Clinical and Experimental Hepatology最新文献

The picture of drug-induced liver injury (DILI) is polymorphic, with variable intensity of clinical symptoms and prognosis. Most cases of DILI are acute, although the incidence of chronic hepatopathy has been reported to range from 3.4% to 39.0% in the period 6-12 months after discontinuation of the drug. The long-term chronic consequences of DILI in terms of morbidity and mortality are unclear. The rare obstructive bile duct syndrome is associated with an unfavorable prognosis - a higher risk of chronic liver failure and the need for liver transplantation. Other long-term forms of hepatopathy following DILI include progressive liver fibrosis, autoimmune hepatitis, hepatic steatosis, secondary sclerosing cholangitis, vascular lesions, and liver tumors. Recently, immune checkpoint inhibitors, which can cause an autoimmune-like phenotype, have also been shown to cause sclerosing cholangitis with infiltration of cytotoxic T cells in the biliary tract.

Aim of the study: One of the main causes of cancer-related death worldwide is hepatocellular carcinoma (HCC), which is significantly common in Egypt because of the high prevalence of hepatitis C virus (HCV) infection. The development of HCC has been linked to genetic variations in the TM6SF2 (rs58542926) and PNPLA3 (rs738409) genes. The aim of this study was to assess PNPLA3 and TM6SF2 genetic variants as risk factors for HCC in Egyptian patients with chronic HCV disease.

Material and methods: The study included 286 participants divided into three groups: 100 healthy controls, 89 chronic HCV patients without HCC, and 97 HCC patients with chronic HCV. Demographic and clinical data were collected. TaqMan assays were used to genotype PNPLA3 and TM6SF2.

Results: The PNPLA3 CG/GG genotypes were significantly associated with an increased risk of HCC (OR = 6.8, 95% CI: 2.93-15.8 for CG, and OR = 5.49, 95% CI: 1.45-20.85 for GG). The G allele of PNPLA3 was more prevalent in HCC patients (27.4%) compared to controls (7.0%) (p < 0.001). Conversely, the TM6SF2 CT/TT genotypes did not show a significant association with HCC risk (p = 0.93), and the T allele frequency was similar across all groups (p = 0.66).

Conclusions: The PNPLA3 (rs738409) polymorphism is a significant risk factor for HCC in Egyptian patients with chronic HCV, with the G allele notably increasing the risk. In contrast, TM6SF2 (rs58542926) polymorphisms did not show a significant association with HCC risk in this population. These findings highlight the potential for genetic screening to identify HCV patients at elevated risk for HCC.

Safe and effective pain treatment for patients with chronic liver diseases (CLD) often poses a challenge in clinical practice. The widespread use of painkillers can lead to drug-induced liver injury. CLD can alter drug response by affecting drug-metabolizing enzymes and half-life, thereby impacting the strength and safety of drug use. This study reviews the safety and hepatotoxicity of selected analgesics in CLD. Paracetamol is the safest drug when used in standard doses. Metamizole is not contraindicated for short-term treatment. Non-steroidal anti-inflammatory drugs should be avoided due to their significant hepatotoxic potential. Tramadol is not recommended for cirrhosis due to its unpredictable effects. Codeine should also be avoided. Proper management includes the selection of drugs based on factors such as the type and severity of pain, duration of treatment, patient sensitivity, drug interactions, stage of liver disease, and the presence of other conditions. Patients should be closely monitored for adverse effects.

Common respiratory viral pathogens, including SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), can lead to extrapulmonary manifestations, including clinically significant liver involvement. This review synthesizes current evidence on the epidemiology, mechanisms, and prognostic implications of hepatic injury associated with these viruses. We discuss the distinct mechanisms of liver dysfunction, ranging from the possibility of direct viral infection of hepatocytes to indirect effects of systemic inflammatory responses, hypoxic injury, preexisting liver disease, and drug-related hepatotoxicity. Liver involvement in COVID-19 has been explored to a much greater extent than in the case of influenza or RSV infections, highlighting the need for further studies. Clinically, recognizing liver involvement in respiratory viral infections is crucial, particularly in high-risk populations such as patients with chronic liver disease, transplant recipients, and children. We underscore the importance of integrating hepatic evaluation into the clinical approach to severe respiratory viral illnesses to improve patient outcomes.

Hepatitis E virus (HEV) is a significant yet underdiagnosed cause of acute and chronic hepatitis, particularly in pediatric populations. While HEV infection in children is often asymptomatic or mild, it can progress to severe outcomes in immunocompromised patients, such as organ transplant recipients or those undergoing chemotherapy. HEV genotypes 1 and 2 are predominantly responsible for waterborne outbreaks in endemic regions, whereas genotypes 3 and 4 are associated with zoonotic transmission in developed countries. Emerging evidence also links HEV to extrahepatic manifestations, including neurological, renal, hematological, and pancreatic complications. Diagnosis remains challenging due to frequent asymptomatic presentation and limitations in serological testing, highlighting the importance of polymerase chain reaction (PCR)-based detection. Although vaccination shows promise, especially in endemic areas, its availability remains limited for pediatric populations. Addressing research gaps and improving surveillance, prevention, and treatment strategies are critical for reducing HEV-related morbidity in children.

Aim of the study: Hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids (PA-HSOS) is a form of drug-induced liver injury (DILI) associated with portal hypertension (PH). The serum-ascites albumin gradient (SAAG) is known to be directly related to PH. However, the clinical value of SAAG for predicting the severity of PA-HSOS is unknown. We aimed to evaluate the association between SAAG and hepatic venous pressure gradient (HVPG) and portal pressure (PP) in patients with PA-HSOS and to investigate the clinical value of SAAG for predicting the severity of PA-HSOS.

Material and methods: We retrospectively collected the clinical data from all patients with PA-HSOS undergoing PP measurement and abdominocentesis between January 2015 and December 2021. Pearson's correlation (R), intraclass correlation coefficient (ICC), and scatter plot analysis were performed to evaluate associations.

Results: In total, 28 patients were analyzed. The correlation between SAAG and HVPG was moderate (R = 0.41, ICC = 0.40, p = 0.031), while the correlation between SAAG and wedge hepatic vein pressure (WHVP) was poor (R = 0.36, ICC = 0.34, p = 0.060). The correlation between SAAG and portal pressure gradient (PPG) was moderate (R = 0.49, ICC = 0.42, p = 0.030), while the correlation between SAAG and portal pressure was good (R = 0.57, ICC = 0.52, p = 0.008). SAAG differed significantly different between mild and moderate/severe patients according to the Drum Tower Severity Scoring (DTSS) system (15.3 vs. 17.7 g/l, p = 0.042).

Conclusions: The SAAG provides a simple and minimally invasive method for predicting the severity of PA-HSOS, and may facilitate prognostic prediction and treatment decisions.

Aim of the study: To analyze long-term epidemiological patterns and trends in the burden of infection and mortality due to viral hepatitis in Poland before and during the COVID-19 pandemic.

Material and methods: Data for the burden of the most common viral hepatitis types (HAV, HBV ±HDV, HCV, and HEV) over 2009-2023 were extracted from the national registries in Poland. The joinpoint regression model was used to analyze trends in viral hepatitis infections and mortality.

Results: The burden of viral hepatitis infection and mortality in Poland changed between 2009 and 2023. Before the COVID-19 pandemic, the trend of newly diagnosed HAV infection was characterized by a sharp increase over 2015-2018 compared to the other types of hepatitis. At the beginning of the COVID-19 pandemic, the burden of infection and mortality among most types of hepatitis showed a change in the direction of the trend from negative to positive, which continued in subsequent years. A pronounced increasing trend for both infection and mortality occurred in the category of other viral hepatitis. Over the whole period of 2009-2023, there was only one decreasing trend for mortality due to HBV infection.

Conclusions: The findings of the study draw attention to the noticeable impact of the COVID-19 pandemic on the burden of viral hepatitis in Poland, which threatens to disrupt the beneficial direction of virus elimination. Trends of viral hepatitis infection and mortality require further monitoring. It is also necessary to increase preventive measures and improve access to diagnostics and the linkage to health care.

Aim of the study: Portal vein thrombosis (PVT) is frequently observed in liver cirrhosis patients and correlates with the severity of the underlying liver disease. Thrombocytopenia and thrombocytopathy are signs of liver cirrhosis. A disruption in platelet function may have an impact on the development of thrombosis, considering that platelets are essential in the formation of thrombosis. Previous studies on platelet function in liver disease have not been conclusive; therefore, this study aimed to evaluate in vitro platelet function to identify its possible role in the development of PVT in cirrhosis.

Material and methods: The study included 100 subjects (30 cirrhotic patients with PVT, 40 cirrhotic without PVT, and 30 healthy individuals as a control group). Platelet function was evaluated using light transmission aggregometry (LTA) in addition to serum von Willebrand factor antigen (vWF-Ag) to assess the platelet activation and adhesion function.

Results: Platelet aggregation was decreased in response to aggregating agonists (ADP and ristocetin) in cirrhotic patients with and without PVT compared to healthy controls. Notably, among cirrhotic patients, platelet aggregation was higher in those with PVT compared to those without. Univariate analysis identified six PVT-associated factors: Child-Pugh classification (p = 0.004), D-dimer (p = 0.011), platelet count (p = 0.001), platelet aggregation following stimulation with ADP and ristocetin (p < 0.001, p = 0.023, respectively) and vWF-Ag concentration (p = 0.001). After adjusting multiple confounding variables, multivariate analysis revealed that only vWF-Ag level was an independent risk factor for PVT pathogenesis in cirrhosis.

Conclusions: Platelet aggregation is significantly higher in cirrhotic PVT patients compared to non-PVT patients. Additionally, elevated vWF-Ag level is an independent risk factor for PVT development in cirrhotic patients. These findings suggest the role of platelet activation in the pathogenesis of PVT and could enhance critical care strategies in patient management and prevention of PVT.

Aim of the study: Cholestasis is characterized by impaired bile flow from the liver to the small intestine. Beyond liver damage, cholestasis significantly affects other organs, particularly the kidneys, causing a condition known as cholemic nephropathy (CN). Sildenafil is a phosphodiesterase type 5 (PDE5) enzyme inhibitor with a wide range of pharmacological effects. Several studies have described the nephroprotective properties of sildenafil.

Material and methods: Rats underwent bile duct ligation (BDL) surgery to induce cholestasis and CN. Afterward, BDL animals received sildenafil (5, 10, and 20 mg/kg/day, i.p., for 14 consecutive days). Urine, blood, and kidney samples were collected for further evaluation.

Results: Elevated levels of blood urea nitrogen (BUN) and creatinine (Cr) and urinalysis revealed renal injury in this model (p < 0.001). Oxidative stress markers, including depleted antioxidant capacity, increased ROS formation, lipid peroxidation, and protein carbonylation, were evident in the kidneys of BDL rats (p < 0.001). Moreover, the activity of enzymatic antioxidant systems (CAT, SOD, GR, and GPx) was also significantly decreased in the kidney of BDL animals (p < 0.001). Tissue pro-inflammatory cytokines (TNF-a, IL-6, and IL-1b) were also considerably higher in the kidney of cholestatic rats (p < 0.001). Renal histopathological changes in BDL animals included inflammatory cell infiltration, tubular atrophy, necrosis, significant fibrotic changes, and cast formation. It was found that sildenafil significantly reduced pathological changes, mitigated oxidative stress biomarkers, and suppressed inflammation in the kidneys of BDL animals. The nephroprotective effects of sildenafil were not dose-dependent in the current study.

Conclusions: The data obtained from this study revealed that sildenafil could significantly protect against renal damage in cholestasis. The effect of sildenafil on oxidative stress and the inflammatory response plays an essential role in its nephroprotective mechanisms.

The number of patients whose chronic metabolic liver disease leads to the development of hepatocellular carcinoma (HCC) is increasing. In patients with non-alcoholic fatty liver disease (NAFLD), HCC can arise in both cirrhotic and non-cirrhotic livers. This complicates appropriate surveillance and causes HCC to be diagnosed at a more advanced stage. Current therapeutic guidelines do not take into account the etiology of HCC when selecting the type of systemic treatment, as the data on the effectiveness of immunotherapy in HCC caused by metabolic dysfunction-associated steatotic liver disease (MASLD) are insufficient and come from post-hoc subgroup analysis in phase 3 trials. In order to improve survival in the group of patients with chronic liver disease and metabolic disorders, it is crucial to use non-pharmacological and pharmacological methods to prevent progression of fatty liver disease, treat comorbidities with modification of cardiometabolic risk factors, and implement effective programs for early detection of HCC.