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Predictive factors of portal hypertensive enteropathy exacerbations based on long-term outcomes

BMC Gastroenterology volume 24, Article number: 287 (2024) Cite this article

Abstract

Background

Portal hypertensive enteropathy (PHE) is a small-bowel lesion observed in patients with portal hypertension. The clinical significance of endoscopic findings in PHE remains unclear. We aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings in patients with PHE based on long-term outcomes.

Methods

This retrospective study enrolled 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23–87) followed for > 3 years using capsule endoscopy (CE) between February 2009 and May 2023. We evaluated the clinical factors affecting PHE exacerbations and the effects of PHE exacerbations on gastrointestinal bleeding by comparing exacerbated and unchanged PHE groups.

Results

Overall, 3 (5%) patients showed improvement, 33 (60%) remained unchanged, and 19 (35%) showed exacerbation on follow-up CE. In the exacerbated group, the rates of worsened fibrosis-4 index, exacerbated esophageal varices, and exacerbated portal hypertensive gastropathy were significantly higher than those in the unchanged group (21%, 32%, and 42% vs. 3%, 6%, and 12%, respectively; P < 0.05), and the rate of splenectomy was significantly lower in the exacerbated group than in the unchanged group (5% vs. 39%, respectively; P < 0.01). In multivariate analysis, exacerbation of esophageal varices and absence of splenectomy were significantly associated with PHE exacerbation. The rate of gastrointestinal bleeding after follow-up CE was significantly high in the exacerbated group (log-rank, P = 0.037).

Conclusions

Exacerbation of esophageal varices and splenectomy were significantly associated with exacerbation of PHE. Exacerbated PHE requires specific attention to prevent gastrointestinal bleeding.

Peer Review reports

Background

Portal hypertension, a common complication of liver cirrhosis (LC), is defined as increased pressure in the portal circulation, as estimated by the measurement of the hepatic venous pressure gradient (HVPG) [1]. HVPG does not exceed 5 mmHg in the absence of significant liver disease, and complications of portal hypertension are known to develop when the HVPG exceeds 10 mmHg [2]. Portal hypertension causes various changes in the entire gastrointestinal tract. Esophageal varices (EVs), gastric varices (GVs), and portal hypertensive gastropathy (PHG) are well-known gastrointestinal lesions in patients with portal hypertension [3, 4]. Moreover, rectal varices and portal hypertensive colopathy (PHC) are known as lower gastrointestinal lesions in patients with portal hypertension [3, 5].

Capsule endoscopy (CE) was first developed in 2000 [6], and recent advances in endoscopic equipment have made various CE models available worldwide. CE can be performed by swallowing a capsule-type endoscope, has a high diagnostic ability comparable to device-assisted enteroscopy [7, 8], and has high safety profiles [9]. Thus, CE is positioned as the first-line modality of small-bowel endoscopy in guidelines in Japan [10], Europe [11], and the United States [12], owing to its low invasiveness and high diagnostic yield. The widespread use of CE in recent years has revealed the presence of small-bowel lesions in patients with portal hypertension [13]. Portal hypertensive enteropathy (PHE) is defined as mucosal inflammatory-like abnormalities (edema, erythema, granularity, brittle lesions) or vascular lesions (cherry red spots, telangiectasias, or angiodysplasia-like lesions and varices) [14].

The presence of PHE findings is associated with Child–Pugh classification, portosystemic shunts, ascites, portal vein thrombus, EVs, PHG, and a history of endoscopic injection sclerotherapy (EIS)/ endoscopic variceal ligation (EVL) [15, 16]. We reported that exacerbations of PHE were associated with exacerbated EVs and PHG based on short-term outcomes [17]. However, there are no reports on the clinical factors associated with the exacerbation of PHE in long-term outcomes. Additionally, the clinical significance of the changes in endoscopic findings due to PHE remains unclear. Thus, we aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings of PHE based on long-term outcomes.

Methods

Study design and participants

This retrospective study included 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23–87) diagnosed and followed up for PHE findings using CE for > 3 years at Hiroshima University Hospital between February 2009 and May 2023. CE was performed using a video capsule with a PillCam™ SB2 or SB3 (Covidien, Mansfield, MA, USA). Images were analyzed using a RAPID™ 8 workstation (Covidien, Mansfield, MA, USA). A flowchart of this study is shown in Fig. 1. CE was mainly performed when the outpatient physician indicated that evaluation of PHE was necessary, such as when patients with LC had suspected bleeding in the small-bowel, when evaluation of small-bowel mucosal damage was required before the introduction of chemotherapy for hepatocellular carcinoma (HCC), or thrombolytic therapy for portal vein thrombosis. The causes of portal hypertension included LC and idiopathic portal hypertension, which were diagnosed based on the patient’s medical history, laboratory findings (impaired synthetic liver function, thrombocytopenia, hepatitis B surface antigen, antibodies against Hepatitis C virus, autoimmune markers, and immunoglobulin), computed tomography (CT) imaging findings of the upper abdomen (nodules, irregular liver contours, splenomegaly, and ascites), transabdominal ultrasound findings, or liver biopsy findings.

Fig. 1
figure 1

Flowchart of this study. CE, capsule endoscopy; PHE, portal hypertensive enteropathy

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All patients underwent periodic dynamic CT in a 1.25-mm slice thickness high-quality scanning mode to check for the presence of HCC, ascites, collateral veins, and portal vein thrombosis during the follow-up for portal hypertension. Additionally, they underwent esophagogastroduodenoscopy (EGD) to evaluate the presence of EVs, GVs, and PHG. This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of our institution (approval number: E2022-0186). All patients provided written informed consent.

Study outcome measures

In this study, we evaluated the clinical factors affecting PHE exacerbation and their effects on gastrointestinal bleeding. The images captured via CE were reviewed and interpreted independently by two experienced experts who had reviewed more than 100 examinations, and no patient information was provided to the examiners. The CE images of the patients with portal hypertension are shown in Fig. 2. PHE was diagnosed if lesions were observed on CE scans. The appearance of new lesions or increase in existing lesions of PHE by CE was defined as “exacerbation” (Fig. 3), and the disappearance of lesions or decrease of existing lesions by CE was defined as “improvement.” The severity of villous edema was evaluated based on the inability to identify the lumen of the small-bowel with edema. No villous edema was defined when the small-bowel lumen was visible, with no mucosal edema (Fig. 2a). Mild villous edema was defined as when the lumen was visible with edematous mucosal change (Fig. 2b), and severe villous edema was defined as when the lumen was not visible owing to edema (Fig. 2c) [18]. Patients were divided into two groups: those with PHE exacerbation and those with unchanged PHE. We evaluated the relationships between the two groups with respect to patient clinical characteristics, including sex, age, observation period, liver function (Child–Pugh classification, FIB-4 index), etiology of portal hypertension, albumin, platelet count, prothrombin activity, HCC, EVs, GVs, PHG, portal diameter, splenomegaly, portal thrombosis, ascites, splenectomy, EIS, and EVL. We analyzed the data obtained from the most recent CT and EGD conducted when the CE was performed. HCC, portal diameter, splenomegaly, portal thrombosis, and ascites were evaluated using dynamic CT. EVs, GVs, and PHG were evaluated using EGD images. Exacerbation of EVs and GVs was defined as worsening of the degree of form or new appearance of a red color sign [19]. Exacerbation of PHG was defined as a progression from mild to severe as defined by the McCormack classification system [20]. Exacerbation of portal diameter was defined as a dilatation of 5 mm or more on follow-up CT, compared to initial CT. Exacerbation of portal thrombosis was defined as the appearance of new portal thrombosis or extension thrombosis on follow-up CT compared to the initial CT. Additionally, exacerbation of ascites was defined as an increase in the thickness of the ascites surrounding the liver on follow-up CT compared to the initial CT. The FIB-4 index was divided into three levels based on the literature [21]: low, ≤ 1.3; intermediate, 1.3–2.67; and high, ≥ 2.67, and an increase in the level was considered an exacerbation. We also evaluated the rate of gastrointestinal bleeding after follow-up CE. In this study, gastrointestinal bleeding was defined as episodes of overt bleeding characterized by hematemesis, melena, hematochezia, or a drop in hemoglobin levels > 2 g/dL [22].

Fig. 2
figure 2

Capsule endoscopic images of patients with portal hypertension. (a) Normal, (b) Mild villous edema, (c) Severe villous edema, (d) Erythema, (e) Erosion, (f) Angioectasia

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Fig. 3
figure 3

Representative images of the case with exacerbated PHE findings. CE images of initial (a, b) and followed-up (c, d). New angioectasia emerging at follow-up CE (yellow circle). CE, capsule endoscopy; PHE, portal hypertensive enteropathy

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Statistical analysis

Comparisons were made using the Student’s t-test for quantitative data and the chi-square test for categorical data. Fisher’s exact test was also used as appropriate. All tests were two-sided, and a P-value < 0.05 was considered statistically significant. Predictors found to be significant in the univariate analysis were included in the multivariate analysis using the stepwise method. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the impact of clinical variables on the long-term outcomes of PHE. The cumulative gastrointestinal bleeding rate after follow-up CE was estimated using the Kaplan–Meier method. Statistical analyses were performed using JMP15 (SAS Institute Inc., Cary, NC, USA).

Results

The baseline characteristics of the enrolled patients are shown in Table 1. LC was the predominant cause of pulmonary hypertension in 52 patients (95%).

Table 1 Baseline characteristics of enrolled patients
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All patients were observed in the entire small-bowel during both initial and follow-up CE. Of the 55 patients, 3 (5%) showed improvement in PHE findings, 33 (60%) remained unchanged in PHE findings, and 19 (35%) experienced exacerbation of PHE findings. In this study, 33 patients (22 males; median age: 61 years; median observation period: 71 months) were compared with 19 who experienced exacerbations (10 males; median age: 64 years; median observation period: 69 months). A comparison of the CE findings at the initial time points between the unchanged and exacerbated groups is shown in Table 2. Villous edema was the most common initial finding of PHE in both groups. There were no significant differences in the PHE findings on CE between the two groups. The breakdown of the PHE findings at follow-up in the exacerbated group was as follows: 17 patients (89%) had villous edema, 13 (68%) had erythema, 6 (32%) had erosions, and 5 (26%) had angioectasia. The breakdown of the exacerbated PHE findings on follow-up CE is shown in Table 3. The most frequently exacerbated CE findings were villous edema (88%) and angioectasia (80%). The clinical factors associated with PHE exacerbation based on CE findings are shown in Table 4. Regarding liver function, the rate of worsening of the FIB-4 index was significantly higher in the exacerbated group than in the unchanged group (21% vs. 3%, P = 0.03). On EGD, the rates of exacerbations in EVs and PHG were significantly higher in the exacerbated group than in the unchanged group (32% and 42% vs. 3% and 12%; P = 0.007, 0.014). Regarding the treatment of portal hypertension, the rate of splenectomy was significantly higher in the unchanged group than in the exacerbated group (13% vs. 5%, P < 0.01). In the multivariate analysis of the predictors of exacerbated PHE, EV exacerbation, and no splenectomy were significantly associated with the exacerbation of PHE (Table 5).

Table 2 Capsule endoscopic findings of PHE at the initial examination
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Table 3 Breakdown of PHE findings in the exacerbated group at follow-up CE
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Table 4 Clinical factors associated with exacerbated PHE findings
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Table 5 Multivariate analysis of factors associated with exacerbated PHE findings
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Additionally, we analyzed the occurrence of gastrointestinal bleeding after follow-up CE. The Kaplan–Meier curve of the cumulative gastrointestinal bleeding rate after follow-up CE is shown in Fig. 4. The PHE exacerbated group had a significantly higher rate of gastrointestinal bleeding events than the PHE unchanged group (log-rank, P = 0.037).

Fig. 4
figure 4

Cumulative gastrointestinal bleeding rate after follow-up CE. The PHE exacerbation group has significantly more gastrointestinal bleeding events than the PHE unchanged group (log-rank P = 0.037). CE, capsule endoscopy; PHE, portal hypertensive enteropathy

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A list of patients with improved PHE findings is presented in Table 6. Representative images of patients with improved PHE are shown in Fig. 5. All three patients had LC due to HCV infection (all achieved a sustained virological response [SVR]), and the Child–Pugh classification was grade A, B, or C, one case each. Concerning changes in the FIB-4 index, two patients remained unchanged, and one showed improvement. None of these three patients had EVs or PHG exacerbation, and two of them had undergone splenectomy.

Table 6 List of cases with improvement in PHE findings
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Fig. 5
figure 5

Representative images of the case with improved PHE findings. The presented patient is Case No. 3 in Table 6. CE images of initial (a, b) and follow-up (c, d). The patient undergoes splenectomy 12 months after the initial CE. This patient then undergoes follow-up CE 54 months after splenectomy. Although erythema (a) and villous edema (b) are observed at initial CE, there is no edematous change of small-bowel mucosa at follow-up CE (c, d). CE, capsule endoscopy; PHE, portal hypertensive enteropathy

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Discussion

The present study revealed a significant association between the exacerbation of EVs and the absence of splenectomy with exacerbation of PHE findings through CE. Additionally, the exacerbation of PHE findings on CE was clinically associated with the occurrence of gastrointestinal bleeding. In previous reports, PHE findings, prevalence, and predictors of the presence of PHE have been reported [1, 14, 15, 23]. However, the clinical significance of PHE remains unclear. The effects of PHE on long-term outcomes are unknown, with only one report on changes in PHE [17], which was based on short-term outcomes at 6 months. Furthermore, based on short-term results, we reported that PHE exacerbations were associated with exacerbations of EVs and PHG [17]. Our findings using long-term outcomes further revealed that exacerbation of EVs was significantly associated with exacerbation of PHE. The present study indicates that splenectomy maintained a long-term reduction in portal pressure and controlled PHE.

Portal pressure above 10 mmHg, clinically termed “portal hypertension,” is associated with the formation of varices; meanwhile, portal pressure above 12 mmHg is associated with variceal bleeding. EVs and GVs are complications of portal hypertension, present in approximately 50% and 20% of patients with LC, respectively [24,25,26,27]. Ido et al. [28] reported that the mean portal pressure with EVs was significantly higher than that without EVs. They also reported that EVs tended to extend their localization and intensify their features, such as engorgement and tortuosity, by increasing portal pressure. Previous reports have revealed that EVs are correlated with the presence and exacerbation of PHE [16, 17]. The results of the present study are similar to those of previous reports. The exacerbation of EVs suggests elevated portal pressure and exacerbation of PHE.

Splenectomy effectively decreased portal pressure in models of LC and non-LC portal hypertension in animals and humans [29,30,31]. It has been reported that a decrease in splanchnic blood flow by eliminating splenic blood flow and a reduction in intrahepatic vascular resistance by normalizing hepatic concentrations of endothelin-1 and nitric oxide metabolites may have jointly contributed to decreasing portal pressure by splenectomy [30]. Moreover, splenic hyperplasia produces mediators that promote liver fibrosis and inhibit liver regeneration, such as transforming growth factor-β1, tumor necrosis factor-α, and hepatocyte growth factor activity inhibitory factor, all of which are eliminated by splenectomy [32,33,34]. This study revealed an association between splenectomy and the stabilization of PHE. Splenectomy appeared to effectively lower or prevent an increase in portal pressure, which in turn prevents the exacerbation of PHE. This suggests an indirect relationship between portal pressure and the progression of PHE. Takashi et al. [35] reported a correlation between the presence and severity of small-bowel mucosal edema and HVPG. In this study, exacerbations of PHE were more frequent in patients with villous edema. This result may reflect an elevated portal pressure. We posit that the absence of PHE exacerbations suggests the maintenance of portal pressure. The measurement of portal pressure is invasive and difficult to perform regularly. However, evaluation of PHE using CE is relatively easy. Follow-up of PHE using CE may have potential utility owing to its minimal invasiveness and ease of CE with portal hypertension.

Patients with portal hypertension are known to have a variety of gastrointestinal lesions, such as PHG and PHC, resulting in gastrointestinal bleeding [19, 36,37,38]. The prevalence of acute gastrointestinal bleeding due to PHG has been reported to be 2–12%, and the bleeding rate due to PHC is estimated to be 0–9% [3, 39]. Chronic gastrointestinal bleeding and active bleeding have occasionally been reported in some patients with PHE, with active ileal bleeding observed in 5–10% of patients with cirrhosis [14, 40]. Small-bowel angioectasia is the major bleeding source for small-bowel bleeding [41, 42], and LC has been reported as a risk factor for the presence of small-bowel angioectasia [43, 44]. In the present study, 6 of the 52 enrolled patients (12%) had small-bowel angioectasia. Additionally, 4 of the 19 patients (22%) with exacerbated PHE had increased size or number of small-bowel angioectasias. These factors may have contributed to the increase in gastrointestinal bleeding observed in the PHE-exacerbated group. The results of the present study suggest that evaluating the small-bowel mucosa through CE is important in addition to EGD and CS in patients with PHE because exacerbation of PHE findings contributes to gastrointestinal bleeding.

Moreover, three patients showed improvement in PHE. All of these three patients had type C cirrhosis and achieved SVR. In other words, the cause of accelerated liver fibrosis disappeared, and portal hypertension was controlled. Additionally, splenectomy was performed in two of the three patients. Pezzoli et al. [45] reported that a transjugular intrahepatic portosystemic shunt improved small-bowel mucosal damage caused by portal hypertension. We hypothesize that PHE can be improved by decreasing portal pressure. However, there are few cases of improvement in PHE, and the cause remains unclear. With the advent of direct-acting antivirals for HCV, the number of long-term follow-up patients who achieve SVR is expected to increase [46]. The number of patients with PHE improvement may increase in the future. Therefore, it is necessary to accumulate data from patients with improved PHE for further analysis.

Our study has some limitations. First, the sample size was relatively small, and our study group was retrospectively recruited from a single center. Second, there was a possibility of selection bias because not all patients with portal hypertension underwent CE. Third, treatment approaches for LC have evolved over time, and we were unable to account for all these changes. Fourth, the follow-up periods varied. Thus, a prospective trial is required to resolve these issues. Fifth, the diagnosis was based solely on CE findings, and the possibility of other factors, such as drugs being the cause of the lesion, could not be ruled out because of the lack of histological evaluation. Sixth, various findings were encompassed by the PHE findings. De Palma et al. [14] categorized PHE findings into two groups: inflammatory and vascular lesions, which differ in clinical significance. Additionally, challenges such as risk stratification of the severity of PHE findings remain unresolved. Finally, we used two different CEs (PillCam™ SB2 and SB3), which may have led to an over-assessment of PHE exacerbations. Moreover, CE is a relatively expensive and burdensome procedure for physicians. Thus, it is necessary to identify a marker that can determine PHE exacerbations more easily.

Conclusions

In conclusion, the exacerbation of EVs and splenectomy were significantly associated with the exacerbation of PHE. Splenectomy was associated with a long-term improvement in portal pressure and a reduction in PHE exacerbation.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

PHE:

Portal hypertensive enteropathy

CE:

Capsule endoscopy

LC:

Liver cirrhosis

HVPG:

Hepatic venous pressure gradient

EVs:

Esophageal varices

GVs:

Gastric varices

PHG:

Portal hypertensive gastropathy

PHC:

Portal hypertensive colopathy

EIS:

Endoscopic injection sclerotherapy

EVL:

Endoscopic variceal ligation

HCC:

Hepatocellular carcinoma

CT:

Computed tomography

EGD:

Esophagogastroduodenoscopy

ORs:

Odds ratios

CIs:

Confidence intervals

SVR:

Sustained virological response

References

  1. Mekaroonkamol P, Cohen R, Chawla S. Portal hypertensive enteropathy. World J Hepatol. 2015;7:127–38.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Burroughs AK, Groszmann R, Bosch J, Grace N, Garcia-Tsao G, Patch D, et al. Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point? Gut. 2002;50:425–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Urrunaga NH, Rockey DC. Portal hypertensive gastropathy and colopathy. Clin Liver Dis. 2014;18:389–406.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kovacs TOG, Jensen DM. Varices: esophageal, gastric, and rectal. Clin Liver Dis. 2019;23:625–42.

    Article  PubMed  Google Scholar 

  5. Hosking SW, Smart HL, Johnson AG, Triger DR. Anorectal varices, haemorrhoids, and portal hypertension. Lancet. 1989;1:349–52.

    Article  PubMed  CAS  Google Scholar 

  6. Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature. 2000;405:417.

    Article  PubMed  CAS  Google Scholar 

  7. Fukumoto A, Tanaka S, Shishido T, Takemura Y, Oka S, Chayama K. Comparison of detectability of small-bowel lesions between capsule endoscopy and double‐balloon endoscopy for patients with suspected small‐bowel disease. Gastrointest Endosc. 2009;69:857–65.

    Article  PubMed  Google Scholar 

  8. Shishido T, Oka S, Tanaka S, Aoyama T, Watari I, Imagawa H, et al. Diagnostic yield of capsule endoscopy vs double-balloon endoscopy for patients who have undergone total enteroscopy with obscure gastrointestinal bleeding. Hepatogastroenterology. 2012;59:955–9.

    PubMed  Google Scholar 

  9. Liao Z, Gao R, Xu C, Li ZS. Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. Gastrointest Endosc. 2010;71:280–6.

    Article  PubMed  Google Scholar 

  10. Yamamoto H, Ogata H, Matsumoto T, Ohmiya N, Ohtsuka K, Watanabe K, et al. Clinical practice guideline for enteroscopy. Dig Endosc. 2017;29:519–46.

    Article  PubMed  Google Scholar 

  11. Pennazio M, Rondonotti E, Despott EJ, Dray X, Keuchel M, Moreels T, et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2023;55:58–95.

    Article  PubMed  Google Scholar 

  12. Gerson LB, Fidler JL, Cave DR, Leighton JA. ACG Clinical Guideline: diagnosis and management of small bowel bleeding. Am J Gastroenterol. 2015;110:1265–87.

    Article  PubMed  CAS  Google Scholar 

  13. Jeon SR, Kim JO. Capsule Endoscopy for portal hypertensive enteropathy. Gastroenterol Res Pract. 2016;2016:8501394.

    Article  PubMed  Google Scholar 

  14. De Palma GD, Rega M, Masone S, Persico F, Siciliano S, Patrone F, et al. Mucosal abnormalities of the small-bowel in patients with cirrhosis and portal hypertension: a capsule endoscopy study. Gastrointest Endosc. 2005;62:529–34.

    Article  PubMed  Google Scholar 

  15. Aoyama T, Oka S, Aikata H, Igawa A, Nakano M, Naeshiro N, et al. Major predictors of portal hypertensive enteropathy in patients with liver cirrhosis. J Gastroenterol Hepatol. 2015;30:124–30.

    Article  PubMed  Google Scholar 

  16. Abdelaal UM, Morita E, Nouda S, Kuramoto T, Miyaji K, Fukui H, et al. Evaluation of portal hypertensive enteropathy by scoring with capsule endoscopy: is transient elastography of clinical impact? J Clin Biochem Nutr. 2010;47:37–44.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kunihara S, Oka S, Tanaka S, Otani I, Igawa A, Nagaoki Y, et al. Predictive factors of portal hypertensive enteropathy exacerbation in patients with liver cirrhosis: a capsule endoscopy study. Digestion. 2018;98:33–40.

    Article  PubMed  Google Scholar 

  18. Otani I, Oka S, Tanaka S, Tsuboi A, Kunihara S, Nagaoki Y, et al. Clinical significance of small-bowel villous edema in patients with liver cirrhosis: a capsule endoscopy study. J Gastroenterol Hepatol. 2018;33:825–30.

    Article  PubMed  CAS  Google Scholar 

  19. The Japan Society for Portal Hypertension. The General Rules for Study of Portal Hypertension, Kanehara, Tokyo, Japan, 4th edition; 2022.

  20. McCormack TT, Sims J, Eyre-Brook I, Kennedy H, Goepel J, Johnson AG, et al. Gastric lesions in portal hypertension: inflammatory gastritis or congestive gastropathy? Gut. 1985;26:1226–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Yung DE, Koulaouzidis A, Avni T, Kopylov U, Giannakou A, Rondonotti E, et al. Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding: a systematic review and meta-analysis. Gastrointest Endosc. 2017;85:305–17.

    Article  PubMed  Google Scholar 

  23. Chandrasekar TS, Janakan GB, Chandrasekar VT, Kalamegam RY, Suriyanarayanan S, Sanjeevaraya PM. Spectrum of small-bowel mucosal abnormalities identified by capsule endoscopy in patients with portal hypertension of varied etiology. Indian J Gastroenterol. 2017;36:32–7.

    Article  PubMed  CAS  Google Scholar 

  24. Miñano C, Garcia-Tsao G. Clinical pharmacology of portal hypertension. Gastroenterol Clin North Am. 2010;39:681–95.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Maruyama H, Yokosuka O. Pathophysiology of portal hypertension and esophageal varices. Int J Hepatol. 2012;2012:895787.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Procopet B, Berzigotti A. Diagnosis of cirrhosis and portal hypertension: imaging, non-invasive markers of fibrosis and liver biopsy. Gastroenterol Rep (Oxf). 2017;5:79–89.

    Article  PubMed  Google Scholar 

  27. Kaplan DE, Ripoll C, Thiele M, Fortune BE, Simonetto DA, Garcia-Tsao G, et al. AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology. 2024;79:1180–211.

    Article  PubMed  Google Scholar 

  28. Ido K, Sakai H, Horiguchi M, Furusugi Y, Nogami W, Tanaka M, et al. A comparative study of portal vein pressure and endoscopic findings of esophageal varices in 50 cases of liver cirrhosis. Nihon Shokakibyo Gakkai Zasshi. 1980;77:871–7.

    PubMed  CAS  Google Scholar 

  29. Schwabl P, Seeland BA, Riedl F, Schubert TL, Königshofer P, Brusilovskaya K, et al. Splenectomy ameliorates portal pressure and anemia in animal models of cirrhotic and non-cirrhotic portal hypertension. Adv Med Sci. 2022;67:154–62.

    Article  PubMed  CAS  Google Scholar 

  30. Kawanaka H, Akahoshi T, Kinjo N, Iguchi T, Ninomiya M, Yamashita YI, et al. Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension. Br J Surg. 2014;101:1585–93.

    Article  PubMed  CAS  Google Scholar 

  31. Matsubara S, Ouchi K, Matsuno S. Portal venous pressure following splenectomy in patients with portal hypertension of differing etiology. Eur Surg Res. 1992;24:372–7.

    Article  PubMed  CAS  Google Scholar 

  32. Ueda S, Yamanoi A, Hishikawa Y, Dhar DK, Tachibana M, Nagasue N. Transforming growth factor-beta1 released from the spleen exerts a growth inhibitory effect on liver regeneration in rats. Lab Invest. 2003;83:1595–603.

    Article  PubMed  CAS  Google Scholar 

  33. Murata K, Shiraki K, Sugimoto K, Akase K, Nakano T, Furusaka A, et al. Splenectomy enhances liver regeneration through tumor necrosis factor (TNF)-alpha following dimethylnitrosamine-induced cirrhotic rat model. Hepatogastroenterology. 2001;48:1022–7.

    PubMed  CAS  Google Scholar 

  34. Kaido T, Oe H, Yoshikawa A, Okajima A, Imamura M. Expressions of molecules associated with hepatocyte growth factor activation after hepatectomy in liver cirrhosis. Hepatogastroenterology. 2004;51:547–51.

    PubMed  CAS  Google Scholar 

  35. Takahashi Y, Fujimori S, Narahara Y, Gudis K, Ensaka Y, Kosugi Y, et al. Small intestinal edema had the strongest correlation with portal venous pressure amongst capsule endoscopy findings. Digestion. 2012;86:48–54.

    Article  PubMed  Google Scholar 

  36. Primignani M, Carpinelli L, Preatoni P, Battaglia G, Carta A, Prada A, et al. Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC). Gastroenterology. 2000;119:181–7.

    Article  PubMed  CAS  Google Scholar 

  37. Kozarek RA, Botoman VA, Bredfeldt JE, Roach JM, Patterson DJ, Ball TJ. Portal colopathy: prospective study of colonoscopy in patients with portal hypertension. Gastroenterology. 1991;101:1192–7.

    Article  PubMed  CAS  Google Scholar 

  38. Naveau S, Bedossa P, Poynard T, Mory B, Chaput JC. Portal hypertensive colopathy. A new entity. Dig Dis Sci. 1991;36:1774–81.

    Article  PubMed  CAS  Google Scholar 

  39. Rockey DC. An update: Portal Hypertensive Gastropathy and Colopathy. Clin Liver Dis. 2019;23:643–58.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Figueiredo P, Almeida N, Lérias C, Lopes S, Gouveia H, Leitão MC, et al. Effect of portal hypertension in the small bowel: an endoscopic approach. Dig Dis Sci. 2008;53:2144–50.

    Article  PubMed  Google Scholar 

  41. Schmit A, Gay F, Adler M, Cremer M, Van Gossum A. Diagnostic efficacy of push-enteroscopy and long-term follow-up of patients with small bowel angiodysplasias. Dig Dis Sci. 1996;41:2348–52.

    Article  PubMed  CAS  Google Scholar 

  42. Damjanovska S, Isenberg G. Endoscopic treatment of small bowel bleeding. Gastrointest Endosc Clin N Am. 2024;34:331–43.

    Article  PubMed  Google Scholar 

  43. Igawa A, Oka S, Tanaka S, Kunihara S, Nakano M, Aoyama T, et al. Major predictors and management of small-bowel angioectasia. BMC Gastroenterol. 2015;15:108.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yamada A, Niikura R, Kobayashi Y, Suzuki H, Yoshida S, Watabe H, et al. Risk factors for small bowel angioectasia: the impact of visceral fat accumulation. World J Gastroenterol. 2015;21:7242–7.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Pezzoli A, Fusetti N, Simone L, Zelante A, Cifalà V, Carella A, et al. Portal hypertensive enteropathy diagnosed by capsule endoscopy and demonstration of the ileal changes after transjugular intrahepatic portosystemic shunt placement: a case report. J Med Case Rep. 2011;5:90.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Nakagawa M, Asahina Y, Kakinuma S, Okamoto R. Impact of eradication of hepatitis C virus on liver-related and -unrelated diseases: morbidity and mortality of chronic hepatitis C after SVR. J Gastroenterol. 2023;58:299–310.

    Article  PubMed  Google Scholar 

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Acknowledgements

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Funding

This study received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Yuka Matsubara, Akiyoshi Tsuboi, Issei Hirata, Akihiko Sumioka, Takeshi Takasago, Hidenori Tanaka, Ken Yamashita, Yuichi Hiyama, Hidehiko Takigawa, Eisuke Murakami, Masataka Tsuge, Yuji Urabe & Shiro Oka

  2. Department of Gastroenterology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Akiyoshi Tsuboi

Authors
  1. Yuka Matsubara
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  13. Shiro Oka
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Contributions

Conception and design: A.T. and S.O. Clinical data collection: Y.M., A.T., I.H., A.S., T.T., H.T., K.Y.,Y.H., H.T., E.M., M.T., Y.U., S.O. Analysis and interpretation of data: Y.M. and A.T. Drafting and critical revision of the article for important intellectual content: Y.M., A.T., and S.O. All authors reviewed the manuscript. Final approval of the article: All authors.

Corresponding author

Correspondence to Akiyoshi Tsuboi.

Ethics declarations

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Hiroshima University Hospital (approval number: E2022-0186).

Informed consent

All patients were informed of the risks and benefits of all examinations and provided written informed consent to undergo the procedure. We provided details of the study on our website, and patients were allowed to opt-out. None of the patients declined participation in the study.

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Not applicable.

Competing interests

The authors declare no competing interests.

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All authors.

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Matsubara, Y., Tsuboi, A., Hirata, I. et al. Predictive factors of portal hypertensive enteropathy exacerbations based on long-term outcomes. BMC Gastroenterol 24, 287 (2024). https://doi.org/10.1186/s12876-024-03377-7

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  • DOI: https://doi.org/10.1186/s12876-024-03377-7

Keywords

BMC Gastroenterology

ISSN: 1471-230X

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