Hepatology Forum最新文献

Background and aim: Patients suspected of Alpha 1-Antitrypsin (A1AT) abnormality based on low serum concentration are routinely confirmed through polymerase chain reaction (PCR) testing of peripheral blood. Genotyping formalin-fixed paraffin-embedded (FFPE) tissue is a novel approach that could aid in detecting variant A1AT. We performed qPCR on FFPE liver explants with Periodic Acid Schiff after Diastase (PASD)- and A1AT-positive globules to confirm and estimate the frequency of A1AT deficiency in transplant cases.

Materials and methods: Eighteen (12.68%) of 142 patients with end-stage liver disease showed PASD/A1AT positive globules. FFPE of the explants was tested through qPCR to detect S and Z alleles. A second age- and sex-matched control group consisting of five liver transplant patients with negative globules was included in the study.

Results: qPCR assay was successful with all the samples meeting QC parameters. All patients included in the study elucidated Z allele variants; 2 homozygous (11.1%) and 16 heterozygous (88.9%). The control group demonstrated normal wild-type MM allele.

Conclusion: Screening for A1AT deficiency using serum levels is not sufficiently sensitive to detect deficiency, especially in carriers. If A1AT testing was not performed preoperatively and the risk is high based on the PASD/A1AT-positive globules in the explants, then molecular testing of FFPE tissue can be a viable method for confirming the diagnosis.

A 36-year-old patient presented with severe early-onset obstetric cholestasis on a background of having pre-term induction of labor at 33 weeks during her only previous pregnancy. The patient had significantly abnormal liver biochemistry with a bilirubin of 78 µmol/L, ALP of 318 u/L, ALT of 280 µmol/L, and bile acid levels of 420 µmol/L. The patient received ursodeoxycholic acid 750 mg 3 times a day, rifampicin 500 mg twice a day, aspirin 150 mg once a day, and metformin 500 mg 3 times a day. However, despite this, the patient still suffered from intractable pruritus and her bile acid level was still above the 100 µmol/L target that the obstetrics team was aiming for to avoid early delivery at 32 weeks. Due to the nature and severity of her cholestasis, the patient had a number of investigations done postnatally including genetic analysis, which confirmed that the patient was heterozygous for a pathogenic variant of the ATP-binding cassette subfamily B member 4 gene (c.959C>T [p.Ser320Phe]) and also a variant of unknown significance (c.1679C>T [p.Thr560Met]).

Background and aim: Alcohol-induced liver disease has become one of the major causes of chronic liver disease worldwide with the increasing use of alcohol in society. The most important step in treatment is cessation of alcohol consumption. In patients with advanced liver disease, the most effective treatment is liver transplantation. Careful evaluation of patients with alcoholic liver disease before transplantation can help identify those at high risk of relapsing.

Materials and methods: Of a total of 42 patients who underwent liver transplantation for alcohol-related liver failure in our hospital between 2011 and 2022, 26 surviving patients were included in the study. Patient data were analyzed retrospectively. Demographic data, MELD score, history of alcohol consumption, alcohol treatment, post-transplant prognosis and survival were analyzed. The Barratt Impulsivity Scale-11 Short Form (BIS-11 SF) was applied to the surviving patients for impulsivity analysis to predict the possibility of relapse.

Results: Of the 26 patients who were included in the study, all were male. The mean age at transplantation was 53 (31-71) years. Mean MELD score was 22.31 (9-36). 12 patients (46.2%) received living donor liver transplantation and 14 patients (53.8%) received cadaveric liver transplantation. 25 patients (96.2%) had no post-transplant dependence, while 1 patient (3.8%) had post-transplant dependence. 5 patients (19.2%) continued to consume alcohol after transplantation.

Conclusion: In our study, we observed that patients with high motor impulsivity tendency according to BSI-11 SF had alcohol relapse. We believe that revising this scale with more detailed questions for alcohol-dependent liver patients and applying it to patients before transplantation will be effective in better selection for transplantation and guiding patients to appropriate therapy and thus preventing relapse after transplantation.

Living Donor Liver Transplantation (LDLT) is a valuable solution to the shortage of donor organs for patients with end-stage liver disease. However, the eligibility of obese donors for LDLT remains a subject of debate. This literature review explores global practices and perceptions of LDLT, identifies donor eligibility criteria, and discusses special considerations and ethical caveats. The review highlights the need for standardized guidelines for donor selection, considering the global distribution of Body mass index and variations in population-specific criteria. It also emphasizes the importance of non-invasive testing and pre-operative optimization of liver steatosis for select obese donors. Furthermore, the review examines the outcomes and complications associated with obese donors in LDLT. The findings of this review contribute to the ongoing discussion on the inclusion of obese donors in LDLT and provide insights for future research and guideline development.

Background and aim: Combined hepatocellular-cholangiocarcinoma (CHC) requires attention clinically and pathologically after liver transplantation (LT) because of its unique biology, difficulties in diagnosis, and being rare. We aimed to present our single-center experience for this incidental combined tumor. It is aimed to present our single-center experience for this incidental combined tumor.

Materials and methods: Seventeen patients with CHC were included in the study. There were 260 hepatocellular carcinoma (HCC) patients determined as the control group. Patients were evaluated for demographic, etiological, pathological features, and survival.

Results: Macrovascular and microvascular invasion levels were significantly higher in the CHC group (p<0.05). P53, CK19, and CK7 levels were significantly higher in the CHC group (p<0.05). Hepatocyte-specific antigen level was significantly higher in the HCC group. The mean overall survival was significantly higher in the HCC group (p<0.05).

Conclusion: Even though CHC is a rare liver tumor, it has features that need to be clarified regarding both survival and tumor biology. İnvestigating prognostic factors, especially in terms of survival and recurrence, will be very beneficial to identify candidates who will benefit from LT and be included in the indications for LT for CHC. This study evaluated the outcomes of patients showing combined HCC-intrahepatic cholangiocarcinoma in explant pathology.

Background and aim: The purpose of this study was to investigate the hepatoprotective effects of quercetin, a potent antioxidant, against hepatotoxicity caused by cyclophosphamide (CYC) in the rat liver using histopathological parameters.

Materials and methods: Thirty female rats were divided into five groups - control, quercetin (Q), CYC, Q+CYC, and CYC+Q. At the end of the study, the liver tissues were removed and stained with routine histological hematoxylin and eosin, Periodic acid-Schiff, and Masson's trichrome. Caspase-3 (Cas-3), B-cell lymphoma protein 2-associated X (Bax), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) levels were investigated in immunohistochemically stained liver tissues.

Results: Histopathological examination showed that CYC caused impairment and degeneration in the structure of the hepatocyte cordon, necrosis in the periportal space, sinusoidal dilatation (p=0.000), congestion and edema (p=0.000), mononuclear cell infiltration, and increased connective tissue density (p=0.000). Cas-3, Bax, TNF-α, and IL-1β immunoreactivities were significantly higher in the CYC group (for all, p=0.000). Q administration gradually reduced histopathological structural damage and Cas-3, Bax, TNF-α (p=0.000), and IL-1β (p=0.000) intensity in the rat liver.

Conclusion: The administration of Q protected the liver tissue against CYC-induced damage, and successfully protected the liver against apoptosis, inflammation, and histopathological changes.

Background and aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC).

Materials and methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study.

Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed.

Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

Background and aim: Metabolic-associated fatty liver disease (MAFLD) has emerged as a significant global health concern. However, the prevalence and predictors of MAFLD in post-liver transplantation (LT) patients remain uncertain. This study aimed to determine the prevalence and predictors of MAFLD in LT recipients and to assess the effectiveness of controlled attenuation parameter (CAP) values in diagnosing post-transplant MAFLD.

Materials and methods: A cross-sectional prospective study was conducted involving 128 adult patients who had undergone LT, and had received liver imaging, and vibration-controlled transient elastography (VCTE). MAFLD was diagnosed on the basis of the presence of liver steatosis detected through imaging and specific metabolic risk abnormalities.

Results: The prevalence of MAFLD after LT was 34.4%, with 22.1% categorized as de novo MAFLD, and 12.3% as recurrent MAFLD. Posttransplant diabetes (OR: 4.88; 95% CI 1.30-18.34; p=0.019) and higher CAP values (OR: 1.04; 95% CI 1.02-1.06; p=0000) were identified as independent predictors of post-LT MAFLD. A CAP cutoff value of 270 dB/m exhibited an area under the receiver operating curve of 0.84 in detecting MAFLD.

Conclusion: These findings underscore the notable prevalence of MAFLD in liver transplant recipients and suggest the potential utility of VCTE as a non-invasive tool for its detection.

Background and aim: Genes related to the circadian rhythm control various biological processes. The aim of this study was to comprehensively investigate the mutational and mRNA profile of core circadian rhythm genes in hepatocellular cancer (HCC) samples.

Materials and methods: In this study, the gene profile of a total of 369 patients with HCC was examined over the data obtained from the cancer genome atlas database through-cBioPortal. The effects of mutations on protein were examined by scoring the Polymorphism Phenotyping v2, Mutation Assessor, and SIFT-databases. While the association of genes with other genes was determined with the GeneMANIA-database, the association of expression levels in the genes with overall survival (OS) was evaluated with the Kaplan-Meier Plot database.

Results: As a result of the analyses, there were a total of 25 mutations. Decreased expression levels of PER1 (1.3e-05), PER3 (p=0.046), and CRY2 (p=1.8e-06) genes were found statistically associated with shorter OS. It was also found that increased expression levels of the PER2 (p=0.045) gene were associated with longer OS, and increased expression levels of the NPAS2 (p=9e-04) gene were associated with shorter OS.

Conclusion: In particular, changes in the PER1, PER2, CRY2, and NPAS2 genes may provide possible molecular targets in chemotherapy and immunotherapy for HCC patients.