Response to single dose hepatitis B vaccine in Congolese non-HIV hemodialysis patients: a prospective observational study

Introduction Because of the cost, in the hemodialysis centers of Kinshasa, the double dose of hepatitis B (HBV) vaccine is administered only to HIV infected patients while other patients receive a single dose. This study aimed to evaluate the single-dose vaccination Protocol and identify determinants of seroconversion's lack of anti-HBs after vaccination schedule. Methods 56 non-HIV chronic hemodialysis patients serologically negative for HBs Ag, anti-HBs and anti-HBc were selected between January 2014 and December 2016. The recombinant DNA vaccine (Euvax B®20 μg) was administered intramuscularly in the deltoid muscle at days 0, 30, 60 and 180. Serum anti-HBs titer was assayed at day 240. The endpoint was seroconversion, defined as anti-HBs titer ≥ 10 IU/l (10-99 IU/l = low protective vaccine response; ≥ 100 IU/l = highly protective vaccine response). Anti-HBs titer < 10 IU/l defined a lack of seroconversion. A Logistic regression model was used to identify factors associated with the lack of seroconversion. Results In the study group (mean age 55.6± 15.1 years; 73 % men, 36% diabetic and 86% hypertensive), low and highly protective vaccine responses were seen in 32% and 50% respectively versus 18% of patient had a lack of seroconversion. CRP > 6 mg/L (aOR: 8.96), hypoalbuminemia (aOR: 6.50) and KT/V < 1.2 (aOR: 3.70) were associated with the lack of seroconversion. Conclusion Half of the patients in the study had either a lack or low protective vaccine response. Patient-related factors and hemodialysis parameters were the main factors associated with the lack of anti-HbS seroconversion. These results highlight the need to maximize doses of vaccine in all patients.


Introduction
Hepatitis B virus (HBV) is relatively stable in the environment and remains viable for at least one week on environmental surfaces at room temperature; its transmission happens through per cutaneous or mucosal exposition to infected blood or body fluids [1]. It is the most causes of cirrhosis and hepatocellular carcinoma in the world [2]. The prevalence of this infection varies worldwide. Higher prevalence is encountered in low-income countries, including those of sub-Saharan Africa (SSA) where HBV infection is hyperendemic.
Indeed, in the general population, more than 8% of people are hepatitis B surface antigen (HBs Ag) chronic carriers [3]. Five HBV genotypes are more frequently detected in Africa, A, B, C, D and E genotypes [4]. Patients on chronic hemodialysis are considered as a high risk group for hepatitis B infection because of many therapeutic procedures routinely used in this group increase probability of HBV infection [5]. In this regard, HBs Ag has been detected in dialysis centers on clamps, scissors, dialysis machine control knobs, and door knobs [6]. Thus, blood-contaminated surfaces that are not routinely cleaned and disinfected represent a reservoir for HBV transmission.
In addition, dialysis staff members can transmit HBV to patients from contaminated surfaces by hands, gloves or through use of contaminated equipment and supplies [6]. Thus, controlling the spread of HBV infection in dialysis centers has been one of the major advances in the treatment of patients with end stage renal disease (ESRD). Nowadays, especially in developed countries, the prevalence of HBs Ag carriers on chronic dialysis has decreased significantly through preventive measures, such as routine vaccination of patients and health care workers, regular use of erythropoietin as a substitute for blood transfusions, early serological diagnosis, isolation of infected patients, and cleaning and disinfecting procedures [7]. Many protocols recommend routine HBV vaccination prior to dialysis with four doses of 40 μg each administered intramuscularly in the deltoid muscle within 0, 1, 2, and 6 months of the procedure [7][8][9]. However several worldwide studies have shown that one-third of chronic hemodialysis patients do not respond adequately to immunization [7,10,11]. The decline in immunity observed in chronic hemodialysis patients plays an important role in explaining this nonresponse [12]. Few studies have examined the efficacy of HBV vaccination in SSA chronic hemodialysis patients [13,14].

Methods
We conducted a prospective study including all consent patients who   Table 2).  Table 3).

Discussion
Our finding of a low HBV vaccine response is consistent with previous reports on HBV vaccine among chronic HD patients relative to the general population. Indeed, while HBV vaccination induces seroprotection in 90 to 95% of cases in the general population, immunogenicity is lower in patients with renal failure [7,10,11]. This weak induced immunogenicity is thought to rely upon an altered humoral and cellular immunity with subsequent decrease in the activity of immune system cells (B and T lymphocytes, monocytes, macrophages) [12,13]. This decreased cellular activity results in reduced phagocytosis by polynuclear cells, production of interleukin-1 and interleukin-2 by macrophages and T4 lymphocytes, respectively, and production of antibodies by B lymphocytes [13].
Potential factors explaining this altered immune system activity include, among others, decreased uremic toxin clearance, nutritional deficiency and, also, immunosuppressive drugs used to treat some glomerular diseases [13,14]. This immune dysfunction is responsible for the decline in the vaccine seroconversion rate as well as a more rapid decrease in antibody levels compared to healthy subjects [7,10,11].  [25].
Hypoalbuminemia showed a negative impact on the vaccine response to HBV. Malnutrition, with subsequent hypoalbuminemia, has a negative influence on the vaccine response. This condition is common in hemodialysis patients and can be explained by loss of appetite due to uremic waste products and toxins, intermediate metabolic abnormality and increased catabolism due to hyperparathyroidism and acidosis, loss of amino acids and glucose in dialysate and chronic inflammation [27]. KT/V <1.2 was significantly associated with lack of response. Many studies have shown association between vaccine response to HBV and the quality of dialysis expressed by KT/V [28].
In our study, age did not influence seroconversion, perhaps because of the small sample. Previous reports from the literature found a declining vaccine response with increasing age [29]. The mechanisms underlying the bad vaccine response with aging could be immunosenesis, various anatomical and physiological changes related to aging but also malnutrition and comorbidities; these abnormalities limit the capacity of host vaccine response [29].