Hepatology Forum最新文献

The liver is a crucial organ in the regulation of metabolism, signaling, and homeostasis. Using recent advanced sequencing technologies, several mutations of genes in major metabolic and signaling pathways have been discovered in the pathogenesis of hepatocellular carcinoma (HCC). These gene signatures alter expression and ultimately affect biochemical pathways by modifying enzyme/protein levels, resulting in numerous clinical outcomes related to HCC. It comes with varying forms of genetic and biochemical alterations, associated with carbohydrate, lipid, nucleic acid, and amino acid metabolism, as well as signaling pathways linked to tumorigenesis. Here, we aim to summarize the main components and mechanisms involved in the progression of HCC with a special focus on the metabolic regulation of key effectors of tumorigenesis, through the crosstalk between genetics and biochemistry. This paper provides an overview of hepatocellular carcinoma, underlying the fundamental effect of gene variations on metabolic and signaling pathways. Since there is still an unmet need for biomarkers and novel therapeutic targets, some of these signature genes or proteins can be used as novel biomarkers for diagnosis, prognosis, and novel potential therapeutic targets for the treatment of HCC.

COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.

Background and aim: It is reported that miRNAs play an important role in hepatocellular carcinogenesis and may serve as non-invasive biomarkers for hepatocellular carcinoma (HCC). MiR-4510 and miR-146b-5p expression levels have been found to be associated with HCC. However, their associations with hepatitis B virus (HBV)-related HCC (HBV-HCC) are yet to be explored. We aimed to assess the predictive value of expression levels of serum miR-4510 and miR-146b-5p in patients with HBV-HCC and performed bioinformatics analyses based on the miRNA expression profile.

Materials and methods: This cross-sectional study used the serum of 16 patients with Chronic Hepatitis B (CHB), 15 hepatitis B virus-related cirrhosis (HBV-cirrhosis), 15 HBV-HCC, and 16 healthy subjects. The total RNA was isolated from serum, and the expression of miRNAs was measured by qRT-PCR, calculated using the 2^-ΔΔCt methods. MIENTURNET was used to predict miRNA-target gene interactions. The Network Analyst was used to build protein-protein interactions.

Results: There was a significant difference in miR-146b-5p between study groups (p=0.009). MiR-146b-5p expression was found to be significantly reduced in HBV-HCC compared to the HBV-cirrhosis group and healthy controls (p=0.005 and p=0.006, respectively).

Conclusion: The serum miR-146b-5p levels might be a promising tool to be used as a non-invasive diagnostic biomarker for HCC. Our findings shed light on potential biomarkers for the diagnosis of HBV-HCC in terms of selected miRNAs. The target pathways of miR-146b-5p identified by our in-silico analysis to reveal the functional mechanism are "MAPK signaling pathways" and "Pathways in cancer."

Hereditary hemochromatosis (HH) is an autosomal recessive inherited iron-loading disorder and is characterized by chronic hepatitis, cirrhosis, diabetes, and bronze skin. The hemochromatosis gene (C282Y homozygosity)-related hemochromatosis is the most common form of HH. The prevalence of HH is varied. Here, we defined six cases with C282Y homozygosity-related HH in a single center in Turkiye.

Background and aim: The histological diagnosis of autoimmune hepatitis (AIH) is challenging. A new consensus recommendation was provided by the International AIH Pathology Group to address the problems in the histological diagnosis. The purpose of this study is to compare the 2008 'simplified' criteria for AIH with the 'consensus recommendation' of 2022 in terms of diagnostic sensitivity.

Materials and methods: A retrospective analysis was conducted on pathological specimens of patients diagnosed with Autoimmune Hepatitis (AIH) between 2010 and 2022. Out of 188 patients enlisted, 88 were selected based on exclusion criteria. The specimens were examined by two experienced hepatopathologists and a resident pathologist. All specimens were analyzed using both the "simplified" criteria and the new consensus recommendations.

Results: Out of a total of 78 patients, the 2022 consensus recommendations raised the diagnostic category of 16 patients (20.5%) to a higher level. Six patients who were previously diagnosed as "atypical" were now considered "possible AIH", while 10 patients with a "compatible" diagnosis were elevated to "likely AIH" category. No patients were found to fall into a lower diagnostic category according to the new recommendations. A significant difference in diagnostic sensitivity was observed between the 2008 criteria and the 2022 consensus report (p<0.001).

Conclusion: The 2022 consensus recommendation may be more sensitive in the diagnosis of AIH in comparison to the 2008 'simplified' histological criteria. More studies are needed both for the validation of the sensitivity of the new consensus recommendation and for the determination of the specificity.

Background and aim: Asymmetric dimethylarginine (ADMA) is an enzyme involved in vascular tone, blood pressure, and platelet activation. Serum ADMA levels are increased in liver diseases such as liver cirrhosis, hepatitis, and acute liver failure. The aim of our study was to assess the correlation of ADMA with proinflammatory, liver injury, and cancer biomarkers in patients with liver dysfunction of various etiologies.

Materials and methods: We analyzed the demographic and clinical data, including serum ADMA concentration and other biochemical markers such as albumin, platelet count, international normalized ratio, bilirubin, and others in patients with hepatitis, compensated and decompensated liver cirrhosis, and hepatocellular carcinoma. The one-way ANOVA, Student's t-test, Mann-Whitney U test, univariate, and multivariate correlations were performed, and a p-value <0.05 was set as significant.

Results: In n=83 analyzed patients, we observed a negative correlation of ADMA with albumin concentration (p=0.049). We found a negative correlation between ADMA and platelet count in n=31 patients with compensated liver cirrhosis (p=0.022). We observed no significant correlations of ADMA with proinflammatory and cancer biomarkers in patients with hepatitis, compensated and decompensated liver cirrhosis, and hepatocellular carcinoma.

Conclusion: ADMA can potentially be used as a subsidiary marker of disease progression in patients with liver dysfunction. Our research suggests that ADMA cannot be useful in detecting hepatocellular carcinoma (HCC).

The use of marginal grafts is very challenging and is associated with post-reperfusion syndrome and early allograft dysfunction. The outcomes of machine perfusion for the preservation of marginal grafts have been compared with that of static cold storage, with studies reporting a reduced risk of ischemic cholangiopathy and graft loss. We performed this systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of machine perfusion of liver grafts to static cold storage (SCS) of liver grafts during liver transplantation. Two independent researchers thoroughly searched for literature in the following databases: PubMed (Medline), Cochrane Central Register of Controlled Studies (CENTRAL), clinical trial registry, ResearchGate, Google Scholar, and Scopus (ELSEVIER) databases (last search: November 2023). The search terms used were: "dynamic perfusion," "normothermic perfusion," "hypothermic perfusion," "liver transplantation," "static cold storage," "NMP," "HOPE," "extended criteria grafts," "marginal grafts," "RCTs," "randomized controlled trials," "warm ischemia," and "cold ischemia." Eight RCTs published between 2019 and 2023 were included in the data synthesis and meta-analysis. The primary outcome considered was the overall incidence of early allograft dysfunction (EAD) between the two methods of graft perfusion after liver transplantation. The secondary outcome considered was the rate of retransplantation. Our meta-analysis revealed that SCS is associated with more EAD when compared with machine perfusion, with a p-value of <0.00001. We also found that the rate of retransplantation is higher among patients who received a liver preserved by SCS, with a p-value of 0.02. The use of machine perfusion in the preservation of liver grafts showed a significant reduction in early allograft dysfunction and retransplantation.

Simultaneous liver-kidney transplantation (SLK) is a feasible option for patients with end-stage liver disease and concomitant renal dysfunction or end-stage renal disease. SLK has gained significant attention primarily due to multiple alterations in the allocation criteria over the past two decades. This review aims to summarize the most recent updates and outcomes of the SLK allocation policy, comparing SLK outcomes with those of liver transplantation alone and exploring the implications of donation after cardiac death in SLK procedures.

Background and aim: This study aimed to define the relapse frequency and risk determinants in chronic hepatitis B (CHB) patients who discontinued nucleoside analog (NA) treatment, were HBeAg-negative, and had achieved both a virological and biochemical response.

Materials and methods: This retrospective cohort study reviewed patients with HBeAg-negative CHB who received antiviral therapy for at least 65 months between January 1, 2013, and December 31, 2020. These patients discontinued treatment after demonstrating a biochemical and virological response and were evaluated at 6, 12, and 24 months post-treatment discontinuation.

Results: Sixty-seven patients with CHB who received NA therapy for at least 65 months, discontinued treatment, and had undetectable HBV DNA and normal ALT values were evaluated. After cessation of NA therapy, a relapse was observed in 38 patients (56.7%). The relapse rate was 71.0% in patients treated with tenofovir disoproxil fumarate (TDF) as the last NA type and 37.9% in patients treated with entecavir (ETV) (p=0.017). The cutoff value for the best estimate of age for predicting relapse was 42 years. The relapse rate was 69.2% in patients aged ≥42 years and 39.2% in patients aged <42 years (p=0.007). The relapse rate was 51.3% in patients with a pre-treatment fibrosis score of 2, 56.0% in those with a fibrosis score of 3, and 100% in those with a fibrosis score of 4 (p=0.089).

Conclusion: Among HBeAg-negative CHB patients who achieved a virological and biochemical response to long-term antiviral therapy, those aged 42 years and older, those with high fibrosis scores before treatment, and those who used TDF before treatment cessation should be closely monitored for relapse, especially in the first 12 months after stopping NA treatment.