Clinical and Experimental Hepatology最新文献

Aim of the study: The treatment of autoimmune hepatitis (AIH) is based on steroids and azathioprine (AZA). AZA is a pro-drug which is converted among others into 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP). The aim of the study was to determine the relationship between the AZA active metabolite 6-TG and both the biochemical and histological remission outcomes.

Material and methods: The authors conducted a retrospective analysis of a single chart review. The sample size consisted of 44 pediatric patients with AIH. Biochemical remission was defined as an alanine aminotransferase (ALT) level below 40 U/l and histological remission was defined as a situation when the control biopsy revealed inflammation grade G1 (or lower) in the Batts-Ludwig score. Statistical analysis was applied to assess the difference in remission outcomes in patients with different levels of 6-TG.

Results: In the benchmark variant of our statistical analysis, we found that the correlation between 6-TG and ALT in the sample was not statistically significant. Moreover, the difference between the mean levels of ALT in the populations in and without remission was not statistically significant (the p-value of the t-test was 0.16).

Conclusions: Our results tend to support the claim that there is no statistically significant relationship between 6-TG concentration and remission (both biochemical and histological) in pediatric patients with AIH.

Aim of the study: Akt is involved in upregulating the insulin-signaling pathways essential for maintaining glucose metabolism. Glycosphingolipids are involved in the pathogenesis of glucose intolerance and associated target organ injury. On the other hand, oral administration of b-glucosylceramide (GC) has been shown to alleviate insulin resistance. The present study aimed to determine the effects of oral administration of insulin and GC, separately and in combination, on Akt expression and the subsequent effect on metabolic syndrome characteristics in leptin-deficient mice.

Material and methods: Four groups of leptin-deficient ob/ob mice were orally administered for four weeks: vehicle, GC, short-acting insulin, and GC combined with insulin. Mice were followed for hepatic Akt expression and changes in tumor necrosis factor a (TNF-a) level, hyperlipidemia, and liver damage.

Results: In mice that received insulin or GC, particularly those that received both, the liver phosphorylation of Akt was significantly increased compared to those that received only vehicle. Serum TNF-a levels decreased in insulin-treated mice. These effects were associated with alleviating glucose intolerance and hyperlipidemia, as manifested by a significant glucose tolerance test improvement and reductions in serum triglyceride and cholesterol levels. Significant liver damage alleviation was noted by liver enzyme reductions in all treated groups, along with liver steatosis in the insulin-treated mice.

Conclusions: These data established the potential use of oral insulin administration with glycosphingolipids to alleviate glucose intolerance and associated liver damage and hyperlipidemia via increased Akt expression in the liver. The data support targeting Akt as a potent therapeutic target for metabolic syndrome.

Aim of the study: Owing to the association between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia, there is a need for new treatment strategies to manage both conditions concomitantly. Our aim in this study was to evaluate the effectiveness of pemafibrate in alleviating dyslipidemia-associated NAFLD, including the evaluation of its effects on liver function and body composition.

Material and methods: The study sample included 67 patients with dyslipidemia-associated NAFLD (29 males, mean age 65.7 years [range, 58.4-73.7]) who were administered pemafibrate continuously for a period of at least 12 months, between June 2019 and January 2022. Outcomes were the change in body composition indices (visceral adipose tissue index - VATI, subcutaneous adipose tissue index - SATI, and skeletal muscle index - SMI), lipid biochemistry, and liver function, reserve, and fibrosis score, from baseline to the 12-month time point of pemafibrate treatment.

Results: Pemafibrate treatment improved liver function (alanine aminotransferase, aspartate aminotransferase, g-glutamyl transpeptidase, and alkaline phosphatase), and lipid biochemistry (triglycerides and total cholesterol). Improvements in ferritin and hepatic reserve (Mac-2 binding protein, albumin-to-bilirubin score, and NAFLD fibrosis score) were also observed, as well as a decrease in SATI.

Conclusions: Pemafibrate improved dyslipidemia, liver function, and hepatic reserve. The positive effects of pemafibrate on body composition likely contributed to the improvements in liver function. Longer-term treatment may be necessary to influence VATI and thus to further evaluate the relationship between improved body composition and NAFLD with pemafibrate treatment.

Aim of the study: Hepatocellular carcinoma (HCC) is a leading cause of mortality among patients with liver cirrhosis. According to the current practice guidelines, different ablations are used either as curative or palliative therapies. The current study aimed at determining bacterial infections as causes of fever and the predictive role of procalcitonin (PCT) among patients with HCC who had ablation therapy.

Material and methods: This cross sectional study was carried out on 100 patients with HCC during the period from November 2019 to December 2021. All patients were evaluated by full history taking, clinical examination, complete blood picture (CBC), liver biochemistry, coagulation profile, kidney function, C-reactive protein (CRP), serum PCT and blood cultures. All were done for all participants at the 4^th day follow-up after the procedures of ablation. HCC was treated according to the guidelines.

Results: The frequency of fever after HCC ablation was 64% with variable intensities. Bacterial cultures were positive in 20 patients (20%). Twenty-four out of 100 patients had abnormally high PCT level. There was a highly statistically significant increase of PCT level in patients with a high CRP count and positive blood culture, p < 0.05. There was a statistically significant correlation between increased levels of PCT and levels of CRP, WBCs, albumin, AST, ALT, degree of fever, creatinine and BUN.

Conclusions: Bacterial infection accounts for 20% of fever among HCC patients after ablation therapy. PCT is 100% sensitive and specific for detection of the bacterial causes of fever among those patients.

In addition to having inflammation in the liver, overweight people also have changes in the composition of their immune systems and subsets of their immune systems. There are several genes involved in liver metabolism that have been implicated in nonalcoholic fatty liver disease (NAFLD), a liver disease associated with obesity, which is caused by high triglycerides and liver transaminases. NAFLD, a global liver disease, may differ in gene expression depending on where a person lives. In some alleles, the risk factors were independent. Finally, the researchers identified many genetic variations connected to fatty liver disease in those who did not drink alcohol regularly. These variants were located in genes involved in RNA metabolism, protein catabolism, and energy metabolism.

Aim of the study: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver. It is also one of the world's most common cancers and an important leading cause of cancer mortality in many parts of the world. As a result, it is essential to look for efficient markers for early and accurate HCC diagnosis. CXCL9 and pentraxin 3 are involved in the pathway of many cancers. The aim of the study was to assess the value of serum CXCL9 and pentraxin 3 as diagnostic markers of HCC among cirrhotic hepatitis C virus (HCV) patients.

Material and methods: The current study was conducted on 90 candidates divided into 3 groups: group I - 30 patients with HCV induced liver cirrhosis without HCC; group II - 30 patients with HCV induced liver cirrhosis with HCC; group III - 30 healthy subjects (control group). All candidates were subjected to detailed history taking and thorough clinical examination, laboratory investigations, serum CXCL9, serum pentraxin 3, ultrasound abdomen and CT triphasic liver in group III.

Results: Serum CXCL9 and serum pentraxin 3 levels were significantly higher in group II than group I and significantly higher in group I than group III.

Conclusions: Serum CXCL9 and serum pentraxin 3 could be utilized as diagnostic markers for HCC.

Aim of the study: Cholestasis/cirrhosis could induce erythrocyte lysis. The incidence of various types of anemia in cirrhosis is approx. 75%. Several studies have mentioned the pivotal role of oxidative stress in this complication. Taurine (TAU) is the human body's most abundant free amino acid. TAU is known as a robust cell membrane stabilizer. Many studies have mentioned that TAU could counteract oxidative stress in various experimental models. The current study was intended to evaluate the effect of TAU on erythrocytes in cirrhotic rats.

Material and methods: Bile duct ligation (BDL) surgery was carried out on rats. Then, complete blood count (CBC), hemoglobin (Hgb), hematocrit (HTC), and erythrocytes' G6PD, catalase (CAT), and superoxide dismutase (SOD) activity were measured. Moreover, biomarkers of oxidative stress were assessed, and the erythrocytes' morphological changes were monitored in the cirrhotic mice exposed to TAU (0.25%, 0.5%, and 1% w : v in drinking water).

Results: Significant changes in the assessed erythrocyte parameters (G6PD activity, Hgb, HTC, and erythrocyte count) and red blood cells (RBC) morphological alterations were detected on day 42 after BDL surgery. Biomarkers of oxidative stress also did not change at the time points, except on post-BDL days 28 and 42. A significant decrease in blood parameters was evident at post-BDL day 42. All doses of TAU (0.25%, 0.5%, and 1% w : v in drinking water) significantly improved erythrocyte parameters and encountered oxidative stress in the erythrocytes of cirrhotic animals.

Conclusions: These data indicate that TAU could be a safe agent to mitigate cirrhosis-induced erythrocyte damage and anemia. Further investigations are necessary to prove this in clinical settings.

The recommendations define the principles of diagnosis and treatment of hepatitis C virus (HCV) infection according to the latest knowledge. The main goal of the treatment of HCV infection is to eliminate the virus from the body, which in turn leads to stopping the progression or causes the regression of previously formed changes in the liver. The current version of the guidelines prioritizes pangenotypic regimens and includes guidelines for special patient populations such as children, patients with cirrhosis, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection, patients with renal failure, liver failure and lack of response to previous therapies as well as patients in the peri-transplant period.

Aim of the study: There is a paradigm shift in the management of gastric varices with the availability of endoscopic ultrasound and radiologic interventions. The optimal choice of intervention remains a dilemma for most treating physicians.

Material and methods: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and ScienceDirect for studies comparing endoscopic glue injection, endoscopic thrombin injection (THB), variceal band ligation, EUS-guided coiling, EUS-guided glue injection, EUS-guided coiling with glue (EUS-C+G), balloon occluded retrograde transvenous obliteration (BRTO), and transjugular intrahepatic portosystemic shunt (TIPS) for gastric varices in adults. The data on four outcomes - obliteration of varices, rebleeding, adverse effects, and mortality - were pooled using a random-effects model. Treatment estimates were calculated as odds ratios (ORs) along with their 95% confidence interval (CI). The relative ranking of interventions for various outcomes was calculated as their surface under the cumulative ranking curve (SUCRA).

Results: We identified 34 studies (10 randomized controlled trials, 24 non-randomized trials) with 2783 patients. Based on SUCRA plots, BRTO (SUCRA 95.1) had the highest rate of variceal obliteration followed by EUS-C+G (SUCRA 80.9). The risk of rebleeding was lowest with BRTO (SUCRA 85.1) followed by EUS-C+G (SUCRA 78.8). Moderate-severe adverse effects were least likely with THB (SUCRA 92.5) and highest with TIPS (SUCRA 3.7). In terms of mortality, EUS-C+G (73.5) had the lowest probability of overall mortality followed by TIPS (69.1).

Conclusions: In this network meta-analysis, we found BRTO and EUS-guided therapies to be superior to endoscopic glue injection. However, the level of evidence remains low.

Aim of the study: To evaluate the role of MIF gene polymorphism rs755622 G>C in occurrence and progression of hepatocellular carcinoma (HCC) among a cohort of Egyptian patients.

Material and methods: This case-control study was conducted on 50 patients with HCC after chronic viral hepatitis and 50 healthy volunteers, recruited between July 2021 and January 2022. All patients with HCC were evaluated for severity of liver disease using a Child-Pugh score, and TNM and BCLC scoring systems. MIF 173 G>C (rs755622) single nucleotide polymorphism was performed for all participants by polymerase chain reaction using restriction fragment length polymorphism technique (RFLP-PCR).

Results: Overall results showed significantly higher frequencies of GG (wild homozygous genotype) and mutant heterozygous genotype GC and G allele (OR = 6.303, 95% CI: 3.374-11.775) among patients with HCC compared to the control group (p = 0.001) for all. Also, significantly higher frequency of genotype GG was detected among patients with advanced Child scores (B and C) (p = 0.039) and TNM stages (III and IV) (p = 0.013). There was significantly higher frequency of the G allele among patients with multiple hepatic focal lesions compared to those with a single focal lesion (p = 0.01).

Conclusions: An obvious role of MIF (rs755622) gene polymorphism could have an important role in susceptibility and progression of HCC among patients with chronic viral hepatitis induced liver cirrhosis.