Fang XH, Xie M, Rao W. Helicobacter pylori in solid organ transplantation: Challenges and treatment strategies. World J Gastroenterol 2026; 32(46): 122731 [DOI: 10.3748/wjg.122731]
Corresponding Author of This Article
Wei Rao, Organ Transplantation Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao 266100, Shandong Province, China. qdfy_raowei@qdu.edu.cn
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Transplantation
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Fang XH, Xie M, Rao W. Helicobacter pylori in solid organ transplantation: Challenges and treatment strategies. World J Gastroenterol 2026; 32(46): 122731 [DOI: 10.3748/wjg.122731]
Author contributions: Fang XH contributed to writing - original draft; Xie M and Rao W contributed to guidance.
AI contribution statement: This article did not utilize AI tools.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Wei Rao, Organ Transplantation Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao 266100, Shandong Province, China. qdfy_raowei@qdu.edu.cn
Received: May 6, 2026 Revised: July 30, 2026 Accepted: October 8, 2026 Published online: December 14, 2026 Processing time: 167 Days and 19.7 Hours
Abstract
It has been reported that the incidence of de novo gastric cancer is significantly increased in solid organ transplantation (SOT) recipients. At least 90% of non-cardia gastric cancers are related to Helicobacter pylori (H. pylori) infection. This article aims to assess the prevalence and sequelae of H. pylori infection in SOT recipients, and to evaluate the efficacy of eradication therapy. A systematic search of the literature was conducted to elucidate the prevalence and impact of H. pylori in SOT recipients and to summarize the outcome of eradication regimens. This study demonstrated an estimated prevalence of H. pylori in SOT recipients of 33%, but the research showed significant heterogeneity, which may be related to the detection methods used. Overall, the prevalence of H. pylori infection in SOT recipients is generally lower than that observed in the general population. Studies indicate that H. pylori infection plays a significant role in the development of gastrointestinal complications, particularly among SOT recipients. However, other studies have found no evidence that H. pylori infection increases the risk of postoperative gastrointestinal complications. Although H. pylori infection is less common in SOT recipients than in the general population, eradication therapy is still advised on diagnosis.
Core Tip: Helicobacter pylori (H. pylori) prevalence among solid organ transplant recipients has decline substantially over the past several years, with contemporary estimates approximating 33%. Notably, pooled analysis suggests a reduced risk of H. pylori infection in transplant recipients compared with non-transplant populations, likely attributable to frequent perioperative antibiotic prophylaxis and routine proton-pump inhibitor use rather than altered susceptibility from immunosuppression. However, given the adverse consequence of H. pylori infection, periodic H. pylori screening and timely eradication with dose-adjusted immunosuppression represent a rational long-term surveillance strategy.
Citation: Fang XH, Xie M, Rao W. Helicobacter pylori in solid organ transplantation: Challenges and treatment strategies. World J Gastroenterol 2026; 32(46): 122731
Although the continuous refinement of solid organ transplantation (SOT) techniques and perioperative management has led to substantial improvements in early post-transplant outcomes, long-term immunosuppression is still required to prevent graft rejection. Long-term prognosis of SOT recipients remains challenged by mid- to long-term complications, including infection, disease recurrence, and metabolic syndromes[1,2]. This article aims to assess the prevalence and sequelae of Helicobacter pylori (H. pylori) infection in SOT recipients, and to evaluate the efficacy of eradication therapy.
H. pylori is a microaerophilic Gram-negative rod-shaped bacterium and one of the most common chronic infectious pathogens in humans, affecting approximately 50% of the global population[3]. H. pylori colonizes the gastric mucosa of humans, triggering complex inflammatory responses and chronic gastritis, most of which are asymptomatic. Furthermore, H. pylori infection induces a range of upper gastrointestinal diseases such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphatic tissue (MALT) lymphoma, and gastric adenocarcinoma[4].
The structure of H. pylori itself is closely related to its pathogenicity. H. pylori can produce urease, enabling it to survive in the low pH environment of gastric acid. H. pylori can use its flagella to penetrate the gastric mucosal layer, thereby adhering to host cell receptors and ultimately colonizing the gastric mucosa[5,6]. Subsequently, H. pylori disrupts host cell signaling through virulence factors such as cytotoxin-associated gene A and vacuolar cytotoxin A, inducing and sustaining chronic inflammation in the gastric mucosa to achieve immune evasion[7,8].
LITERATURE REVIEW
The prevalence of H. pylori infection among SOT recipients was determined by a systematic meta-analysis of published literature. A literature search was conducted using the National Library of Medicine database (pubmed.ncbi.nlm.nih.gov) to gather potentially related articles from January 1991 to April 2026. Articles were searched using the following key words: Helicobacter pylori, solid organ transplantation, liver transplantation, kidney transplantation, lung transplantation, heart transplantation, prevalence, gastrointestinal complications, eradication, and a combination of these words.
We included studies for analysis when they met the following criteria: (1) Observational studies evaluating the prevalence of H. pylori in SOT recipients or the association between H. pylori and SOT published as original studies or conference abstracts; (2) H. pylori infection was determined by the 13C or 14C urea breath test (UBT), enzyme-linked immunosorbent assay, biopsy, or H. pylori stool antigen test; and (3) Prevalence, odds ratio, relative risk (RR), or hazard ratio with 95% confidence intervals (CIs) were provided. The following studies were excluded: (1) Articles not relevant to H. pylori or SOT; (2) Meta-analysis or review; (3) Letter, editorial, comment or reply to questions; (4) Non-English language articles; (5) Articles with insufficient postoperative data; (6) Articles with insufficient methodological or contextual detail; and (7) Zoopery. The validated Newcastle-Ottawa quality assessment scale was used for cohort and case-control studies and the modified Newcastle-Ottawa scale for cross-sectional studies, respectively[9].
PREVALENCE OF H. PYLORI INFECTION IN SOT RECIPIENTS
Following the literature search, 177 potentially eligible articles were identified. By examining the titles and abstracts, 50 potentially relevant articles were identified. After reading the full text, 31 studies were finally included for analysis (Figure 1). The characteristics and quality assessment of the included studies are presented in Table 1. In these studies, the H. pylori infection rate in liver transplant recipients ranged from approximately 5.6% to 85.0%; kidney transplant recipients had an infection rate of 3.1% to 70.9%; while studies on H. pylori infection in heart-lung transplant recipients are relatively scarce. As shown in Table 1, H. pylori infection rates among SOT recipients vary considerably (from 3.1% to 85.0%), which may be attributed to differences in sample size, postoperative follow-up duration, and H. pylori detection methods across studies[10,11].
Following a rigorous quality assessment of the included studies, four low-quality studies and one randomized controlled trial were excluded; thus, 26 studies were included in the analysis to assess the prevalence of H. pylori among SOT recipients. The prevalence of H. pylori among SOT recipients was found to be 33.0% (95%CI: 27%-39%; I2 = 95.5%). Of the 26 included studies, nine compared the H. pylori infection prevalence between SOT recipients and the general population. The pooled RR of H. pylori in SOT recipients was 0.50 (95%CI: 33%-76%; I2 = 77.1%) when compared with non-transplant patients.
With regard to detection methods, 13 studies used endoscopy and histology, three studies used the 13C-UBT and 10 studies used the serological antibody tests. Meta-regression results indicated that the detection method is the main source of inter-study heterogeneity (P = 0.009). Subgroup analyses of the detection methods showed that the infection rates were 33.0% (95%CI: 22.9%-44.0%) using endoscopy and histology, 24.1% (95%CI: 2.6%-56.8%) with the UBT, and 34.3% (95%CI: 28.2%-40.6%) with serological antibody tests.
Studies have shown that SOT recipients undergoing immunosuppressive therapy may experience a higher rate of H. pylori infection compared to the general population, as the suppression of immune responses can increase susceptibility to various infections. However, several studies have indicated that the incidence of H. pylori infection following organ transplantation is relatively low. Rao et al[12] conducted a study involving 102 adult liver transplant recipients and 306 healthy individuals undergoing routine physical examinations, and found that the H. pylori infection rate among liver transplant recipients within 33 months post-transplantation was significantly lower than that in the general population (11.8% vs 32.0%). In another prospective comparative study by Xie et al[10] involving 153 liver transplant recipients and 459 healthy controls, the post-transplant H. pylori infection rate over 31.9 months was significantly lower than that in controls (19.6% vs 43.6%). The infection rate was found to increase with time since transplantation: 10.6% at < 1 year, 17.5% at 1-3 years, and 30.6% at ≥ 3 years, demonstrating a significant upward trend (P = 0.04). A single-center study involving 109 kidney transplant recipients who had survived beyond one year post-surgery, and 161 healthy control subjects, revealed that the prevalence of H. pylori infection among the kidney transplant recipients was significantly lower compared to the control group, with rates of 43.04% vs 68.9%, respectively[13]. Telkes et al[14] performed endoscopic examinations in 543 individuals who had undergone kidney transplants. After removing 62 participants with undetermined H. pylori infection status, it was found that the H. pylori infection rate within 3.4 years post-surgery was approximately 20.9% (101/481), which was lower compared with the general population and uremic patients (20.96%-21.05%, P < 0.0001). According to a random-effects meta-analysis by Cheungpasitporn et al[15], which included 11 studies, the pooled prevalence of H. pylori infection in kidney transplant recipients was approximately 35.0% (95%CI: 26%-45%). Conversely, the analysis demonstrated a significantly lower risk of infection in this population compared to non-transplant patients, with a risk ratio of 0.57.
However, certain clinical studies have reported divergent findings. An early study by Hruby et al[16] investigated H. pylori infection rates among 29 kidney transplant recipients, 25 patients with chronic kidney disease on dialysis, and 16 healthy controls. The findings revealed a significantly higher H. pylori infection rate in kidney transplant recipients assessed at a mean post-transplant interval of 40.5 ± 34.5 months (range: 4-127 months), compared to both healthy controls and dialysis-dependent patients (62% vs 43.6% vs 34.6%, respectively). A Japanese study examined endoscopic findings from 29 liver transplant recipients both before and after transplantation. The H. pylori infection rate was approximately 50% two weeks prior to surgery, decreasing to 5.6% at eight weeks post-transplantation[17]. Furthermore, consistent with earlier studies, spontaneous seroreversion of H. pylori in some recipients during long-term follow-up may be attributed to a low preoperative bacterial load coupled with the prolonged use of antibacterial agents post-transplantation[18,19].
The present study included relevant research on H. pylori infection in pediatric SOT recipients. After excluding this study, a meta-analysis of the remaining 25 studies revealed that the infection rate of H. pylori in adult SOT recipients was 35.0% (95%CI: 29%-41%; I2 = 94.7%). From this, it can be seen that the infection rate of H. pylori in adult SOT recipients seems to be higher than that in pediatric SOT recipients (35.0% vs 3.1%). A meta-analysis of the general population in foreign countries also indicated that there are age differences in the infection rate of H. pylori, with the adult infection rate higher than that of children (62% vs 42%)[20]. This may be related to the longer duration of H. pylori infection in adults. Although studies have shown that the incidence of complications such as gastric/duodenal ulcers or erosions in children with H. pylori infection is much lower compared to adults with H. pylori infection, some research has found that the H. pylori infection rate among pediatric kidney transplant candidates is relatively high (24%), and is associated with chronic active gastritis[21]. The H. pylori infection process in SOT recipients is more complex, but currently there are relatively few studies on H. pylori infection in pediatric SOT recipients. H. pylori infection in pediatric SOT recipients deserves attention, and large-scale studies on the infection rate and complications in pediatric SOT recipients should be conducted in the future.
In summary, H. pylori infection rates in SOT recipients are highly variable and generally lower than those in the general population. This suppression may result from prolonged use of antibiotics and acid-suppressive drugs perioperatively, which can partially eradicate H. pylori. However, as patient survival time increases, long-term immunosuppression and daily exposures may paradoxically increase susceptibility to new or recurrent H. pylori infection over time[12,19].
Currently, H. pylori infection can be detected via a range of methods, including non-invasive options such as serological (blood, saliva, urine) antibody tests, UBT, and the stool antigen test, as well as invasive techniques that require endoscopic biopsy for histopathology, rapid urease test, bacterial culture, or polymerase chain reaction (PCR). Among these, studies indicate that histopathological examination yields superior sensitivity compared to UBT and PCR[22-24]. The observed heterogeneity in H. pylori infection rates among SOT recipients may also be influenced by the diagnostic methods employed. A study by Fujiwara et al[11] illustrated this issue, wherein kidney transplant recipients underwent endoscopic examination, rapid urease testing, and serum antibody detection. Notably, they found that patients with positive histopathological results exhibited lower titers of specific H. pylori antibodies, suggesting that serological assays may underestimate the true infection prevalence in this population. Our meta-analysis further revealed that methodological differences across studies constitute the primary source of heterogeneity in reported H. pylori infection prevalence estimates. Recent studies demonstrate that novel molecular techniques, such as quantitative PCR, real-time PCR, and droplet digital PCR, have been successfully applied in various medical contexts, including viral detection in kidney transplant patients and the diagnosis of H. pylori infections, and applied to gastric mucosa, can not only diagnose H. pylori infection but also simultaneously detect bacterial antibiotic resistance[25,26].
H. PYLORI AND GASTROINTESTINAL COMPLICATIONS
Studies have reported notably high incidences of gastrointestinal complications among SOT recipients, with rates varying across different types of transplants. For instance, in pediatric lung transplant recipients, these complications can occur at any time post-surgery and are associated with increased morbidity and mortality. In liver transplant recipients, the incidence of gastrointestinal complications ranges from 2% to 45%, with certain complications such as upper gastrointestinal bleeding having a clinical incidence rate of 3% to 50%. Studies indicate that around 20% of kidney transplant recipients experience gastrointestinal complications, with specific examples including esophagitis, gastrointestinal bleeding, and perforation, as detailed in the literature. In liver transplant recipients, the incidence of de novo gastric cancer post-transplantation can reach up to 3.8%, as evidenced by a study of 157 liver transplant recipients, which found that six out of 157 patients developed gastric cancer. Furthermore, 84% of lung transplant recipients experience at least one gastrointestinal complication following transplantation[27-29]. Kondo et al[30] reported a significantly higher incidence of gastric and duodenal ulcers in kidney transplant recipients compared to patients with end-stage renal disease (6.5% vs 2.1%, P = 0.026). A study summarizing 30 years of SOT cases demonstrated that the incidence of colorectal cancer among SOT recipients was 2.6-fold higher than that in the general population at 10 years post-transplantation[31]. A comparative analysis revealed that the incidence of gastric cancer was significantly elevated among 509 kidney transplant recipients relative to 10080 controls from the general population (2.9% vs 0.1%, P < 0.001)[32].
Postoperative gastrointestinal complications in SOT recipients not only have an increased incidence but also differ from those in the general population. For instance, de novo gastrointestinal tumors following transplantation tend to exhibit a more aggressive phenotype, consequently leading to less favorable outcomes. A markedly reduced five-year survival rate has been reported for de novo colorectal cancer in kidney transplant recipients (27%) compared with that in the general population (57%)[33]. It is projected that within the next two decades, the incidence of de novo malignancies, including those originating from the transplanted organ itself, is expected to rise significantly, potentially surpassing cardiovascular complications as the leading cause of mortality among SOT recipients[34-36].
H. pylori infection significantly contributes to the development of new-onset upper gastrointestinal disorders in SOT recipients. H. pylori infection is associated with mucosal inflammation and the promotion of gastric mucosal cell over-proliferation, as evidenced by increased expression of proliferating cell nuclear antigen and epidermal growth factor receptor in infected individuals. This can lead to chronic inflammation, DNA damage, progressive mucosal injury, and intestinal metaplasia, thereby compromising the defensive capacity of the gastric mucosa. Furthermore, H. pylori infection is associated with increased secretion of gastrin and gastric acid, which contributes to the development of chronic atrophic gastritis, gastric ulcers, duodenal ulcers, gastric cancer, and MALT lymphoma[4].
An early study investigating de novo peptic ulcers following liver transplantation analyzed the endoscopic findings of 40 liver transplant recipients. The postoperative H. pylori infection rate was 62.5% (25/40). Six patients developed de novo duodenal ulcers postoperatively, and all cases were associated with H. pylori infection (P < 0.01)[37]. A higher incidence of peptic ulcers has been observed in H. pylori-positive kidney transplant recipients compared to those without the infection[11,38,39]. Kakizoe et al[40] conducted endoscopic examinations in 117 liver transplant recipients, among whom the postoperative incidence of gastroduodenal ulcers was 8.5% (10/117). The prevalence of H. pylori-related gastritis was significantly higher in patients with ulcers (40%) than in those without ulcers (10%) (P = 0.024). A case series reported four instances of gastric MALT lymphoma following liver transplantation. The study demonstrated that all four patients were infected with H. pylori, and eradication therapy led to clinical improvement in three of these patients[41].
Contrary to the aforementioned results, a study by Telkes et al[14], which examined endoscopic data from 543 kidney transplant recipients, found that the incidence of postoperative peptic ulcers ranged from 5% to 20%, aligning with broader findings in the field. Notably, they demonstrated no significant link between the ulcers and H. pylori infection (26% infection rate in ulcer patients; P = 0.28). In a cohort study of 2968 liver transplant recipients monitored for a median of 56.0 ± 30.7 months, the incidence of de novo gastric cancer was found to be 0.64% (19/2968), aligning with findings from other studies that reported similar rates of new-onset gastric cancer in this patient population. Of these 19 cases, only one had confirmed H. pylori infection[42]. Therefore, for SOT recipients with detected H. pylori infection, eradication therapy should be offered irrespective of symptoms or complications. This is because eradication at any stage can mitigate the inflammatory cascade that drives the progression from atrophy to intestinal metaplasia and dysplasia, thereby playing a beneficial role in reducing gastric cancer risk[43]. The risk factors for H. pylori infection in SOT recipients are complex and diverse. However, H. pylori infection has a negative impact on the quality of life of SOT recipients. Therefore, once H. pylori infection is detected in SOT recipients, eradication treatment is still recommended (Figure 2).
Figure 2 Risk factors for Helicobacter pylori infection and its pathogenic mechanisms in solid organ transplant recipients.
SOT: Solid organ transplant.
H. PYLORI ERADICATION FOR SOT RECIPIENTS
H. pylori infection in SOT recipients is associated with upper gastrointestinal diseases and adversely affects their quality of life. An increased incidence of de novo gastric cancer after SOT has been reported to be as high as 1.06% to 12.9%, seriously impacting patient survival rates[42]. Amal Mohammed et al[44] confirmed that H. pylori are capable of extra-gastric colonization in liver transplant recipients, which is linked to dysplastic changes in graft tissue and hepatocellular carcinoma. These researchers therefore advocate for early eradication to prevent the detrimental effects of this extra-gastric infection. Xie et al[10] conducted a prospective study involving 153 liver transplant recipients, in which H. pylori infection was assessed using the 13C-UBT, a non-invasive and reliable diagnostic method for detecting H. pylori infection. The results showed an H. pylori infection prevalence of approximately 19.6% (30/153). In a study involving 30 patients with confirmed H. pylori infection, 23 were treated with a bismuth-containing quadruple regimen for 14 days. Post-treatment evaluation using the 13C-UBT revealed a high eradication rate of 91.3% (21/23), which is consistent with the success rates reported in recent clinical studies. For instance, one source indicated that the eradication rate for quadruple therapy can reach 85% to 95%, while another suggests that the success rate is approximately 90%. During the course of eradication therapy, immunosuppressant trough concentrations were monitored in 12 H. pylori-infected liver transplant recipients, 10 receiving tacrolimus and two receiving sirolimus. Within three days of initiating H. pylori treatment, immunosuppressant blood concentrations increased by 1.7- to 3.6-fold compared to baseline levels, prompting dose adjustments to maintain therapeutic safety and efficacy[10]. Hamura et al[45] reported a case of successful H. pylori eradication in a 54-year-old female liver transplant recipient. The patient had been maintained on tacrolimus for the first four months post-transplantation, after which the immunosuppressive regimen was switched to cyclosporine A. Three years after transplantation, H. pylori infection was diagnosed, and the patient received triple therapy consisting of amoxicillin, lansoprazole, and clarithromycin. Eradication of H. pylori was confirmed five weeks after initiation of treatment. During the course of antimicrobial therapy, a marked increase in cyclosporine A trough concentrations was observed, indicating a potential drug-drug interaction. An early study by Huwez et al[46] examined gastric and duodenal biopsy specimens from 47 heart transplant recipients collected within 44 months post-transplantation. The prevalence of H. pylori infection was found to be 49% (23/47). Eight patients who developed gastrointestinal symptoms underwent triple anti-H. pylori therapy; however, treatment failure occurred in six of these eight patients, as evidenced by either persistent or recurrent infection, indicating a low H. pylori eradication rate. However, this study was limited by a relatively small sample size, and prior research has not systematically monitored blood concentrations of immunosuppressants. These limitations raise the possibility that immunosuppressant therapy may influence the eradication therapy; therefore, it is advisable to monitor blood levels of immunosuppressants and adjust dosages accordingly.
Although there is no universal agreement on the necessity of anti-H. pylori therapy for candidates undergoing SOT, recent expert consensus and clinical studies suggest that H. pylori eradication may play a significant role in reducing the risk of gastric cancer, a concern for SOT recipients. Preoperative eradication of H. pylori in surgical patients is associated with a reduced incidence of postoperative gastrointestinal complications, as evidenced by studies indicating that such eradication can decrease the risk of gastric cancer and precancerous lesions. Among 61 kidney transplant candidates studied by Cocchiara et al[38], 32 (52.4%) were preoperatively infected with H. pylori. Of these, 17 patients comprised the eradication group, while 15 did not receive treatment. During a follow-up of at least one year with post-operative gastroscopy, the incidence of peptic ulcers was significantly higher in the non-eradication group compared to the eradication group (P < 0.05). Sarkio et al[47] collected preoperative data from 500 kidney transplant recipients and reported a preoperative H. pylori positivity rate of 31.0% (155/500). During postoperative follow-up, 92 patients underwent gastroscopy, among whom 35 were H. pylori-positive and 47 were H. pylori-negative. Studies have shown that the incidence of peptic ulcers is significantly higher in individuals infected with H. pylori compared to those without the infection, with rates of 6% vs 3%, respectively. During a 6-year follow-up period, two cases of gastric and duodenal tumors were identified in individuals with H. pylori infection, which aligns with the increased risk of gastric cancer associated with this infection. No such cases were observed in the H. pylori-negative group.
Despite the potential benefit of preoperative H. pylori eradication in reducing gastrointestinal complications among SOT recipients, logistical challenges associated with the transplant waiting list can limit its successful implementation. Maioli et al[48] conducted a prospective study involving 51 H. pylori-positive renal transplant candidates. Of the initial cohort, 33 received 14-day triple therapy (omeprazole, clarithromycin, amoxicillin), while 18 were lost to follow-up. A post-treatment assessment 8-12 weeks later revealed an eradication rate of only 48.5% (16/33). Hesitation in treating H. pylori infections is rooted in several key issues: First, transplant candidates often have long-standing end-stage chronic disease, and prolonged antimicrobial therapy during the transplant waiting period-combined with perioperative prophylactic antibiotics-may promote the development of antimicrobial resistance; second, hemodialysis or peritoneal dialysis can significantly reduce serum drug concentrations, compromising therapeutic efficacy and increasing the risk of treatment failure; third, post-transplant H. pylori infection rates are consistently low, with documented cases of spontaneous clearance, leading some clinicians to question the clinical necessity of routine preoperative eradication[10].
Internationally recommended bismuth quadruple therapy [proton pump inhibitor (PPI), bismuth, and two antibiotics] has shown high efficacy in SOT recipients, achieving H. pylori eradication rates of over 90% in relevant studies[10,43]. The efficacy of H. pylori eradication is diminishing worldwide, largely due to growing antibacterial resistance. Reported success rates have dropped from 95% to 80% globally and from 89% to 78% in China, with declining clarithromycin susceptibility being a key contributing factor[49,50]. Potassium-competitive acid blockers (P-CABs) represent a newer class of acid suppressants that provide stronger and more sustained acid inhibition compared to PPIs. This pharmacological profile contributes to their enhanced efficacy in improving H. pylori eradication rates[51]. Driven by increasing antibiotic resistance and the introduction of novel acid suppressants, modified regimens including high-dose dual therapy are now widely used. The efficacy of P-CABs in significantly enhancing treatment outcomes for acid-related diseases has been substantiated by a multitude of studies. Yang et al[52] compared a 14-day bismuth quadruple therapy with a modified high-dose dual therapy for H. pylori eradication. The results indicated that the dual therapy achieved similar eradication rates with a more favorable adverse effect profile, supporting its use as a first-line treatment. A Japanese study compared the efficacy of two vonoprazan-based regimens for H. pylori eradication: Dual therapy (vonoprazan 20 mg + amoxicillin 750 mg) or triple therapy (vonoprazan 20 mg + amoxicillin 750 mg + clarithromycin 200 mg, twice daily for 7 days). The overall eradication rates were 84.5% for the dual regimen and 89.2% for the triple regimen, with the triple regimen showing a higher eradication rate, although the difference was not statistically significant (P = 0.203). In the context of clarithromycin-resistant strains, the dual regimen demonstrated a significantly higher eradication rate compared to the triple regimen, with rates of 92.3% and 76.2%, respectively (P = 0.048), as highlighted in a systematic review and network meta-analysis. These findings indicate that in clarithromycin-resistant H. pylori infections, the vonoprazan-amoxicillin dual therapy may offer superior efficacy[53]. Peng et al[54] compared the efficacy of a bismuth quadruple therapy (esomeprazole 20 mg, bismuth potassium citrate 220 mg, amoxicillin 1 g, and clarithromycin 500 mg, twice daily for 14 days) with vonoprazan-amoxicillin dual therapy (vonoprazan 20 mg twice daily + amoxicillin 750 mg four times daily, for 14 days) for H. pylori eradication. The eradication rates were 81.0% for the quadruple regimen and 89.9% for the dual regimen, with the dual regimen showing a statistically significant improvement (P = 0.037). This is consistent with findings from large-scale studies, such as the one conducted by Peking University Cancer Hospital, which demonstrated that quadruple therapy significantly reduces the incidence of gastric cancer. The results demonstrated that the vonoprazan-amoxicillin dual therapy not only reduced antibiotic exposure but also achieved superior eradication efficacy compared to the quadruple therapy[54]. High-dose dual therapy has been incorporated into major national and international guidelines, with a recommendation as a first-line or rescue treatment option for H. pylori eradication[43].
Given that most SOT recipients are affected by chronic conditions and have a history of long-term antibiotic use, they often exhibit high rates of antibiotic resistance. Several studies have compared SOT-specific antibiograms to widely accepted hospital antibiograms; these studies have all found important differences in resistance rates among bacterial pathogens[55]. For instance, Escherichia coli isolates causing urinary tract infections in kidney transplant recipients exhibit significantly higher resistance rates to β-lactams and trimethoprim-sulfamethoxazole than those from non-transplant populations. Furthermore, the prevalence of resistance genes conferring resistance to β-lactams, trimethoprim, and aminoglycosides is markedly higher in these isolates[56]. However, there are currently few studies on H. pylori drug resistance in SOT recipients. Deng et al[57] conducted a study on a kidney transplant recipient who had previously used multiple antibiotics and immunosuppressants. Bacterial resistance gene detection revealed relevant resistance gene mutations for clarithromycin, levofloxacin, and metronidazole. Whole genome sequencing showed that the infecting strain was a highly virulent and pathogenic strain. Moreover, kidney transplant recipients frequently have preexisting end-stage renal disease or other severe chronic conditions prior to transplantation. Aydemir et al[58] assessed H. pylori susceptibility to amoxicillin and clarithromycin in patients with end-stage renal disease and reported a significantly higher clarithromycin resistance rate among these patients compared with the general population (36.4% vs 15.2%, P < 0.05). Maioli et al[48] conducted H. pylori eradication treatment (omeprazole 20 mg + amoxicillin 500 mg + clarithromycin 500 mg, for 14 days) in kidney transplant candidates. The H. pylori eradication rate was 48.5%. When analyzing the reasons for the low H. pylori eradication rate, the authors indicated that this might be related to the unknown resistance rate of patients to clarithromycin. Based on the results of these multiple studies, it is reasonable to assume that the improved dual therapy may also achieve good results in the eradication treatment of H. pylori in SOT recipients, especially in those who are resistant to clarithromycin. Moreover, considering that SOT recipients usually exhibit high antibiotic resistance, pre-treatment drug sensitivity tests for H. pylori before eradication treatment are worthy of attention, as this can not only guide selection of eradication therapy, but also play an important role in curbing bacterial resistance. As a result, it is reasonable to hypothesize that modified dual therapy may also achieve favorable outcomes in this population. Although the efficacy of such newer regimens has not been extensively studied in H. pylori-positive SOT recipients, their overall high eradication rates and low resistance risk in other populations support their potential applicability. Further clinical studies are warranted to evaluate the efficacy and safety of modified dual therapy specifically in SOT recipients. Nevertheless, considering its high eradication rate and low resistance risk, this regimen holds promise for future use in the prevention and management of H. pylori infection in SOT recipients.
Early studies indicated that colonization of H. pylori was not related to cyclosporine levels and the dosage of steroids taken by SOT recipients. However, almost all immunosuppressants increased the incidence of postoperative gastrointestinal complications. Eighty percent of gastrointestinal complications after kidney transplantation were related to the use of immunosuppressants[39,59]. The factors causing gastrointestinal complications due to immunosuppressants are diverse. Immunosuppressants inhibit the body’s immune defense function and disrupt the micro-environment of gastrointestinal tract flora. These factors may increase the number of various pathogens in the gastrointestinal tract, such as cytomegalovirus, Candida, and Clostridium difficile, leading to gastrointestinal complications such as colitis and gastric cancer[60,61]. A systematic review of articles related to changes in the human or animal gut microbiota induced by immunosuppressants revealed that 70% of the articles mention changes in the levels of anaerobic bacteria, including Streptococcaceae, Micromonosaccaceae, Firmicutes, Bacteroides, and Clostridia[62]. However, the effects of immunosuppressive drugs on the intestinal microbiota and H. pylori, as well as the association between the dosage of immunosuppressive drugs and changes in the intestinal microbiota and the colonization of H. pylori, have not been reported to date. Animal studies have shown that the dosage of immunosuppressants affects the stability of the intestinal microbiota after transplantation, and the optimal dosage of immunosuppressants can stabilize the intestinal microbiota after transplantation[63]. The aforementioned studies on the eradication of H. pylori in SOT recipients also revealed fluctuations in the blood concentration of immunosuppressants during the treatment period. Therefore, monitoring the blood concentration of immunosuppressants in SOT recipients and promptly adjusting the drug dosage can help improve the stability of the intestinal flora in SOT recipients and prevent the long-term colonization of H. pylori.
CONCLUSION
There is a large degree of heterogeneity in the prevalence of H. pylori in SOT recipients with an overall estimated prevalence of 33%, which is lower than that in the general population. Our meta-analysis further revealed that methodological differences across studies constitute the primary source of heterogeneity in reported H. pylori infection prevalence estimates. This may be attributed to the prolonged use of antibiotics and acid-suppressive therapies among SOT recipients. Nevertheless, a substantial body of evidence indicates that H. pylori infection is significantly associated with gastrointestinal complications in this patient population, leading to a marked impairment in quality of life. Current evidence, supported by various studies, indicates that H. pylori eradication therapy is not only safe and effective in SOT recipients but also plays a crucial role in reducing the incidence of postoperative gastrointestinal complications. For instance, the oral cavity’s role as a reservoir for H. pylori has been highlighted, suggesting that oral eradication may facilitate the successful eradication of gastric H. pylori and reduce the risk of recurring stomach infection. However, existing anti-H. pylori treatment regimens may interfere with the pharmacokinetics of immunosuppressive agents, potentially altering their blood concentrations. Therefore, close therapeutic drug monitoring of immunosuppressants is recommended during H. pylori eradication therapy, with dose adjustments made as necessary to maintain optimal immunosuppressive control. Considering the frequent exposure of SOT recipients to prolonged antibiotic therapy, it is imperative to carefully evaluate the impact of antimicrobial resistance when devising strategies for H. pylori eradication. Modified therapeutic regimens that achieve high eradication rates while minimizing the risk of the prevalence of H. pylori infection and its antibiotic resistance warrant further investigation and should be systematically evaluated in this patient population.
ACKNOWLEDGEMENTS
We thank all the staff working in the Hepatology, Liver Disease Center, Department of Organ Transplantation, Department of Gastroenterology, Department of Ultrasound, The Affiliated Hospital of Qingdao University.
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Footnotes
Peer review: Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific quality: Grade B
Novelty: Grade B
Creativity or innovation: Grade C
Scientific significance: Grade B
P-Reviewer: Li LB, Professor, China S-Editor: Wang JJ L-Editor: A P-Editor: Lei YY
