Introduction

Currently, non-alcoholic liver disorder (NAFLD) is the most predominant chronic liver disorder. NAFLD has been linked to hepatic and extra-hepatic morbidities. The need for non-invasive prediction of hepatic and extra-hepatic consequences of NAFLD is a demand, due to the complexity of the disease, high burden, and the need for early intervention.

Aims & Methods

to investigate the role of serum microRNA-130b and liver stiffness [as measured by acoustic radiation force impulse (ARFI)], to non-invasively predict chronic kidney disease (CKD) in NAFLD patients.
Patients and Methods: In a case-control design, we included 40 NAFLD patients (20 NAFLD with CKD, and 20 NAFLD without CKD), and 20 healthy controls. After clinical evaluation, laboratory assessments including liver test profile, renal function test, and quantification of microRNA-130b were done. Liver stiffness was evaluated using ARFI.

Results

The median values (interquartile range “IQR”) of mRNA-130b in patients with NAFLD+CKD, patients with NAFLD without CKD, and healthy subjects were [32.10 (27.3 -37.3), 27.01 (24.8 – 31.7), and 25.36 (23.5 – 27.1), copies/µl, respectively, P <0.001]. The median (IQR) value of Liver stiffness as measured by ARFI was significantly higher among NAFLD with CKD patients compared to NAFLD without CKD [2.97 (2.87 – 3.3) vs. 2.45 (2.18 – 2.8) m/sec, P = 0.002]. The median (IQR) value of microRNA-130b was significantly higher among NAFLD with CKD patients compared to NAFLD without CKD [P = 0.032]. In the current study, ARFI readings were negatively correlated with platelet count (n = 40, rs = -0.33, P = 0.038). ARFI readings were positively correlated to serum mRNA-130b values in both groups (rs = 0.49, P = 0.02 and rs = 0.64, P = 0.002, respectively). At a cut-off value > 28.13 copies/µl, microRNA-130b could differentiate between “NAFLD with CKD” and “NAFLD without CKD” patients with a sensitivity and specificity of 75%, and 70 %, respectively (AUC = 71.9 %, P = 0.018, 95% CI: 0.56 – 0.87). Similarly, At a cut-off value > 2.81 m/sec, ARFI could differentiate between “NAFLD with CKD” and “NAFLD without CKD” patients with a sensitivity and specificity of 80% (AUC = 77.8 %, P = 0.003, 95% CI: 0.62 – 0.93).

Conclusion

MicroRNA-130b and liver stiffness measurements are suggested as potential markers for the prediction of CKD among NAFLD patients. Serum microRNA-130b, and ARFI are valuable non-invasive tools for the assessment of NAFLD severity.

Clinical Case Summary

Introduction: Locally advanced pancreatic tumors can lead to both biliary and duodenal obstruction by invasion or compression. Quality of life is severely affected if obstruction occurs: jaundice, emesis and pain can become invalidating and patients become too frail for palliative chemotherapy and are sometimes declared unfit even for derivative surgery. Recently, endoscopic techniques under EUS or ERCP guidance are being used to create biliodigestive and enteral anastomoses.
Clinical case: A 75-year-old female was diagnosed with locally advanced pancreatic head adenocarcinoma in January 2024. The tumor was declared unresectable and chemotherapy was initiated. A plastic stent was inserted into the main biliary duct (MBD) to ensure biliary drainage. In May 2024, she presented with cholangitis and emesis. EGD revealed duodenal stenosis and ERCP failed due to tumor infiltration. A combined endoscopic approach was performed: EUS-guided hepatico-gastrostomy (EHG) for biliary drainage and EUS-guided gastro-enterostomy using a lumen-apposing metal stent (LAMS). In July 2024, the plastic stent was removed, and in August 2024, two fully covered 60 x 10 mm SEMS were inserted antegrade through the EHG into the MBD to improve patency. At 11 months post-intervention, the patient returned for routine reassessment, declaring good clinical performance: she remained asymptomatic, with routine blood tests, including bilirubin levels within normal range and with all stents patent and correctly positioned (confirmed radiologically and endoscopically). The patient was able to maintain oral intake and continue chemotherapy. No late adverse events were noted.
Conclusion: This case demonstrates the long-term clinical and technical success of a staged endoscopic triple bypass for the management of complex biliary and duodenal obstruction due to unresectable pancreatic cancer. The approach was minimally invasive, well tolerated and remarkably improved the patient's quality of life.

References

1. Adler, Douglas G MD; Baron, Todd H MD, FACP. Endoscopic Palliation of Malignant Gastric Outlet Obstruction Using Self-Expanding Metal Stents: Experience in 36 Patients. American Journal of Gastroenterology 97(1):p 72-78, January 2002. | DOI: 10.1111/j.1572-0241.2002.05423.x
2. Giovannini, Marc. (2019). EUS-guided hepaticogastrostomy. Endoscopic Ultrasound. 8. 35. 10.4103/eus.eus_47_19.
3. Dumonceau, Jean-Marc & Tringali, Andrea & Blero, Daniel & Devière, J & Laugiers, R & Heresbach, D & Costamagna, Guido. (2012). Biliary stenting: Indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy. 44. 277-98. 10.1055/s-0031-1291633.
4. Van Der Merwe, S. W., Van Wanrooij, R. L., Bronswijk, M., Everett, S., Lakhtakia, S., Rimbas, M., ... & Van Hooft, J. E. (2022). Therapeutic endoscopic ultrasound: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy, 54(02), 185-205. 10.1055/a-1717-1391

Clinical Case Summary

In advanced chronic liver disease (ACLD) patients, the endoscopic evidence of esophageal and/or gastric varices denotes the presence of clinically significant portal hypertension (CPSH), representing the main clinical consequence of portal hypertension (PH).
In this setting, although infrequently, besides typical sites (i.e., esophagus and stomach), PH-related varices can manifest even in other atypical portosystemic-shunt districts, including the vagina. CSPH-related vaginal varices bleeding can occur as a rare complication documented by limited case reports.
A 62-year-old female patient with viral (eradicated Hepatitis C Virus infection)-related- decompensated (grade 2 ascites)-ACLD, complicated by CSPH (grade F2 esophageal varices), was admitted to our Department in February 2025 for microcitic anemia. Anamnesis revealed a previous gastric cancer managed with total gastrectomy resection in 2021.
On admission, abdominal imaging showed radiological signs of ACLD/PH (coarse pattern, splenomegaly, dilated splenic-portal axis). Esophagogastroduodenoscopy ruled out active sources of bleeding, whereas colonoscopy revealed anal congestive not-bleeding varices. During the hospitalization, an episode of metrorrhagia imposed gynecologic evaluation with vaginal speculum examination. This assessment documented vaginal varices with the relative rupture as the current cause of the bleeding, suggesting this site is the further district for (CS)PH manifestation consequently to potentially occurred total gastrectomy-determined changes in abdominal vascular anatomy.
In ACLD patients receiving surgery altering abdominal vascularization, variceal bleeding represents a possible CSPH-related complication occurring even in atypical sites, such as the vagina. This scenario imposes an adequate tailored management, monitoring unusual bleeding signs, and adopting appropriate preventive strategies by including gynecologic evaluation in follow-up.

References

1. McHugh PP, Jeon H, Gedaly R, Johnston TD, Depriest PD, Ranjan D. Vaginal varices with massive hemorrhage in a patient with nonalcoholic steatohepatitis and portal hypertension: Successful treatment with liver transplantation. Liver Transpl. 2008 Oct;14(10):1538-40. doi: 10.1002/lt.21506. PMID: 18825698.
2. Kreek MJ, Raziano JV, Hardy RE, Jeffries GH. Portal hypertension with bleeding vaginal varices. Ann Intern Med. 1967 Apr;66(4):756-9. doi: 10.7326/0003-4819-66-4-756. PMID: 6067181.
3. Chan G, Taqi A, Drage M, Quan D. A case report of massive vaginal variceal hemorrhage in a patient with cirrhosis secondary to nonalcoholic steatohepatitis unresolved even after successful liver transplantation. Transplant Proc. 2013 Mar;45(2):835-7. doi: 10.1016/j.transproceed.2012.04.033. Epub 2012 Sep 19. PMID: 23267803.
4. Lebrec D, Benhamou JP. Ectopic varices in portal hypertension. Clin Gastroenterol. 1985 Jan;14(1):105-21. PMID: 3872747.
5. Nagata J, et al. Vaginal bleeding in a patient with type C liver cirrhosis without a past history of laparotomy: successful treatment with partial splenic artery embolization. Clin J Gastroenterol. 2012 Aug;5(4):275-81. doi: 10.1007/s12328-012-0316-3. Epub 2012 Jun 30. PMID: 26182393.

Introduction

Recent reports have evaluated the difficult biliary cannulation (DBC) during endoscopic retrograde cholangiopancreatography (ERCP) based on the shape of the papilla ¹⁾²⁾. However, it is more important to elucidate how the difficulty of biliary cannulation changes depending on the morphology of the papilla. We performed a morphological evaluation to investigate the causes of DBC during ERCP, including the relationship between the shapes of the papilla and intra-ampullary pancreaticobiliary bifurcations (IAPBs).

Aims & Methods

We prospectively established a database and retrospectively assessed the difficulty of selective biliary cannulation (SBC) with contrast-assisted cannulation (CAC) during ERCP, in which any morphological IAPBs are visualized. In all cases, both the bile and pancreatic ducts were cannulated or imaged in a naïve major duodenal papilla. The database included papilla shapes with Haraldsson's classification of Type 1-Type 3, the number of papillary orifices classified as Mono or Dual. The IAPBs were classified into four types based on their branching angle (Figure V for acute branching, Figure T for perpendicular branching, Figure X for orifice of bile duct located just above the papillary orifice inside, and​ pancreaticobiliary maljunction classified as Figure I). In addition, small intra-ampullary cysts (choledochocele, IAC) were classified into three types based on their location: the common channel (Ac) type, equivalent to Elton's dilated common channel syndrome ³⁾;, the bile duct (Ab) type, including a cyst within the papilla; and the common bile duct (CBD) type, corresponding to Alonso Lej type III. DBC was defined as cannulation longer than 5 minutes, and when guidewire placement in the pancreatic duct (P-GW) was attempted to facilitate SBC. We conducted a logistic regression analysis to investigate the association among the anatomical morphology of the papilla, the variation of IAPBs, and the presence of IAC.

Results

We analyzed a database of 1,700 consecutive cases. The shape of papilla Type 1 was found in 621 (36.5%), Type 2 in 82 (4.8%), and Type 3 in 997 cases (58.6%). Mono orifice was confirmed in 1,192 cases (70.1%), and P-GW was performed in 709 cases (41.7%). IAC was observed in 203 cases (11.9%). The odds ratio (OR) for DBC in relation to papilla morphology was analyzed with Type 1 as the reference. The OR for Type 2 was 1.9 (95% confidence interval [CI], 1.5-3.0) (p=0.07), and for Type 3, it was 1.7 (95% CI, 1.3-2.1) (p<0.01). In the analysis of the number of orifices, the OR was calculated with Dual as the reference. Mono was 2.5 (95% CI, 2.0-3.2) (p<0.01). In the analysis of IAPBs, the ORs were calculated with Dual as the reference. The ORs for Figures V, T, X and I were 1.6 (95% CI, 1.2–2.1) (p<0.01), 2.4 (95% CI, 1.7–3.2) (p<0.01), 5.1 (95% CI, 3.8–7.0) (p<0.01) and 0.6 (95% CI, 0.3–1.4) (p=0.39), respectively. In the analysis of IAC, the ORs were calculated with the absence of IAC as the reference. The ORs for Ac, Ab and CBD were 1.3 (95% CI, 0.9–2.0) (p=0.17), 1.5 (95% CI, 0.9–2.6) (p=0.14), and 0.6 (95% CI, 0.3–1.4) (p=0.23), respectively. When the shape of papilla was Type 3 and had a Mono orifice with IAPBs of Figures V, T, or X, the difficulty of SBC significantly increased.

Conclusion

Our study suggests that morphological DBC depends not only on the shape of the major duodenal papilla, but also on the number of orifices, the type of IAPBs, and the presence of IAC. Sometimes, IAPBs can exhibit unexpected bifurcations that make SBC difficult. To overcome this difficulty, it is important to perform SBC using CAC to confirm IAPBs.

References

1) Haraldsson E et al, Macroscopic appearance of the major duodenal papilla influences bile duct cannulation: a prospective multicenter study by the Scandinavian association for digestive endoscopy study group for ERCP. Gastrointest Endosc 2019;90:957–963
2) Rachid Mohamed et al, Morphology of the major papilla predicts ERCP procedural outcomes and adverse events; Surg Endosc. 2021 December ; 35(12): 6455–6465
3) E Elton et al, Dilated Common Channel Syndrome: Endoscopic Diagnosis, Treatment, and Relationship to Choledochocele Formation Gastrointest Endosc. 1998 ;47:471-8.

Clinical Case Summary

Sarcoidosis is a multisystem disease characterized by the presence of non-caseating granulomas in affected organs. Hepatic involvement is often silent and underdiagnosed. Otherwise, it can result in cholestasis and, more rarely, portal hypertension (PH) in long-standing hepatic disease. Here, we report the case of portal vein thrombosis (PVT) in a non-cirrhotic patient, revealing systemic sarcoidosis. A 58-year-old male presenting with dull abdominal pain and erythematous skin nodes on the lower limbs. The initial lab analysis revealed an elevation in GGT to 2.5 ULN and an elevated CRP level at 30 mg/L. Abdominal ultrasound showed dysmorphic liver and portal cavernoma. Thoraco-abdominopelvic CT revealed hilar and mediastinal enlarged lymph nodes, dysmorphic liver, thrombotic material within portal vein and the consequent development of a portal cavernoma and perisplenic collaterals. Ultrasound elastography showed a result of 4,4 KPa. Esophagogastroduodenoscopy was negative for varices. Thorough immunological workup, homocysteine, protein C and anti-thrombin III S assays were normal. The search for JAK2V617F and factor II mutations were negative as well as the flow cytometric measurement of PNH clone. Tuberculosis screening, including a tuberculin test, a chest x-ray and interferon gamma release assay (IGRA) was negative. Calcium and phosphorus levels were normals. Angiotensin converting enzyme (ACE) level was high at 101 UI/L. Spirometry, bronchial fibroscopy and bronchoalveolar lavage were normals. Skin biopsy showed granulomatous dermatitis without caseous necrosis. Liver biopsy revealed the presence of non-caseating granulomas in the lobules. Based on these results, the diagnosis of multisystemic sarcoidosis has been retained. The patient was put on direct oral anticoagulants, corticosteroids and hydroxychloroquine. His symptoms improved and a follow-up CT scan done four months later showed a repermeabilisation of the portal vein.

Disclosure

There is not any actual or potential conflict of interest

Introduction

Hepatocellular Carcinoma (HCC) is a major type of primary liver cancer and one of the most frequent human malignant neoplasm. Owing to the lack of reliable clinical HCC markers, fewer than 20% of patients are diagnosed at a stage where curative treatment can be performed. It is now clear that microRNAs (miRNAs) can potentially regulate every aspect of cellular activity, including differentiation and development and proliferation; they play a role in regulating apoptotic cell death and tumorigenesis. MiRNA‑192 is hepatocyte‑specific miRNA and it is released from damaged hepatocytes early in liver injury in animal models have made miRNA‑192 an attractive biomarker for liver damage. Many studies have demonstrated that miRNA expression profiles in HCC and nontumor tissue are significantly different.

Aims & Methods

The aim is to evaluate the role of serum miRNA‑192 as potential serum marker of HCC among HCV related liver cirrhosis.
The study was carried out on 80 Egyptian patients with HCV related liver cirrhosis (Liver cirrhosis (LC) group: 40 patients with HCV related liver cirrhosis without HCC and HCC group: 40 patients with HCV related liver cirrhosis and HCC) and 20 healthy volunteers as controls from Menoufia University Hospitals (Egypt). They underwent history taking, physical examination and laboratory investigations (CBC, liver profile {ALT, AST, albumin, bilirubin, INR}, urea, creatinine, AFP, HBsAg, HCV Ab and serum miRNA‑192). Abdominal ultrasonography was done for all patients and controls. HCC is further confirmed by triphasic CT. Patients with malignancy other than HCC, received previous treatment for HCC or chronic liver disease other than HCV were excluded from the study.

Results

In HCC group, according to BCLC classification, one patient (2.5%) at very early stage, 3 (7.5%) at early stage, 13 (32.5%) at intermediate stage, 8 (20%) at advanced stage and 15 (37.5%) at terminal stage. In HCC group, 10 patients (25%) had HCC size˂3 cm and 30 patients (75%) had HCC size˃3 cm. 65% of the patients (n=26) had single lesion, 5% (n=2) had 2 lesions and 30% (n=12) had multifocal lesions. Eleven patients (27.5%) have portal vein thrombosis (PVT). Serum miRNA‑192 ratio was significantly higher in HCC group (195.8±256.3) than LC (42.6±35.6) and control group (25.7±18.2) (P=0.001 for all) but there was no significant difference between LC and controls (P=0.06). In HCC group, miRNA‑192 ratio was higher in patients with tumor size ˃3 cm (317.9±402) than tumor size ˂3cm (170.7±254.5) (P=0.02) but there was no significant difference according to number of focal lesion or presence of PVT (P˃0.05). AFP level (ng/ml) was significantly higher in HCC group (6572±12563) than LC (28.1±35.1) and control group (14.7±13.3) (P=0.006 for both) but there was no significant difference between LC and controls (P=0.1). Serum miRNA‑192 ratio cutoff level >62.6 have 77.5% sensitivity and 82.5% specificity for detection of HCC. AFP at cutoff level >35.7 ng/ml have 70% sensitivity and 65% specificity for detection of HCC. MELD score, APRI score and FIB-4 were significantly higher in HCC group (20.5±3.5, 3.2±2.7 and 7.2±4.5 respectively) than LC group (7.9±2.2, 0.76±0.92 and 2.3±2.9 respectively) (P˂0.001 for all). In HCC and LC groups, there was a significant positive correlation between miRNA‑192 ratio and AFP (P˂0.001)

Conclusion

MiRNA‑192 could be used as a diagnostic biomarker for detection of HCC in HCV‑related cirrhosis, as it showed significant upregulation in patients with HCC in comparison with non‑HCC patients with higher sensitivity and specificity than AFP for detection of HCC.

References

1-Giordano S and Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology 2013; 57:840–847.
2-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012; 56:1946–1957.
3-Blanco‑Calvo M, Calvo L, Figueroa A, Haz‑Conde M, Anton‑Aparicio L, Valladares‑Ayerbes M. Circulating microRNAs: molecular microsensors in gastrointestinal cancer. Sensors 2012; 12:9349–9362.
4-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases.
Hepatology 2012; 56:1946–1957.