Clinical and Experimental Hepatology最新文献

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with an increasing incidence. Pemafibrate is a novel selective peroxisome proliferator-activated receptor-a (PPAR-a) modulator which is expected to improve NAFLD. The aim of this study is to identify predictors of improvement of hepatic inflammation and fibrosis after pemafibrate therapy in patients with NAFLD.

Material and methods: Seventy-one non-diabetic patients with NAFLD treated with pemafibrate for more than six months were included in this retrospective review. Hepatic inflammation and fibrosis were evaluated by alanine aminotransferase (ALT) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, respectively.

Results: During six months of pemafibrate therapy, significant improvements were observed in ALT and M2BPGi levels regardless of the body mass index (BMI) compared to baseline. Lean NAFLD was identified as a significant positive predictor for > 50% reduction of ALT showing reduced hepatic inflammation. Subsequent multivariate analysis confirmed this result. Reduction of ALT in the lean NAFLD group (BMI < 25) was significantly greater than in the obese NAFLD group (BMI > 30) (p = 0.034). Lean NAFLD and age > 50 years were identified as significant positive predictors for > 20% reduction of M2BPGi showing reduced hepatic fibrosis. Subsequent multivariate analysis confirmed these results. Reduction of M2BPGi in the lean NAFLD group was significantly greater than in the obese NAFLD group (p = 0.022).

Conclusions: Pemafibrate therapy improves markers of hepatic inflammation and fibrosis regardless of BMI. Patients with lean NAFLD have a greater response to pemafibrate therapy compared to those with obese NAFLD.

Aim of the study: Identifying persons at increased risk of developing hepatocellular carcinoma (HCC) after exposure to directly acting antivirals (DAAs) is of utmost importance. Our aim was to identify the predictors of de novo HCC occurrence among cirrhotic patients after hepatitis C virus (HCV) treatment using DAAs.

Material and methods: 529 cirrhotic patients who initiated treatment for HCV using DAAs were followed up for 2 years from the end of treatment for development of HCC. Pretreatment clinical and laboratory data were assessed as possible predictors for HCC occurrence. Genotyping for tolloid-like 1 gene (TLL1) variant rs17047200 was assessed in all patients who developed HCC and in the matched control group.

Results: Pretreatment bilirubin, FIB-4 and platelet-albumin-bilirubin (PALBI) scores were significantly higher among those who developed HCC than those who did not develop HCC during the 2-year follow-up period while hemoglobin level was significantly lower. ROC curve analysis revealed that at a cut-off ≥ 3.07, pretreatment FIB-4 had a sensitivity of 76.5%, and negative predictive value (NPV) of 92%. At a cut-off ≥ -2.5, pretreatment PALBI score had a sensitivity of 82.4%, and NPV of 93.2%. Regarding genotyping for TLL1 rs17047200 there were no statistically significant differences between those who developed HCC during follow-up and the matched control group.

Conclusions: TLL1 rs17047200 genotyping is not helpful in predicting HCC occurrence after DAAs. On the other hand, lower pretreatment hemoglobin level and higher pretreatment bilirubin, FIB-4 and PALBI scores are associated with higher risk of HCC development after DAAs.

Introduction: Data of minimal hepatic encephalopathy (MHE) before and after hepatitis C virus (HCV) treatment remain scarce. We aimed to describe the prevalence, evolution and predictive factors of MHE before and after a sustained virological response (SVR).

Material and methods: It was a prospective study that included adults with cirrhosis due to HCV treated by direct-acting agents (DAA). MHE was assessed using the Psychometric Hepatic Encephalopathy Score (PHES).

Results: 104 patients (65% female, age 60 ±10 years; 69% with diabetes, 47% with hypertension; 82% Child-Pugh A) were included. MHE was assessed just before therapy and 12 (IQR 7-15) months after SVR. Prevalence of MHE before HCV treatment and after SVR were 16% and 22%, respectively (p = 0.18). Resolution of MHE after SVR occurred in a few patients (n = 4/17) and 10 of 87 patients (11.5%) without MHE before treatment developed this condition after SVR. MHE after SVR was more common in patients with MHE before treatment (57% vs. 5%, p < 0.001). In multivariate analysis, older age, hypertension and hypoalbuminemia after treat-ment were predictors of MHE after SVR. In the absence of all these variables, none of the patients had MHE. In contrast, the prevalence of MHE was 42% and 70% in the case of presence of any 2 of these factors and all these conditions, respectively.

Conclusions: MHE is frequent in patients with cirrhosis who achieved SVR after DAA. SVR is associated with low probability of resolution of MHE and may not entirely protect patients from developing de novo MHE. Presence of MHE before DAA, older age, hypertension and hypoalbuminemia after SVR were independently associated with this condition.

Gallbladder cancer (GBC) has a high incidence in certain geographical regions. Morphologically, GBC presents as a mass replacing the gallbladder, a polypoidal lesion, or wall thickening. The incidence of preoperative diagnosis of wall thickening type of GBC is less well studied. The patterns of mural involvement and extramural spread are not well described in the literature. Additionally, wall thickening in the gallbladder does not always indicate malignancy and can be secondary to inflammatory or benign gallbladder diseases and extracholecystic causes and systemic pathologies. Objective reporting of gallbladder wall thickening will help us appreciate GBC's early features. In this review, we illustrate the imaging patterns of wall thickening type of GBC.

Aim of the study: Biliary complications are the leading causes of morbidity and mortality after liver transplant (LT). However, national data on endoscopic retrograde cholangiopancreatography (ERCP) usage and outcomes in LT patients are lacking. Our study aims to identify the trends, outcomes, and predictors of ERCP and related complications in this patient subgroup.

Material and methods: We derived our study cohort from the Nationwide Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) between 2007 and 2017. LT patients were identified using ICD-9/10CM diagnosis codes and patients who underwent ERCP were identified by ICD-9/10-CM procedure codes. We utilized the Cochrane-Armitage trend test and multivariate logistic regression to analyze temporal trends, outcomes, and predictors.

Results: A total of 372,814 hospitalizations occurred in LT patients between 2007 and 2017. ERCP was performed in 2.05% (n = 7632) of all hospitalizations. There was a rise in ERCP procedures from 1.96% (n = 477) in 2007 to 2.05% (n = 845) in 2017. Among LT patients who underwent ERCP, the in-hospital mortality rate was 1% (n = 73) and 8% (n = 607) were discharged to facilities. Mean length of hospital stay was 7 ±0.3 days. Septicemia was the most common periprocedural complication (18.3%, n = 1399) followed by post-ERCP pancreatitis (8.8%, n = 674).

Conclusions: There has been an increase in ERCP procedures over the past decade among LT patients. Our study highlights the periprocedural complications and outcomes of ERCP in LT patients from a nationally representative dataset.

Aim of the study: This study aimed to evaluate the methylation status of two genes in the peripheral blood as possible non-invasive biomarkers for hepatocellular carcinoma (HCC) development in Egyptian patients with hepatitis C virus (HCV)-related liver cirrhosis, compare them with α-fetoprotein (AFP), and assess their relationship with the clinicopathological characteristics of the tumor.

Material and methods: Thirty healthy volunteers, forty patients with HCC on top of HCV-associated liver cirrhosis, and forty patients with HCV-associated liver cirrhosis participated in this study. Using methylation-specific polymerase chain reaction (MSP), the methylation status of RASSF1A and CDKN2A was assessed.

Results: The tumor group was significantly more methylated in both genes than the cirrhosis and the control groups. The RASSF1A gene was highly methylated in advanced tumor characteristics. There was no association between AFP levels in the blood and the methylation state of both genes. The combined diagnostic performance of the methylation status of both genes in predicting HCC in cirrhotic patients was high but not to the degree of that of AFP.

Conclusions: Methylated RASSF1A and CDKN2A levels in the blood may be employed as a non-invasive biomarker for the detection of HCC, especially in high-risk individuals.

Seaweed is a food that is widely consumed by Asian people and has many health benefits, including lipid and glycemic reduction, but the effect of seaweed on non-alcoholic fatty liver disease (NAFLD) has not been widely discussed. This study aims to compare the effect of seaweed consumption on improving liver injury in NAFLD patients. The primary outcome is the change of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and g-glutamyl transferase [GGT]), while the secondary outcome includes body weight, waist circumstance, body mass index (BMI), lipid profile, insulin level, and insulin sensitivity and any related metabolic indicators. There was significant liver improvement in the intervention group, but some parameters from secondary outcomes showed no significant effect. Further studies with larger and heterogeneous populations are still needed to confirm the effectiveness of seaweed supplementation in NAFLD patients.

Taurine (TAU) is a free amino acid abundant in the human body. Various physiological roles have been attributed to TAU. At the subcellular level, mitochondria are the primary targets for TAU function. Meanwhile, it has been found that TAU depletion is associated with severe pathologies. Cholestasis is a severe clinical complication that can progress to liver fibrosis, cirrhosis, and hepatic failure. Bile duct ligation (BDL) is a reliable model for assessing cholestasis/cirrhosis and related complications. The current study was designed to investigate the effects of cholestasis/cirrhosis on tissue and mitochondrial TAU reservoirs. Cholestatic rats were monitored (14 and 42 days after BDL surgery), and TAU levels were assessed in various tissues and isolated mitochondria. There was a significant decrease in TAU in the brain, heart, liver, kidney, skeletal muscle, intestine, lung, testis, and ovary of the BDL animals (14 and 42 days after surgery). Mitochondrial levels of TAU were also significantly depleted in BDL animals. Tissue and mitochondrial TAU levels in cirrhotic animals (42 days after the BDL operation) were substantially lower than those in the cholestatic rats (14 days after BDL surgery). These data indicate an essential role for tissue and mitochondrial TAU in preventing organ injury induced by cholestasis/cirrhosis and could justify TAU supplementation for therapeutic purposes.

Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. A non-synonymous single nucleotide polymorphism (SNP) of the transmembrane 6 superfamily member 2 (TM6SF2) gene is associated with non-alcoholic fatty liver disease. SNPs of the TM6SF2 gene play an important role in the pathogenesis of HCC in alcoholic cirrhosis, but there are limited data regarding other possible etiologies. We aimed to evaluate the role of the rs58542926 polymorphism in the development of HCC in Egyptian chronic liver disease (CLD) patients.

Material and methods: A total of 120 participants, including 40 HCC patients, 40 CLD patients, and 40 healthy controls, were selected. Real-time polymerase chain reaction (RT-PCR) was used to detect the TM6SF2 rs58542926 polymorphism.

Results: There were no significant differences among the three studied groups regarding age (p = 0.06) and gender (p = 0.75). Frequencies of the CT, TT, CT + TT genotypes and the T allele were significantly higher in HCC patients than in the CLD and control groups (p < 0.001, p = 0.005, and p < 0.001, respectively). CLD patients with the CT genotype had a significantly increased risk of HCC development (OR = 4.67, 95% CI: 1.67-12.90). Patients with the TT genotype had a significantly increased risk of HCC (OR = 9.33, 95% CI: 1.72-50.61). Moreover, the T allele was correlated with an increased risk of HCC (OR = 5.44, 95% CI: 2.09-14.17) compared to the C allele.

Conclusions: The TM6SF2 rs58542926 genotype is associated with an increased risk of HCC in the Egyptian population.

Aim of the study: Non-alcoholic fatty liver disease (NAFLD), which encompasses a wide variety of liver pathology, is now the most common chronic liver disease worldwide. The presence of hypothyroidism has been linked to the development of NAFLD. However, its correlation with liver fibrosis, an important clinical entity in NAFLD, is less clear. We aimed to summarize the association between hypothyroidism and liver fibrosis risk.

Material and methods: We conducted a search of PubMed and ProQuest from inception to June 30, 2021, for studies assessing the association between hypothyroidism and liver fibrosis risk. The quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS). We analyzed the pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed and random-effects model. Heterogeneity was assessed using I ².

Results: Eight studies with a total of 14,588 patients were included. The quality of studies ranged from 6 to 8 stars. Thyroid stimulating hormone (TSH) ≥ 2.5 was significantly associated with increased risk of significant liver fibrosis (OR = 1.61, 95% CI = 1.21-2.15). Subclinical hypothyroidism was also correlated with an increased risk of advanced fibrosis (OR = 2.77, 95% CI = 1.65-4.65). A significant association was found between overt hypothyroidism and non-alcoholic steatohepatitis (NASH) risk (OR = 2.38, 95% CI = 1.61-3.53). However, no significant association was found between subclinical hypothyroidism and significant liver fibrosis.

Conclusions: Hypothyroidism is associated with an increased risk of fibrosis in NAFLD patients.