Outcomes and Recurrence Rate of Esophageal Varices after Endoscopic Treatment in Patients with Alcoholic Cirrhosis and Viral Cirrhosis.

BACKGROUND: The incidence of alcoholic liver cirrhosis (ALC) is increasing. However, few reports have focused on ALC-derived esophageal varices (EV). We retrospectively examined differences in overall survival (OS) and EV recurrence rate in patients after endoscopic injection sclerotherapy (EIS) for ALC and hepatic B/C virus liver cirrhosis (B/C-LC). METHODS: We analyzed data from 215 patients (B/C-LC, 147; ALC, 68) who underwent EIS. The primary endpoints were OS and EV recurrence in patients with unsuccessful abstinence ALC and those with uncontrolled B/C-LC, before and after propensity score matching (PSM) to unify the patients' background. The secondary endpoints were predictors associated with these factors, as determined by multivariate analysis. RESULTS: The observation period was 1,430 ± 1,363 days. In the analysis of all patients, OS was significantly higher in the ALC group than in the B/C-LC group (p = 0.039); however, there was no difference in EV recurrence rate (p = 0.502). Ascites and history of hepatocellular carcinoma (HCC) (p = 0.019 and p < 0.001, respectively) predicted OS, whereas age and EV size predicted recurrence (p = 0.011 and 0.024, respectively). In total, 96 patients without an HCC history were matched by PSM, and there was no significant difference in OS or EV recurrence rate (p = 0.508 and 0.246, respectively). CONCLUSION: When limited to patients without a history of HCC, OS and the EV recurrence rate were comparable in patients with ALC who continued to consume alcohol and those with B/C-LC without viral control.

Enlargement of the Spleen Index Is a Predictor of the Occurrence of Esophageal Varices and Hepatocellular Carcinoma after Administering Direct-acting Antiviral Agents.

Objective Direct-acting antiviral agents (DAAs) can eliminate hepatitis C virus at a high rate, although the long-term incidence of portal hypertension and hepatocellular carcinoma (HCC) has not yet been elucidated. In this observational study, we clarified the predictors associated with the incidence of esophageal varices (EVs) and HCC after DAAs treatment based on ultrasound findings and blood examinations. Methods A total of 78 patients treated with DAAs were enrolled in this study. The primary endpoint was to identify the predictors associated with EVs and HCC occurrence using univariate and multivariate analyses. Secondary endpoints were to extract the cutoff values for EVs and HCC occurrence and clarify the changes in liver stiffness (LS), spleen stiffness (SS), spleen index (SI), portal venous flow volume (PVF), and blood examination at 12 weeks after the end of DAAs treatment. Results The mean observation period was 1,402±546 days. SI change (SI after DAAs-SI before DAAs) was a predictor of EVs occurrence in multivariate analysis (p=0.045). The treatment history of HCC, albumin value before DAAs, and SI change were predictors of HCC occurrence in multivariate analysis (p=0.002, p=0.032, and p=0.009, respectively). LS, SS, PVF, SI, and liver function significantly improved after DAAs treatment. Conclusion Portal hypertension seems to improve after DAAs treatment over a long period. Patients with splenomegaly deterioration after DAAs treatment need to be carefully monitored for the occurrence of EVs and HCC.

Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study.

BACKGROUND: Tricuspid regurgitation pressure gradient (TRPG) measurement by echocardiography is recommended as the most objective examination to detect portopulmonary hypertension (PoPH). This study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a scoring model for identifying patients who are most likely to benefit from echocardiography investigations. RESULTS: A total of 486 patients who underwent echocardiography were randomly allocated to the derivation and validation sets at a ratio of 2:1. Of the patients, 51 (10.5%) had TRPG ≥ 35 mmHg. The median brain natriuretic peptide (BNP) was 39.5 pg/mL. Shortness of breath (SOB) was reported by 91 (18.7%) patients. In the derivation set, multivariate analysis identified female gender, shortness of breath, and BNP ≥ 48.9 pg/mL as independent factors for TRPG ≥ 35 mmHg. The risk score for predicting TRPG ≥ 35 mmHg was calculated as follows: - 3.596 + 1.250 × gender (female: 1, male: 0) + 1.093 × SOB (presence: 1, absence: 0) + 0.953 × BNP (≥ 48.9 pg/mL: 1, < 48.9 pg/mL: 0). The risk score yielded sensitivity of 66.7%, specificity of 75.3%, positive predictive value of 25.5%, negative predict value of 94.3%, and predictive accuracy of 74.4% for predicting TRPG ≥ 35 mmHg. These results were almost similar in the validation set, indicating the reproducibility and validity of the risk score. CONCLUSIONS: This study clarified the characteristics of patients with suspected PoPH and developed a scoring model for identifying patients at high risk of PoPH, which may be used in selecting patients that may benefit from echocardiography.

Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study.

AIM: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy. METHODS: This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy. RESULTS: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. CONCLUSIONS: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis.

Endoscopic submucosal dissection using traction by a spring-and-loop with clip for a laterally spreading tumor in the inferior aspect of the cecum: a nonreferral center experience.

Video 1Endoscopic submucosal dissection using traction by a spring-and-loop with clip for a laterally spreading tumor in the inferior aspect of the cecum: a nonreferral center experience.

Liver and spleen stiffness on ultrasound elastography are predictors of the occurrence of esophagogastric varices after balloon-occluded retrograde transvenous obliteration.

BACKGROUND: Balloon-occluded retrograde transvenous obliteration (BRTO) is an effective treatment for gastric varices, but predictors associated with overall survival rate (OS) and occurrence of esophagogastric varices (EGV) have not yet been clarified. In this study, we clarified these predictors by performing ultrasound elastography and blood tests at various time points. METHODS: A total of 34 patients were enrolled. The primary endpoint was to identify predictors associated with OS and EGV occurrence by univariate and multivariate analyses. Secondary endpoints were to extract the cut-off values for OS and EGV occurrence, and to clarify chronological changes in liver stiffness (LS), spleen stiffness (SS), spleen index (SI), and portal vein flow volume (PVF). Time points were set as before BRTO (Bf), and 1 day (D1), 7 days (D7), 1 month (1M), 3 months (3M), and 6 months (6M) after BRTO. RESULTS: Albumin-bilirubin score Bf, fibrin-4 index change 6M, and branched chain amino acids tyrosine molar ratio (BTR) 1M were predictors of OS on univariate analysis (P = .021, .033, and .019, respectively) but were not extracted by multivariate analysis. The factors of LS 6M > 19.9 kPa and SS D7 > 21.7 kPa were predictors of the occurrence of EGV on multivariate analysis (P = .029 and .025, respectively). PVF significantly increased with time after BRTO. CONCLUSION: Albumin-bilirubin score and BTR had the possibility to associate with OS, and the predictors of reduced occurrence of EGV were LS < 19.9 and SS < 21.7.

Experimental study of a physician-controlled electrocautery-enhanced delivery system incorporating a newly developed lumen-apposing metal stent for interventional endoscopic ultrasound (with videos).

BACKGROUND/PURPOSE: Although the lumen-apposing metal stent (LAMS) is useful for interventional endoscopic ultrasound (EUS) procedures, there has been some concern about the potential for stent-induced adverse events because of the high lumen-apposing force. A newly designed LAMS with less lumen-apposing force has been developed for use with a physician-controlled electrocautery-enhanced delivery system. The aim of this animal study was to evaluate the feasibility of performing interventional EUS using this newly designed LAMS system. METHODS: Endoscopic ultrasound-guided cystogastrostomy was performed using the novel LAMS three times in a wet simulation model. EUS-guided gastroenterostomy and EUS-guided gallbladder drainage were then performed using the system in four pigs. RESULTS: The LAMS was successfully placed in all three EUS-guided cystogastrostomy procedures using the wet simulation model and in all four EUS-guided gastroenterostomy and gallbladder drainage procedures in the animal model. In the 3 weeks following the procedure, eating behavior was normal in all animals and there were no adverse events. The stents remained patent during this time and were removed without difficulty. The fistula was mature in all cases and a standard upper gastrointestinal endoscope was easily advanced via the fistula to observe the afferent and efferent loops or the lumen of the gallbladder. Necropsy confirmed complete adhesion between the stomach and the wall of the jejunum or gallbladder. CONCLUSIONS: Our study findings demonstrate the feasibility of this new LAMS system and its potential clinical value for interventional EUS.

Red dichromatic imaging reduces endoscopic treatment time of esophageal varices by increasing bleeding point visibility (with video).

BACKGROUND: Red dichromatic imaging (RDI) is a novel image-enhanced endoscopy released in 2020, which increases the visibility of deeper vessels. In this study, we retrospectively investigated whether RDI can shorten treatment times of endoscopic injection sclerotherapy (EIS), and which operational procedure times are affected compared with white light imaging (WLI). METHODS: A total of 155 patients (RDI, 70; WLI, 85) with risky esophageal varices (EV), who were treated with EIS were analyzed. Treatment times were compared, and predictors associated with treatment time were analyzed by multivariate analysis. For 24 cases (RDI, 12; WLI, 12) in which treatment videos were recorded, the procedure times of each step (observation of EV, needle flush, positioning, puncture, observation of bleeding, hemostasis, observation after hemostasis) were measured. Regarding the seven patients with EV bleeding, color differences were calculated between the bleeding point and the blood pool using the CIE (L*a*b*) color measurement method, and results were compared between using RDI and WLI. RESULTS: Treatment times were shorter in the RDI group (RDI vs. WLI = 35.1 vs. 42.2 min; P < 0.01). 'RDI function' and 'amount of sclerosant' were extracted as independent predictors of treatment time. Times for 'observation of EV' and 'observation of bleeding' were shorter in the RDI group (P = 0.01 and <0.01, respectively). Regarding the color difference, RDI significantly increased bleeding point visibility (RDI vs. WLI = 31.4 ± 11.8 vs. 8.6 ± 6.2, P < 0.001). CONCLUSION: Red dichromatic imaging can shorten the treatment time of EIS by increasing bleeding point visibility.

Prognostic and recurrence factors after endoscopic injection sclerotherapy for esophageal varices: Multivariate analysis with the propensity score matching: Multivariate analysis with propensity score matching.

BACKGROUND: Peri-esophageal collateral veins have been reported to be associated with the recurrence of esophageal varices (EVs). In this study, we retrospectively analyzed whether endoscopic ultrasonography (EUS) findings obtained just before endoscopic injection sclerotherapy (EIS) are associated with the success rate of intravariceal injection, recurrence rate of EVs, and overall survival rate (OS) of patients. Furthermore, we investigated the independent predictors associated with these factors by multivariate analysis. METHODS: A total of 91 patients with risky EVs treated by EIS were analyzed. The primary endpoint was to identify independent predictors associated with the success rate of intravariceal injection, recurrence rate, and OS by multivariate analysis, to confirm the usefulness of EUS examination. The secondary endpoint was to clarify differences in recurrence rate and OS between patients who underwent additional argon plasma coagulation (APC) and those who did not, by the propensity score matching method. RESULTS: Luminal diameter of EVs and F factor were predictors of the success rate of intravariceal injection. APC was predictor of OS and recurrence of EVs. EUS findings were not associated with these factors. Propensity score matching (APC, 23; without APC, 23) showed that recurrence rate was significantly improved in the APC group (P = 0.050) and that OS had the tendency to be higher in the APC group (P = 0.068). CONCLUSION: Endoscopic ultrasonography findings before EIS were associated with successful intravariceal injection but were not associated with recurrence rate or OS. Additional APC could improve OS and reduce the recurrence of EVs.

The Risk of Cirrhosis and Its Complications Based on PNPLA3 rs738409 G Allele Frequency.

BACKGROUND: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. OBJECTIVE: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. METHODS: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC was composed of the presence and absence of complications, such as variceal bleeding, hepatic ascites, and hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort and (ii) the presence and absence of complications in the patients with LC. RESULTS: There was a significant difference among the patients without LC and those with alcohol, NAFLD-related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD-related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol-related cirrhosis unless there was a presence of G alleles. CONCLUSION: The PNPLA3 polymorphism was associated with the risk of NAFLD-related LC and its complications.

Lusutrombopag has slightly stronger effects on patients with mild thrombocytopenia compared with those with severe thrombocytopenia: A multicenter propensity score matching study.

BACKGROUND: Lusutrombopag effectively increases platelet count in patients with severe thrombocytopenia. However, no multicenter studies analyzing the effects of Lusutrombopag on patients with mild thrombocytopenia (platelet count > 50 000/µL) have been performed. In this study, we aimed to clarify the efficacy of Lusutrombopag on these patients by unifying background factors by propensity score matching. METHODS: A total of 139 patients with thrombocytopenia were enrolled, and matched for age, sex, etiology, disease, treatment, liver function, renal function, peripheral blood count, and spleen index. The primary endpoint was to compare the increase in platelet count from baseline between the high-platelet group (>50 000/µL) and the low-platelet group (<50 000/µL) after Lusutrombopag treatment, using propensity score matching. The secondary endpoint was to clarify platelet transfusion avoidance rate and adverse events, moreover, to identify independent predictors associated with the increase in platelet count. RESULTS: The mean increase in platelet count was 67 000/µL vs 48 000/µL in all patients (high- vs low-platelet group, P = .024), and 64 000/µL vs 48 000/µL (P = .12) after propensity score matching. The increase in platelet count and the platelet transfusion avoidance rate tended to be higher in the high-platelet group. There was no significant difference between adverse events. Predictors associated with an increase in platelet count were sex, estimated glomerular filtration rate, and spleen index by multivariate analysis. CONCLUSION: Lusutrombopag has a little stronger effect in patients with mild thrombocytopenia than those with severe thrombocytopenia and showed a more substantial effect in patients with impaired renal function and small spleen.

Two Cases of Hemorrhagic Ampullary Lesions Successfully Treated by Endoscopic Papillectomy.

We herein report two cases of hemorrhagic ampullary lesions in which endoscopic papillotomy was performed to control bleeding and resulted in successful treatment. Both patients were pathologically diagnosed with an underlying pathology characterized by inflammatory cell infiltration and capillary proliferation. They also had disposing factors for bleeding, such as antithrombotic therapy and idiopathic thrombocytopenic purpura. Endoscopic treatment was selected because the risk of surgical resection was high due to the patients' hemorrhagic condition. Both patients were successfully treated without any serious adverse events and had an uneventful postoperative course with no relapse of bleeding.

[A case of endoscopic injection sclerotherapy for duodenal varices].

A 67-year-old man with a history of esophageal and gastric varices that were treated endoscopically was treated for Budd-Chiari syndrome and immunoglobulin G4-related sclerosing cholangitis in our facility. Varices in the second portion of the duodenum were revealed in follow-up upper endoscopy. The draining vein formed a venous plexus that was detected on computed tomography. Treatment with interventional radiology was difficult;therefore, endoscopic injection sclerotherapy (EIS) was performed instead. No recurrence has been observed to date. Thus, in this case, EIS for duodenal varices was effective.

Elucidation of spleen elasticity and viscosity in a carbon tetrachloride rat model of liver cirrhosis using a new ultrasound elastography.

PURPOSE: Measurement of spleen stiffness (SS) using ultrasound (US) elastography is useful for predicting portal hypertension. However, the mechanism leading to increased SS remains unclear. We jointly developed a new US elastography system (Aplio i-series, Canon Medical Systems) that can easily measure organ viscosity (dispersion slope: DS). We analyzed the cause of increased SS by calculating the shear wave speed (SWs, which reflects fibrosis) and DS of the spleen in carbon tetrachloride (CCL4) rat liver cirrhosis models. METHODS: A total of 13 Sprague-Dawley rats were randomly divided into four groups (C group: 3 rats as control, 2D group: 3 rats injected with CCL4 twice in 1 week, 4D group: 4 rats injected 4 times in 1 week, 6W group: 3 rats injected twice a week for 6 weeks). The SWs and the DS of each group were calculated, and histopathological analysis was performed. RESULTS: The spleen SWs of the 6W group was significantly higher than that of the C group (p = 0.044). The spleen DS did not change after CCL4. The liver SWs of the 4D and 6W groups was significantly higher than that of the C group (p = 0.012 and 0.007, respectively) with fibrosis change on histopathology, and the DS of the 4D group was significantly higher than that of the C group (p = 0.033). Splenic fibrosis was confirmed in the 6W group, but inflammation and necrosis were not seen. CONCLUSION: SS increased due to fibrosis and can be predicted based on SWs and DS values.

Morphological study of the gastrointestinal tract around the ligament of Treitz using upper gastrointestinal radiography: Fundamental data for EUS-guided gastrojejunostomy.

BACKGROUND/PURPOSE: We developed EUS-guided double-balloon occluded gastrojejunostomy (EPASS) for gastric drainage tract obstruction. The success of EPASS depends on the proximity of the stomach and the gastrointestinal (GI) tract near the ligament of Treitz. The aim of this study is to clarify the GI anatomy near the ligament of Treitz. METHODS: One thousand and sixteen cases imaged upper GI radiography using barium were retrospectively evaluated. Morphologically, the GI tract running near the ligament of Treitz was divided in three types: Type I: The 4th portion of the duodenum (D4) approaches the stomach; Type II: D4 does not approach the stomach; Type III: D4 forms a loop to the jejunum. The minimum distance between the stomach and the GI tract near the ligament of Treitz was measured. RESULTS: Based on the morphological classification, 74.6% in the study group was classified in Type I, 22.0% in Type II, and 3.3% in Type III, respectively. The median minimum distance in Type II/III group were significantly longer, compared with the Type I (P < .01). CONCLUSIONS: The GI anatomy near the ligament of Treitz was clarified using upper GI radiography. It is divided into three patterns, and one-fourth of cases may have difficulty in EUS-guided gastrojejunostomy.