Clinical and Experimental Hepatology最新文献

Aim of the study: To analyze the hepatitis B virus (HBV) infection and mortality in Poland according to sociodemographic characteristics, trends over time, and the impact of the COVID-19 pandemic on hepatitis B epidemiology.

Material and methods: We examined HBV infection cases and deaths reported by national registries and used Joinpoint analysis to estimate time trends in the years 2005-2021. To assess the impact of the COVID-19 pandemic on HBV infection, we used monthly information and compared 2020-2022 with 2019.

Results: The Joinpoint analysis showed that in Poland between 2005 and 2021, there were pronounced decreasing trends of acute HBV infection, and during the pandemic period, acute HBV infection dramatically decreased (annual percent change, APC_2019-2021 for men -57.65%, and women -42.10%, both p_trend < 0.05). There was a fluctuation in trends for chronic HBV infection, shifting from positive to negative in both genders in 2016, and over the pandemic, there were decreasing trends (APC_2019-2021 for men -26.94% and women -28.96%, both p_trend < 0.05). From March to July 2022, the value of the diagnosis rate of HBV infection was lower compared to the respective months in 2019, but from September to December 2022, the rate changes were positive. Mortality due to HBV infection decreased in both genders, mainly within the 2005-2019 period.

Conclusions: During the COVID-19 pandemic, a sharp decrease in HBV diagnosis rates in Poland, especially in acute cases, was observed. However, trends of hepatitis B infection require further monitoring. It is necessary to introduce a national screening program that also encompasses the population of migrants and improve the linkage to care.

Aim of the study: There is a close relationship between the development of diabetes and nonalcoholic fatty liver disease (NAFLD). The aim of the study was to determine the frequency and associated factors of NAFLD in type 2 diabetes mellitus (T2DM) patients according to the ultrasound examination and noninvasive hepatic fibrosis indices.

Material and methods: 316 patients who were followed up in the Internal Medicine Diabetes clinic, over the age of 18, diagnosed with T2DM were included retrospectively. NAFLD was noted using ultrasound. NAFLD fibrosis score (NFS), fibrosis-4 index (FIB-4) and AST to platelet ratio index (APRI) were used as non-invasive hepatic fibrosis indices.

Results: The prevalence of NAFLD with hepatic ultrasound was 89.7% in T2DM patients. Among non-invasive fibrosis indices, NFS and FIB-4 were similar, but APRI was significantly higher in moderate-severe hepatosteatosis group (p values = 0.355, 0.246 and 0.003 respectively). In logistic regression analysis, while mild hepatosteatosis was associated with BMI and NFS (p = 0.004, p = 0.008), moderate to severe hepatosteatosis as associated with BMI and serum triglycerides (p < 0.001, p = 0.019).

Conclusions: The prevalence of NAFLD is high in patients with T2DM. The frequency and degree of NAFLD is associated with the NFS, BMI and hypertriglyceridemia. While NFS is associated with mild hepatosteatosis; moderate to severe hepatosteatosis is associated with BMI and serum triglycerides.

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.