Introduction

Ustekinumab has been shown to be effective in the treatment of UC. Data on its effectiveness in clinical practice are needed both in the short and long term.

Aims & Methods

Primary aim: To assess the durability of ustekinumab treatment in patients with ulcerative colitis (UC).
Secondary aims: To assess the short-term effectiveness, the durability of response, and the tolerability of ustekinumab in clinical practice.
Methods: Retrospective, multicenter study including UC patients who had received the 1^st ustekinumab dose at least 16 weeks before inclusion. Patients were followed-up from the 1^st ustekinumab dose to treatment discontinuation or last visit. Only patients with active disease [Partial Mayo Score (PMS)>2] at ustekinumab start were considered in the effectiveness analysis. Clinical effectiveness was based on PMS. Patients who stopped ustekinumab before their last visit were considered not in remission at subsequent time points (negative imputation).

Results

620 patients with UC were included, 57% with extensive colitis, 95% exposed to biologics (mean number of biologics 2), and 25% to tofacitinib. 78% of patients who started ustekinumab maintenance treatment, did it with 90 mg every-8-weeks dose. 155 patients (25%) withdrew ustekinumab during follow-up [median=12 months (m)]. Incidence rate of ustekinumab discontinuation was 20% per patient-year of follow-up. The probability of maintaining ustekinumab was 78% at 1 year and 68% at 2 years. Among patients who withdrew ustekinumab, the main reasons were primary non-response (39%) and loss of response (35%). Anaemia at baseline (HR=1.5, 95%CI=1.1-2.1), steroids at baseline (HR=1.5; 95%CI=1.06-2.08), and more severe clinical activity at baseline (HR=1.5; 95%CI=1.09-2.06) were associated with higher risk of ustekinumab discontinuation. At the end of the induction (week 16), 226 (40%) patients were in steroid-free remission; 11 (20%) patients were in steroid-free remission at week 4, and 191 (34%) at week 8. In the long-term, the proportion of patients in steroid-free remission was 50% at 1 year, 49% at 2 years and 49% at 3 years. Moderate-severe vs. mild disease activity at baseline (OR=0.3, 95%CI=0.2-0.5), male sex (OR=0.5; 95%CI=0.4-0.8), and increased number of previous biologics (OR=0.6, 95%CI=0.6-0.8) were associated with lower likelihood of steroid-free remission at week 16. A total of 57 (25%) patients among those with active disease at baseline and with steroid-free remission at week 16, lost response during a median follow-up of 8 m (IQR=3-16 m); 75% of patients maintained effectiveness at 1 year, and 57% at 2 years. The dose was escalated in 72% of patients with loss of response, and 80% improved (67% remission); an intravenous reinduction was given in 3 patients, and none of them improved. A total of 176 patients (28%) had at least one adverse event, with infections being the most frequent (11%). No negative impact on extraintestinal manifestations and/or immunomediated diseases was seen.

Conclusion

Ustekinumab was effective in inducing remission even in highly refractory UC patients. A proportion of patients discontinued the treatment, mostly due to primary failure and loss of response. Dose escalation may be effective to regain response after loss of effectiveness. The safety profile was consistent with previous studies.

Disclosure

This is an investigator-initiated study with financial support from Janssen (CNTO1275UCO4008).

Introduction

Endoscopic ultrasound-guided tissue acquisition, including both fine needle aspiration (EUS-FNA) and fine needle biopsy (EUS-FNB), has been widely performed to obtain samples from pancreatic and non-pancreatic lesions.^{1, 2} The impact of the diagnostic yield between FNA and FNB remains unclear.

Aims & Methods

We conducted this study to compare the diagnostic performance and accuracy of the 22-gauge FNA needles with the 22-gauge FNB needles in sampling solid pancreatic and non-pancreatic lesions. This is a prospective multicenter study conducted on 465 cases presented with solid pancreatic or non-pancreatic lesions.

Results

Patients were 275 male and 190 females with a mean age of 59 years. Three hundred twenty-seven patients had solid pancreatic lesions, while 138 had non-pancreatic lesions; 245 cases underwent EUS-FNA, and the remaining 211 cases underwent EUS-FNB. The presence of intact tissue core and sample adequacy were significantly higher in the FNB cases in solid pancreatic and non-pancreatic lesions. Blood contamination was significantly more in cell blocks and smears of EUS-FNA compared to that of EUS-FNB in solid pancreatic and non-pancreatic lesions. Based on histologic assessment of cell block only, EUS-FNB had more diagnostic accuracy (99%) than FNA (61%) (P-value<0.005). However, cytological diagnosis by smears only showed no significant difference. The combined cytological and histological evaluation had 100% sensitivity, specificity, and accuracy.

Conclusion

EUS-FNA and EUS-FNB have comparable accuracy in diagnosing solid pancreatic and non-pancreatic lesions without ROSE. EUS-FNB is superior to EUS-FNA in acquiring intact tissue core and adequate samples with little blood contamination. Based on histological assessment (cell block/tissue core) only, EUS-FNA has less accuracy than EUS-FNB in diagnosing solid pancreatic lesions.

References

1. Wani S, Muthusamy VR, McGrath CM, et al. AGA white paper: opti- mizing endoscopic ultrasound-guided tissue acquisition and future di- rections. Clin Gastroenterol Hepatol 2018; 16: 318-27.

1. Wong T, Pattarapuntakul T, Netinatsunton N, et al. Diagnostic performance of endoscopic ultrasound-guided tissue acquisition by EUS-FNA versus EUS-FNB for solid pancreatic mass without ROSE: a retrospective study. World J Surg Oncol. 2022; 20(1): 215. doi:10.1186/s12957-022-02682-3.

Clinical Case Summary

The ubiquitous availability of digital media does not only have advantages. Inexperienced mushroom pickers increasingly frequently use APPs for mushroom identification and consume forest mushrooms with false security. Currently, for example, life-threatening Amanita phalloides poisoning is becoming more frequent.
A 65-year-old patient presented with a latency period of approximately 40 hours after consumption of the mushrooms. Nausea and vomiting, as well as loss of strength and cramps in arms and legs, had already been present for about 24 hours. Laboratory tests revealed coagulation failure and markedly elevated transaminases (INR 2.1, GOT 2590 U/l, GPT 3119 U/l). The Meld Score was 33. Only when asked explicitly the patient reported eating wild mushrooms he had collected. The vomit and mushroom debris were recovered and immediately examined by a mushroom expert. Immediately after admission to our intensive care unit, liver protective therapy with Silibinin and N-Acetylcysteine was initiated.
Analysis by a fungal expert revealed evidence of Amanita phalloides. At an INR of 3.3 with massive diffuse skin hemorrhages and rising transaminases (GOT 4825U/l, GPT 4104U/l), repeated therapeutic plasma exchange (exchange of 1.3 times the plasma volume) was performed to control the complications of liver failure. In the course, transaminases and coagulation parameters stabilized, and liver transplantation was not necessary. The patient is now in excellent general health.
Our patient case shows that early diagnosis, as well as therapy, are crucial to reducing the lethality of tuberous leaf fungus poisoning. Patients are often unaware of the danger, so if they have symptoms, they should be asked explicitly about consuming collected mushrooms. As a bridging therapy for the stabilization and regeneration of liver function, therapeutic plasma exchange is an excellent option.

Disclosure

No conflicts of interests

Introduction

The incidence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) are notably higher in individuals diagnosed with type 2 diabetes mellitus (T2DM). However, studies evaluating the progression of MASLD in patients with T2DM and normal serum aminotransferase (ALT) levels are limited.

Aims & Methods

This 5-year prospective cohort study aimed to evaluate the progression of MASLD in T2DM patients with normal ALT. People with type 2 diabetes who had MASLD (defined by controlled attenuation parameter (CAP) >250 dB/min) and ALT levels that stayed normal (defined by ALT ≤40 IU/L for at least two occasions spanning at least six months) at Rajavithi Hospital, Bangkok, from November 2016 to 2017 were included. We excluded patients with viral hepatitis and alcohol consumption exceeding moderate levels. Transient elastography (TE) and CAP measurements were performed at baseline and ≥5 years of follow-up. The cutoffs to define significant and advanced fibrosis were TE >8 kPa and TE >12 kPa, respectively. All patients were instructed to reduce their weight and abstain from herbal remedies; medications for comorbidities were prescribed without limitations, subject to the physician's assessment. (most patients were under endocrinologist care.)

Results

The study included 84 patients, 57% of whom were female and had a mean age of 58.5 years. Of these, 62% were obese, with a mean BMI of 28.6 kg/m2. At baseline, the median TE was 6.92±3.35 kPa; 57 (68%) had no significant fibrosis, 22 (26%) had significant fibrosis, and 5 (6%) had advanced fibrosis, and after a 5-year follow-up, the median TE was 6.54±3.57 kPa; 69 (82%) had no significant fibrosis, 15 (18%) had significant fibrosis, and 2 (2%) had advanced fibrosis. During the follow-up, fibrosis decreased in 45 (54%), remained stable in 6 (7%), and increased in 33 (39%) patients, while a small proportion of patients experienced changes in the stages of fibrosis: 1.2% progressed from significant to advanced fibrosis; 17.4% regressed from advanced to significant fibrosis or transitioned from significant to no fibrosis; 12.8% remained stable with significant and advanced fibrosis; and the majority (66.3%) remained without significant fibrosis. A significant factor associated with fibrosis progression was alcohol consumption (p=0.013), while the use of angiotensin receptor blockers (p=0.042) was associated with fibrosis regression. Significant factors associated with steatosis progression included high baseline BMI (p=0.013), an increase in BMI ≥ 5% (p=0.04), high fasting plasma glucose, and LDL cholesterol levels, while a decrease in BMI ≥ 5% (p=0.002) the use of calcium channel blockers (p=0.038) and coffee consumption >3 cups per day (p=0.031) were associated with steatosis regression. ALT elevation during the follow-up occurred in a small proportion of patients, and it was not significantly associated with fibrosis or steatosis progression.

Conclusion

The majority of MASLD patients with T2DM and normal ALT maintained a relatively stable liver disease during 5 years of follow-up. Obesity, weight gain, alcohol consumption, and inadequate metabolic control were all associated with the progression of MASLD, whereas weight loss, coffee consumption, angiotensin receptor blockers, and calcium channel blockers were all associated with the improvement of MASLD.

Disclosure

I have nothing to disclose

Clinical Case Summary

Familial intrahepatic cholestasis is a heterogeneous group of genetic diseases with autosomal recessive transmission. BSEP (Bile-Salt Export Pump) is the main bile acid export pump in hepatocytes. Mutations in the gene encoding BSEP, ABCB11, are associated with heterogeneous clinical phenotypes ranging from diseases with a benign course to severe forms requiring liver transplantation. Here we report the case of a 17-year-old girl admitted to our Clinic because of severe jaundice and itching. She reported a similar episode 2 years earlier with spontaneous recovery. Family history is positive for cholelithiasis. On admission, laboratory tests showed: total and direct bilirubin values of 24.5 mg/dl and 18.9 mg/dl, AST 307 IU/L and ALT 238 IU/L, respectively. GammaGT was normal. Viral, autoimmune, metabolic causes, and biliary obstruction were excluded. Liver biopsy showed a picture of hepatocellular and intracanalicular cholestasis with cholestatic rosettes, inflammatory activity, and mild portal and pericellular fibrosis. Immunohistochemical staining for BSEP showed only weak diffuse expression. Genetic testing documented compound heterozygosity of the ABCB11 gene with the variants c.1460G>A - p(Arg487His) of paternal origin and c2599C>T -(Gln867*) of maternal origin. Genetic testing of relatives is also ongoing. The patient was treated with ursodesoxycholic acid, cholestyramine and cetirizine for 4 months with disappearance of jaundice and pruritus and normalization of bilirubin levels. Follow-up at 1 year was free of events without therapy. This is the first time that the c2599C>T -(Gln867*) variant has been described in a patient with familial intrahepatic cholestasis. Application of the "temporal test" will allow this new variant to be attributed to the BRIC2 form rather than PFIC2.