Introduction

Pancreatic steatosis (PS) frequently coexists with metabolic dysregulation, including insulin resistance, type 2 diabetes, and obesity. Magnetic resonance imaging (MRI) can be useful in quantifying intrapancreatic fat through the three-dimensional volumetric multi-echo gradient echo sequence (IDEAL-Q) to obtain pancreatic proton density fat fraction (P-PDFF).

Aims & Methods

Our study aims to establish a correlation between P-PDFF and metabolic indices. We enrolled 26 patients with increased parenchymal echogenicity in the pancreatic body on ultrasound evaluation and subsequently subjected them to MRI for quantification of intrapancreatic fat. The mean age of the patients was 56.26 years, including 16 women and 10 men, with an average BMI of 29.33+/- 8.38 kg/m2. Patients underwent standard oral glucose tolerance test (OGTT) with 75g glucose load. We calculated the area under the curve of glucose (AUC-Glu) and insulin (AUC-Ins) responses during OGTT. Further, we evaluated beta-cell function through Disposition Index and Insulinogenic Index and insulin sensitivity through Matsuda Index and Homeostasis Model Assessment Index (HOMA-IR). MRI was performed in order to calculate PDFF within three pancreatic body regions of interest (ROIs). Linear correlations were conducted between mean PDFF and metabolic parameters, including the Matsuda Index, HOMA-IR, Insulinogenic Index, Disposition Index, and BMI.

Results

In the cohort of patients, 73.1% presented normal glucose tolerance (NGT), while the remaining 26.9% displayed impaired glucose tolerance (IGT). Diabetic patients were excluded from the analysis. Stratification of patients was conducted according to the median of P-PDFF. Comparative analysis between these stratified groups revealed no statistically significant differences in Matsuda Index, HOMA-IR, Insulinogenic Index, or Disposition Index. Linear correlations between the mean PDFF and the analyzed metabolic parameters revealed no statistically significant associations, except for BMI (p < 0.05).

Conclusion

Our findings suggest there is no significant correlation between PDFF measured pancreatic steatosis, with glucose levels, insulin secretion and beta cell function. However, PDFF was significantly related to BMI suggesting that overweight and obesity is significantly related to pancreatic fat accumulation. Our study seem to suggest that pancreatic fat accumulation does not impact on endocrine pancreatic function.

Introduction

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established interventional treatment for complications of portal hypertension. Post-TIPS transient or persistent acute bilirubin elevation (ABE) is common, possibly due to impairment of portal perfusion. The outcomes of patients with ABE is not clear.

Aims & Methods

This study investigates the incidence, clinical outcomes, and prognostic factors associated with ABE in cirrhotic patients undergoing TIPS. Between January 2009 and November 2022, 1,287 patients (882 men, 405 women; mean age, 52 years) were included in this retrospective analysis. ABE was defined as a total serum bilirubin level exceeding 85.5 μmol/L (5 mg/dL) within one week after TIPS. Statistical analyses included the Kaplan-Meier method, log-rank test, multivariate Cox regression, and stepwise regression.

Results

Post-TIPS ABE occurred in 67 patients (5.2%). Patients with ABE had significantly higher baseline Child-Pugh scores (8.39 ± 1.62 vs. 7.41 ± 1.54, P < 0.001) and MELD scores (13.98 ± 4.13 vs. 10.72 ± 2.99, P < 0.001). Refractory ascites as the TIPS indication was more frequent in the ABE group (17.91% vs. 7.21%, P = 0.001). ABE was associated with a significantly higher incidence of hepatic encephalopathy (HE): 62.7% vs. 38.3% at 1 year and 80.6% vs. 62.8% at 5 years (P = 0.042). During follow-up, 441 patients died, with causes including liver failure (n = 129), gastrointestinal bleeding (n = 100), sepsis (n = 16), multi-organ dysfunction (MOD) (n = 41), hepatocellular carcinoma (HCC) (n = 43), and other or unknown causes (n = 112). Survival rates were significantly lower in the ABE group: 1-year (52.2% vs. 85.2%), 3-year (34.3% vs. 68.3%), and 5-year (25.4% vs. 46.6%) (P < 0.001). Multivariate analysis identified ABE (hazard ratio [HR]: 2.09; 95% confidence interval [CI]: 1.41–3.10; P < 0.001), age (HR: 1.05; 95% CI: 1.04–1.06; P < 0.001), albumin level (HR: 0.95; 95% CI: 0.94–0.97; P < 0.001), pre-TIPS grade 4 HE (HR: 1.93; 95% CI: 1.19–3.14; P = 0.008), presence of HCC (HR: 1.81; 95% CI: 1.24–2.65; P = 0.002), baseline MELD score (HR: 1.09; 95% CI: 1.04–1.14; P < 0.001), and change in MELD score (HR: 1.08; 95% CI: 1.06–1.11; P < 0.001) as independent predictors of post-TIPS mortality.

Conclusion

AEB is not rare in cirrhotic patients undergoing TIPS and is associated with an increased risk of HE and mortality. Risk factors for post-TIPS mortality include AB, older age, higher and fluctuating MELD scores, concurrent HCC, severe pre-TIPS HE, and lower albumin levels. Early identification, close monitoring, and prompt management of complications are essential to improving clinical outcomes and reducing the risk of liver failure after TIPS.

Clinical Case Summary

Case report: We report a case of a 51-year-old patient who initially presented in 2014 with thrombocytopenia, and splenomegaly. Liver parameters were within the normal range. Comprehensive diagnostic evaluations, including CT scans and liver biopsy, excluded cirrhosis, vascular occlusions, bypass circuits and other potential etiologies such as toxic, autoimmune, or infectious causes. Additional investigations, including bone marrow and spleen puncture as well as genetic tests did not reveal any hematological or neoplastic diseases.
At the age of 66, the patient suffered an episode of variceal hemorrhage due to grade IV oesophageal varices. Subsequently, after referral to our clinic in March 2020, a transjugular portosystemic shunt (TIPSS) was placed for persistent grade III varices (Figure 1), reducing the varices to grade I (2024). Despite successful management of varices, the patient developed mild hepatic encephalopathy, managed with lactulose and rifaximin.
Biopsy revealed nodular regenerative hyperplasia (Figure 2). We diagnosed idiopathic non-cirrhotic portal hypertension (INCPH), an infrequent yet significant clinical entity characterized by intrahepatic portal hypertension without cirrhosis or other liver diseases. Management challenges included the patient's intolerance to non-selective beta-blockers due to sinus bradycardia and ongoing low-grade hepatic encephalopathy, which precluded further TIPSS modification. Future management may include splenic vein embolization should varices recur.
Conclusion: The diagnosis of INCPH necessitates evident portal hypertension, no cirrhosis or advanced fibrosis, and no hepatic or portal vein thrombosis on imaging. Due to limited data, management typically mirrors that of cirrhosis-induced portal hypertension. This case highlights the diagnostic and management challenges of INCPH, stressing the importance of comprehensive assessments to rule out other causes and customize treatment for complications.

Introduction

Hepatic encephalopathy (HE) after Transjugular Intrahepatic Portosystemic Shunt (TIPS) affect 35-50% of patients. The use of prophylactic agents (Lactulose and Rifaximin) to prevent post-TIPS HE remains controversial and currently not recommended by professional guidelines. Our aim was to assess real world practice and identify potential predictors for post-TIPS HE and benefit from post-TIPS prophylaxis.

Aims & Methods

Retrospective cohort study of patients undergoing TIPS at the Tel-Aviv Medical Center (2016-2024). The primary outcome was overt HE, with secondary outcomes of liver transplantation (LT) and mortality.

Results

Seventy-nine patients underwent TIPS, median age was 60 years and 52% were male. Primary liver disease was metabolic dysfunction-associated steatohepatitis (MASH) in 34%, viral (20%), and alcohol-related liver disease (ALD) (16.5%). Indications for TIPS were variceal bleeding (52%) and refractory ascites (38%). Prior to the procedure 31% had ≥ 1 episodes of HE, 21.5% were treated with Lactulose and/or Rifaximin, and 58% were on betablocker treatment. At the time of the procedure, the patient's Child-Pugh score was A/B/C in 19%/66%/11% respectively, with a median MELD-Na of 10.9. Median follow up was 22.75 months. Overall, 22 patients died during follow-up and 8 underwent liver transplantation. 45 patients (57%) developed post-TIPS HE, 60% of them during the first three months. Early post-TIPS HE treatment was given to 49%: 10% Lactulose, 5% Rifaximin, and 34% both. Among those patients, 44% were previously (pre-TIPS) on HE treatment. Development of HE was not predicted by pre-or post-TIPS MELD-Na or Child-Pugh score, TIPS diameter, postTIPS gradient, or post-procedure ammonia levels. Rates of HE also did not differ according to initial prophylaxis treatment (59% with treatment, 56% without, p=1). Pre-TIPS AST and albumin were associated with post-TIPS HE (36.6U/L vs. 60.44 U/L, p=0.03; 34.6g/dl vs. 31.8g/dl, p = 0.05). Prior beta-blocker treatment was associated with post-TIPS HE (14% vs 32%, p = 0.01) but not varices as the indication for TIPS. Mortality rate was not affected by the occurrence of post-TIPS HE (28% among those who developed HE vs. 26% among those who didn't, p = 1).

Conclusion

Early post-TIPS preventive treatment was mostly given to patients previously treated with Lactulose/Rifaximin, however it did not affect the rate of post-TIPS HE. Development of HE did not increase mortality.

References

1. Wolfgang el al. ASSLD practice Guidance, Hepatology (2024)
2. Yao el al.J Gastrointestin Liver Dis (2015)

Clinical Case Summary

Diffuse nodular lymphoid hyperplasia (DNLH) of the gastrointestinal tract is a rare benign disease characterized by multiple polypoid nodules, associated with inborn errors of immunity (IEI) such as common variable immunodeficiency (CVID) and infections like Giardia lamblia. To date, there are few cases reported in Southeast Asia. We present a patient in Singapore with DNLH associated with CVID.
A 39-year-old man presented with one year of intermittent diarrhoea with nocturnal episodes, associated with abdominal pain. Colonoscopy revealed a normal colon, but there were multiple diminutive polyps in the terminal ileum (TI). Histology showed mild chronic inflammation with lymphoid aggregates, without any microorganisms. Magnetic resonance enterography did not identify any sizeable polyps within the small bowel, which would have led to further evaluation for gastrointestinal lymphoma.
Stool studies, sent on a subsequent bout of diarrhoea, returned positive for Giardia lamblia. He was treated with metronidazole but his diarrhoea persisted. On probing further, he had a history of recurrent rhinosinusitis and febrile illnesses since childhood, prompting further laboratory studies which showed a normal full blood count, erythrocyte sedimentation rate of 11mm/hour, and hypogammaglobulinemia. A diagnosis of CVID was made and he was initiated on regular intravenous immunoglobulin (IVIG) replacement with resolution of his diarrhoea.
Surveillance colonoscopy three years later demonstrated prominent lymphoid follicles from the ascending to rectosigmoid colon, in addition to the TI. Histology was consistent with DNLH without dysplasia. He remains well and asymptomatic on regular IVIG.
In summary, as DNLH is associated with IEI and parasitic diseases, it is important to evaluate for these diseases upon diagnosis. DNLH is also associated with gastrointestinal lymphoma that may warrant surveillance, though the clinical course is unclear and there are no guidelines for surveillance.

References

ALBUQUERQUE. A. Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review. World J. Gastrointest. Endosc., 2014, 6 (11) : 534-540.
Illustrative material in final poster
1. Endoscopic image of prominent lymphoid follicles in colon and terminal ileum
2. Pathological image of terminal ileum biopsy demonstrating lymphoid aggregates