Clinical and Experimental Hepatology最新文献

Aim of the study: Hepatitis C virus (HCV) is one of the most common causes of liver-related deaths worldwide. Non-hepatic cancers such as lung and pancreatic cancers have been linked to HCV infection. This study aimed to determine whether HCV seropositivity was related to the development of extrahepatic malignancies and whether this had an impact on patients' survival.

Material and methods: This retrospective case control study included 1476 patients with lung, colorectal, pancreatic and breast cancers compared to 1550 age- and sex-matched controls regarding HCV seropositivity. In the cancer group, HCV seropositive and seronegative subjects were compared for TNM staging, histologic grading and survival.

Results: There was no significant difference between cancer patients and controls regarding age and sex. The percentage of HCV seropositivity was significantly higher in the total cancer group compared to that in the control group (11.6% vs. 7.3%) [OR = 1.67, p < 0.001] and in cancer types: lung (20.1%) [OR = 3.20, p < 0.001], colorectal (11.8%) [OR = 1.70, p = 0.025], pancreatic (25.4%) [OR = 4.33, p < 0.001] and breast cancer (8.1%) [OR = 1.47, p = 0.03]. There was a significant decrease in survival among HCV seropositive subjects compared to seronegatives in colorectal [HR = 2.77, p = 0.002] and pancreatic cancer [HR = 2.2, p = 0.004], a non-significant decrease in lung cancer [HR = 1.02, p = 0.93] and a non-significant increase in breast cancer [HR = 0.79, p = 0.51].

Conclusions: HCV seropositivity was associated with increased risk of lung, colorectal, pancreatic and breast cancer development; it was also associated with reduced survival in colorectal and pancreatic but not in lung and breast cancers.

Aim of the study: Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population.

Material and methods: The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023.

Results: The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively.

Conclusions: A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.

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: 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: 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: 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.