Clinics and research in hepatology and gastroenterology最新文献

Background

Inflammation played a critical role in non-alcoholic fatty liver disease (NAFLD). Here, we aimed to explore the relationship between inflammatory biomarkers and the prevalence of NAFLD and hepatic fibrosis in US participants.

Methods

Individuals with complete data from National Health and Nutrition Examination Survey (NHANES), 2017–2020 pre-pandemic cycle dataset were referred to this study. We identified NAFLD by vibration-controlled transient elastography (VCTE) on the basis of controlling attenuation parameter (CAP) ≥274dB/m. Liver fibrosis was confirmed by liver stiffness measurement (LSM) ≥8.2kPa. Multivariate logistic regression models were applied to estimate the correlations between inflammatory biomarkers and the prevalence of NAFLD and hepatic fibrosis based on sample weights.

Results

All together 5026 subjects were incorporated into the study cohort. Among these subjects, 2209 were classified as having NAFLD, and 8.35 % were diagnosed with hepatic fibrosis. Pan immune inflammatory value (PIV), instead of systemic immune inflammatory index (SII), was positively correlated with the rate of NAFLD or hepatic fibrosis. Subgroup analysis for NAFLD revealed that the positive relationships of the PIV existed in males (OR=1.52, 95 % CI: 1.01–2.28, p = 0.046) and participants below 60 years of age (OR=1.49, 95 % CI: 1.05–2.1, p = 0.028). Moreover, subgroup analysis for hepatic fibrosis revealed that the positive relationships of the PIV existed in females (OR=2.09, 95 % CI: 1.2–3.63, p = 0.014) and participants below 60 years of age (OR=1.74, 95 % CI: 1.09–2.77, p = 0.023).

Conclusions

A higher PIV, but not SII, is associated with a higher likelihood of NAFLD and liver fibrosis, suggesting that the PIV is a more valuable inflammatory marker for assessing NAFLD and liver fibrosis in participants, especially for those who are below 60 years of age.

Background

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum antimitochondrial antibody levels in 90–95 % of cases. However, the exact causal relationship between mitochondrial proteins and PBC remains unclear. This study aims to investigate and clarify this relationship.

Methods

Genome-wide association data for mitochondrial proteins and PBC were obtained from public databases. The assessment of causal relationships between exposures and outcomes employed the Inverse Variance Weighted (IVW) method, MR Egger regression, and Weighted Median. Sensitivity analyses were systematically carried out to appraise the robustness of the Mendelian Randomization (MR) findings.

Results

The analysis revealed two mitochondrial proteins exhibiting a causal relationship with PBC. Elevated SIRT5 levels demonstrated a positive correlation with an augmented susceptibility to PBC in the IVW approach (odds ratio, OR: 1.2907, 95 % CI: 1.062–1.568, p = 0.0102). Conversely, increased MRPL33 levels were associated with a decreased risk of PBC (OR: 0.8957, 95 % CI: 0.807–0.993, p = 0.0376). Sensitivity analysis corroborated these findings consistently.

Conclusion

This investigation advances the notion of a potential causal association between elevated SIRT5 levels and an increased risk of PBC, alongside a decreased risk of PBC linked to elevated MRPL33 levels. The identified mitochondrial proteins may serve as viable biomarkers, offering pertinent insights for the understanding and addressing of PBC.

Objectives

Colonic volvulus is a common cause of bowel obstructions and surgery is the definitive treatment. Functional status is often associated with adverse postoperative outcomes but its effect on colectomy for volvulus remained under-explored. This study sought to analyze the effect of functional status on the 30-day outcomes of colectomy for volvulus.

Materials and method

National Surgical Quality Improvement Program (NSQIP) targeted colectomy database from 2012 to 2022 was utilized. Only patients with volvulus as the primary indication for colectomy were included. Thirty-day postoperative outcomes were compared between patients with dependent functional status (DFS) and independent functional status (IFS), adjusted for demographics, baseline characteristics, preoperative preparation, indication for surgery, and operative approaches by multivariable logistic regression.

Results

There were 1,476 patients with DFS (945 partially DFS and 531 fully DFS) and 8,824 (85.67 %) IFS patients who underwent colectomy for volvulus. After multivariable analysis, DFS patients had higher risks of mortality (aOR=1.671, 95 CI=1.37–2.038, p < 0.01), pulmonary complications (aOR=2.166, 95 CI=1.85–2.536, p < 0.01), sepsis (aOR=1.31, 95 CI=1.107–1.551, p < 0.01), prolonged postoperative nothing by mouth (NPO) or nasogastric tube (NGT) use (aOR=1.436, 95 CI=1.269–1.626, p < 0.01), discharge not to home (aOR=3.774, 95 CI=3.23–4.411, p < 0.01), and 30-day readmission (aOR=1.196, 95 CI=1.007–1.42, p = 0.04). Moreover, DFS patients had a longer length of stay (p = 0.01).

Conclusion

DFS was identified as an independent risk factor for increased mortality and complications after colectomy for volvulus. Given the substantial overlap between DFS patients and those who have colonic volvulus, these insights can contribute to preoperative risk assessments and postoperative care in these patients.

Background

Genetic testing can be used to evaluate disease risk. We evaluated if the use of three Single Nucleotide Polymorphisms (SNPs), alone or combined into a genetic risk score (GRS), can aid identify significant fibrosis in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods

We assessed three known risk variants: PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567. The study included 414 adult individuals invited from the Danish population, who were defined as at-risk of MASLD due to elevated ALT and body mass index (BMI) >25 kg/m². Participants were assessed clinically and by the Fibrosis-4 (FIB-4) index and Fibroscan.

Results

In total, 17 participants (4.1 %) had alcohol-related liver disease, 79 (19.1 %) had no evidence of liver disease, and four (1.0 %) were diagnosed with other liver diseases, including malignant disease. The remaining 314 participants (75.8 %) were diagnosed with MASLD. Of the 27 who underwent a liver biopsy for suspected fibrosis, 15 had significant fibrosis (≥F2) and 12 had no/mild fibrosis (F0/F1). The GRS was not associated with significant fibrosis (p = 0.09) but PNPLA3 was with an odds ratio of 6.75 (95 % CI 1.29 – 50.7; p = 0.039) risk allele CG/GG versus CC. The diagnostic accuracy of PNPLA3 combined with an increased Fib-4 (>1.3) was excellent for detecting significant fibrosis with a sensitivity of 1.00 (95 % CI 0.72–1.00), but the specificity was no better than for FIB-4 alone.

Conclusions

This study found no evidence to support the use of GRS for diagnosing significant fibrosis in MASLD. However, the combination of PNPLA3 and Fib-4 increased sensitivity considerably. In addition, ALT remains a useful tool for screening diagnosing other liver diseases than MASLD.

Background and aims

Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is an important diagnostic tool for suspected parenchymal lesions in the gastrointestinal tract and adjacent organs. Our study aimed to evaluate the safety and effectiveness of EUS-FNA in focal liver lesions (FLLs).

Method

Data from 88 patients diagnosed with FLLs by imaging who underwent EUS-FNA from 1 January 2017 to 31 August 2022 were reviewed in our retrospective study at the Second Affiliated Hospital of Soochow University and Ruijin Hospital of the School of Medicine of Shanghai Jiao Tong University. The EUS-FNA biopsy results were compared with the final diagnosis to evaluate diagnostic value. The relevant factors were analysed to determine their influence on EUS-FNA biopsy results.

Results

The 88 patients analysed in this study resulted in a final diagnosis of 86 malignant and two benign cases. The overall diagnostic accuracy of EUS-FNA in FLLs was 93.18 % (82/88; 95 % Confidence Interval [CI], 87.9–98.5), with a sensitivity, specificity, positive predictive value, and negative predictive value of 93.02 % (80/86; 95 %CI, 87.6–98.4), 100 % (2/2; 95 %CI, 100–100), 100 % (80/80; 95 %CI, 100–100), and 25 % (2/8; 95 %CI, -5–55.0), respectively. The parameters related to lesion and procedure were not significantly different between these two groups (p > 0.05). The number of puncture needles in the groups showed a statistically significant difference between multiple and single punctures (p = 0.001).

Conclusion

Our data revealed that EUS-FNA is a safe and reliable diagnostic method for FLLs that shows high accuracy.

Purpose: This study investigated the dynamic changes in circulating immune cells following immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), and interventional therapy in hepatocellular carcinoma (HCC).

Methods: HCC patients undergoing transarterial chemoembolization (TACE), TKI, and ICI treatment were included in the treatment group. Peripheral blood samples were collected from these patients before each cycle of PD-1 blockade treatment. Flow cytometry analysis was conducted to assess the composition of peripheral immune cells and identify PD-1-expressing T cells.

Results: The treatment group showed a median time-to-tumor progression (TTP) of 8 months and an overall survival (OS) of 19 months. In comparison, the control group had 6 months and 15 months respectively. These differences were statistically significant (P = 0.029 for TTP and P = 0.020 for OS). In HCC patients receiving Lenvatinib, more circulating natural killer (NK) cells were noted. After 1–2 cycles of PD-1 antibody treatment, a general decline in the proportion of circulating PD-1⁺T cells was found, indicating individual variations in response.

Conclusion: Circulating immune cells have the potential to serve as indicators of the response to immunotherapy, providing a means to monitor dynamic changes and optimize treatment for HCC.

In recent years, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been steadily rising, emerging as a major chronic liver disease of global concern. The course of MASLD is varied, spanning from MASLD to metabolic dysfunction associated steatohepatitis (MASH). MASH is an important contributor to cirrhosis, which may subsequently lead to hepatocellular carcinoma. It has been found that PANoptosis, an emerging inflammatory programmed cell death (PCD), is involved in the pathogenesis of MASLD and facilitates the development of NASH, eventually resulting in inflammatory fibrosis and hepatocyte death. This paper reviews the latest research progress on PANoptosis and MASLD to understand the mechanism of MASLD and provide new directions for future treatment and drug development.

Introduction

Endoscopy is still the gold, standard for assessing disease activity in Crohn's disease (CD). Its invasiveness, poor acceptability, and cost limit its use in the era of tight control and treat-to-target management. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are non-invasive alternatives to colonoscopy to assess disease activity. We aimed to evaluate the performance of IUS and FC to assess mucosal healing in CD.

Methods

All consecutive CD patients who underwent colonoscopy for mucosal healing assessment and IUS and/or FC within four weeks between September 2019 and April 2022 were included in a prospective cohort. The bowel-wall thickness (BWT) and color Doppler signal (CDS) were assessed for each segment. Endoscopic remission was defined by a CDEIS score < 3.

Results

In total, 153 patients were included, of whom 122 showed endoscopic mucosal healing. Eighty-two (53.6 %) were female, the median was age 36 years (IQR, 28–46), and the median disease duration was 10 years (IQR, 4–19). The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of a BWT < 3 mm to predict endoscopic mucosal healing were 56 %, 88 %, 95 %, and 36 %, respectively (patients misclassified as mucosal healing, 2.5 %). The best FC threshold (< 92.9 µg/g) provided similar results: 77 %, 89 %, 96 %, and 67 %, respectively (patients misclassified, 2.2 %). The association of an FC < 250 µg/g with a BWT < 3 mm and the absence of CDS increased the Sp and PPV: Se 58 %, Sp 95 %, PPV 97 %, VPN 43 %; patients misclassified, 1.3 %.

Conclusion

Noninvasive evaluation of mucosal healing by IUS or calprotectin efficiently identifies patients with CD who have achieved endoscopic mucosal healing.