Introduction

Sudden decrease of colonoscopy (CS) can be related with the status of colorectal cancer (CRC).

Aims & Methods

The aim of this study is to evaluate the status of CS, esophagogastroduodenoscopy (EGD), and CRC according to big national disasters such as the Great East Japan Earthquake in 2011 and the spread of COVID-19 infection in 2020. As a study population, we retrospectively used commercially anonymized health insurance claims data covering 4,601,921 patients ≥50 years old (Male 2,403,826/ Female 2,198,095) from January 2010 to December 2022. Main outcome was a yearly analysis for 2010-2022 about 1. rate of CS and EGD, 2. rate of CRC and positive rate of CS for CRC, 3. number of surgeries for CRC. Additionally, a monthly analysis for those rates were performed to examinate the effect of the earthquake and COVID-19 infection.

Results

The rates of CS and EGD in 2010/2011/2012 were 3.10%/3.41%/3.42% and 6.94%/6.96%/7.00%. Those in 2019/2020/2021 were 5.20%/4.74%/5.37% and 7.47%/6.42%/6.84%. Deficiencies for CS and EGD were found not in 2011 (The earthquake) but were present in 2020 (COVID-19). The rates of CRC in 2019/2020/2021 were 0.20%/0.17%/0.19% with a decrease rate of 12.0% in 2020. The positive rate for CRC decreased from 6.74% in 2010 to 3.44% in 2022. However, there were no definite changes in 2011 and 2020. The rate of surgery for CRC in 2019/2020/2021 were 0.087%/0.079%/0.087% and the deficiency was found in 2020.

Conclusion

The rates of CS and CRC decreased in 2020 due to COVID-19. On the other hand, they were not affected by the earthquake.

Clinical Case Summary

Background: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that rarely present with gastrointestinal (GI) bleeding due to tumor erosion. GISTs commonly arise in the stomach, followed by the small bowel. They are typically diagnosed through histopathology and immunohistochemistry.¹ The presence of mucosal ulceration and tumor locations outside the stomach are linked with a greater risk of tumor progression to malignancy.^1,2 This case highlights a benign ulcerated jejunal GIST presenting as GI bleeding.
Case summary: A 42-year-old male presented with dark stools and light-headedness over five days. On examination, he was hypotensive, tachycardic, tachypneic, and had pallor. Laboratory tests revealed normocytic normochromic anemia, with a significant one-day drop in hemoglobin (from 7.2 g/dL to 6.4 g/dL). Upper GI endoscopy and colonoscopy were normal, but double-balloon enteroscopy [Figure 1] revealed a subepithelial lesion distal to the duodenojejunal flexure, and an overlying ulcer. These findings were suggestive of GIST and were corroborated by a contract-enhanced CT abdomen scan, which revealed a well-defined, homogenously-enhancing solid exophytic lesion (30 x 22 x 26 mm) arising from the proximal jejunal loops. He underwent resection anastomosis with complete en-bloc surgical removal of the lesion. Histopathological analysis of the resected specimen showed spindle cells arranged in a long, fascicular pattern, with minimal pleomorphism, low mitotic index, without any necrosis or epithelioid cells [Figure 2]. Immunohistochemistry confirmed the GIST which displayed diffuse immunopositivity for CD117 and DOG1 markers. His hemoglobin levels were stable on regular follow-ups, and there was no documented recurrence six months later.
Conclusion: GISTs can present with GI hemorrhage and should be suspected in cases of unexplained GI bleeding. Early diagnosis and complete surgical resection are key to favorable outcomes.

References

1. Parab TM, DeRogatis MJ, Boaz AM, Grasso SA, Issack PS, Duarte DA, Urayeneza O, Vahdat S, Qiao JH, Hinika GS. Gastrointestinal stromal tumors: a comprehensive review. J Gastrointest Oncol. 2019 Feb;10(1):144-154. doi: 10.21037/jgo.2018.08.20.
2. Carter BM, Bronsert MR, Wilky BA, McCarter MD. Mucosal Ulceration in Gastrointestinal Stromal Tumor is an Independent Predictor of Progression-Free Survival. J Surg Res. 2023 Apr;284:221-229. doi: 10.1016/j.jss.2022.11.076.

Introduction

The CRAFITY (CRP and AFP in ImmunoTherapY) score is a biomarker composed of CRP and AFP that predicts clinical outcomes of patients undergoing immunotherapy for hepatocellular carcinoma (HCC), independently of Child-Pugh score and performance status [1]. We previously validated its utility in predicting the prognosis of patients with HCC receiving atezolizumab and bevacizumab therapy [2].

Aims & Methods

In this study, we investigated the applicability of the CRAFITY score in patients with unresectable HCC treated with the combination of durvalumab and tremelimumab (Dur/Tre). In this multicenter study, a total of 325 patients who received the STRIDE regimen between March 2023 and December 2024 were included. Baseline characteristics were as follows: median age, 73.0 (IQR 68.0–78.0) years; sex (male/female), 272/53; performance status (0/1/≥2), 252/58/15; etiology (hepatitis B/C/B+C/non-B, non-C), 55/88/3/179; Child-Pugh score (5/6/≥7), 137/133/73; BCLC stage (≤A/B/≥C), 22/91/212; neutrophil-to-lymphocyte ratio (NLR), 2.97 (1.98–4.31); CRP, 0.44 (0.15–1.59) mg/dL; AFP, 58.1 (5.0–1921.0) ng/mL; observation period, 7.9 (4.1–13.3) months; and treatment line (first-line/second-line or beyond), 121/204 patients.

Results

Patients were stratified by CRAFITY score (0/1/2): 120/149/56, and significant differences were observed among the groups for most baseline characteristics, except for sex, body mass index (BMI), and prothrombin time (PT). Median progression-free survival (PFS) was 3.8 months (95% CI: 3.0–4.3), and median overall survival (OS) was 17.0 months (95% CI: 14.1–NA). Best response rates based on RECIST version 1.1 were: complete response (CR) 2.1%; partial response (PR) 16.8%; stable disease (SD) 30.9%; progressive disease (PD) 50.2%; with an objective response rate (ORR) of 18.9% and disease control rate (DCR) of 49.8%. Significant differences in best response (p = 0.042) and DCR (p = 0.043) were observed across CRAFITY score groups. The incidence of immune-related adverse events (imAEs, ≥10% in any category) was 25.8% for skin toxicity, 21.8% for hepatotoxicity, 12.9% for diarrhea/enteritis, and 10.2% for fever. No significant differences in adverse events, including other imAEs, were found among CRAFITY groups. In multivariate analysis, both treatment line (second-line or later: HR 1.47; 95% CI: 1.11–1.96; p = 0.007) and CRAFITY score of 2 (HR 1.62; 95% CI: 1.08–2.42; p = 0.020) were independently associated with PFS. Additionally, in multivariate analysis, non-B non-C etiology (HR 0.63; 95% CI: 0.43–0.93; p = 0.020), CRAFITY score of 1 (HR 2.00; 95% CI: 1.22–3.27; p = 0.006), and score of 2 (HR 3.42; 95% CI: 1.91–6.12; p < 0.001) were independently associated with OS. For the prediction of 12-month OS, the integrated discrimination improvement (IDI) was 0.007 (95% CI, 0.022 to 0.137; p < 0.001) for AFP and 0.066 (95% CI, 0.018 to 0.135; p < 0.001) for CRP, respectively, when compared with the CRAFITY score. Similarly, the net reclassification improvement (NRI) was 0.360 (95% CI, 0.092 to 0.474; p = 0.002) for AFP and 0.170 (95% CI, 0.024 to 0.348; p = 0.016) for CRP, indicating the superior prognostic performance of the CRAFITY score. Subgroup analyses showed significant differences in OS by CRAFITY score among patients with Child-Pugh class A, NLR less than 3, and BCLC stage C or higher.

Conclusion

The CRAFITY score appears to be a promising prognostic biomarker for patients with unresectable HCC treated with Dur/Tre.

References

1. Bernhard Scheiner, Katharina Pomej, Martha M. Kirstein et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy – development and validation of the CRAFITY score. J Hepatol. 2022; 76 (2): 353-363.
2. Takeshi Hatanaka, Satoru Kakizaki, Atsushi Hiraoka et al. Prognostic impact of C-reactive protein and alpha-fetoprotein in immunotherapy score in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: a multicenter retrospective study. Hepatol Int. 2022; 16 (5): 1150-1160.

Disclosure

Toshifumi Tada: lecture fees from AbbVie, AstraZeneca, Eisai, and Chugai
Atsushi Hiraoka: lecture fees from Eisai, Bayer, Eli Lilly, and Otsuka
Hidenori Toyoda: lecture fees from AbbVie, Eisai, Gilead, Terumo, and Bayer

Introduction

Although patients with acute-on-chronic liver failure (ACLF) often demonstrate preserved thrombin generation (TG), they concurrently display hypocoagulable profiles on rotational thromboelastometry (ROTEM) [1]. The extent to which these findings explain the increased bleeding risk in acutely ill cirrhotic patients remains unclear [1–5]. Moreover, most studies do not distinguish between portal hypertensive (PH) and non-PH bleeding, complicating accurate estimation of NPH bleeding prevalence.

Aims & Methods

This is a case-control study, comparing haemostatic profiles of acute decompensation (AD) and ACLF (=cases) to stable cirrhosis (SC) (=controls). Coagulation profiles were evaluated including INR, aPTT, PT, fibrinogen, coagulation factors and inhibitors and advanced global haemostatic tests (ROTEM, TG assay (TGA) ± thrombomodulin (TM)). Secondary objectives focused on identifying associations between coagulation parameters and NPH bleeding and thrombotic events.

Results

A total of 215 patients were included (SC: 122; AD: 53; ACLF: 40). The median Child-Pugh (CP) and MELD-Na scores increased progressively from SC to AD to ACLF (P< 0.001). NPH bleeding occurred in 8,4% (n=18), with higher rates in ACLF (30,8%, P<0,001) and AD (18.9%, P=0.011) than in SC (5.7%). Thrombotic events were observed in 7.0% (n=15).
TGA without TM revealed that ACLF patients had significantly shorter lag time compared to SC, shorter time to peak, reduced peak height and endogenous thrombin potential (ETP) compared to SC/AD; though TM normalized these effects. ETP inhibition by TM was reduced significantly across the three groups. ROTEM parameters showed marked hypocoagulable features in ACLF vs SC/AD, while AD and SC were comparable. Hypocoagulability (≥5 abnormal ROTEM parameters out of 6 parameters) was present in 1.8% of SC, 8.3% of AD, and 22.2% of ACLF patients (P<0.001 for SC vs ACLF); hypercoagulability was rare (2.8% in ACLF). INR and aPTT were significantly prolonged and FVIII elevated, while fibrinogen, PT, and pro- and anticoagulants were reduced in AD/ACLF compared to SC. ROTEM and TGA parameters correlated significantly with MELD-Na and CP scores (P<0,001).
Patients with NPH bleeding had higher CP and MELD-Na scores (P<0,001 and P=0,006), and a greater prevalence of AD (33,3%) and ACLF (38,9%) compared to non-bleeders (22,8% AD; 16,1% ACLF). Hypocoagulability on ROTEM was more frequent among bleeders (31.3% vs 4.5% in non-bleeders, P=0.002). Bleeders also showed greater impairment in INR, aPTT, PT, and most coagulation factors (except FVIII and PS). Multivariate analysis identified ROTEM-defined hypocoagulability as an independent risk factor for NPH bleeding (OR 12.93, 95% CI: 1.13–150.28, P=0.041). No significant differences in coagulation parameters were observed between patients with and without thrombotic complications.

Conclusion

TG demonstrated accelerated initiation and reduced thrombin potential in ACLF vs SC/AD, though TM normalized these effects. ROTEM demonstrated pronounced hypocoagulability in AD/ACLF vs SC. These coagulation abnormalities are paralleling their advanced liver dysfunction.
NPH bleeding events clustered in AD/ACLF cohorts and were associated with ROTEM-defined hypocoagulability. The convergence of ROTEM hypocoagulability as an independent risk factor for NPH bleeding and its prominence in acutely ill cirrhotic patients underscores the heightened NPH bleeding prevalence and ROTEM detected coagulation dysfunction in this patient population.

References

1. Campello E, Zanetto A, Bulato C, Maggiolo S, Spiezia L, Russo FP, et al. Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure. Liver International. 2021 Oct 16;41(10):2455–66.
2. Drolz A, Horvatits T, Roedl K, Rutter K, Staufer K, Kneidinger N, et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology. 2016 Aug 9;64(2):556–68.
3. Blasi A, Calvo A, Prado V, Reverter E, Reverter JC, Hernández‐Tejero M, et al. Coagulation Failure in Patients With Acute‐on‐Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio. Hepatology. 2018 Dec 9;68(6):2325–37.
4. Bihari C, Patil A, Shasthry SM, Baweja S, Kumar G, Sarin SK. Viscoelastic test-based bleeding risk score reliably predicts coagulopathic bleeding in decompensated cirrhosis and ACLF patients. Hepatol Int. 2020 Jul 17;14(4):597–608.
5. Ow TW, Fatourou E, Rabinowich L, van den Boom B, Nair S, Patel VC, et al. Prevalence of Bleeding and Thrombosis in Critically Ill Patients with Chronic Liver Disease. Thromb Haemost. 2022 Jun 12;122(06):1006–16.

Disclosure

The reagents for the ROTEM analyses were sponsored by Werfen. This study received a Gilead fellowship, and K.F. received a BSTH-CSL Behring encouragement award.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has emerged as one of the leading causes of chronic liver disease worldwide. MASLD is closely associated with components of metabolic syndrome, including obesity, insulin resistance, dyslipidemia, and hypertension. The role of gut microbiota dysbiosis in MASLD pathogenesis is increasingly recognized, with microbial imbalance contributing to systemic inflammation and metabolic disturbances.

Aims & Methods

The aim was to determine gut microbiota composition in patients with MASLD and evaluate the impact of probiotic therapy on metabolic, inflammatory, and lipid parameters. The study included 152 patients diagnosed with MASLD. Diagnosis was based on clinical, laboratory, and imaging findings, including ultrasound and steatometry, alongside cardiometabolic risk factors. Gut microbiota composition was evaluated using quantitative real-time PCR (qRT-PCR). Patients received a combined probiotic therapy containing Saccharomyces boulardii CNCM I-745, Lactobacillus acidophilus (LA-5), and Bifidobacterium lactis (BB-12). Changes in biochemical markers, lipid profiles, inflammatory parameters, and gut microbiota composition were assessed before and after therapy.

Results

At baseline, patients with MASLD demonstrated gut microbiota dysbiosis, characterized by an increased proportion of Firmicutes (50.3%) and Actinobacteria (15.34%), and an elevated Firmicutes/Bacteroides (F/B) index (5.02). Following probiotic therapy, significant improvements were observed: the proportions of Firmicutes and Actinobacteria decreased, the F/B index was reduced, and levels of ALT, AST, high-sensitivity C-reactive protein (hsCRP), total cholesterol, and triglycerides declined, while HDL-C levels increased. Positive correlations were identified between elevated Firmicutes and Actinobacteria and markers of cardiometabolic risk, such as hsCRP and triglycerides.

Conclusion

Gut microbiota dysbiosis is strongly associated with metabolic and inflammatory disturbances in MASLD. Combined probiotic therapy effectively corrected microbial imbalance, reduced systemic inflammation, and improved metabolic and lipid parameters. These findings support the role of microbiota-targeted interventions as an adjunctive approach in the comprehensive management of MASLD.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver pathology globally and is closely associated with metabolic syndrome components, including obesity, insulin resistance, dyslipidemia, and hypertension. Recent evidence emphasizes the significant role of gut microbiota dysbiosis in MASLD pathogenesis, with specific bacterial shifts contributing to metabolic disturbances and systemic inflammation.

Aims & Methods

The aim was to evaluate the gut microbiota composition in MASLD patients and assess the impact of probiotic therapy on metabolic, inflammatory, and lipid profile parameters. The study included 152 patients diagnosed with MASLD. Gut microbiota profiling was conducted using quantitative real-time PCR (qRT-PCR), and metabolic parameters were assessed via biochemical analyses. Patients received a combined probiotic regimen containing Saccharomyces boulardii CNCM I-745, Lactobacillus acidophilus (LA-5), and Bifidobacterium lactis (BB-12) for gut microbiota correction. Changes in biochemical markers, lipid profiles, and microbiota composition were evaluated before and after therapy.

Results

At baseline, MASLD patients showed a marked imbalance in gut microbiota, characterized by increased proportions of Firmicutes (50.3%) and Actinobacteria (15.34%), along with an elevated Firmicutes/Bacteroides (F/B) ratio (5.02). Probiotic intervention significantly reduced Firmicutes and Actinobacteria percentages and lowered the F/B ratio. Biochemically, there were significant decreases in ALT, AST, alkaline phosphatase, high-sensitivity C-reactive protein (hsCRP), total cholesterol, triglycerides, and increases in HDL-C levels. Positive correlations were found between elevated Firmicutes and Actinobacteria abundance and markers of cardiometabolic risk, such as hsCRP and triglycerides.

Conclusion

Gut microbiota dysbiosis plays a crucial role in the metabolic and inflammatory disturbances associated with MASLD. Combined probiotic therapy effectively improved gut microbial composition, reduced systemic inflammation, and positively influenced lipid metabolism, supporting its role as an adjunctive treatment strategy for MASLD.

Clinical Case Summary

Female patient, 53 years old, with personal history of autosomal dominant polycystic kidney disease (ADPKD) with polycystic liver disease that presented to the emergency department with jaundice and choluria. She denied other symptoms, such as fever, nausea or abdominal pain. The patient had started therapy with tolvaptan for ADPKD three months before, suspended after two months due to suspected liver toxicity. The patient denied taking other new medication, consumption of alcohol, herbal products or contact with animals. Laboratory tests revealed elevated C-reactive protein and markedly elevated liver enzymes (>10xULN) with bilirubin level of 6mg/dL. Abdominal ultrasound and CT scan showed an enlarged liver with multiple cysts, the largest measuring 12.5cm in diameter, with heterogeneous content and no mural enhancement and mild dilation of right intrahepatic bile ducts. A diagnosis of cholangitis was considered, empiric antibiotic therapy was initiated, and the patient was admitted. Abdominal MRI on day 7 demonstrated mild to moderate dilation of right biliary ducts, most likely caused by extrinsic compression from liver cysts. Due to this and to worsening cholestasis, with total bilirubin level reaching 11.7mg/dL, ultrasound-guided percutaneous drainage of the larger cyst was performed, without significant improvement in cholestatic parameters. Therefore, a percutaneous liver biopsy was obtained and revealed changes indicative of biliary outflow impairment but also histological evidence of mild resolving hepatitis, suggestive of possible concomitant drug toxicity. The patient improved over time, with normal bilirubin level two months after admission. Liver function was maintained throughout the course of disease. This case illustrates concurrent damage due to liver cysts biliary duct compression but also drug induced liver injury (DILI) caused by tolvaptan, a therapeutic agent with increasing use for slowing the progression of kidney function decline in ADPKD.