Clinical and Experimental Hepatology最新文献

Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. A non-synonymous single nucleotide polymorphism (SNP) of the transmembrane 6 superfamily member 2 (TM6SF2) gene is associated with non-alcoholic fatty liver disease. SNPs of the TM6SF2 gene play an important role in the pathogenesis of HCC in alcoholic cirrhosis, but there are limited data regarding other possible etiologies. We aimed to evaluate the role of the rs58542926 polymorphism in the development of HCC in Egyptian chronic liver disease (CLD) patients.

Material and methods: A total of 120 participants, including 40 HCC patients, 40 CLD patients, and 40 healthy controls, were selected. Real-time polymerase chain reaction (RT-PCR) was used to detect the TM6SF2 rs58542926 polymorphism.

Results: There were no significant differences among the three studied groups regarding age (p = 0.06) and gender (p = 0.75). Frequencies of the CT, TT, CT + TT genotypes and the T allele were significantly higher in HCC patients than in the CLD and control groups (p < 0.001, p = 0.005, and p < 0.001, respectively). CLD patients with the CT genotype had a significantly increased risk of HCC development (OR = 4.67, 95% CI: 1.67-12.90). Patients with the TT genotype had a significantly increased risk of HCC (OR = 9.33, 95% CI: 1.72-50.61). Moreover, the T allele was correlated with an increased risk of HCC (OR = 5.44, 95% CI: 2.09-14.17) compared to the C allele.

Conclusions: The TM6SF2 rs58542926 genotype is associated with an increased risk of HCC in the Egyptian population.

Aim of the study: Non-alcoholic fatty liver disease (NAFLD), which encompasses a wide variety of liver pathology, is now the most common chronic liver disease worldwide. The presence of hypothyroidism has been linked to the development of NAFLD. However, its correlation with liver fibrosis, an important clinical entity in NAFLD, is less clear. We aimed to summarize the association between hypothyroidism and liver fibrosis risk.

Material and methods: We conducted a search of PubMed and ProQuest from inception to June 30, 2021, for studies assessing the association between hypothyroidism and liver fibrosis risk. The quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS). We analyzed the pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed and random-effects model. Heterogeneity was assessed using I ².

Results: Eight studies with a total of 14,588 patients were included. The quality of studies ranged from 6 to 8 stars. Thyroid stimulating hormone (TSH) ≥ 2.5 was significantly associated with increased risk of significant liver fibrosis (OR = 1.61, 95% CI = 1.21-2.15). Subclinical hypothyroidism was also correlated with an increased risk of advanced fibrosis (OR = 2.77, 95% CI = 1.65-4.65). A significant association was found between overt hypothyroidism and non-alcoholic steatohepatitis (NASH) risk (OR = 2.38, 95% CI = 1.61-3.53). However, no significant association was found between subclinical hypothyroidism and significant liver fibrosis.

Conclusions: Hypothyroidism is associated with an increased risk of fibrosis in NAFLD patients.

Introduction: Hepatic encephalopathy (HE) is a serious clinical problem leading to severe neurological disorders and death. No specific treatment is available for the management of HE-associated neurological damage. This study aimed to evaluate the effect of dextromethorphan (DXM) on oxidative stress and disturbed locomotor activity in an animal model of HE.

Material and methods: In the current study, BALB/c mice received acetaminophen (APAP; 1000 mg/kg, intraperitoneally [IP]). Dextromethorphan (0.5, 1, 5, 10 mg/kg, subcutaneously [SC]) was injected in three doses (every 6 h), starting two hours after acetaminophen. Animals' locomotor activity, brain and plasma ammonia levels, as well as biomarkers of oxidative stress and inflammatory cytokines in the brain tissue, were assessed 24 hours after acetaminophen injection.

Results: It was found that APAP administration was significantly associated with liver damage and increased plasma biomarkers of liver injury. Ammonia levels in plasma and brain tissue of APAP-treated mice also increased significantly. There was also a significant difference in motor activity between the control and APAP-treated animals. The acute liver injury also increased the brain level of pro-inflammatory cytokines (tumor necrosis factor a [TNF-a], interleukin 6 [IL-6], and interleukin 1b [IL-1b]). It was found that DXM could significantly improve the motor activity of animals in all doses and decrease the biomarkers of inflammation and oxidative stress in the brain tissue of animals with hyperammonemia.

Conclusions: The effect of dextromethorphan on oxidative stress and inflammation seems to be a major mechanism for its neuroprotective properties in HE. Based on these data DXM could be applied as an effective pharmacological option against HE-associated brain injury.

Aim of the study: To review the findings of multi-detector computed tomography (MDCT) in synchronous hepatocellular carcinoma (HCC) and other solid malignancies.

Material and methods: A total of 74 cases were included in this retrospective analysis, all of them confirmed with a diagnosis of synchronous HCC and other solid malignancies. They were 41 women and 33 men (mean age, 63.36 years). The whole body and triphasic abdominal CT scanning utilized 128 MDCT scanners in all 74 patients. The pathological diagnoses of all 148 malignancies were confirmed in all 74 cases.

Results: Out of 3480 patients with HCC, 74 patients (2.1%) were diagnosed with another synchronous primary solid malignancy. The pathology of all 148 cancers was verified, and each one was correctly characterized, assessed, and staged. Hepatocellular carcinoma was detected in all 74 patients. The most frequent extra-hepatic primary malignant sites were breast (18/74, 24.3%), followed by kidney (15/74, 20.3%), lymphoma (9/74, 12.2%), uterus (7/74, 9.5%), ovary (5/74, 6.8%), colon (5/74, 6.8%), prostate (5/74, 6.8%), urinary bladder (3/74, 4.1%), thyroid (2/74, 2.7%), gall bladder (1/74, 1.4%), stomach (1/74, 1.4%), pancreas (1/74, 1.4%), esophagus (1/74, 1.4%) and lung (1/74, 1.4%).

Conclusions: The possibility of synchronous double malignancies with HCC should always be considered during pretreatment evaluation. Using an MDCT scanner, researchers were able to assess this occurrence accurately. An increased number of such findings may lead to an improved therapeutic method for these patients.

Aim of the study: Portal vein thrombosis (PVT) is a well-known consequence of cirrhosis. Its pathophysiology is complex, with possible downstream hepatic decompensation. This study was conducted to describe the changes of protein C (PC), protein S (PS) and D-dimer blood levels associated with PVT formation in cirrhosis and the relation to the degree of liver dysfunction.

Material and methods: This was a case-control study that included 50 cirrhotic patients who presented with acute de novo non-malignant PVT and 50 cirrhotic patients without PVT as a control group. The severity of liver disease was classified as per the Child-Turcotte-Pugh (CTP) score. Doppler ultrasonography identified acute portal vein occlusion, and dynamic contrast-enhanced computed tomography confirmed the extent and nature of PVT. Blood PC, PS and D-dimer levels were measured using enzyme-linked immunosorbent assay.

Results: PC and PS levels were significantly lower, and the D-dimer level was significantly higher, in cirrhotic patients with PVT compared to the control group. PC and PS levels were significantly decreased in patients with higher CTP score of both groups. The D-dimer level did not vary significantly with the degree of liver dysfunction in patients of either group. PC, PS and D-dimer at the cut-off points of ≤ 77 IU/dl, ≤ 63 IU/dl, and > 300 ng/ml, respectively, significantly suggested PVT occurrence.

Conclusions: Alteration of the anticoagulant proteins and D-dimer contributed to PVT formation in cirrhotic patients and could help stratify the degree of liver dysfunction. Blood level of these hemostatic proteins could be incorporated into a probability score for early diagnosis and treatment of PVT in cirrhosis.

Introduction: This study was conducted to evaluate the results of hepatectomy for hepatocellular carcinoma (HCC) by the combination of extrafascial extrahepatic (Takasaki method) and extrafascial intrahepatic pedicle approaches (Ton That Tung method).

Material and methods: A longitudinal follow-up study was conducted on 83 patients undergoing hepatectomy for HCC using the combination of extrafascial extrahepatic (Takasaki method) and extrafascial intrahepatic pedicle approaches at Nghe An Provincial Hospital from April 2017 to July 2021. Survival analysis was applied.

Results: The cumulative overall survival (OS) rates after 1, 2, 3 and 4 years were 88.4%, 76.3%, 69.5% and 56.9%, respectively. The mean OS time was 40.68 ±2.17 months. The 1-, 2-, 3- and 4-year disease-free survival (DFS) rates were 67.1%, 56%, 53.1% and 50%, respectively. The mean DFS time was 32.58 ±2.56 months. Surgical margin > 1 cm was an independent predictor of both overall and disease-free survival (HR = 5.194, 95% CI = 1.467-18,385, p = 0.011 for OS; HR = 2.822, 95% CI = 1.231-6.468, p = 0.014 for DFS).

Conclusions: Hepatectomy for HCC by a combination of extrafascial extrahepatic (Takasaki method) and extrafascial intrahepatic pedicle approaches (Ton That Tung method) is effective and safe, and side effects and complications can be controlled. Patient selection is a key issue and plays a very important role in the outcome of treatment.

Aim of the study: Homeobox transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA classified as an oncogene and has been implicated in liver cancer initiation and progression. This study investigated the clinical usefulness of serum HOTAIR to predict hepatocellular carcinoma (HCC) and prefigure the tumor stage.

Material and methods: This study included 80 patients with de novo HCC divided into 40 late-stage HCC patients (group IA) and 40 early-stage HCC patients (group IB), 40 patients with non-tumorous liver cirrhosis (group II), and 20 healthy controls (group III). Serum HOTAIR was measured using real-time quantitative polymerase chain reaction. Serum α-fetoprotein (AFP) was measured via enzyme-linked immunosorbent assay.

Results: Serum HOTAIR was significantly higher in groups IA, IB and II compared to healthy subjects. Serum HOTAIR was significantly higher in group IA than group IB, and in groups IA and IB compared to group II. Serum HOTAIR at cut-off value > 15.45 (AUC = 0.71) showed 66% sensitivity and 78% specificity in discriminating HCC patients of group IB from HCC patients of group IA. When combined with AFP, the discriminative sensitivity and specificity increased to 74% and 90% respectively (AUC = 0.85). Serum HOTAIR at cut-off value > 9.42 (AUC = 0.823) showed 67.5% sensitivity and 93.3% specificity in discriminating HCC patients of group IB from patients with non-tumorous cirrhotic liver. When combined with AFP, the discriminative sensitivity and specificity increased to 80% and 98.3% respectively (AUC = 0.954).

Conclusions: Circulating HOTAIR is a potential biomarker which may be used solely, or preferably in combination with AFP, to help HCC detection in cirrhotic liver and prefigure the tumor stage.

Aim of the study: Occult hepatitis C virus (HCV) infection (OCI) is a potential source of relapse after liver transplantation with subsequent graft damage. The aim of the study was to detect OCI in patients with living donor liver transplantation (LDLT) who achieved sustained virological response (SVR) after sofosbuvir-based antiviral treatment, and to detect risk factors associated with the development of OCI as well as to determine the effect of direct acting antiviral (DAA) therapy after liver transplantation.

Material and methods: 41 patients with living donor liver transplantation who did not receive DAAs before with recurrent HCV infection who achieved a SVR with sofosbuvir-based therapy for 12-24 weeks were recruited. These patients were tested for OCI by HCV-RNA in peripheral blood mononuclear cells (PBMNCs). Those patients with OCI were followed up every 6 months with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum HCV-RNA by PCR for 2 years.

Results: 92.7% of treated patients achieved HCV SVR 12 weeks. OCI was detected in 4 patients. After follow-up for 18 months, 3 patients continued to have OCI, but one patient presented with progressive elevation of liver enzymes and developed overt HCV infection with positive HCV-RNA PCR in the serum. This patient was retreated with sofosbuvir 400 mg + ledipasvir 90 mg for 12 weeks with resultant negative HCV-RNA PCR in both serum and PBMNCs in addition to normalization of liver enzymes.

Conclusions: Occult HCV infection is a potential source of HCV relapse after liver transplantation which should be investigated for in PBMNCs or liver biopsy.