 3.1 ± 2.1 IU/L among nonseroprotected children. Multivariate logistic analysis revealed that older age and female gender were the significant predicting variables for having non seroprotective level,with adjusted odds ratio 3.3,9.1and 14.2 among children aged 5 to 10,10 to 15 and ≥ 15 years respectively compared to those 5 years and 1.1 among girls compared to boys with P 0.01. HBs Ag was positive in 0.11% and breakthrough infection was 0.36% and 0.39% depending on positivity of anti-HBc and DNA detection respectively. The prevalence of HBV infection was significantly higher among children aged ≥ 7 years(0.59%) compared to 0.07% among younger children with odds ratio equal to 8.4(95%CI:1.1-64.2) and P 0.01.The prevalence was higher among girls(0.48%) than boys(0.29%) with P 0.05. C ON C LU S I ON :T he E gy pt ian c ompuls or y H B V vaccination program provides adequate protection. Occult HBV infection exists among apparently healthy vaccinated children. Adherence to infection control measures is mandatory.     

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ² and/or Fisher’s exact test.RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05).CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.     

Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients

AIM:To analysis the factors that predict the response to entecavir therapy in chronic hepatitis patients with hepatitis B virus (HBV) genotype C. METHODS:Fifty patients [hepatitis B e antigen (HBeAg)-negative:HBeAg-positive = 26:24] with HBV genotype C, who received nave entecavir therapy for 2 years, were analyzed. Patients who showed HBV DNA levels ≥ 3.0 log viral copies/mL after 2 years of entecavir therapy were designated as slow-responders, while those that showed 3.0 log copies/mL were termed rapid- responders. Quantitative hepatitis B surface antigen (HBsAg) levels (qHBsAg) were determined by the Architect HBsAg QT immunoassay. Hepatitis B core-related antigen was detected by enzyme immunoassay. Pre-C and Core promoter mutations were determined using by polymerase chain reaction (PCR). Drug-resistance mutations were detected by the PCR-Invader method. RESULTS:At year 2, HBV DNA levels in all patients in the HBeAg-negative group were 3.0 log copies/mL. In contrast, in the HBeAg-positive group, 41.7% were slow-responders, while 58.3% were rapid-responders. No entecavir-resistant mutants were detected in the slow-responders. When the pretreatment factors were compared between the slow-and rapid-responders; the median qHBsAg in the slow-responders was 4.57 log IU/mL, compared with 3.63 log IU/mL in the rapid-responders (P 0.01). When the pretreatment factors predictive of HBV DNA-negative status at year 2 in all 50 patients were analyzed, HBeAg-negative status, low HBV DNA levels, and low qHBsAg levels were significant (P 0.01). Multivariate analysis revealed that the low qHBsAg level was the most significant predictive factor (P = 0.03). CONCLUSION:Quantitation of HBsAg could be a useful indicator to predict response to entecavir therapy.     

Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014

AIM To assess the etiology of chronic liver diseases(CLD) from 1998 to 2014 at the outpatient clinic of Gastroenterology of the main hospital in Northwest of Italy among those dedicated to hepatology.METHODS A random sample of charts of patients referred to for increased liver enzymes between January 1998 and December 2006, and between January 2012 and December 2014 were reviewed. Etiology search included testing for hepatitis B virus(HBV), hepatitis C virus(HCV), autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hereditary hemocromatosis. A risky alcohol consumption was also considered. Nonalcoholic fatty liver disease(NAFLD) was diagnosed in patients with histological and/or ultrasound evidence of steatosis/steatohepatitis, and without other causes of CLD.RESULTS The number of patients included was 1163. Of them, 528(45%) had positivity for HCV and 85(7%) for HBV. Among the virus-free patients, 417(36%) had metabolic disorders whereas the remaining had history of alcohol abuse, less prevalent causes of CLD or concomitant conditions. In comparison to 1998-2000(41%), a reduction of HCV alone-related cases was detected during the periods 2001-2003(35%, OR = 0.75, 95%CI: 0.53-1.06), 2004-2006(33%, OR = 0.70, 95%CI: 0.50-0.97) and 2012-2014(31%, OR = 0.64, 95%CI: 0.46-0.91). On the contrary, in comparison to 1998-2000(31%), metabolic-alone disorders increased in the period 2004-2006(39%, OR = 1.37, 95%CI: 0.99-1.91) and 2012-2014(41%, OR = 1.53, 95%CI: 1.09-2.16). The other etiologies remained stable. The increase of incidence of metabolic-alone etiology during the period 2004-2006 and 2012-2014 tended to be higher in older patients(≥ 50 years) compared to younger(P = 0.058).CONCLUSION In the Northwest of Italy, during this study period, the prevalence of HCV infection decreased notably whereas that of NAFLD increased.     

Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome

AIM: To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC).METHODS: Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 ± 11.2 vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.     

Rates and impact of hepatitis on human immunodeficiency virus infection in a large African cohort

AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) population in Nigeria.METHODS:HBV and HCV as well as HIV infections are endemic in sub Saharan Africa.This was a retrospective cohort study of 19 408 adults who were recruited between June 2004 and December 2010 in the AIDS Prevention Initiative in Nigeria in Nigeria programme at Jos University Teaching Hospital.Serological assays,including HBV surface antigen(HBsAg) and hepatitis C antibody were used to categorise hepatitis status of the patients.HBsAg was determined using enzyme immunoassay(EIA)(Monolisa HBsAg Ultra3;Bio-Rad).HCV antibody was tested using third generation EIA(DIA.PRO Diagnostic,Bioprobes srl,Milan,Italy).HIV RNA levels were measured using Roche COBAS Amplicor HIV-1 monitor test version 1.5(Roche Diagnostics,GmbH,Mannheim,Germany) with a detection limit of 400 copies/mL.Flow cytometry was used to determine CD4+ cell count(Partec,GmbH Munster,Germany).Comparison of categorical and continuous variables were achieved using Pearson’s χ 2 and Kruskal Wallis tests respectively,on MedCalc for Windows,version 9.5.0.0(MedCalc Software,Mariakerke,Belgium).RESULTS:With an overall hepatitis screening rate of over 90% for each virus;HBV,HCV and HBV/HCV were detected in 3162(17.8%),1983(11.3%) and 453(2.5%) HIV infected adults respectively.The rate of liver disease was low,but highest among HIV monoinfected patients(29,0.11%),followed by HBV coinfected patients(15,0.08%).Patients with HBV coinfection and triple infection had higher log 10 HIV RNA loads(HBV:4.6 copies/mL vs HIV only:4.5 copies/mL,P<0.0001) and more severe immune suppression(HBV:645,55.4%;HBV/HCV:97,56.7%) prior to initiation of HAART compared to HIV mono-infected patients(1852,48.6%)(P<0.0001).Of 3025 patients who were 4.4 years on HAART and whose CD4 cell counts results at baseline and end of follow up were available for     

Latent hepatitis B is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C

AIM:To study the potential association between hepatocellular carcinoma(HCC)in patients with chronic hepatitis C(CHC),cirrhosis and latent hepatitis B(LHB)infection,defined as the absence of detectable serum hepatitis B surface antigen(HBsAg)and the presence of hepatitis B core antibody(HBcAb).METHODS:This retrospective analysis is comprised of 185 cirrhotic patients with HCC who were hepatitis C virus antibody(HCV Ab)(+)and HBsAg(-)at Wayne State University between 1999 and 2008.From these,108 patients had HCV polymerase chain reaction confirmation of viremia while the remaining(77)were considered to have CHC on the basis of a positive HCV Ab and the absence of any other cause of liver disease.Controls were drawn from our institutional database from the same time period and consisted of 356 HBsAg(-)age,race and gender matched patients with HCV RNA-confirmed CHC and without evidence of HCC.A subgroup of controls included 118matched patients with liver cirrhosis.χ2test and t test were used for data analysis.RESULTS:Seventy-seven percent of patients in all3 groups were African Americans.Patients with HCC had a significantly higher body mass index(P=0.03),a higher rate of co-infection with human immunodeficiency virus(HIV)(P=0.05)and a higher prevalence of alcohol abuse(P=0.03)than the controls.More patients with HCC had LHB than controls(78%vs39%,P=0.01).Sixty three percent of patients with HCC were both hepatitis B surface antigen(HBsAb)(-)and HBcAb(+)compared to 23%of controls(P<0.01).When compared to cirrhotic controls,the frequency of HBcAb(+)remained higher in patients with HCC(78%vs 45%,P=0.02).Patients with HCC were more likely to be both HBsAb(-)and HBcAb(+)than the cirrhotic controls(63%vs 28%,P=0.01).Although not statistically significant,100%of CHC and HIV coinfected patients with HCC(n=11)were HBcAb(+)when compared to controls(44%;n=9).CONCLUSION:These data suggest that LHB occurs at a significantly increased frequency in patients with CHC and HCC than in patients with CHC without HCC.     

Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis

AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub Med, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ2 and I2 tests were used to evaluate heterogeneity between studies. Pooled hazard ratios(HRs) with 95% confidence intervals(CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied.RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and diseasefree survival, and the pooled HRs were significant at 0.76(95%CI: 0.70-0.83) and 0.78(95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group(HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio(OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase(AST) and alpha-fetoprotein(AFP)(OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9(CA19-9)(OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis(OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation(OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis(OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies.CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.     

Risk factors of hepatitis B virus infection in Turkey: A population-based, case-control study: Risk Factors for HBV Infection

Background

Although the World Health Organization (WHO) classifies Turkey as a country with a moderate-high prevalence of hepatitis B virus (HBV) infection, there is little data on HBV transmission in this country.

Objectives

To identify risk factors for HBV infection, we performed a retrospective case-control study between January 2007 and December 2009.

Patients and Methods

Acute HBV patients and population controls were selected, and data from these groups were analyzed by logistic regression method.

Results

The study included 129 patients with acute HBV infection and 219 controls. Hemodialysis (OR:8.2, 95% CI: 4.17-16.61, p < 0.05), having an HBsAg (+) spouse (OR: 4.3, 95% CI:2.17-8.53, p < 0.05), living with an HBsAg (+) parent(s) (OR: 3.25, 95% CI:1.73-6.12, p < 0.05), and being male (OR: 1.34, 95% CI: 0.82-2.21, p < 0.05) were independent risk factors that were potentially associated with HBV infection. More than one-third of female patients had a significantly higher risk (34.5% vs. 13.5%, p < 0.05) of acquiring HBV from their sexual partners. Hemodialysis was the most frequent risk factor (46.9% vs. 20%, x (2) = 10.45, p < 0.05) for patients aged over 31 years, and living with HBsAg (+) parents was a significantly higher risk factor (28.8% vs. 10.2%, x (2) = 6.15, p < 0.05) that is more likely to lead to HBVin patients aged under 30 years.

Conclusions

This study suggests that persons in Turkey who undergo hemodialysis are at high risk for acquiring HBV. Having an HBsAg (+) spouse (sexual transmission) or living with HBsAg (+) parents (household transmission) are significant risk factors for HBV transmission. Vaccination appears to be better preventive method against the spread of HBV.