Significance of screening antibodies to hepatitis B core antigen among chronic hepatitis C patients before antiviral therapy

Results: Out of 178 chronic hepatitis C patients, Eighty four patients (47.2%) were treated with triple therapy (Sofosbuvir/ Daclatasvir/Ribavirin) and ninety four patients (52.8%) with dual therapy (Sofosbuvir/Daclatasvir). A65 patients (36.5%) were reactive for anti-HBc. Of 84 patients, 34 (40.5%) who treated with triple therapy were reactive for anti-HBc. Of 94 patients, 31 (33%) who treated with dual therapy were reactive for it. All patients were negative for anti-HBs and anti-HBc–positive patients were no detected HBV DNA at baseline and 12 weeks after DAAs.


INTRODUCTION
Hepatitis B virus (HBV) and Hepatitis C virus infection are leading causes of chronic liver disease worldwide, affecting 350-400million and 170 million people, respectively [1].HCV is currently the most significant public health problem in Egypt [2].The recently published Egyptian Demographic and Health Survey (EDHS) in 2015 estimated an overall antibody to hepatitis C virus (anti-HCV) prevalence of 6.3% [3].Antihepatitis B core (anti-HB C ) seropositivity in general population in Egypt is reported to be 10-13% [4].
HBV and HCV share common modes of transmission, thus simultaneous infection is quite frequent, particularly where both viruses are endemic as among people with a high risk for parenteral infections [5].HCV infection has a suppressive effect on the replication of HBV, shown by the loss of replicative markers as HBV-DNA [6].The extensive application of sensitive molecular tests such as polymerase chain reaction (PCR) and real-time PCR has enabled HBV-DNA to be detected in specimens from individuals without serological evidence of chronic HBV infection [7].
Occult HBV infection (OBI) can be defined by the presence of HBV-DNA in the serum of patients who are negative for HB S Ag [8].In the last decade, OBI pattern has been documented and frequently identified in patients with chronic hepatitis C (CHC) infection [9].The prevalence of OBI in chronic HCV patients was higher in subjects having either anti-HBs or anti-HB C or both [4].Sero- Treatment of chronic hepatitis C virus (HCV) infection has been revolutionized in the last few years by the introduction of highly effective and well-tolerated DAAs able to achieve high rates of sustained virological response(SVR) in many groups of patients [11].In past years, HBV reactivation occurring in HBV/HCV-co-infected patients treated with IFN-based therapy has been reported, probably as a consequence of an unbalanced HBV replication caused by treatmentrelated suppression of HCV, although a direct immune-modulatory effect of IFN might also be advocated for either on-or off-treatment HBV reactivation [12].
In contrast, DAAs have no effect on HBV replication, but such therapies may release HBV from HCV suppressive effects, resulting in HBV reactivation in CHC patients with a concomitant overt or occult HBV Infection, leading to acute hepatitis with the risk of liver failure both on-or off-treatment [13,14].Despite this, up to 2015 EASL and AASLD guidelines on HCV treatment did not provide specific indications for the management of OBI during or after HCV clearance by DAAs [11].
This study was performed to determine the prevalence of anti-HBc and frequencies of hepatitis B virus (HBV) DNA and antibodies to hepatitis B surface antigen (anti-HBs) among chronic hepatitis C patients before antiviral therapy.

RESULTS
A Total of 178 chronic hepatitis C patients initiated treatment with DAAs.Eighty four patients (47.2%) were treated with difficult treatment (SOF/DAC/RBV) and ninety four patients (52.8%) with easy treatment (SOF/ DAC).one hundred and seventy patients were treated for 12 weeks and eight treated for 24 weeks (Table 1).There were no significant differences between chronic hepatitis C patients with positive HBcAb vs. those with negative HBcAb regarding sex, age, history of smoking, Hemoglobin, and HCV RNA.However, positive HBcAb patients had significantly diabetes mellitus (Table 2).There was no significant correlation between liver enzymes and HBcAb seropositivity.However ALT and AST had reasonable sensitivity around 70% at cut off points 29.5 and 32.5 respectively the specificity dropped to25.4%and 40.4%, respectively (Figure 1).[15] reported that this seemed to be applicable to genotype 4, where HBV-DNA positive patients in their study showed higher baseline HCV viral load than HCV mono-infected patients.
Also, Chen et al. [19] reported that patients with both OBI and HCV infection had lower ALT Few studies however evaluated the impact of occult hepatitis B infection on the current standard treatment of HCV infection and viral replication of HBV.European Medicines Agency (EMA, 2016) reported all the cases of OBI patients should be interpreted with caution before establishing a clear correlation between effective DAAs treatment and HBV reactivation, due to the presence of at least one possible confounding factor.
In recent study, De Monte et al., reported HBV reactivation in an HIV/HCV co-infected male who discontinued TDF 14 months before starting DAAs due to bone toxicity [20].In this case the role of HIV infection and/or the immune reconstitution after effective HAART cannot be excluded as causes of the HBV reactivation, not to mention discontinuation of TDF that is effective on HBV.So, it is important to screen all CHC patients for HBV markers (HBsAg, anti-HBc and anti-HBs) before starting DAAs .OBI patients serum HBV DNA should be assessed with a very sensitive test at baseline and monitored during and after DAAs in those patients with positive baseline.Whereas no periodic monitoring of serum HBV DNA or HBsAg during and after DAAs treatment is recommended in patients with undetectable.
Baseline serum HBV DNA.In the latter patients periodic monitoring of ALT may be enough to detect hepatic flare reflecting HBV reactivation to treated with anti-HBV therapy.Current EASL guidelines even suggest starting concurrent HBV nucleoside/nucleotide analogue therapy if HbsAg is present or HBV-DNA is detectable in OBI [11].
However, further prospective studies in large cohorts of OBI patients better characterized from the virological point of view at baseline and during and after EOT are needed to quantify and stratify the risk of HBV reactivation in parallel with HCV eradication, and to standardize the management of such patients in order to avoid the risk of fatal complication.

CONCLUSION
In conclusion, occult hepatitis B Infection is highly prevalent in chronic hepatitis C infection and not depend on HBs Ag only in diagnosis for HBV infection.In future we need to check for HBsAg, anti HBc, and if positive screen for HBVDNA PCR in chronic hepatitis C infection treated with oral direct acting antiviral drug in initial visit, end of treatment and after 12 weeks of treatment for fear of reactivation of HBV infection.

Ethics:
The study confirmed to the 1975 Declaration of Helsinki and was approved by the Ethics Committee of Suez Canal University Faculty of Medicine in February 2016.Written, informed consent was obtained from each patient included in this study.
Also, there is a recent Asian study in 124 HCV infections with OBI patients treated with DAAs showing no cases of HBV reactivation [21].Yeh et al., observed a minimal impact of anti-HBc seropositivity on HCV efficacy and safety, while the risk of reactivation was present for CHC patients with current infection [22].Similarly, Belperio et al., and Sulkowski et al., affirmed the rarity of HBV reactivation after DAA, even in the setting of isolated anti-HBc [23,24].

Type of Study: Follow up descriptive study. Site of Study: Port
-Said center for treatment of viral hepatitis in Port-Said Fever Hospital.Assay of Anti-HB c : Antibody to Hepatitis B virus Core Antigen Elisa Kit was provided by Wkea med supplies corp.
5-In treatment experience patients type of IFN and date of last dose taking.6-History of schistosomal infection ,if present type of treatment taking.7-Clinical examination of patients which include: B-General examination: with special emphasis on vital signs and the presence of signs of chronic liver disease such as darking of the face, wasting of temporalis and maseter muscles and prominent zygomatic bone, bilateral parotid enlargement, jaundice, fetor hepaticus, palmar erythema, lower limb edema, flapping tremors and impaired level of consciousness.C-Local examination: withspecial emphasis on liver examination and detection of ascites.Fathallah et al., Afro-Egypt J Infect Endem Dis 2018; 8(4):202-208 https://aeji.journals.ekb.eg/http://mis.zu.edu.eg/ajied/home.aspxE-