Virus-related Liver Cirrhosis Research Articles

Impact of Treatment with Direct Antivirals on Coagulation Parameters in Patients with Hepatitis C Virus-Related Liver Cirrhosis and Sustained Virological Response.

Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy.

Associations between single nucleotide polymorphisms of cytokines and hepatitis B virus-related liver cirrhosis: A case-controlstudy.

Various inflammatory and immune cytokines play key roles in the progression of hepatitis B virus (HBV)-related liver cirrhosis (LC). This study explored the relationship between single nucleotide polymorphisms (SNPs) in cytokines with the combined effect of polymorphisms and gender-polymorphisms interaction and LC risk. In this study, a case-control design was used, samples were selected from 45 patients with hepatitis B-related cirrhosis and 45 age-gender-matched chronic HBV-infected patients without cirrhosis attending the tumor hospital of Wuwei Academy of Medical Sciences. Fifteen SNPs were examined using a real-time polymerase chain reaction allelic discrimination system. Logistic regression was utilized to assess cytokine-associated SNPs and the association between SNPs and LC progression in HBV-infected patients. The multivariate-adjusted logistic model revealed that the GG/AG dominant model (OR, 16.38; 95% CI, 1.13-236.70) and G allele (OR, 5.93; 95% CI, 0.98-36.01) of rs1800896 were associated with an increased risk of cirrhosis in CHB patients. Instead, rs2227306 CT presented a reduced cirrhosis risk (OR, 0.22; 95% CI, 0.04-1.38). Rs2055979 AA/AC was negatively associated with the risk of cirrhosis, potentially reversed in males (p = 0.021). Rs1799964 CC/CT was positively related to the risk of cirrhosis but reduced the risk of cirrhosis in males (OR, 0.13; 95% CI, 0.022-0.808; p = 0.028). Both rs1799964 TT and rs1799724 CT/TT genotype showed a synergistic effect in reducing the risk of cirrhosis with rs1800896 AA (OR, 0.08; 95% CI, 0.01-1.43 and OR, 0.12; 95% CI, 0.01-2.21). Polymorphisms rs1800896 and rs2227306 are potentially associated with the risk of cirrhosis. For the first time, the study highlights that the rs2055979 AA/AC and rs1799964 CC/CT polymorphism interact with gender and its potential reversal of cirrhosis risk in males. Furthermore, rs1800896 AA showed a synergistic effect with rs1799964 TT and rs1799724 CT/TT to prevent the progression of HBV infection to cirrhosis.

Evaluation of Serum Kallistatin in Patients with Hepatocellular Carcinoma

Abstract Background Liver cirrhosis is the most frequent long-term consequence of all chronic liver diseases. Cirrhosis is often asymptomatic and unsuspected until complications. The annual incidence rates of liver cirrhosis and hepatocellular carcinoma is related with chronic hepatitis B or C all over the world. The majority of patients with liver cirrhosis or hepatocellular carcinoma die from complications, which happened relatively early in the course of the disease. Thus, the early diagnosis of liver diseases is the only solution for this great problem. Aim of the Work In the current study we aimed to evaluate serum kallistatin in Egyptian patients with hepatitis C virus related liver cirrhosis and hepatocellular carcinoma. Patients and Methods This case control study enrolled 90 Egyptian subjects aged ≥ 18 years old at Ain shams university hospitals, participants were classified into 3 groups as follow: Group 1: 30 patients with hepatocellular carcinoma (patients have been diagnosed with triphasic CT). Group 2: 30 patients with hepatitis C virus related liver cirrhosis (patients diagnosed according to clinical, laboratory and radiological findings. Group 3: 30 healthy subjects serving as a control group. Results This study found that patients with liver cirrhosis and HCC have lower levels of serum Kallistatin compared to a control group. In the HCC group, patients with more severe liver disease (Child class C) had lower Kallistatin levels than those with less severe disease (Child class A and B). Kallistatin was negatively correlated with certain markers of liver disease and inflammation in both groups, and positively correlated with hemoglobin and albumin. The study also tested the diagnostic accuracy of Kallistatin for detecting liver cirrhosis and HCC, and found that it had 66.5% accuracy for cirrhosis and 98% accuracy for HCC at specific cutoff points. Conclusion Serum Kallistatin has a potential rule as a new biomarker for the diagnosis and evaluation of liver cirrhosis and HCC. The present study was limited by the small sample size. Also, all participants were from the Egyptian population with liver disease induced by HCV- infection with no information if our findings would be valid for other population with different etiologies. Thus, further investigation should be carried out in order to validate these findings

Ratio of von Willebrand factor to ADAMTS13 is a useful predictor of esophagogastric varices progression after sustained virologic response in patients with hepatitis C virus-related liver cirrhosis.

Esophagogastric varices (EGV) are a serious complication of hepatitis C virus (HCV)-related liver cirrhosis (HCV-LC). In most cases, portal hypertension improves after a sustained virologic response (SVR) is achieved with direct-acting antiviral (DAA) treatment; however, in some cases, EGV exacerbation occurs after HCV elimination. We investigated whether von Willebrand factor (VWF) and a disintegrin-like metalloproteinase with thrombospondin type-1 motif 13 (ADAMTS13) can predict EGV progression with HCV-LC after SVR achievement. This retrospective study enrolled 47 patients with HCV-LC who achieved an SVR after DAA treatment. Eighteen patients experienced EGV progression after the SVR was achieved (EGV progression group). Twenty-nine patients did not experience EGV progression after the SVR was achieved (non-EGV progression group). Plasma VWF antigen levels and ADAMTS13 activity were measured the day before DAA treatment. The EGV progression group had significantly higher plasma VWF antigen levels (p=0.00331) and VWF-to-ADAMTS13 ratios (p=0.000249) than the non-EGV progression group. Multivariate logistic regression models found that a VWF-to-ADAMTS13 ratio >2.3 was the only risk factor for EGV progression after the SVR was achieved (hazard ratio [HR], 18.4; 95% confidence interval [CI], 3.08-109; p=0.00138). During the observation period, patients with a VWF-to-ADAMTS13 ratio >2.3 had a significantly higher cumulative incidence of EGV progression after SVR achievement than patients with a VWF-to-ADAMTS13 ratio ≤2.3 (HR, 6.4; 95% CI, 1.78-22.96; p=0.0044). The VWF-to-ADAMTS13 ratio before DAA treatment for HCV could predict EGV progression after SVR achievement.

Serum Level of Golgi Protein 73 as a Tumor Marker in Patients with Hepatocellular Carcinoma and Hepatitis C Virus-Related Liver Cirrhosis

Serum Level of Golgi Protein 73 as a Tumor Marker in Patients with Hepatocellular Carcinoma and Hepatitis C Virus-Related Liver Cirrhosis

Role of serum micro-RNA 486-5p in Egyptian cirrhotic hepatitis C patients with hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the prevailing primary liver tumor. To pick HCC at the initial stages is quite strenuous, despite the advent of serum biomarkers, mainly alpha-fetoprotein (AFP), to predict the development and progression of HCC. One proposed biomarker for the diagnosis of HCC is micro-RNA 486-5p (miRNA 486-5p). Hence, the current study was conducted to interrogate the role of miRNA 486-5p in the diagnosis of HCC in a cohort of Egyptian patients with hepatitis C virus (HCV) related liver cirrhosis (LC). This case–control study included twenty-five patients with HCC as studied cases and twenty-five patients with LC as controls. Patients in both groups were classified according to the Child–Pugh score. HCC patients were further classified according to the Barcelona Clinic Liver Cancer (BCLC) classification.ResultsMiRNA 486-5p was found to be statistically notably elevated in patients with HCC than in those with LC. It was found to significantly correlate with portal vein invasion.ConclusionsSerum miRNA 486-5p could be a particularly sensitive biomarker in the diagnosis of HCC as well as prediction of portal vein invasion, as firmly advocated by this study.

Dual metabolic platform to analyze differential metabolites in hepatitis B virus-related liver cirrhosis patients with pre-sarcopenia

Dual metabolic platform to analyze differential metabolites in hepatitis B virus-related liver cirrhosis patients with pre-sarcopenia

Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

Noninvasive risk assessment of hepatic decompensation in patients with hepatitis B virus-related liver cirrhosis.

Hepatic decompensation is a major complication of liver cirrhosis. We validated the predictive performance of the newly proposed CHESS-ALARM model to predict hepatic decompensation in patients with hepatitis B virus (HBV)-related cirrhosis and compared it with other transient elastography (TE)-based models such as liver stiffness-spleen size-to-platelet (LSPS), portal hypertension (PH), varices risk scores, albumin-bilirubin (ALBI), and albumin-bilirubin-fibrosis-4 (ALBI-FIB-4). Four hundred eighty-two patients with HBV-related liver cirrhosis between 2006 and 2014 were recruited. Liver cirrhosis was clinically or morphologically defined. The predictive performance of the models was assessed using a time-dependent area under the curve (tAUC). During the study period, 48 patients (10.0%) developed hepatic decompensation (median 93months). The 1-year predictive performance of the LSPS model (tAUC=0.8405) was higher than those of the PH model (tAUC=0.8255), ALBI-FIB-4 (tAUC=0.8168), ALBI (tAUC=0.8153), CHESS-ALARM (tAUC=0.8090), and variceal risk score (tAUC=0.7990). The 3-year predictive performance of the LSPS model (tAUC=0.8673) was higher than those of the PH risk score (tAUC=0.8670), CHESS-ALARM (tAUC=0.8329), variceal risk score (tAUC=0.8290), ALBI-FIB-4 (tAUC=0.7730), and ALBI (tAUC=0.7451). The 5-year predictive performance of the PH risk score (tAUC=0.8521) was higher than those of the LSPS (tAUC=0.8465), varices risk score (tAUC=0.8261), CHESS-ALARM (tAUC=0.7971), ALBI-FIB-4 (tAUC=0.7743), and ALBI (tAUC=0.7541). However, there was no significant difference in the predictive performance among all models at 1, 3, and 5years (P>0.05). The CHESS-ALARM score was able to reliably predict hepatic decompensation in patients with HBV-related liver cirrhosis and showed similar performance to the LSPS, PH, varices risk scores, ALBI, and ALBI-FIB-4.

Interleukin-16 genetic polymorphisms in Guangxi Chinese with hepatitis B virus-related liver cirrhosis

Our previous study has reported that interleukin-16 (IL-16) genetic polymorphisms are significantly related to chronic hepatitis B (CHB) and hepatitis B virus-related (HBV-related) hepatocellular carcinoma (HCC). As CHB, liver cirrhosis (LC), and HCC are development processes, this study aimed to determine genetic correlation of IL-16 polymorphisms with HBV-related LC in a Chinese population. IL-16 gene rs11556218, rs4072111, and rs4778889 polymorphism in 129 patients with HBV-related LC and 168 healthy individuals were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). PCR-RFLP results were verified by DNA sequencing. The allelic and genotypic distributions of IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms in HBV-related LC patients showed no significant difference from those in healthy controls. Furthermore, no relationship was observed between the haplotype distribution and susceptibility to HBV-related LC. This work provided the first evidence that the IL-16 genetic polymorphisms may not be associated with HBV-related LC risk.

Yes-associated protein inhibition ameliorates liver fibrosis and acute and chronic liver failure by decreasing ferroptosis and necroptosis

Background/aimsThis study aims to determine which cell death modes contribute most in the progression of cirrhosis and acute-on-chronic liver failure (ACLF), and to investigate whether Yes associated protein (YAP) affects the disease process by regulating cell death. Materials and methods30C57BL/6 male mice were divided into five groups: control, carbon tetrachloride (CCl4)-induced liver fibrosis model, CCl4+verteporfin, CCl4+lipopolysaccharides (LPS) combined with the D-(+)-Galactosamine (LPS/D-GalN)-induced ACLF model, and ACLF + verteporfin. Patients with chronic hepatitis B (CHB), hepatitis B virus (HBV) related liver cirrhosis or ACLF were enrolled. Histology, immunohistochemistry, transmission electron microscopy, Western blot and ELISA were conducted to assess the roles of YAP and cell death in liver cirrhosis and ACLF, and to explore the effect of YAP inhibition on cell deaths. ResultsYAP was markedly increased in mice with liver fibrosis and ACLF, along with ferroptosis and necroptosis. Furthermore, YAP inhibition significantly suppressed fibrosis in CCl4-mediated liver fibrosis and ACLF-associated liver injury. Notably, CCl4 induced up-regulation of ACSL4 and RIPK3 and down-regulation of SLC7A11, key factors in ferroptosis and necroptosis. This was significantly abrogated by verteporfin treatment. Similar changes in ferroptosis and necroptosis were found in ACLF and ACLF + verteporfin groups. Consistent with the above findings in mice, we found that plasma YAP levels were gradually increased with the development of HBV-related liver fibrosis and ACLF. ConclusionFerroptosis and necroptosis are involved in the development of liver cirrhosis and ACLF. Inhibition of YAP improved liver fibrosis and liver damage in ACLF through a reduction in ferroptosis and necroptosis. Our findings may help better understanding the role of YAP in liver fibrosis and ACLF.

Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis.

Alcoholic and hepatitis B virus (HBV)-related liver cirrhosis has placed a tremendous burden on the healthcare system with limited treatment options. This study explored the differences in the immune status of alcoholic and HBV-related liver cirrhosis. A total of 15 human liver samples from the Third Xiangya Hospital of Central South University, including five healthy controls (HC group), five alcoholic cirrhosis patients (ALC group), and five HBV-related cirrhosis patients (HBV group) were used. Of these, eight samples, including 3 HC group, 2 ALC group and 3 HBV group, were randomly collected to do single-cell RNA sequencing (scRNA-seq). The degree of steatosis was assessed by H&E staining and the presence of intrahepatic immune cells was evaluated by immunochemistry (IHC). The immune status of alcoholic and HBV-related liver cirrhosis differed significantly. ScRNA-seq analysis identified a higher ratio of intrahepatic monocyte/macrophages and an obvious decreased ratio of T cells and B cells in the ALC group than in the HBV group. IHC staining of intrahepatic monocyte/macrophages, T and B cell exhibited similar results with scRNA-seq analysis. CD5L+ Kupffer cells, a cell type involved in lipid metabolism, were the major monocyte/macrophage subset in ALC liver tissue. H&E staining indicated that the level of steatosis was more severe in the ALC than in the HBV group. Ligand/receptor analysis showed that the T cell exhaustion observed in the ALC liver may be related to the expression of Galectin-9 on Kupffer cells. Fewer B cells were also found in the ALC group and most had higher lipid metabolism, reduced ribosomal activity, and a dysregulated mitochondrial oxidative phosphorylation system. Moreover, scRNA-seq showed a significantly lower ratio of plasma B cells, indicating that the humoral immune response in the ALC liver was similarly dysfunctional. Ligand/receptor analysis also discovered that Galectin-9 expressed on Kupffer cells may inhibit humoral immunity. Patients with ALC have different immune characteristics than those with HBV-induced cirrhosis, including an increased ratio of intrahepatic monocyte/macrophages and a dysfunctional adaptive immune response in the liver. Galectin-9 could serve as a potential therapeutic target for ALC treatment.

Local tumor control of intermediate and advanced stage hepatocellular carcinoma after local ablative treatment with image-guided interstitial high-dose-rate brachytherapy: A subgroup analysis of 286 HCC nodules

Image-guided interstitial high-dose-rate brachytherapy (iBT) has been demonstrated to offer high local tumor control rates (LTC) of >90% after local ablation of intermediate and advanced hepatocellular carcinoma (HCC; BCLC B and C). The purpose of this study was to show the efficacy of iBT stratified by subgroups and to identify clinical characteristics associated with superior local tumor control (LTC) based on a highly heterogenous patient population METHODS AND MATERIALS: A cumulative number of 286 HCC nodules in 107 patients were retrospectively analyzed. Clinical and imaging follow-ups were conducted every 3 months after treatment. Analyzed clinical factors were: etiology, presence of liver cirrhosis, radiographic features, lesion size, pretreatment, administered dose, presence of portal hypertension, portal vein thrombosis, and level of alpha-fetoprotein (AFP). LTC rate was 88.8% for a median follow-up of 14.3 months (range 3-81 months; 95% CI: 85-92%). Median minimal enclosing tumor dose (D100) was 16.1 Gy (range 7.1-30.3 Gy; reference dose 15 Gy). Subgroup analysis showed significant fewer local recurrences for alcoholic liver disease (ALD)-related HCCs compared to those related to other causes of liver cirrhosis (nonalcoholic fatty liver disease, virus-related liver cirrhosis and other causes) (p = 0.015). LTC was significantly lower after prior surgical resection (p = 0.046). No significant variance was observed for the applied D100 in each group or for all other clinical factors tested. IBT achieves high LTC rates across treated subgroups. However, further studies should particularly address the possible impact of underlying etiology on local recurrence with emphasis on a possible higher radiosensitivity of ALD-related HCCs.

Вирусные циррозы печени: клинический профиль современного пациента, танатогенез и патоморфология

Objective. To analyze the profile of a patient with virus-related liver cirrhosis examined at different levels of healthcare, to identify the main causes of death, and describe morphological changes in liver tissue. Patients and methods. This study included 921 patients with chronic viral hepatitis (CVH) treated in day hospitals, 844 patients treated in inpatient facilities, and 455 CVH patients who died. We analyzed autopsy results of 97 patients with clinical signs of liver cirrhosis and described morphological characteristics of liver tissue depending on the Child–Turcotte–Pugh score. Results. Chronic hepatitis C is the most prevalent form of hepatitis in both inpatient and outpatient units. The highest incidence of latent hepatitis B was observed among inpatients. The majority of outpatients with virus-related liver cirrhosis were employable (or employed), socially adapted, not addicted to alcohol, and had compensated disease (class A in 97%) with minimal clinical manifestations, and were motivated for treatment and examination. The mean age of inpatients was 50 years; 100% of them had some comorbidities; 90% of them had subcompensated or decompensated cirrhosis; 60% of them systematically abused alcohol. Conclusion. The majority of deceased patients were employable, abused alcohol, and were not systematically followed-up by a specialist. Almost one-third of them (30%) had subcompensated disease and incomplete cirrhotic transformation of hepatic tissue; they died due to other reasons. This affects the course of chronic virus-related hepatitis and comorbidities and necessitates the creation of integrated comprehensive models of healthcare. Key words: virus-related liver cirrhosis, comorbidity, morphological examination, latent hepatitis, chronic viral hepatitis

Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure.

To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach. Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

Surgical Resection of a Recurrent Hepatocellular Carcinoma with Portal Vein Thrombosis: Is It a Good Treatment Option? A Case Report and Systematic Review of the Literature.

Background: Hepatocellular carcinoma (HCC) is the sixth most frequent diagnosed tumor worldwide and the third leading cause of cancer related death. According to the EASL Guidelines, HCC with portal vein tumor thrombosis (PVTT) is classified as an advanced stage (BCLC stage C) and the only curative option is represented by systemic therapy. Therefore, treatment of HCC patients with PVTT remains controversial and debated. In this paper, we describe the case of a 66-year-old man with a recurrent HCC with PVTT who underwent surgical resection. A systematic review of the literature, comparing surgical resection with other choices of treatment in HCC patients with PVTT, is reported. Methods: A systematic review of the literature regarding all prospective and retrospective studies comparing the survival outcomes of HCC patients with PVTT treated with surgical resections (SRs) or other non-surgical treatments (n-SRs) has been conducted. Case presentation: A 66-year-old Caucasian man with a history of Hepatitis C Virus (HCV) related liver cirrhosis and previous hepatocellular carcinoma of the VI segment treated with percutaneous ethanol infusion (PEI) seven years before presented to our clinics. A new nodular hypoechoic lesion in the VI hepatic segment was demonstrated on follow-up ultrasound examination. A hepatospecific magnetic resonance imaging (MRI) scan confirmed also the presence of a 18 × 13 mm nodular lesion in the V hepatic segment with satellite micronodules associated with V–VIII sectoral portal branch thrombosis. The case was then discussed at the multidisciplinary team meeting, and it was decided to perform a right hepatectomy. The postoperative course was regular and uneventful, and the discharge occurred seven days after the surgery. At eight-month follow-up, there was no clinical nor radiological evidence of neoplastic recurrence, with well-preserved liver function (Child-Pugh A5). Results: Nine studies were included in the review. Median Overall Survaival (OS) ranged from 8.2 to 30 months for SRs patients and from 7 to 13.3 for n-SRs patients. In SR patients, one-year survival ranged from 22.7% to 100%, two-year survival from 9.8% to 100%, and three-year survival from 0% to 71%. In n-SRs patients, one-year survival ranged from 11.8% to 77.6%, two-year survival from 0% to 47.8%, and three-year survival from 0% to 20.9%. Conclusion: The present systematic literature review and the case presented demonstrated the efficacy of surgery as a first-line treatment in well-selected HCC patients with PVTT limited or more distal to the right and left portal branches. However, further studies, particularly randomized trials, need to be conducted in future to better define the surgical indications.

Effect of Direct-Acting Antiviral Agents on Gastroesophageal Varices in Patients with Hepatitis C Virus-Related Cirrhosis.

Aim: In patients with hepatitis C virus-related liver cirrhosis (LC) who achieve sustained virological responses (SVRs) through treatment with direct-acting antiviral agents (DAAs), it remains unclear whether there are improvements in gastroesophageal varices (GEVs) and portal hypertension. We investigated changes in liver function and GEVs that occurred after DAA therapy. Materials and Methods: We evaluated the medical records of 195 patients with hepatitis C virus-related LC who received DAAs. A total of 171 patients achieved SVRs, among whom 36 had GEVs before or after receiving DAA therapy. The liver function, fibrosis, and GEVs were re-evaluated every 6 months after receiving DAA therapy. The risk factors for progressive GEVs were investigated. Results: DAA therapy resulted in improvements in liver function (indicated by aspartate transaminase, alanine transaminase, and serum albumin levels) and fibrosis (indicated by type IV collagen levels and the Fibrosis-4 index). After receiving DAA therapy, 27 patients had stable GEVs and 9 had progressive GEVs. With respect to GEV grades before DAA therapy, there was a significant difference between patients with stable and progressive GEVs (p = 0.027). Presence of grade-2 GEVs before starting DAA therapy was a risk factor for GEV progression (odds ratio: 5.83; p = 0.04). Patients with grade-2 GEVs had significantly shorter progression-free periods than those with grade < 2 GEVs (p = 0.025). Conclusions: DAA therapy does not ameliorate GEVs. Furthermore, grade-2 GEVs can worsen after DAA therapy. Therefore, patients with GEVs of grades ≥ 2 should undergo endoscopic surveillance after receiving DAAs.

Non-Invasive Prediction Models for Esophageal Varices and Red Signs in Patients With Hepatitis B Virus-Related Liver Cirrhosis.

Background: Red signs are closely related to esophageal variceal bleeding, and, despite improvements in therapy, the mortality rate remains high. We aimed to identify non-invasive predictors of esophageal varices and red signs in patients with hepatitis B virus-related liver cirrhosis. Methods: This retrospective study included 356 patients with hepatitis B virus-related liver cirrhosis after applying inclusion and exclusion criteria among 661 patients. All patients underwent endoscopy, ultrasonography, laboratory examinations, and computed tomography/magnetic resonance imaging. Univariate and multivariate logistic regression analysis were performed, and prediction models for esophageal varices and red signs were constructed. Results: Multivariate analysis revealed that spleen diameter, splenic vein diameter, and lymphocyte ratio were independent risk factors for esophageal varices and red signs. On this basis, we proposed two models: i) a spleen diameter-splenic vein diameter-lymphocyte ratio-esophageal varices prediction model (SSL-EV model); and ii) a spleen diameter-splenic vein diameter-lymphocyte ratio-red sign prediction model (SSL-RS model). The areas under the receiver operating characteristic curve for the two prediction models were 0.843 and 0.783, respectively. With a cutoff value of 1.55, the first prediction model had 81.3% sensitivity and 76.1% specificity for esophageal varices prediction. With a cutoff value of −0.20, the second prediction model had 72.1% sensitivity and 70.7% specificity for the prediction of red signs. Conclusions: We proposed a new statistical model, the spleen diameter-splenic vein diameter-lymphocyte ratio-red sign prediction model (SSL-RS model), to predict the presence of red signs non-invasively. Combined with the spleen diameter-splenic vein diameter-lymphocyte ratio-esophageal varices prediction model (SSL-EV model), these non-invasive prediction models will be helpful in guiding clinical decision-making and preventing the occurrence of esophageal variceal bleeding.

Recurrent hepatocellular carcinoma with osteoclast-like giant cells: a case report

BackgroundHepatocellular carcinoma with osteoclast-like giant cells is very rare and has an extremely poor prognosis. Here, we report a case of hepatocellular carcinoma with osteoclast-like giant cells that had a relatively better prognosis.Case presentationA 70-year-old Japanese man with hepatitis B virus-related liver cirrhosis was admitted to our hospital for the treatment of recurrent hepatocellular carcinoma. At the age of 60 years, he was first diagnosed as having hepatocellular carcinoma in the right lobe (9 cm in diameter), and liver resection of segment 7/8 was performed. Histological findings showed well-differentiated hepatocellular carcinoma. Since then, imaging studies have been performed every 3 or 4 months. One year later, hepatocellular carcinoma recurred in the lateral segment, and radiofrequency ablation was performed. Nine years after the first presentation, hepatocellular carcinoma recurrences were detected in the caudate lobe and segment 5 by imaging studies. Surgical resection of the caudate lobe was performed, and ultrasonography-guided radiofrequency ablation was subsequently performed for the segment 5 tumor. The resected tumor was simple nodular, well-differentiated HCC; it measured 21 × 21 mm and contained many osteoclast-like giant cells. As neither vascular nor bile duct invasion was found, we believe that radical resection was achieved. Since then, the hepatocellular carcinoma has not recurred for over a year and a half.ConclusionHepatocellular carcinoma with osteoclast-like giant cells is very rare and the prognosis is extremely poor, but early detection can lead to a better clinical course.

Do old urinary biomarkers have a place in the new definition of hepatorenal syndrome in the Egyptian cirrhotic patients? A single-center experience

BackgroundHepatorenal syndrome is still a diagnosis of exclusion despite new classification.AimsTo validate the accuracy of urinary neutrophil gelatinase-associated lipocalin, interleukin-18, and kidney injury molecule-1 in the new diagnostic criteria of hepatorenal syndrome in Egyptian patients with hepatitis C virus-related liver cirrhosis using serum creatinine as a gold standard test for acute kidney injury.MethodsOne-hundred twenty cirrhotic patients with ascites were recruited and divided into two groups depending on the presence or absence of renal impairment, and 40 age- and sex-matched cirrhotic patients without ascites used as controls participated in the study. Urinary biomarkers were measured and compared with conventional biomarkers used to assess kidney function (serum creatinine, estimated glomerular filtration rate).ResultsThe mean urinary neutrophil gelatinase-associated lipocalin, interleukin-18, and kidney injury molecule-1 were statistically significantly higher in patients with hepatorenal syndrome and were found to be helpful in the early detection with cutoff values of 125 ng/ml, 34.8 pg/ml, and 3.1 pg/ml, respectively.ConclusionsUrinary neutrophil gelatinase-associated lipocalin, interleukin-18, and kidney injury molecule-1 levels are higher in patients with cirrhotic ascites complicated by HRS-AKI using the new definition of HRS, but IL-18 has lower sensitivity and specificity for the prediction of HRS-AKI as compared to NGAL and KIM-1.