Clinical and Experimental Hepatology最新文献

Aim of the study: Non-alcoholic fatty liver disease (NAFLD) is regarded as the most relevant liver disease of the twenty-first century, affecting at least one third of the general population. NAFLD is associated with increased mortality due to cardiovascular disease (CVD) and cancer. The carotid intimal media thickness (CIMT), mean platelet volume (MPV) and endocan level could be markers for generalised atherosclerotic burden and endothelial dysfunction. The aims of the study were to evaluate the association between non-alcoholic fatty liver disease and early atherosclerosis by measuring CIMT, MPV and endocan level, as markers of endothelial dysfunction, in NAFLD patients.

Material and methods: This cross-sectional study included 50 patients who were divided into two groups: group I included 25 subjects with NAFLD and group II included 25 healthy subjects. Complete blood count with MPV, liver profile, lipid profile, fasting blood glucose level, 2-hour postprandial kidney function test, and serum concentrations of endocan were measured for all patients. NAFLD fibrosis score (NFS) was calculated. Abdominal ultrasonography and carotid ultrasound scan for measurement of CIMT were performed.

Results: Serum endocan levels, MPV and CIMT were significantly higher (p < 0.005) in NAFLD patients (0.6, 9.3 ±1.2 and 0.9 ±0.3 respectively) than healthy subjects (0.1, 8.1 ±0.6 and 0.6 ±0.1 respectively). The analysis of diagnostic performance of these factors revealed that they have good sensitivity and specificity in prediction of endothelial dysfunction with AUC (0.950, 0.844 and 0.849 respectively).

Conclusions: Serum endocan levels, MPV and CIMT could be considered as good predictors of endothelial dysfunction and therefore early detection of subclinical atherosclerosis in NAFLD patients.

Aim of the study: Bone morphogenic proteins (BMPs) have both inhibitory and stimulatory effects on growth of a tumor that depend on the type of cells, the dosage and the tumor microenvironment. We aimed to investigate the impact of the bone morphogenic protein-7 (BMP-7) single nucleotide polymorphism (SNP) rs230205 [A/G] on susceptibility to hepatocellular carcinoma (HCC) progression from liver cirrhosis after viral hepatitis infection in Egyptian patients.

Material and methods: The amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) method was used to genotype the rs230205 [A/G] SNP in 150 subjects (50 patients with post-hepatitis C or B cirrhosis, 50 HCC patients, and 50 controls). Expression level of BMP-7 protein was assessed using enzyme-linked immunosorbent assay (ELISA).

Results: The results revealed insignificant changes in distribution of all genotypes/alleles of the BMP-7 rs230205 [A/G] SNP between cirrhotic patients, HCC patients and controls. The AA genotype and A allele could be considered risk factors for cirrhosis (OR = 1.75, 1.50) and HCC (OR = 2.19, 1.74), respectively. The AA genotype (95% CI: 0.45-6.79) and A allele (OR = 1.50, 95% CI: 0.77-2.93) may be viewed as cirrhosis risk factors based on group segregation. Additionally, the A allele, AG and AA genotypes and their combined ORs of 2.19 (95% CI: 0.58-8.23), 1.74 (95% CI: 0.90-3.37), and 1.70 (95% CI: 0.68-4.29) could all be risk factors for HCC. No genotype or allele could be regarded as a risk factor for progression of cirrhosis to HCC, according to OR values.

Conclusions: The results showed no correlation between BMP-7 rs230205 [A/G] SNP and progression of cirrhosis to HCC. To confirm our findings, additional prospective large-scale research is required.

Aim of the study: Hepatocellular carcinoma (HCC) prognosis heavily depends on early diagnosis. We aimed to determine the role of serum urothelial carcinoma-associated 1 (UCA1) and wd repeat containing antisense to TP53 (WRAP53) as diagnostic tools of HCC.

Material and methods: A case-control study including 90 subjects (30 patients having HCC, 30 patients having liver cirrhosis without HCC and 30 healthy controls) was performed. In all participants, the serum levels of UCA1 and WRAP53 were assessed by quantitative real-time polymerase chain reaction together with serumαa-fetoprotein (AFP).

Results: Serum levels of both UCA1 and WRAP53 were upregulated in patients with HCC being significantly higher than in patients with liver cirrhosis and healthy control (p < 0.001). They were also correlated with some clinicopathological characteristics of HCC. Using the receiver operating curve, both UCA1 and WRAP53 showed higher diagnostic performance for HCC (AUC = 0.9, 73.3% sensitivity, 100% specificity and AUC = 0.85, 63.3% sensitivity, 80% specificity respectively) and their combination with AFP resulted in improved sensitivity and specificity (AUC = 0.97, 90% sensitivity, 100% specificity).

Conclusions: Serum UCA1 and WRAP53 have the potential to be used alone, or in combination or with AFP, as diagnostic non-invasive biomarkers for HCC with accepted sensitivity and specificity. This study has been registered in clinicaltrials.gov with clinical trial registration number NCT05088811.

Aim of the study: Cholangiocarcinoma (CCA) comprises a diverse group of malignancies that occur anywhere along the biliary tree. Gene polymorphisms are risk factors for CCA development. Expression levels of epidermal growth factor (EGF) are correlated with progressive tumor growth and metastasis by increasing tumor cell proliferation and migration. The EGF rs4444903 (G) allele seems to enhance carcinogenesis in several types of cancer. The aim was to study the association between epidermal growth factor EGF (rs4444903) gene polymorphism and risk of CCA in Egyptian patients.

Material and methods: This case-control study included 100 subjects, 50 CCA patients and 50 healthy individuals as controls. The EGF (rs4444903) genotyping was performed by real-time polymerase chain reaction (PCR).

Results: The risk of CCA increased more in subjects with GG and AG genotypes than in those with AA genotype compared to the control group (p = 0.009, 0.037, OR = 4.20, 2.83, 95% CI: 1.40-12.60, 1.05-7.60 respectively). The variant G allele showed a highly significant association with CCA risk in the dominant model (p = 0.009). However, in the recessive model the G allele showed a nonsignificant association with the risk of CCA (p = 0.075). There were no significant differences between the EGF rs4444903 SNP genotypes in terms of the size of foci and presence of chronic hepatitis C virus (HCV) infection in the CCA group (p = 0.220, 0.645, respectively).

Conclusions: EGF rs4444903 polymorphism may have a role in the pathogenesis of CCA and the minor G allele may predispose to CCA, but it has no effect on severity of the disease.

Aim of the study: Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits have been shown to negatively affect their daily functioning and quality of life. Treatment with probiotics has shown benefit in some clinical trials. This review aimed to systematically analyze the efficacy of probiotics in the treatment of MHE.

Material and methods: A systematic search of the electronic databases PubMed, Science Direct, and Cochrane Library was conducted for randomized controlled trials (RCTs) in adult patients with MHE who had been given probiotics intervention. The primary outcomes were reversal of MHE and improvement of neuropsychometric tests, while the secondary outcome was the reduction of serum ammonia.

Results: Nine RCTs involving 776 MHE patients were included, consisting of 311 patients receiving probiotics and 465 patients receiving comparator (placebo or no treatment, lactulose, L-ornithine L-aspartate [LOLA], or rifaximin). The meta-analysis showed that probiotics significantly reversed MHE (OR = 3.95, p < 0.0001, 95% CI: 2.05 to 7.60) compared with placebo or no treatment. Probiotics also significantly reduced serum ammonia compared with placebo (pooled mean difference -25.94, p = 0.04, 95% CI: -50.21 to -1.66). However when compared to lactulose and LOLA, probiotics did not show a significant difference in reversal of MHE or reduction of serum ammonia levels.

Conclusions: Probiotics were more effective in reversal of MHE and reduced serum ammonia levels in patients with MHE compared to placebo or no treatment, but not more effective than lactulose or LOLA.

Aim of the study: Akt is involved in upregulating the insulin-signaling pathways essential for maintaining glucose metabolism. Glycosphingolipids are involved in the pathogenesis of glucose intolerance and associated target organ injury. On the other hand, oral administration of b-glucosylceramide (GC) has been shown to alleviate insulin resistance. The present study aimed to determine the effects of oral administration of insulin and GC, separately and in combination, on Akt expression and the subsequent effect on metabolic syndrome characteristics in leptin-deficient mice.

Material and methods: Four groups of leptin-deficient ob/ob mice were orally administered for four weeks: vehicle, GC, short-acting insulin, and GC combined with insulin. Mice were followed for hepatic Akt expression and changes in tumor necrosis factor a (TNF-a) level, hyperlipidemia, and liver damage.

Results: In mice that received insulin or GC, particularly those that received both, the liver phosphorylation of Akt was significantly increased compared to those that received only vehicle. Serum TNF-a levels decreased in insulin-treated mice. These effects were associated with alleviating glucose intolerance and hyperlipidemia, as manifested by a significant glucose tolerance test improvement and reductions in serum triglyceride and cholesterol levels. Significant liver damage alleviation was noted by liver enzyme reductions in all treated groups, along with liver steatosis in the insulin-treated mice.

Conclusions: These data established the potential use of oral insulin administration with glycosphingolipids to alleviate glucose intolerance and associated liver damage and hyperlipidemia via increased Akt expression in the liver. The data support targeting Akt as a potent therapeutic target for metabolic syndrome.

Aim of the study: The treatment of autoimmune hepatitis (AIH) is based on steroids and azathioprine (AZA). AZA is a pro-drug which is converted among others into 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP). The aim of the study was to determine the relationship between the AZA active metabolite 6-TG and both the biochemical and histological remission outcomes.

Material and methods: The authors conducted a retrospective analysis of a single chart review. The sample size consisted of 44 pediatric patients with AIH. Biochemical remission was defined as an alanine aminotransferase (ALT) level below 40 U/l and histological remission was defined as a situation when the control biopsy revealed inflammation grade G1 (or lower) in the Batts-Ludwig score. Statistical analysis was applied to assess the difference in remission outcomes in patients with different levels of 6-TG.

Results: In the benchmark variant of our statistical analysis, we found that the correlation between 6-TG and ALT in the sample was not statistically significant. Moreover, the difference between the mean levels of ALT in the populations in and without remission was not statistically significant (the p-value of the t-test was 0.16).

Conclusions: Our results tend to support the claim that there is no statistically significant relationship between 6-TG concentration and remission (both biochemical and histological) in pediatric patients with AIH.

Aim of the study: Owing to the association between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia, there is a need for new treatment strategies to manage both conditions concomitantly. Our aim in this study was to evaluate the effectiveness of pemafibrate in alleviating dyslipidemia-associated NAFLD, including the evaluation of its effects on liver function and body composition.

Material and methods: The study sample included 67 patients with dyslipidemia-associated NAFLD (29 males, mean age 65.7 years [range, 58.4-73.7]) who were administered pemafibrate continuously for a period of at least 12 months, between June 2019 and January 2022. Outcomes were the change in body composition indices (visceral adipose tissue index - VATI, subcutaneous adipose tissue index - SATI, and skeletal muscle index - SMI), lipid biochemistry, and liver function, reserve, and fibrosis score, from baseline to the 12-month time point of pemafibrate treatment.

Results: Pemafibrate treatment improved liver function (alanine aminotransferase, aspartate aminotransferase, g-glutamyl transpeptidase, and alkaline phosphatase), and lipid biochemistry (triglycerides and total cholesterol). Improvements in ferritin and hepatic reserve (Mac-2 binding protein, albumin-to-bilirubin score, and NAFLD fibrosis score) were also observed, as well as a decrease in SATI.

Conclusions: Pemafibrate improved dyslipidemia, liver function, and hepatic reserve. The positive effects of pemafibrate on body composition likely contributed to the improvements in liver function. Longer-term treatment may be necessary to influence VATI and thus to further evaluate the relationship between improved body composition and NAFLD with pemafibrate treatment.

Aim of the study: Hepatocellular carcinoma (HCC) is a leading cause of mortality among patients with liver cirrhosis. According to the current practice guidelines, different ablations are used either as curative or palliative therapies. The current study aimed at determining bacterial infections as causes of fever and the predictive role of procalcitonin (PCT) among patients with HCC who had ablation therapy.

Material and methods: This cross sectional study was carried out on 100 patients with HCC during the period from November 2019 to December 2021. All patients were evaluated by full history taking, clinical examination, complete blood picture (CBC), liver biochemistry, coagulation profile, kidney function, C-reactive protein (CRP), serum PCT and blood cultures. All were done for all participants at the 4^th day follow-up after the procedures of ablation. HCC was treated according to the guidelines.

Results: The frequency of fever after HCC ablation was 64% with variable intensities. Bacterial cultures were positive in 20 patients (20%). Twenty-four out of 100 patients had abnormally high PCT level. There was a highly statistically significant increase of PCT level in patients with a high CRP count and positive blood culture, p < 0.05. There was a statistically significant correlation between increased levels of PCT and levels of CRP, WBCs, albumin, AST, ALT, degree of fever, creatinine and BUN.

Conclusions: Bacterial infection accounts for 20% of fever among HCC patients after ablation therapy. PCT is 100% sensitive and specific for detection of the bacterial causes of fever among those patients.