Clinical and Experimental Hepatology最新文献

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 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: 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.

Aim of the study: The gradual clinical worsening of acute-on-chronic liver failure (ACLF) leads to a high 28-day mortality rate. There are several prognostication scores for predicting early mortality in ACLF. Serum phosphate, which is the main component of adenosine tri-phosphate (ATP) synthesis, is utilized for liver synthetic functions, leading to subnormal or decreased serum phosphate levels. Hence more than normal levels of serum phosphate can be used as a marker of decreased liver cell reserve. Hence, we aimed to compare serum phosphate levels with available prognostic scores to assess mortality among ACLF patients.

Material and methods: 100 consecutive ACLF patients according to the Asia Pacific Association for Study of the Liver (APASL) definition were studied. The baseline blood workups and determination of viral bio-markers, serum phosphate, and lactate levels on days 1, 3, and 7 were carried out and prospectively followed up, and the baseline serum phosphate levels were compared with the usual scores to predict the 28-day mortality.

Results: CLIF-SOFA (accuracy 76-91%) followed by CLIF-C score (accuracy 73-84%) and AARC score (accuracy 70-85%) had the statistically significantly highest accuracy as compared with CTP, MELD, and MELD-Na on all three days. Serum phosphate values (accuracy 69-86%) on all three days were not better than the CLIF-SOFA score but better than all other prognostic scores on days 3 and 7.

Conclusions: The high serum phosphate levels on day 3 with a value of more than 6.4 mg/dl showed almost comparable accuracy with CLIF-SOFA for screening short-term mortality. Hence serum phosphate measurement can be used as a simple bedside laboratory investigation to predict mortality in ACLF patients and early interventions in low-resource settings.

Aim of the study: Liver fibrosis and cigarette smoking seem to be directly linked. Nicotine, as an agonist of nicotinic acetylcholine receptors (nAChRs), induces many downstream signaling pathways. The pathways through which nicotine affects the process of liver fibrosis have not been clarified. The present study aimed to investigate the nicotine-induced effects on fibrosis progression in cholestatic rats.

Material and methods: First, the Wistar rats were subjected to sham or bile duct ligation (BDL) surgery. The rats were treated with low and high doses of nicotine (1 or 10 mg/kg) for three weeks. They were monitored for their body weights before and 21 days after BDL. Also, spleens were weighed to calculate the spleen/body weight ratio. Ductular proliferation and fibrosis were evaluated using hematoxylin and eosin (H&E) as well as Masson's trichrome staining. The mRNA expression of α4nAChR, α7nAChR, and fibrosis gene α-smooth muscle actin (α-SMA) was measured by real-time PCR.

Results: The findings showed that nicotine promotes the development of BDL-induced liver fibrosis. The ratio of spleen/body weight was significantly affected by nicotine exposure. H&E and Masson's trichrome staining showed that the level of liver fibrosis was higher in the cholestatic BDL groups, and this effect was significantly augmented in the nicotine-treated rats. Also, α4nAChR, α7nAChR, and α-SMA expression was observed in the BDL rats and increased following nicotine treatment.

Conclusions: The activation of nAChR triggers biliary proliferation and liver fibrosis. Studying the intracellular mechanism of nicotine and alteration in the expression of nicotinic receptors following nicotine exposure can be useful both in diagnosing nicotine-related diseases and finding new treatment strategies.

Syphilis is a sexually transmitted multisystemic disease known as "the great imitator" due to its variable presentations. Despite being preventable and curable, it still constitutes a major health problem. Hepatic manifestation of syphilis is usually mild cholestatic liver injury but in very rare cases can become fulminant. Moreover, syphilitic hepatitis, known for several decades, is considered rare but is probably under-diagnosed. Given the significant morbidity associated with a missed diagnosis, syphilitic hepatitis should be taken into account as an element of differential diagnosis in patients with unexplained elevation of liver enzymes.

Aim of the study: Early paracentesis before antibiotic administration reduces morbidity and mortality in patients with decompensated cirrhosis. We studied the association of variables with antibiotic administration before or after performing paracentesis.

Material and methods: This was a retrospective study of 137 patients with ascites secondary to cirrhosis admitted to a community hospital in New York City. Predictor variables were demographic, disease-related, admission timing, and serum measurement.

Results: We found a significantly increased relative risk for performing paracentesis after antibiotic administration for those admitted at night (relative risk ratio [RRR] = 3.01, 95% CI: 1.02-8.85, p = 0.046). Demographic, disease-related, and serum measurement variables were not significantly associated with performing paracentesis or order of antibiotic administration. Also, increased body mass index was significantly associated with decreased relative risk for paracentesis not done (RRR = 0.84, 95% CI: 0.74-0.96, p = 0.01).

Conclusions: In conclusion, there was increased relative risk for performing paracentesis after antibiotic administration for patients admitted at night. We recommend ongoing resident and hospitalist training to maintain competency in bedside procedures such as paracentesis for patients with cirrhosis. Also, increased staffing or the presence of a resident/hospitalist led interventional team during night shifts may also help optimize the rates of timely paracentesis.

Aim of the study: Hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) are benign liver tumors. Hepatocellular adenoma has potential for growth, metaplasia and rupture; therefore, it should be monitored long term. In the current guidelines biopsy is not recommended in the standard diagnostic protocol. Magnetic resonance imaging (MRI) is accepted as standard in diagnostics and monitoring of these lesions. The aim of the study was to compare contrast-enhanced ultrasound (CEUS) and MRI in imaging of these tumors and determine whether CEUS can be useful in monitoring benign liver tumors.

Material and methods: A retrospective analysis of 47 patients with HCA (32 tumors) and FNH (27 tumors) was carried out. A comparison between MRI and CEUS in predicting malignant transformation was performed.

Results: A similar tumor enhancement profile to unchanged liver parenchyma was observed in both groups. The difference in the arterial phase was on average up to 30 dB. After 20-30 s, the enhancement of HCA and FNH in relation to the liver parenchyma was similar (difference up to 4-5 dB). Homogeneity and equalization of the tumor to background enhancement was observed until the end of the examination. The discriminative feature is the presence of a non-contrasting central fibrous scar observed in both imaging methods in the FNH group.

Conclusions: CEUS can be a promising method in monitoring focal liver lesions due to low cost and low risk of complications. It is essential to analyze the early arterial phase up to 30 s to demonstrate homogeneous enhancement of the tumor and potential presence of a wash-out effect during later phases of examination.

The biological rhythm is a fundamental aspect of an organism, regulating many physiological processes. This study focuses on the analysis of the molecular basis of circadian rhythms and its impact on the functioning of the liver. The regulation of biological rhythms is carried out by the clock system, which consists of the central clock and peripheral clocks. The central clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and is regulated by signals received from the retinal pathway. The SCN regulates the circadian rhythm of the entire body through its indirect influence on the peripheral clocks. In turn, the peripheral clocks can maintain their own rhythm, independent of the SCN, by creating special feedback loops between transcriptional and translational factors. The main protein families involved in these processes are CLOCK, BMAL, PER and CRY. Disorders in the expression of these factors have a significant impact on the functioning of the liver. In such cases lipid metabolism, cholesterol metabolism, bile acid metabolism, alcohol metabolism, and xenobiotic detoxification can be significantly affected. Clock dysfunctions contribute to the pathogenesis of various disorders, including fatty liver disease, liver cirrhosis and different types of cancer. Therefore understanding circadian rhythm can have significant implications for the therapy of many liver diseases, as well as the development of new preventive and treatment strategies.