Clinical and Experimental Hepatology最新文献

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.

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.

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: 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.

Aim of the study: This study was performed to investigate the hepatic expression of glucocorticoid receptors (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in pediatric autoimmune hepatitis (AIH) patients and its relation to the steroid response.

Material and methods: This study included 100 patients diagnosed with AIH on immunosuppressive therapy with different responses to treatment. The patients were subjected to full history taking and thorough clinical examination, laboratory investigations, abdominal ultrasound and liver biopsy for histopathological evaluation and assessment of the hepatic expression of GR and 11β-HSD1.

Results: Out of the 100 cases, 82 cases showed a complete response, 11 a partial response and 7 cases were non-responders. The sex, age distribution and clinical presentation of the disease were comparable among the different response groups. Glucocorticoid receptors reactivity was significantly more intense in patients with a complete response than both patients with a partial response and non-responders. 11β-HSD intensity was higher in complete and partial responders in comparison with non-responders but without significance. The percentage of patients with a GR intensity score ≥ 200 was significantly higher in patients with a complete response than patients with a partial response and non-responders (p < 0.05). The GR intensity score had a significant positive correlation with intensity of 11β-HSD (r = 0.369, p < 0.0001).

Conclusions: Glucocorticoid receptors expression was significantly variable in children with AIH and closely related to the response to therapy. However, the 11β-HSD expression was comparable between different response groups.

Aim of the study: Over the past few years, diffusion-weighted imaging (DWI) has become an increasingly important diagnostic tool in the diagnosis of liver lesions. The objective of the present study was to evaluate the diagnostic benefit of high b-value computed diffusion-weighted imaging (c-DWI) compared with standard DWI in patients with hepatocellular carcinoma (HCC) and whether there is an association with microvascular invasion (MVI).

Material and methods: In total, 37 patients with histopathologically confirmed HCC were retrospectively ana-lyzed. DWI was acquired with b-values of 50, 400, and 800 or 1000 s/mm² on a 1.5 T magnetic resonance imaging (MRI) scanner. The c-DWI was calculated using a monoexponential model with high b-values of 1000, 2000, 3000, 4000, and 5000 s/mm². All high b-value c-DWI images were compared to the standard DWI in terms of volume, detectability of hepatic lesions, and image quality.

Results: Regarding lesion volume and image quality there were no statistically significant differences between standard and c-DWI. HCC lesions measured on DWI images were statistically significantly larger compared to c-DWI images starting from a b value of 2000 s/mm² (DWI vs. c-DWI b 2000 s/mm²: 2 cm³ [1-12] cm³ vs. 1 cm³ [0-17] cm³, p < 0.05). Moreover, there was deterioration of image quality starting at b = 2000 s/mm². There were no significant differences in terms of lesion signal intensity in DWI and c-DWI images. There were no differences for the DWI parameters according to MVI status.

Conclusions: C-DWI images with high b-values up to b = 1000 s/mm² demonstrate comparable detectability of HCC compared to standard DWI. The investigated DWI parameters were not associated with MVI status. Further research is needed to evaluate the potential benefit of high b-value c-DWI.

Aim of the study: This study aimed to establish an objective, simple, and minimally invasive screening method to detect patients with biliary atresia during neonatal checkups by using indocyanine green (ICG) fluorescence in the stool.

Material and methods: We produced a rat model of extrahepatic biliary obstruction (group O, n = 9) and compared the stools from these rats with those of control group rats (group C, n = 6) by a fluorescence technique. ICG was administered (0.5 mg/kg) through the caudal vein; group O received ICG at the end of surgery.

Results: In group C, we collected stools at 3, 6, 12, 24, 48, and 72 hours, and fluorescence disappeared at 48 hours. In group O, stools were collected at 24, 48, 72, 96, and 120 hours after surgery, and fluorescence continued at 120 hours without the loss of fluorescence. Quantitative assessment of lightness showed significant differences between the groups at 48 and 72 hours (p = 0.0016 and p = 0.0004, respectively).

Conclusions: This study shows that ICG is excreted into the gastrointestinal tract via a route other than the bile duct in a rat model of extrahepatic biliary obstruction. Our findings also suggest that ICG has the potential for initial screening of biliary congestive disease in the neonatal period, which could be followed up by detailed testing.

Aim of the study: Jaundice in newborns is a sign of skin and sclera pigmentation. Hyperbilirubinemia and these phenomena do, however, have a relationship. According to many clinical studies, elevated blood bilirubin and low vitamin E (VE) levels in newborns are associated. The aim of the study was to investigate the association of oxidative stress of neonatal hyperbilirubinemia in patients who underwent phototherapy with additional vitamin E supplementation (25 mg/kg/day over the course of three days) and patients without additional vitamin E.

Material and methods: A set of 100 neonatal indirect hyperbilirubinemia patients was enrolled at neonatal intensive care units (NICUs) of the pediatric departments at Al Azhar University Hospitals during the period from February 2021 to October 2022 after obtaining signed written informed consent of all neonates' parents with an explanation of the aim of study.

Results: Significant differences were found between the studied groups regarding serum bilirubin on the third day of admission (p = 0.039). Patients who were treated with vitamin E had lower serum bilirubin on the third day of admission (8.25 ±3.41) than the control group (11.66 ±3.22). Also, among the VE group, serum bilirubin was significantly decreased on the third day of admission (8.25 ±3.41) compared to zero days of admission (14.10 ±4.39) (p = 0.041).

Conclusions: Vitamin E supplementation has an important role in treatment of indirect hyperbilirubinemia in neonates. Early administration of vitamin E in preterm neonates resulted in a significant decrease of serum bilirubin and increased total antioxidant capacity. Vitamin E supplementation in full term decreased the duration of phototherapy.