World Journal of Hepatology最新文献

Background: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure.

Aim: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections.

Methods: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review.

Results: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance.

Conclusion: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Chronic hepatitis B virus (HBV) infection affects over 295 million people globally and an estimated 1.6 million people in the United States. It is associated with significant morbidity and mortality due to cirrhosis, liver failure, and liver cancer. Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression, which in turn has been associated with a decreased risk of liver complications. However, current antiviral regimens are limited by concerns with adverse effects, adherence, resistance, long-term treatment, and ongoing risk for liver events. Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen (HBsAg) loss and suppression of HBV DNA. Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B, including core/capsid inhibitors, entry inhibitors, RNA interference (siRNA/ASO), HBsAg inhibitors, Toll-like receptor agonists, checkpoint inhibitors, and therapeutic vaccines.

Background: The prevalence of metabolic-associated fatty liver disease (MAFLD) is a growing public health issue in people living with human immunodeficiency virus (PLWH). However, the pathophysiology of MAFLD is still unknown, and the role of genetic variables is only now becoming evident.

Aim: To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.

Methods: The study employed transient elastography with a controlled attenuation parameter ≥ 248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand. Candidate single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan^® MGB probe 5' nuclease assays for seven MAFLD-related genes. Statistical analyses included SNP frequency analysis, Fisher's Exact and Chi-square tests, odds ratio calculations, and multivariable logistic regression.

Results: The G-allele carriers of PNPLA3 (rs738409) exhibited a two-fold rise in MAFLD, increasing by 2.5 times in MAFLD with human immunodeficiency virus infection. The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times (P = 0.001) more significant chance of developing aberrant triglyceride among PLWH.

Conclusion: The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

Amebic liver abscess (ALA) is still a common problem in the tropical world, where it affects over three-quarters of patients with liver abscess. It is caused by an anaerobic protozoan Entamoeba hystolytica, which primarily colonises the cecum. It is a non-suppurative infection of the liver consisting primarily of dead hepatocytes and cellular debris. People of the male gender, during their reproductive years, are most prone to ALA, and this appears to be due to a poorly mounted immune response linked to serum testosterone levels. ALA is more common in the right lobe of the liver, is strongly associated with alcohol consumption, and can heal without the need for drainage. While majority of ALA patients have an uncomplicated course, a number of complications have been described, including rupture into abdomino-thoracic structures, biliary fistula, vascular thrombosis, bilio-vascular compression, and secondary bacterial infection. Based on clinico-radiological findings, a classification system for ALA has emerged recently, which can assist clinicians in making treatment decisions. Recent research has revealed the role of venous thrombosis-related ischemia in the severity of ALA. Recent years have seen the development and refinement of newer molecular diagnostic techniques that can greatly aid in overcoming the diagnostic challenge in endemic area where serology-based tests have limited accuracy. Metronidazole has been the drug of choice for ALA patients for many years. However, concerns over the resistance and adverse effects necessitate the creation of new, safe, and potent antiamebic medications. Although the indication of the drainage of uncomplicated ALA has become more clear, high-quality randomised trials are still necessary for robust conclusions. Percutaneous drainage appears to be a viable option for patients with ruptured ALA and diffuse peritonitis, for whom surgery represents a significant risk of mortality. With regard to all of the aforementioned issues, this article intends to present an updated review of ALA.

Hepatitis D virus (HDV) can infect HBsAg-positive individuals, causing rapid fibrosis progression, early decompensation, increased hepatocellular carcinoma risk, and higher mortality than hepatitis B virus (HBV) mono-infection. Most countries lack high-quality HDV prevalence data, and the collection techniques employed often bias published data. In recent meta-analyses, HDV prevalence in HBsAg-positive patients reaches 5%-15% and is even significantly higher in endemic areas. Since HBV vaccination programs were implemented, HDV prevalence has decreased among younger populations. However, owing to immigrant influx, it has increased in some Western countries. The current practice of HDV screening in HBsAg-positive individuals is stepwise, based on physician's discretion, and limited to at-risk populations and may require numerous visits. Double reflex testing, which includes anti-HDV testing in all HBsAg-positive individuals and then HDV RNA testing for anti-HDV-positive ones, is uncommon. Reflex testing can identify more HDV infection cases and link identified patients to further care and follow-up. Moreover, laboratory-based double reflex screening is less biased than physician-led testing. Therefore, healthcare providers should learn about reflex testing, and federal and provincial hepatitis control programs should implement laboratory-based double reflex testing to obtain reliable HDV prevalence estimates. The test's cost-effectiveness depends on the number of HBV-positive patients screened to identify one HDV-positive patient. Such testing may be viable in areas with low HBsAg but high HDV prevalence. However, its economic impact on areas with low HDV prevalence needs further study.

Background: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare.

Aim: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance.

Methods: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.

Results: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively.

Conclusion: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

Succinylation is a highly conserved post-translational modification that is processed via enzymatic and non-enzymatic mechanisms. Succinylation exhibits strong effects on protein stability, enzyme activity, and transcriptional regulation. Protein succinylation is extensively present in the liver, and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism. For instance, histone acetyltransferase 1 promotes liver glycolysis, and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism. Therefore, the effects of succinylation on hepatic glucose, amino acid, and lipid metabolism under the action of various enzymes will be discussed in this work. In addition, how succinylases regulate the progression of different liver diseases will be reviewed, including the desuccinylation activity of sirtuin 7, which is closely associated with fatty liver disease and hepatitis, and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma. In view of the diversity and significance of protein succinylation, targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.

Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD.

Background: A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD). They are now defined as metabolic dysfunction-associated steatotic liver disease (MASLD), which includes cardiometabolic criteria in adults. This condition, extensively studied in obese or overweight patients, constitutes around 30% of the population, with a steady increase worldwide. Lean patients account for approximately 10%-15% of the MASLD population. However, the pathogenesis is complex and is not well understood.

Aim: To systematically review the literature on the diagnosis, pathogenesis, characteristics, and prognosis in lean MASLD patients and provide an interpretation of these new criteria.

Methods: We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023, specifically focusing on lean NAFLD, MAFLD, or MASLD patients. We include original articles with patients aged 18 years or older, with a lean body mass index categorized according to the World Health Organization criteria, using a cutoff of 25 kg/m² for the general population and 23 kg/m² for the Asian population.

Results: We include 85 studies in our analysis. Our findings revealed that, for lean NAFLD patients, the prevalence rate varied widely, ranging from 3.8% to 34.1%. The precise pathogenesis mechanism remained elusive, with associations found in genetic variants, epigenetic modifications, and adaptative metabolic response. Common risk factors included metabolic syndrome, hypertension, and type 2 diabetes mellitus, but their prevalence varied based on the comparison group involving lean patients. Regarding non-invasive tools, Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients. Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles, with some medications showing efficacy to a lesser extent. However, lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.

Conclusion: MASLD is a complex disease comprising epigenetic, genetic, and metabolic factors in its pathogenesis. Results vary across populations, gender, and age. Limited data exists on clinical practice guidelines for lean patients. Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.