Clinics and research in hepatology and gastroenterology最新文献

Background and aims

The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group.

Methods

Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia).

Results

124 patients were identified: 83 with known diagnoses, 16 with TCHep, and 25 with IND-Hep. Patients with TCHep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8–8.9) vs 1.5 mg/dL (IQR 1.0–3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073–5771) vs 2997 IU/mL (IQR 1957–3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0–20.0) vs 1.0 % (IQR 0.8–1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8–54.8) vs 4.0 % (IQR 2.5–5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TCHep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5–33.5) vs 23.6 % (IQR 19.8–25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5–24.5) vs 2.7 (1.8–5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated.

Conclusions

Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure.

Introduction

Experimental hepatopulmonary syndrome (HPS) is best reproduced in the rat common bile duct ligation (CBDL) model. Vildagliptin (Vild) is an anti-hyperglycemic drug that exerts beneficial anti-inflammatory, anti-oxidant and anti-fibrotic effects. Therefore, the present search aimed to explore the possible effectiveness of Vild in CBDL-induced HPS model.

Methods

Four groups of male Wistar rats which weigh 220–270 g were used, including the normal control group, the sham control group, the CBDL group and CBDL+Vild group. The first three groups received i.p. saline, while the last group was treated with i.p. Vild (10 mg/kg/day) from the 15th to 28th day of the experiment.

Results

CBDL decreased the survivability and body weight of rats, increased diameter of the pulmonary vessels, and altered the arterial blood gases and the liver function parameters. Additionally, it increased the pulmonary expressions of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) mRNA as well as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) proteins. The CBDL rats also exhibited elevation of the pulmonary interleukin-6 (IL-6), dipeptidyl peptidase-4 (DPP-4) and nitric oxide (NO) levels along with reduction of the pulmonary total anti-oxidant capacity and glucagon-like peptide-1 (GLP-1) levels. Vild mitigated these alterations and improved the histopathological abnormalities caused by CBDL.

Conclusion

Vild effectively attenuated CBDL-induced HPS through its anti-oxidant and anti-inflammatory effects along with its modulatory effects on ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling implicated in the regulation of intrapulmonary vasodilatation and angiogenesis, respectively.

Background

Diabetes and obesity are associated with altered lipid metabolism and hepatic steatosis. Studies suggest that increases in lipid accumulation in these patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are not uniform for all lipid components. This study evaluates this variation.

Methods

A comprehensive lipidomic analysis of different lipid groups, were performed on liver tissue and plasma samples obtained at the time of histology from a well-defined cohort of 72 MASLD participants. The lipid profiles of controls were compared to those of MASLD patients with obesity, diabetes, or a combination of both.

Results

MASLD patients without obesity or diabetes exhibited distinct changes in the lipid profile of their liver tissue. The presence of diabetes or obesity further modified these lipid profiles (e.g., ceramide 47:7;4O), with positive or negative correlation (p < 0.05). A step-wise increase (long-chain fatty acids, triglycerides, and ceramides) or decrease (ultra-long fatty acids, diglycerides, and phospholipids) for lipid groups was observed compared to control among patients with MASLD without obesity or diabetes to MASLD patients with obesity as a single risk factor, and MASLD patients with obesity and diabetes. Changes in lipids observed in the plasma did not align with their corresponding liver tissue findings.

Conclusion

The changes observed in the composition of lipids are not similar in patients with obesity and diabetes among those with MASLD. This highlights the different metabolic processes at play. The presence of obesity or diabetes in patients with MASLD exacerbates these lipid derangements, underscoring the potential for targeted intervention in MASLD patients.

A 62-year-old man with a past history of sleep apnea syndrome, umbilical and left inguinal hernia repairs, was referred to the emergency room for acute respiratory distress. He had underwent a screening colonoscopy 12 h earlier for a family history of colonic adenoma. This colonoscopy was complete, normal, and uneventful.

A plain chest X-ray showed a distended colon extending to the upper third of the right side of the chest (Fig. 1). Further anamnesis helped the patient to remember a right diaphragmatic hernia, well-documented by CT-scan years ago. He had not previously mentioned this condition, when evaluated for colon screening.

The patient was admitted to the surgical intensive care unit. A CT-scan confirmed a right diaphragmatic hernia with terminal ileum and ascending colon content, no sign of mesenteric ischemia, and massive pulmonary collapse. Conservative treatment with nasogastric suction quickly improved the patient's condition. He was discharged at day-6. Diaphragmatic hernia repair was scheduled 10 weeks later. Laparoscopy showed a complete agenesis of the right diaphragmatic dome (Fig. 2; Fig. 3), and was therefore converted into laparotomy for complete surgical repair. Postoperative course was unremarkable. Patient was discharged on day-6. Follow-up at 1 month was uneventful.

Congenital diaphragmatic hernias are rare and usually diagnosed in the pre- natal period or in neonates with respiratory distress, calling for emergency neonatal repair [1,2]. In underdiagnosed or neglecting adults, the condition can be life-threatening, as seen in our patient [3,4]. Surgical repair is therefore strongly recommended, even in asymptomatic patients [5]. Recurrences are exceptional.

Background and aim

Long non-coding RNAs (lncRNAs) play an important role in tumor progression, including in hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV). Therefore, the aim of this study was to investigate the role of LINC02532 in HCC, mainly for diagnostic prognostic value and cellular function, as well as mechanistic aspects.

Methods

Initially, GEO and VirBase databases were used to screen for aberrant lncRNAs in HBV-HCC.Then, HBV-HCC persons followed up in our center were retrospectively studied to investigate the diagnostic, prognostic value of LINC02532 in HBV-HCC. Subsequently, the role of LINC02532 in HBV-HCC was measured using cellular function assay methods and possible mechanisms were analyzed in conjunction with bioinformatic predictive science.

Results

LINC02532 was a lncRNA abnormally expressed in HBV-HCC. LINC02532 was significantly up-regulated in the expression level in HBV-HCC tissues compared with normal tissues from patients. Moreover, LINC02532 could distinguish HBV-HCC and predict the prognosis of HBV-HCC. In vitro experiments showed that LINC02532 could regulate miR-455–3p and promote the malignant characterization of HBV-HCC cells. CHEK2 was a target gene of miR-455–3p.

Conclusions

: The prognosis and diagnosis of HBV-HCC can rely on the expression of LINC02532. LINC02532 was important for further progression of HBV-HCC, by moderating miR-455–3p/CHEK2.

Background

Patients treated with direct-acting antivirals for hepatitis C exhibit high cure rates and improved survival. However, there is limited knowledge on their long-term clinical evolution.

Aims

In this study, we aimed to analyse the risk of hepatocarcinoma and hepatic decompensation in patients treated with direct-acting antivirals.

Methods

We conducted a retrospective single-centre study of Portuguese patients with advanced fibrosis treated with direct-acting antiviral agents between 2015 and 2022 at a tertiary hospital.

Results

Out of 460 patients, 50 (10.9 %) developed hepatocarcinoma and 36 (7.8 %) experienced hepatic decompensation. The risk for hepatocarcinoma was higher in patients aged over 55 (HR 4.87, 95 % CI 2.34–10.13, p < 0.001), with signs of portal hypertension (HR 3.83, 95 % CI 2.05–7.13, p < 0.001) and arterial hypertension (HR 1.98, 95 % CI 1.09–3.58, p = 0.024). Alcohol consumption (HR 3.30, 95 % CI 1.22–8.94, p = 0.019), signs of portal hypertension (HR 4.56, 95 % CI 2.19–9.48, p < 0.001) and hepatocarcinoma (HR 3.47, 95 % CI 1.69–7.10, p < 0.001) increased the risk of hepatic decompensation.

Conclusion

Our study found a high incidence of hepatocarcinoma and hepatic decompensation, along with high mortality, in patients with advanced fibrosis treated with direct-acting antivirals. We identified risk factors such as arterial hypertension, alcohol consumption, and signs of portal hypertension, highlighting their role in clinical management and patient monitoring.

Background and aims

Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) poses a heightened cardiovascular risk. Identifying efficient biomarkers for early MASLD detection in resource-limited Latin American regions is crucial. We aimed to evaluate the diagnostic efficacy of sixteen biomarkers for MASLD in Mexican individuals.

Methods

In this cross-sectional and analytical study, steatosis was assessed using vibration-controlled transient elastography. MASLD was defined according to international standards. Assessed biomarkers included: Visceral Fat (VF), Waist Circumference (WC), Waist-Height Ratio (WHtr), Waist-Hip Ratio (WHr), Visceral Adiposity Index (VAI), Hepatic Steatosis Index (HSI), Body Mass Index (BMI), Homeostatic Model Assessment (HOMA), Weight-Adjusted-Waist Index (WWI), Lipid Accumulation Product (LAP), Uric Acid-Creatinine Ratio (UACR), Triglyceride-Glucose Index (TyG) and its variants TyG-WC, TyG-HDL, TyG-BMI, TyG-WHtr.

Results

161 participants were included, of which 122 met MASLD criteria (56 % women, age 53.9 years [47.5–64]) and 39 were healthy controls (76 % women, age 52 [45–64]). The AUROCs of the biomarkers for MASLD were: TyG-WC (0.84), LAP (0.84), TyG-BMI (0.82), TyG-WHtr (0.80), WC (0.78), TyG (0.77), WHtr (0.75), BMI (0.76), VF (0.75), HSI (0.75), TyG-HDL (0.75), WHr (0.72), VAI (0.73), UA/CR (0.70), HOMA (0.71), and WWI (0.69). Sex-based differences were observed. After adjusting for sociodemographic variables, the TyG-WC index was the best predictor of MASLD.

Conclusions

In conclusion, our results underscore the potential of several noninvasive biomarkers for MASLD assessment in a Mexican population, highlighting variations in diagnostic efficacy and cut-off values between sexes. After adjusting, TyG-WC was the best MASLD predictor.

Objective

To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA).

Methods

This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events.

Results

Twenty patients (8 females and 12 males; age range 1–26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3–8) versus 14 (5–25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2–101) and 22 (4–41) months, respectively. Two patients in conventional group died of disease progression and infection.

Conclusions

RTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.