Clinical and Experimental Hepatology最新文献

Aim of the study: The new term "metabolic dysfunction associated steatotic liver disease" (MASLD) focuses on the bidirectional interplay between fatty liver and metabolic dysregulation. The aim of this study was to evaluate serum concentrations of uric acid (UA) in overweight/obese children and adolescents and to determine the association of this parameter with MASLD and metabolic dysregulation.

Material and methods: One hundred and ninety-four overweight/obese children with suspected liver disease were included in the study. MASLD was diagnosed according to the latest consensus. Diagnosis of metabolic syndrome (MetS) was based on the International Diabetes Federation criteria in children aged ≥ 10 years (n = 182).

Results: MASLD was diagnosed in 68.56% and MetS in 26.92% of patients. Children with MASLD had significantly higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total cholesterol, triglycerides (TG), UA and carotid intima-media thickness (IMT). Significantly higher levels of insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and UA were observed in patients with MetS. Correlations were observed between UA and ALT, AST, GGT, TG, insulin, HOMA-IR, mean IMT, body mass index (BMI) and high-density lipoprotein cholesterol (HDL-C) in overweight and obese children. UA was helpful in differentiating between children with MetS and without MetS (p = 0.0003), while only borderline statistical significance was observed for MASLD (p = 0.05).

Conclusions: Our results suggest that UA may be a potential additional and readily available marker of metabolic dysfunction in children with MASLD. Further studies on a larger group of patients are needed to confirm this association.

Aim of the study: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition associated with inflammation owing to fat deposition in the liver. Managing hypertriglyceridemia is essential for patients with NAFLD, including treatment with pemafibrate. However, whether pemafibrate affects fat deposition in the liver and whether hypertriglyceridemia is the primary treatment target remain unclear. Thus, in this single-arm, retrospective study, we explored how pemafibrate treatment affects fat deposition in the liver in patients with NAFLD using FibroScan, the only insurance-covered device in Japan for quantitatively measuring fat in the liver.

Material and methods: Patients with NAFLD and hypertriglyceridemia were administered 0.2 mg/day of pemafibrate for either three (n = 51) or six (n = 42) months. The primary endpoint was the FibroScan (FibroScan 430 Mini, Echosens, France) controlled attenuation parameter (CAP) measurement. The secondary endpoints were liver transaminase levels, the FibroScan-aspartate aminotransferase (FAST) score, the hepatic steatosis index (HSI), the fibrosis-4 (FIB-4) index, the aspartate aminotransferase-to-platelet ratio index (APRI), and the albumin-bilirubin (ALBI) score.

Results: Three months of pemafibrate administration significantly improved the CAP values. The FAST score and HSI also significantly improved after three months, suggesting fatty liver improvements. Furthermore, the alanine aminotransferase and γ-glutamyl transpeptidase levels (indicators of hepatitis) decreased, and fibrosis improved in the liver fibrosis prediction assessments, such as the FIB-4 index, APRI, and ALBI score, after three months of pemafibrate administration. Most of these improvements remained after six months.

Conclusions: Oral pemafibrate treatment improved NAFLD in patients with hypertriglyceridemia, indicating that pemafibrate may be a new treatment option for NAFLD.

Aim of the study: The aim of the study was to characterize the population with hepatitis C virus (HCV) infection and steatotic liver disease (SLD) in comparison to the non-SLD HCV-infected patients and to evaluate the effectiveness of treatment with direct-acting antivirals (DAA).

Material and methods: The analysis included 62 patients diagnosed with SLD and 14,284 non-SLD patients from the EpiTer-2 database for the period 2015-2022.

Results: Unlike the non-SLD population, the SLD group was dominated by men (49.5% vs. 53.2%, respectively). The mean age of patients did not differ significantly between groups and was 50.8 ±13.8 and 50.8 ±14.9 years for SLD and non-SLD, respectively. As expected, patients with SLD had significantly different BMI values. Genotype (GT) 1b infection predominated in both populations, but the prevalence of GT3 was significantly higher in the SLD group (19.4% vs. 10.6%). The percentage of patients with advanced liver disease (F3/4) was similar in both groups (38.7% vs. 35.6%). Patients with SLD were more likely to be treatment naïve (82.3% vs. 80.5%), HBV co-infected (24.2% vs. 13.6%), and obese (54.8% vs. 17.1%). Out of 62 patients, 59 (95%) achieved a sustained virologic response (SVR), but after excluding 3 lost to follow-up a response rate of 100% was obtained. The corresponding SVR values in the non-SLD HCV-infected population were 95% and 98%, respectively.

Conclusions: Despite some differences in the characteristics of patients with SLD infected with HCV, the effec-tiveness of DAA therapy does not differ significantly from that observed in the general population infected with HCV.

Aim of the study: Sarcoidosis is characterized by noncaseating granulomas that can affect multiple organs. Due to the lack of prospective studies regarding treatment of hepatic sarcoidosis with ursodeoxycholic acid (UDCA), we set out to evaluate its effects in a single-center, open-label, prospective, pre-post study.

Material and methods: A total of 10 patients were screened from August 2018 to July 2020; seven met the criteria and were enrolled. The study was terminated prior to achieving target enrollment of 10 patients due to the difficulty in recruitment around the COVID-19 pandemic. Most patients were women (4/7; 57.1%) and African American (5/7; 71.4%). One patient dropped out during the first month of observation due to a new diagnosis of esophageal cancer. Six completed the 6-month observation and UDCA treatment periods. One patient stopped UDCA within the first month of active treatment due to the side effect of nausea.

Results: There was a decrease in ALP and GGT after six months of UDCA treatment compared to six months of observation (ALP - 257.6 to 202.2, p = 0.23; GGT - 302.5 to 111.8, p = 0.059), but this did not reach statistical significance. There were also decreases in all key secondary endpoints (ALT - 50.8 to 29.8, p = NS; AST - 40.3 to 31.2, p = NS, VCTE kPa - 8.3 to 6.3, p = NS). As with the primary endpoints, none of the key secondary endpoints reached statistical significance.

Conclusions: There is significant potential for UDCA as first-line treatment of hepatic sarcoid. Multi-center, ideally prospective, studies of longer duration are needed.

Echinococcosis is considered one of the world's most dangerous zoonoses, and the tapeworm that causes it is one of the two most dangerous parasites to humans globally. Untreated cases may be associated with as high as 90% mortality. The incidence of this pathology is increasing. The authors present an up-to-date review of the literature on liver echinococcosis; they also present their own material of 73 patients with liver echinococcosis treated in the Department of General and Transplant Surgery since 2019.

Aim of the study: Gallbladder cancer (GBC) lesions are usually solitary. The presence of multifocal disease can alter resectability and management. There are no systematic imaging-based studies evaluating multifocality in GBC. Thus, we aimed to evaluate multifocality in GBC based on cross-sectional imaging studies.

Material and methods: This retrospective study screened cross-sectional imaging (contrast-enhanced computed tomography [CT] or magnetic resonance imaging [MRI]) of consecutive patients with histopathological or cytological diagnoses of GBC. The CT/MRI images of patients with multifocal disease (defined as the presence of two or more foci of abnormal wall thickening, intraluminal polypoidal lesions or masses in the gallbladder, cystic duct, or the extrahepatic bile ducts with the intervening area of normal gallbladder/extrahepatic bile ducts) were evaluated by two radiologists independently for various imaging findings.

Results: Of the 324 patients, 17 (5.2%; 13 females; mean age, 54 ±11 years) had multifocal disease with two sites of involvement in all cases. The most common sites of involvement were the gallbladder fundus and neck region (58.8% of cases), followed by the gallbladder fundus and common bile duct (29.4%). Wall thickening type of GBC was the most common morphological subtype (85.3%), followed by mass forming type (14.7%). The majority (70.6%) of cases showed the same morphology at both sites, while 29.4% showed different morphology. Most (70.6%) of the patients with multifocal GBC were unresectable at the time of diagnosis.

Conclusions: Although rare, imaging-based diagnosis of multifocal GBC may allow appropriate management.

Aim of the study: This study aimed to investigate the impact of bone marrow-derived mesenchymal stem cell exosomes (BMSC-Exos) on hepatic stellate cell (HSC) activation and explore the underlying molecular mechanisms in liver fibrosis.

Material and methods: BMSC-Exos were co-incubated with LPS-activated LX-2 cells. Fibrosis markers, iron content, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) levels, and ferroptosis-related proteins were assessed. The role of miR-144-3p originating from BMSC-Exos in LX-2 cell activation was studied through dual-luciferase reporter gene and RNA pull-down experiments.

Results: Treatment with BMSC-Exos up-regulated miR-144-3p in LX-2 cells, down-regulated SLC7A11, increased iron content and ROS levels, and reduced fibrosis markers and GSH. BMSC-Exos mediated ferroptosis and inhibited HSC activation by transmitting miR-144-3p targeting SLC7A11.

Conclusions: BMSC-Exos regulate SLC7A11 expression through miR-144-3p transfer, promoting ferroptosis and suppressing HSC activation in liver fibrosis.

Liver injury resulting from the use of dietary supplements, herbs, and commonly available medications is a problem that is becoming increasingly significant due to the widespread availability and growing popularity of these products. Factors contributing to this damage may include supplements used for weight reduction, questionable quality herbs, and commonly available pain-relief and anti-inflammatory medications. Currently, the most appropriate solution to this problem appears to be prevention by patient education and medical community awareness, as well as increased oversight of the market for these types of products.

Aim of the study: To assess the real-life efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in HIV/HCV- positive patients treated with bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

Material and methods: Patients were evaluated in terms of their baseline biochemical characteristics, which included platelet count, serum creatinine and bilirubin levels, alanine transaminase (ALT) activity, international normalized ratio (INR) and Model for End-Stage Liver Disease (MELD) score.The efficacy endpoint was the achievement of a sustained virologic response at posttreatment week 12 (SVR12), defined as undetectable HCV RNA 12 weeks after the scheduled end of therapy.

Results: No significant differences in baseline patient characteristics between the two study groups were observed. Patients treated with sofosbuvir/velpatasvir (SOF/VEL) were more often treatment-naïve, but the difference was not statistically significant (96.0% vs. 86.8% in GLE/PIB group, p = 0.0629). Prevalence of genotype 3 was higher in the group treated with GLE/PIB (36.9% vs. 21.8% in SOF/VEL group, p = 0.183382), while genotype 1 was more frequent in patients treated with SOF/VEL (55.4% vs. 44.7% in GLE/PIB group, p = 0.348202), but again it did not prove to be statistically significant. SVR12 rates reached 78.9% and 80.2% for GLE/PIB and SOF/VEL, respectively, in ITT analysis, and 100% and 98.8%, respectively, in modified intent-to-treat (mITT) analysis.

Conclusions: The study showed that real-life results of direct acting antiviral (DAA) therapy with GLE/PIB or SOF/VEL did not differ significantly in HIV/HCV-coinfected patients treated with B/FTC/TAF. Both regimens allowed encouraging SVR12 rates and treatment safety to be achieved, as well as tolerability, which was also comparable between the study groups.

Aim of the study: This research aimed to investigate the incidence and course of varicella-zoster virus hepatitis in immunocompetent children.

Material and methods: Medical charts of children hospitalised between 2019 and 2022 (excluding the period of the COVID-19 pandemic) due to varicella were retrospectively analysed and compared.

Results: In total, 216 children were included in the analysis. In 24 children (11.1%) alanine aminotransferase (ALT) levels were elevated, whereas in 192 (88.9%) children, ALT levels were within the normal range. In 19 patients, ALT levels exceeded the upper limit of normal (ULN) less than twofold, in 4 patients ALT levels were elevated 2-3-fold, and in only one infant, a value 9.4× ULN was observed. None of the patients developed liver failure. The median age at the time of the diagnosis was significantly higher in the group of patients with elevated ALT - 5.5 years vs. 3 years in the group with normal ALT values (p = 0.02). The median duration of fever and hospitalization was longer by 1 day in the group with elevated ALT. Additionally, varicella lesions lasted longer in this group, 7.5 days vs. 6 days in the group with normal ALT levels (p = 0.01). Although median C-reactive protein (CRP) and procalcitonin (PCT) values did not differ, median leukocyte values were lower (p = 0.01) in the group with elevated ALT (7.3 × 10³/ml vs. 8.8 × 10³/ml).

Conclusions: Elevation of ALT during varicella is observed in 1 out of 10 immunocompetent patients. The course of this hepatitis is predominantly mild.