Clinics and research in hepatology and gastroenterology最新文献

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with metabolic dysfunction, ranging from hepatic steatosis with or without mild inflammation to nonalcoholic steatohepatitis, which can rapidly progress to liver fibrosis and even liver cancer. In 2023, after several rounds of Delphi surveys, a new consensus recommended renaming NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD). Ninety-nine percent of NAFLD patients meet the new MASLD criteria related to metabolic cardiovascular risk factors under the "multiple parallel hits" of lipotoxicity, insulin resistance (IR), a proinflammatory diet, and an intestinal microbiota disorder, and previous research on NAFLD remains valid. The NLRP3 inflammasome, a well-known member of the pattern recognition receptor (PRR) family, can be activated by danger signals transmitted by pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), as well as cytokines involved in immune and inflammatory responses. The activation of the NLRP3 inflammasome pathway by MASLD triggers the production of the inflammatory cytokines IL-1β and IL-18. In MASLD, while changes in the composition and metabolites of the intestinal microbiota occur, the disrupted intestinal microbiota can also generate the inflammatory cytokines IL-1β and IL-18 by damaging the intestinal barrier, negatively regulating the liver on the gut–liver axis, and further aggravating MASLD. Therefore, modulating the gut–microbiota–liver axis through the NLRP3 inflammasome may emerge as a novel therapeutic approach for MASLD patients. In this article, we review the evidence regarding the functions of the NLRP3 inflammasome and the intestinal microbiota in MASLD, as well as their interactions in this disease.

Background

Oesophageal varices (EV) rupture remains one of the most severe complications of cirrhosis. As the gold standard to predict this accident, esophagogastroduodenoscopy (EGD) itself also has a weakness. Not all patients are convenient with this modality in clinical practice apart from the risk and cost burden. Hence, the search for other non-invasive modalities with high accuracy is still noteworthy. Among them, spleen stiffness measurement (SSM) with 100 Hz probe, liver stiffness measurement (LSM), and the aspartate amino transferase to platelet ratio index (APRI) score became popular and intensively studied with good accuracy, but the results remain conflicting. This study aims to investigate the performance of SSM, LSM, APRI score, and their combination especially as a screening tool for predicting EV in liver cirrhosis patients.

Methods

In this cross-sectional study, we included 141 patients with liver cirrhosis who had undergone endoscopy, SSM, LSM, and APRI score calculation between January and March 2023 were enrolled. Diagnostic accuracy was assessed by the area under the receiver-operator curve (AUC). Transient elastography (TE) measurement was performed using a spleen-dedicated FibroScan with a 100-Hz probe.

Results

Of the 141 patients, the most common aetiology was hepatitis B in 71 patients (50.4 %). EV were found in 116 patients. Using the AUC, SSM at a cutoff of 40 kPa had the best performance with an AUC of 0.892 (CI 95 %: 0.814–0.969, p <0.0001), with sensitivity 88.79 % and specificity 80 %). Meanwhile, LSM and APRI score had an AUC of 0.832 (CI 95 %: 0.742–0.922, p <0.0001) and 0.780 (CI 95 %: 0.660–0.900, p <0.0001), respectively. The combination of all measurement tools did not show better performance than SSM alone with an AUC of 0.892 (CI 95 %: 0.802–0.982, P <0.0001)

Conclusion

SSM provides better performance than LSM and APRI scores for predicting EV. Performance of SSM alone is non-inferior compare to multiple diagnostic tools combined.

Objective

The primary objective of this study is to examine the distribution and prognostic implications of serum vitamin D levels among individuals diagnosed with primary hepatic carcinoma (PHC) attributable to hepatitis B virus (HBV) infection.

Methods

A total of 345 patients diagnosed with HBV infection were enrolled in our hospital between August 2014 and October 2020. Among these, 144 individuals were diagnosed with chronic hepatitis B (CHB), 66 individuals were diagnosed with HBV-related hepatic cirrhosis (HBV cirrhosis), and 135 individuals were diagnosed with HBV-related PHC (HBV-PHC). Peripheral serum levels of vitamin D were measured. Patients with cirrhosis underwent examination using the Child–Pugh grading system, and the mortality rates at 1-year and 3-year intervals for patients with HBV-PHC were analyzed.

Results

Vitamin D levels in peripheral serum in the CHB group, HBV cirrhosis group, and HBV-PHC group exhibited varying degrees of reduction compared to healthy individuals. Significant differences were observed between the three groups (F = 4.02, P = 0.019). No significant difference was observed in vitamin D levels between different Child–Pugh grades within the HBV cirrhosis group (F = 0.89, P = 0.417). However, significant differences were observed in vitamin D levels between different Child–Pugh grades within the HBV-PHC group (F = 4.84, P = 0.009). There was no significant difference in 1-year and 3-year mortality rates between patients diagnosed with HBV-PHC and with varying vitamin D levels (P > 0.05).

Conclusions

Vitamin D levels decreased to varying degrees in patients diagnosed with CHB, HBV cirrhosis, and PHC. This decrease was well correlated with disease progression (HBV-PHC group < HBV cirrhosis group < CHB group). In cases where hepatic function was comparable, there was no discernible correlation between serum vitamin D level and mortality rates from PHC.

Background

The hepatitis B surface antigen (HBsAg)–negative and antibody to hepatitis B core antigen (anti-HBc)–positive patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of HBV reactivation (HBVr).

Methods

To analyze the risk factors for HBVr, a total of 1,042 leukemia patients(≥18years of age), who underwent allo-HSCT from January 2016 to April 2022 in The First Affiliated Hospital of Soochow University, were enrolled in the study. Finally, 193 leukemia patients with resolved HBV infection were included into the study.

Results

HBVr occurred in 22 patients (11.39 %), and the median time to HBVr was 24 months (with a range of 11-51months). Hepatitis flares developed in 22.73 % of patients with HBVr, and hepatic failure occurred in 1 patient. During the follow-up period, only 1(1.3 %) patient experienced HBVr among 79 patients with antiviral prophylaxis. While 21(18.42 %) patients experienced HBVr among 114 patients without antiviral prophylaxis. The cumulative incidence of HBV reactivation at 3 years was 44.4. % for anti-HBs-negative donors/recipients with a low anti-HBs titer (<100IU/L) and 7.1 % for anti-HBs-positive donors/recipients with a high anti-HBs titer (≥100IU/L) respectively. In addition, univariate and multivariate Cox regression analyses confirmed the use of rituximab as a risk factor for HBV reactivation.

Conclusion

The univariate and multivariate analyses confirmed that the anti-HBs titer in both recipients and donors are protective indicators to prevent incidence of HBVr. In addition, antiviral prophylaxis can significantly reduce the incidence of HBVr.

Background

Hepatic hydrothorax (HH) is a rare but severe manifestation of cirrhotic ascites. Whether HH development relates to ascites severity is uncertain and simple clinical models to predict HH from all stages of ascites are missing. The recently published CIRrhotic Ascites Severity (CIRAS) model using only ascites-related variables may serve this purpose.

Aim

We investigated if the CIRAS model within one year predicts the development of HH requiring thoracentesis in patients with cirrhosis and ascites.

Methods

We used data from 1090 patients with cirrhosis and all severities of ascites enrolled in three randomized clinical trials with available CIRAS model scores and no history of HH. Fine and Gray regression was applied to estimate the CIRAS model's ability to predict HH.

Results

Thirty-five patients developed HH requiring thoracentesis. The CIRAS model stratified patients at different risks for HH and increasing CIRAS score was associated with a higher risk for HH (sHR 1.49 [95% CI: 1.19–1.86]). The CIRAS model's discriminatory ability achieved an AUC of 0.67 (95% CI: 0.56–0.77); higher than of the cirrhosis severity scores Child-Pugh and MELD variants.

Conclusion

The CIRAS model predicts the development of HH in cirrhosis patients with any grade of ascites, suggesting a potential for improved pre-emptive HH management. This complements the general movement towards personalised treatments and care.

Background and study aims

Chronic kidney disease (CKD) is a well-known risk factor of gastrointestinal angiectasia (GIA). The aim was to compare this population with CDK patients without GIA.

Methods

Patients followed in the Nephrology Department of Tenon Hospital for which an endoscopy was performed between 2012 and 2022 were identified. Those with at least one GIA lesion were included ("GIA+" group). A matched control group for age, sex and GFR stage of patients with CKD and no GIA lesion ("GIA-" group) was constituted. A subgroup analysis compared patients with (SB+) and without (SB-) small-bowel involvement.

Results

A total of 55 patients were included in the GIA+ group. 36.3 % (n = 20) were active smokers and 29.1 % (n = 16) had peripheral arterial disease versus 16.4 % (n = 9) (OR 2.89, p = 0.03), and 9.1 % (n = 5) (OR 4.05, p = 0.015) in the GIA- group. Thirteen patients (23.6 %) had a SB lesion. Duodenal involvement was present in 69.2 % of cases in the SB+ group versus 28.6 % in the SB- group (p = 0.02). Median number of endoscopies, hemostatic technics and hospitalizations was 7, 3 and 6, versus 2 (p = 0.0001), 1 (p = 0.001) and 1 (p = 0.0002) in the SB- group.

Conclusions

CKD patients with GIA had a greater cardiovascular risk with a higher incidence of vascular nephropathy. Small-bowel GIA were associated with a higher morbidity.

Background

Liver cancer (LC) remains a major cause of cancer death worldwide. Grasping prevalence trends is key to informing strategies for control and prevention. We analyzed the global, regional and national trends in LC prevalence and its major causes from 1990 to 2019.

Methods

We obtained LC age-standardized prevalence rate (ASPR) estimates from the Global Burden of Disease study 2019 and assessed trends using Joinpoint regression. LC cases were categorized into those due to hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol use, nonalcoholic steatohepatitis (NASH) and other causes.

Results

While the ASPR of LC has shown a global decrease, there are specific regions where an increase in ASPR has been observed, with the highest rates in America. HBV remained the leading cause of LC (41.45 %) but significant increases occurred for HCV, alcohol use and NASH. Prevalence correlated with socioeconomic development. High-income countries had higher LC rates from HCV and alcohol but lower HBV-related LC. In high-income nations, LC prevalence climbs; the converse holds in middle- and low-income countries.

Conclusions

Despite a global ASPR decrease, LC due to HCV, NASH, and alcohol is rising. Prevention strategies must prioritize HBV vaccination, HCV treatment, and alcohol regulation.

Impact

The study informs targeted LC control policies and emphasizes the importance of continued monitoring and regional cooperation to combat LC.

Background

Hepatobiliary and pancreatic diseases, such as cirrhosis, hepatocellular carcinoma, cholelithiasis, and pancreatitis, are major global health challenges. Lifestyle factors like smoking, alcohol consumption, and coffee intake are commonly studied for their health impacts. However, observational studies often face issues with confounding factors and reverse causality, making it difficult to establish causal relationships.

Methods

This research uses Mendelian randomization (MR) to investigate the causal effects of smoking, alcohol use, and coffee intake on 10 hepatobiliary and pancreatic diseases. Genetic data from the Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) and self-reported GWAS were used to derive instrumental variables (IVs). The outcomes were obtained from the FinnGen and UK Biobank cohorts. Univariable and multivariable MR analyses were conducted to assess the associations.

Results

Genetic predisposition to tobacco use was associated with increased risks of acute pancreatitis, alcoholic hepatitis, chronic pancreatitis, cirrhosis, gallstones, liver cancer, and pancreatic cancer. Alcohol consumption was linked to acute pancreatitis, chronic pancreatitis, alcoholic liver disease, hepatic cancer, and cholangitis. Coffee intake showed minimal associations, with a slight protective effect against non-alcoholic steatohepatitis.

Conclusions

This study confirms the harmful effects of inhaling tobacco and consuming alcohol on hepatobiliary and pancreatic diseases. It highlights the need for public health strategies to reduce tobacco use and heavy alcohol consumption. Coffee intake showed minimal effects, suggesting further research is needed to understand its relationship with hepatobiliary health.