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.

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: 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.

Aim of the study: Non-alcoholic fatty liver disease (NAFLD) is one of the most important causes of chronic liver disease (CLD) in both Western and Asian populations. There is wide inter-individual variability in the occurrence of NAFLD and progression to non-alcoholic steatohepatitis (NASH) even after correcting environmental factors, and its true explanation can be provided by heritability. Two such genetic variations, the glucokinase regulator (GCKR) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes, in NAFLD patients were studied in the Indian population.

Material and methods: A cross sectional analytical study was conducted in the Department of Gastroenterology at a tertiary care centre. In total 100 subjects in the age range of 18-65 years were included in the study; 50 were patients with NAFLD including fatty liver, NASH and NASH related cirrhosis, and 50 were healthy subjects (No NAFLD). The polymorphisms rs780094 and rs1260326 for GCKR and rs641738 for MBOAT7 were determined using PCR followed by the PCR-RFLP.

Results: GCKR rs780094 minor allele A was more common in NAFLD patients (p = 0.00001). Within the spectrum of NAFLD, the A allele was present frequently among cirrhotics as compared to NASH and fatty liver (p = 0.00001). Morbidly obese individuals showed significant association with the homozygous A allele (p = 0.028). These results were not seen with GCKR rs1260326 across all alleles. In MBOAT7 (rs641738) the frequency of the minor allele T for NAFLD was 84% vs. 80% in healthy subjects (p = 0.79). The association of the T allele among the spectrum of NAFLD was not statistically significant (p = 0.79).

Conclusions: GCKR genetic variant rs780094 was found to be significantly associated with NAFLD. The MBOAT7 (rs641738) genetic variant was not found to be significantly associated with NAFLD.

Aim of the study: Texture analysis derived from computed tomography (CT) involves quantitative imaging parameters characterizing possible valuable associations with clinical purposes. Their prognostic capability in patients undergoing percutaneous CT-guided liver biopsy to identify associations with postinterventional bleeding complications and biopsy success is not sufficiently explored.

Material and methods: Three hundred fifteen patients (124 female, 39%) with a mean age of 62.5 ±10.2 years underwent percutaneous CT-guided liver biopsy and were analyzed regarding clinical, procedure-related, and CT texture features.

Results: Thirty patients (9.5%) presented with bleeding after biopsy (including two requiring interventional treatment), whereas 46 patients (14.6%) had negative biopsy successes. Distance of lesion from liver capsule was statistically significantly different in patients with and without bleeding (p = 0.015). Several texture features were statistically significantly different between the groups, S(0,1)SumAverg having the highest significance (p = 0.004). Regarding unsuccessful biopsy results, liver fibrosis was the only clinical feature with statistical significance (p = 0.049). Only two texture features (S(4,-4)InvDfMom and Teta3) were statistically different between the groups according to the biopsy result.

Conclusions: Several CT texture features of the target lesion and the length from the capsule to the lesion were associated with bleeding complications after CT-guided percutaneous liver biopsy. This could be used to identify patients at risk at the beginning of the procedure.

Managing patients with liver cirrhosis and gastric hyperplastic polyps (GHPs) is challenging. Despite being the standard technique for resection of GHPs, hot snare polypectomy (HSP) is risky in the setting of coagulation disorders associated with liver cirrhosis. The aim of the study was to assess the efficacy and safety of endoscopic band ligation (EBL), compared to HSP in resecting GHPs in cirrhotic patients. One hundred consecutive adults with liver cirrhosis and sessile or pedunculated GHPs were enrolled from December 2018 to December 2020. Cases were non-blindly randomized (1 : 1) to two groups to have GHPs managed by either EBL (group I) or HSP (group II). Data of demographic, clinical, and pathological factors, hospitalization expenses and outcomes of both treatment maneuvers were collected and statistically analyzed. Upper endoscopy was repeated for all patients at 3, 6 and 12 months after treatment for recurrence detection. Between the two procedures, the mean operational time was significantly shorter in the EBL than the HSP group (15.1 ±3.80 min vs. 36.6 ±6.72 min, p < 0.001). Concerning complications, 94% of EBL cases had reported no complications compared to 78% with HSP. Bleeding occurred only with HSP (20%) with urgent need for adrenaline and/or argon plasma coagulation (p = 0.003). Regarding cost, it was significantly lower in EBL than HSP (280 ±2.02 EGP vs. 390 ±181.8 EGP, p < 0.001). However, the recurrence rate of GHPs and number of needed sessions were not significantly different. EBL proved to be a safer, more rapid, and economic maneuver when compared to HSP on resecting GHPs in patients with liver cirrhosis.

Aim of the study: To investigate whether serum ferritin and vitamin D levels before starting autoimmune hepatitis (AIH) treatment have a role in disease prognosis regarding a therapeutic response.

Material and methods: The prospective study included 100 children diagnosed with AIH according to simplified criteria for diagnosis of AIH. They attended the Pediatric Hepatology Department, National Liver Institute, Menoufia University. The patients underwent measurement of liver transaminases before starting AIH treatment after 6 months from starting therapy. They underwent liver biopsy before starting treatment for proper diagnosis, grading, and staging; only 25 cases were compliant and underwent liver biopsy before treatment withdrawal.

Results: Serum ferritin and 25 hydroxy vitamin D levels were significantly higher among those with a complete response (1000-3100 ng/ml, 29-48 ng/ml) than a partial response (550-600 ng/ml, 23-28 ng/ml) and non-response (29.28-92.14, 2.16-8.72) (p < 0.001).

Conclusions: Our study showed a relation between serum vitamin D before starting AIH treatment, the severity of AIH and response to therapy. This opens a new area of research on the potential use of vitamin D in patients with AIH. Also, hyperferritinemia at the diagnosis can predict the treatment response.