This chapter has commented on the most important results according to the objectives achieved and with regard to certain data in the literature. Indeed, this study examined the socio-demographic characteristics, risk behaviors, therapeutic modalities, and predictors of success in eradicating Helicobacter pylori infection in patients followed in different hospital institutions in Kinshasa and subjected to sequential quadruple therapy and concomitant quadruple therapy.
Hp Infection and Sociodemographic Characteristics
Although some authors10, 26-27 support a small contribution of sex differences in the prevalence of Hp infection, there is still controversy as to the predominance of one or the other sex on this prevalence. Indeed, for some data in the literature, the prevalence of H. pylori is equal in both sexes, which is in agreement with the prevalence of Hp(+) observed in the 2009 Janulaityte-Gunther study  and by other authors27, 29. Other authors support a small influence in the prevalence of Hp infection in favor of male sex10,27. This is the case of the study conducted by Eisdorfer, where the influence of male sex was demonstrated in the results of the urea breath test (UBT), a test commonly used for the diagnosis of H. pylori infection30. Indeed, male sex is more associated with the risk factors for acquiring Hp infection (alcohol and active smoking) often seen in adult males31. However, male gender predominance was associated with a higher prevalence of H. pylori infection in both children and adults. This observation reinforces the contention that the factors that might explain these differences, or affect UBT values, are not fully understood32.
In the present study, despite the 1:1 sex ratio, there was an overrepresentation of males in the study population. This may be explained by the lifestyle of men (alcohol, smoking).
The mean age of patients with Hp infection (54.2 ± 15.1 years) in the present work reflects the preferred age of onset of symptoms of Hp infection. Indeed, the prevalence of infection in developing countries is greater than 80% in adults older than 50 years. Infected individuals usually acquire H. pylori before the age of 10 years and the infection peaks in adulthood, between 35 and 44 years of age32. It has also been shown that the seroprevalence of H. pylori increases with age, representing the combined effect of a decrease in the rate of exposure during childhood (associated with an improvement in the standard of living) and the acquisition of the infection with age33, with prevalence increasing at ages above 50 years. A study comparing the infection rates of children aged 1 to 19 years with those of adults aged 20 to 75 years found a lower prevalence in the former group (22% vs. 75%)34. Similarly, Mabeku et al. in a study conducted in Cameroon, showed that 62% of women over 68 years of age were infected with Hp32. Factors such as sexual intercourse, particularly fellatio, which is a very common sexual activity, can explain the high prevalence of Hp, especially in older age groups35-36. Although Hp is primarily a gastric organism, studies have reported that infected individuals may carry H. pylori permanently or transiently in their mouth and saliva.
The present study highlighted the harmful effect of excess alcohol with active smoking in the occurrence of Hp infection. Mehmet in a study that investigated the relationship between blood type, sex, age, smoking and Hp, found that there was a susceptibility of smokers to Hp compared to non-smokers33, 37. In previous studies, the authors have pointed out that smoking may be another factor in the sharp increase in H. pylori infection in persons 15 years and older . In addition, it is possible that alcohol consumption, which in some studies is related to HIV status, is an indirect measure of socioeconomic and cultural variables37. In contrast to the present study and others conducted around the world, Olga Sjomina et al.8 in a systemic review showed that there was no association between alcohols, coffee and other factors. Similarly, Wu et al., also found no association between alcohol intake and Hp infection8,38.
Treatment Modalities and Hp Infection
In general, and after several treatment regimens have been evaluated, few consistently achieve high eradication rates in first-line treatment. In addition, there are also limited data on Hp antibiotic resistance rates to guide first-line treat- ment. However, the treatment regimen chosen should take into account local patterns of antibiotic resistance (if known), prior exposure, allergies to specific antibiotics, cost, side effects, and ease of administration   . According to some recommendations, reasonable eradication targets would be ≥90% cure rate on per-protocol analysis and ≥80% cure rate on intention-to-treat analysis40,42. In the present study, successful eradication of Hp infection was more frequent in the 1-line concomitant therapy modality (91.2%; n = 31/34) than in the 1-line sequential therapy modality (56, 7%; n = 17/30). These results are in line with much data in the literature, especially for concurrent quadruple therapy43. However, the eradication rate in this study is much lower than the rates found in the West and in some SSA countries for four-line sequential therapy44-46. Although initially the 1-line sequential therapy achieved high eradication rates and was widely used in Italy44, its efficacy has decreased over time influenced by resistance to clarithromycin and metronidazole21,46. A systematic review and meta-analysis reported that rates of primary and secondary resistance to clarithromycin, metronidazole, and levofloxacin exceeded 15% (alarming levels) in all World Health Organization (WHO) regions21,47-49. As a result, in 2017, clarithromycin-resistant H. pylori were defined as a highpriority bacterium in the WHO priority list of antibiotic-resistant bacteria50. The modality of sequential treatment, which does not allow maximizing the synergy of the different antibiotics used, may explain this low eradication rate. However, Zullo et al.45 reported that sequential treatments of 10 and 14 days achieved treatment success (above 90% according to PP analysis) for first-line H. pylori eradication in clinical practice in Italy. In Korea, where antibiotic resistance rates are relatively high, the efficacy of 10-day sequential therapy was reported at 76.3% and 85.0% on an intention-to-treat (ITT) and perprotocol (PP) analysis, respectively. These results were described as unsatisfactory51. Concomitant therapy contains three antibiotics and a PPI; its eradication rate is not compromised by resistance to clarithromycin or metronidazole, unless there is dual resistance13. A prospective study in Greece showed that eradication rates of concomitant therapies were above 90% by PP analysis and well tolerated. However, 31.3% of treated patients had side effects52.
Predictors of Successful Eradication of Helicobacter Pylori
Infection Several factors influence the outcome of eradication therapy for Hp infection. A study in South Korea showed that resistance to clarithromycin alone or in combination with metronidazole resistance (dual resistance) significantly reduced the eradication success rate after sequential treatment. However, double resistance did not affect the eradication rate after concurrent treatment53. Other factors may also explain the propensity for low success with sequential therapy.
In particular, major adverse events were defined as predictors of eradication in the sequential group. Adherence to treatment had a significant influence on the efficacy outcome in the concurrent treatment group53. As described in some studies32, 54-55, excess alcohol with active smoking had a deleterious effect in the occurrence of Hp infection. Indeed, it has been reported in the literature that metronidazole produces a disulfiram-like reaction (vomiting, nausea, dizziness) when taken in combination with alcohol with the possibility of negatively influencing the success rate of sequential treatment, especially since the adverse effects are no longer observed in this type of therapeutic scheme. A meta-analysis showed that smoking increased the treatment failure rate for H. pylori eradication54,55. Similarly, a multivariate logistic regression analysis showed that smokers had a 2-fold higher probability of failure in Helicobacter pylori eradication than non smokers (OR: 2.0; 95% CI: 1.01 - 3.95)55. However, lifestyle factors, including smoking and alcohol consumption, did not worsen H. pylori eradication failure in the study by Suzuki et al.56. Several studies have investigated the impact of age on the success of eradication of Hp.57-60. In a Chinese study, age was found to be associated with H. pylori eradication. Indeed, the eradication rate was higher in patients ≥ 40 years of age than in patients < 40 years of age (85.7% vs. 54.7%, p = 0.002). In addition, the eradication rate was 100% in patients older than 60 years57. Japanese authors also found a relationship between eradication failure and being in the under-50 age group59-60. These results are in line with the present study which showed that advancing age was a predictor of successful eradication of H. pylori infection. This is thought to be related to the fact that the gastric mucosa of advanced age is more atrophic than that of younger patients and therefore secretes less acid than normal mucosa57-59. The ability of gastric acidity to decrease the effectiveness of antibiotics is, therefore, less important in older people than in younger subjects59.
Strengths and Limitations of the Study
The present study presented strengths balanced by some degree of limitations. The strength of this study lies in its originality. Indeed, it is the first study in Kinshasa to have investigated the eradication rate of sequential and concomitant quadritherapies in patients with Hp infection. However, the weaknesses of this study are inherent in its secondary and documentary nature, which is often characterized by biases in the completeness of information, as well as in its sample size, which did not allow certain conclusions to be drawn. Thus, an analytical study with a larger sample size would be needed to investigate other variables and to look for determinants and/or predictors of Hp eradication rates not analyzed in this study. It would be interesting to subject patients who have failed first-line therapy to second-line therapy and to evaluate its efficacy; as well as to study the efficacy of other therapeutic modalities such as hybrid triple therapy and hybrid reverse therapy which give eradication rates in ITT and PP of 97.5% and 100% respectively60.
The current results will have implications for routine practice, pharmacovigilance, capacity building, and public health perspectives related to Hp infection in DRC. In addition, they will serve as a database for future large-scale studies.