Hepatitis B-associated Liver Cirrhosis Research Articles

Prediction of esophageal varices in patients with hepatitis B-associated liver cirrhosis by non-invasive markers

AimsTo assess the non-invasive markers for diagnosing and grading esophageal varices(EV) in hepatitis B-associated liver cirrhosis by non-invasive method. MethodsA total of 209 treatment-naive patients with hepatitis B-associated liver cirrhosis were included in this study. These patients were divided into no EV, large grade EV and any grade EV groups according to electronic gastroscope (EGD) results. Blood tests, physical examination, and abdominal ultrasound scan (USS) were measured. The non-invasive indexes for predicting esophageal varices were screened, and non conditional logistic regression model was established. Performance was expressed as sensitivity, specificity, positive, and negative predictive values (PPV, NPV), accuracy, and area under the curve (AUC). ResultsIn the 209 patients, 155 (74.2%) EV and 106(50.7%) large EV were found. There were significant differences in spleen-length (SL), portal vein diameter (PVD), platelet blood cell (PLT) and white blood cell (WBC) between patients with any grade or large and without EV by univariate analysis. The logistic regression model was Y=-2.083-0.011∗PLT+0.101∗PVD+0.013∗SL with any grade EV, the prediction formula is Y= ​0.427-0.013∗PLT -0.861∗WBC+0.008∗SL with large EV. ConclusionsSpleen-length, portal vein diameter, platelet and white blood cell can predict esophageal varices and large esophageal varices in hepatitis B-associated liver cirrhosis.

The Applicability of ADA, AFU, and LAC in the Early Diagnosis and Disease Risk Assessment of Hepatitis B-Associated Liver Cirrhosis and Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the applicability of adenosine deaminase (ADA), α-l-fucosidase (AFU), lactic acid (LAC), and their combined detection in the early diagnosis of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC).Methods: A retrospective analysis of hepatitis B-positive liver disease patients admitted between 2015 and 2020 was conducted. The receiver operating characteristic (ROC) curve was used to determine the diagnostic value of each indicator in LC and HCC, and binary logistic regression analysis was performed to determine the factors and risks related to the occurrence of the two conditions.Results: The levels of ADA, AFU, and LAC were significantly increased in patients with CHB, LC, and HCC (p < 0.05). The ROC curve showed that the sensitivity and specificity of ADA, AFU, LAC, and their combined detection in the CHB and LC groups as well as in the LC and HCC groups reflected different degrees of clinical value. In the CHB and LC groups, the adjusted odds ratio (OR) values of ADA, AFU, and LAC among patients in the high-level group were 3.218, 1.859, and 11.474, respectively, when the median was considered the cutoff point. When quartiles were considered the cutoff point, the OR risk values of the adjusted levels of ADA, AFU, and LAC were higher than those of the lowest-level group (Q1) (p < 0.05). In the LC and HCC groups, the adjusted OR values of ADA, AFU, and LAC among patients in the high-level group were 0.967, 2.365, and 38.368, respectively. When quartiles were considered the cutoff point, the OR risk values of AFU and LAC levels were higher than those of the lowest-level group (Q1) (p < 0.05).Conclusion: ADA, AFU, and LAC demonstrated good value in the early diagnosis of LC and HCC. The combined detection of ADA+AFU+LAC is more effective than single detection for the early diagnosis of the two conditions. ADA, AFU, and LAC can serve as risk predictors of LC, while AFU and LAC can be considered early risk predictors of HCC.

CXCR5+ CD4+ T cell subsets and their relationship to immune dysfunction in chronic hepatitis B-associated liver cirrhosis.

Hepatitis B-associated liver cirrhosis (HBC) leads to profound alterations of immune systems, especially disruptions of B cell immune responses. CXCR5+ CD4+ T cells (including T follicular helper [Tfh] cells and T follicular regulatory [Tfr] cells) are responsible for the regulation of B cell functions. The aim of this study was to dissect the roles of CXCR5+ CD4+ T cell subset in B cell disruption caused by HBC. Forty-one patients with HBC and 15 healthy controls were enrolled in this study. ELISA, flow cytometric analysis, and cell coculture were performed to analyze the properties of Tfh and Tfr. We observed significantly decreased memory B cells and increased plasma B cells in HBC patients, as well as significant upregulation of lipopolysaccharide binding protein and soluble CD14 in plasma of decompensated HBCs patients. The downregulation of Tfh17 was observed in HBC patients with spontaneous bacterial peritonitis compared with those without. The decrease of Tfh17 was paralleled with Child-Pugh grade and negatively correlated with plasma B cells and soluble CD14 in HBC patients. Interleukin (IL)-21+ Tfh of HBC patients was also downregulated compared with healthy controls, and it was positively correlated with memory B cells and the upregulation of IL-10+ Tfr. It was then revealed that Tfr could inhibit the secretion of IL-21 by Tfh, and the blocking of IL-10 could diminish this effect. The changes of the frequency and function of Tfh and Tfr may play an important role in disease progression and immune dysfunction of HBC.

Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis

BackgroundRecent studies have shown that T cell-mediated cellular immune mechanisms play important roles in the progression of hepatitis B to liver cirrhosis, but the underlying mechanisms remain unclear. This present study was aimed to determine the relationship between Treg/Th17 and hepatitis B-associated liver cirrhosis.MethodsThe Treg and Th17 cell frequencies in the peripheral blood of all participants, including 93 patients with hepatitis B-associated liver cirrhosis and 40 healthy subjects, were measured by flow cytometer. Cox regression model and receiver operating characteristic(ROC) curves were applied to investigate the prognostic significance of Treg/Th17 ratio in decompensated liver cirrhosis.ResultsWe observed the Treg/Th17 imbalance was present in patients with hepatitis B-associated liver cirrhosis, with reduced Treg cells in their peripheral blood, increased Th17 cells and decreased Treg/Th17 ratio. Treg and Th17 cells were negatively correlated. Treg/Th17 imbalance was closely related to the clinical stage of hepatitis B-associated liver cirrhosis. The Virus load, Treg frequencies and the Treg/Th17 ratio were independent factors predicting decompensated liver cirrhosis from a Cox regression model. The ROC analysis showed that the Treg/Th17 ratio was the best marker for predicting decompensated liver cirrhosis.ConclusionsTreg/Th17 imbalance is involved in the pathogenesis of hepatitis B-associated liver cirrhosis and the Treg/Th17 ratio can be used as a potential marker for predicting decompensated liver cirrhosis.

Relationship Between Chronic Hepatitis B Virus Infection and Nature Killer Cells.

As the main effector cells of innate immunity, nature killer (NK) cells play important roles in preventing hepatitis B virus (HBV) infection. This study aims to investigate the correlation between NK cells and different clinical stages of chronic HBV infection and interferon-α (IFN-α) therapy. Two hundred ninety-five patients diagnosed with chronic hepatitis B (CHB) infection and selected 50 healthy adults were enrolled in this study, the frequency of CD3-CD56+ cells in peripheral blood were measured and analyzed. The level of NK cells was decreased in hepatitis B-associated liver cirrhosis significantly and had no changes in CHB or hepatocellular carcinoma, while the frequency of NK cells gradually decreased from the baseline to week 24 and then increased since week 24-48 in CHB with IFN-α treatment. NK cells played an important role in the process of HBV progression and IFN-α therapy.

Expression of IL-17 and its gene promoter methylation status are associated with the progression of chronic hepatitis B virus infection.

To explore interleukin-17 (IL-17) and its epigenetic regulation during the progression of chronic hepatitis B virus (HBV) infection.A total of 162 patients with chronic HBV infection, including 75 with chronic hepatitis B (CHB), 54 with hepatitis B-associated liver cirrhosis and 33 with hepatitis B-associated hepatocellular carcinoma (HBV-HCC), were enrolled in this study. Thirty healthy adults of the same ethnicity were enrolled in the control group. Whole venous blood was obtained from the patients and normal controls (n = 30). Clinical and laboratory parameters were assessed, and we performed enzyme-linked immunosorbent assay and quantitative real-time PCR to measure the serum levels and relative mRNA expression of IL-17, respectively. IL-17 promoter methylation in peripheral blood mononuclear cells was assessed by methylation-specific PCR. We analyzed the serum and mRNA levels of IL-17 and IL-17 promoter methylation in the 4 groups as well as the effect of methylation on serum IL-17 levels. Correlations between the IL-17 promoter methylation status and clinical parameters were analyzed by Spearman correlation analysis.Compared to the normal control group, the patient groups exhibited significantly higher serum and relative mRNA levels of IL-17. The methylation distribution among the patients was significantly lower than that among the normal controls (P < .05), with the HBV-HCC group showing the lowest IL-17 gene methylation frequency. The average IL-17 promoter CG methylation level was negatively correlated with IL-17 mRNA expression (r = −0.39, P = .03), and negative correlations between IL-17 promoter methylation and prothrombin time activity (r = −0.585, P = .035), alanine aminotransferase (r = −0.522, P < .01), aspartate aminotransferase (r = −0.315, P < .05), and the model for end-stage liver disease score (r = −0.461, P < .05) were observed. IL-17 serum levels in the methylated-promoter groups were significantly lower than those in the unmethylated-promoter groups.IL-17 expression and promoter methylation were associated with chronic HBV infection progression, especially in the HBV-HCC group. The IL-17 promoter status may help clinicians initiate the correct treatment strategy at the CHB stage.

Identification of serum \u03b2-catenin as a biomarker in patients with HBV-related liver diseases

BackgroundSubstantial evidence indicates that β-catenin is a pivotal regulator that contributes to the initiation and development of various types of diseases. Recently, β-catenin can be detected in human serum and also reported to be correlated with several disease progression in a little research. However, very little is known about the relationship between serum β-catenin and HBV-related liver disease.MethodsSerum levels of β-catenin, from 77 patients with chronic hepatitis B (CHB), 63 patients with hepatitis B associated liver cirrhosis (HBLC), 61 patients with hepatocellular carcinoma (HCC), 41 healthy HBV carriers (HHCs) and 78 healthy controls (HCs) were measured by ELISA. Correlations of serum β-catenin with viral replication and liver necroinflammation parameters were analyzed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum β-catenin to grade different stages of HBV-related disorders. Human hepatic cell line L02 was transfected with a HBV plasmid, and β-catenin levels and the underlying mechanism were analyzed.ResultsChronic hepatitis B and HBLC patients but not HHC or HCC showed significantly higher serum β-catenin levels than HCs. β-catenin levels were not correlated with HBV DNA levels but were correlated with necroinflammation parameters. HBV-infected cell model showed elevated levels of phosphorylation at Ser473 in Akt (p-Akt), phosphorylation at Ser9 in GSK3β (p-GSK3β) and β-catenin, all of which was blocked by treatment with Akt inhibitor LY294002. Additionally, ROC analysis of β-catenin for discriminating patients with CHB from HHCs, which yielded an AUC of 0.71 (cutoff value, 42 pg/mL; 95% CI 0.61–0.81) with 64.93% sensitivity, 73.17% specificity and 69.05% accuracy. ROC analysis of β-catenin for discriminating patients with HCC from chronic HBV infection mainly including CHB and HBLC, which yielded an AUC of 0.75 (cutoff value, 42 pg/mL; 95% CI 0.67–0.83) with 66.43% sensitivity, 75.41% specificity and 70.92% accuracy.ConclusionsHBV infection enhances β-catenin expression by activating Akt/GSK3β signaling. Serum β-catenin levels are correlated with necroinflammation parameters but not with viral load. Serum β-catenin has potential to discriminate the phase of HBV-related disorders, particularly predicts the patients with CHB from HHCs and also predicting HCC form chronic HBV infection.

Pure 3D laparoscopic living donor right hemihepatectomy in a donor with separate right posterior and right anterior hepatic ducts and portal veins

BackgroundDespite increases in the performance of pure laparoscopic living donor hepatectomy, variations in the bile duct or portal vein have been regarded as relative contraindications to this technique [1–3]. This report describes a donor with separate right posterior and right anterior hepatic ducts and portal veins who underwent pure laparoscopic living donor right hemihepatectomy, integrated with 3D laparoscopy and indocyanine green (ICG) near-infrared fluorescence cholangiography [1, 4, 5].MethodsA 50-year-old man offered to donate part of his liver to his older brother, who required a transplant for hepatitis B-associated liver cirrhosis and hepatocellular carcinoma. Donor height was 178.0 cm, body weight was 82.7 kg, and body mass index was 26.1 kg/m2. Preoperative computed tomography and magnetic resonance cholangiopancreatography showed that the donor had separate right posterior and right anterior hepatic ducts and portal veins. The entire procedure was performed under 3D laparoscopic view. Following intravenous injections of 0.05 mg/kg ICG, ICG near-infrared fluorescence camera was used to demarcate the exact transection line and determine the optimal bile duct division point.ResultsThe total operation time was 443 min; the donor required no transfusions and experienced no intraoperative complications. The graft weighed 1146 g with a graft-to-recipient weight ratio of 1.88%. The optimal bile duct division point was identified using ICG fluorescence cholangiography, and the bile duct was divided with good patency without any stricture. The right anterior and posterior portal veins were transected with endostaplers without any torsion. The patient was discharged on postoperative day 8, with no complications.ConclusionUsing a 3D view and ICG fluorescence cholangiography, pure 3D laparoscopic living donor right hemihepatectomy is feasible in a donor with separate right posterior and right anterior hepatic ducts and portal veins.

Assessment of high-sensitivity C-reactive protein tests for the diagnosis of hepatocellular carcinoma in patients with hepatitis B-associated liver cirrhosis.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, with high morbidity and mortality. Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma and the majority (~80%) of hepatocellular carcinoma patients in China exhibit co-morbidity with HBV-associated liver cirrhosis. The goal of reliable early diagnostic and prognostic techniques for HBV-associated HCC remains unrealized. The aim of the present study was to explore the efficacy of serum high-sensitivity C-reactive protein (hs-CRP) tests in the early diagnosis of HCC in patients with HBV-associated liver cirrhosis. A cohort of 493 patients with HBV-associated liver disease was divided into three groups: Chronic HBV (CHB) group; liver cirrhosis without HCC (LC) group; and liver cirrhosis with HCC (HCC) group. A further 47 healthy individuals comprised the healthy control (CN) group. Comparative analyses of clinical symptoms, histopathology, ultrasound imagery, computed tomography, magnetic resonance imaging, biochemistry [α-fetoprotein (AFP) and liver function enzymes], and hs-CRP tests were conducted across these four groups. Immunohistochemical analysis showed that CRP is strongly expressed in HCC tumor tissue, but is not expressed elsewhere. Analyses of the correlations between serum hs-CRP levels and HCC clinical parameters indicated that there was no correlation between serum hs-CRP levels, tumor Edmondson grade, tumor-node-metastasis stage and AFP status. Serum hs-CRP and AFP levels were found to be significantly elevated in the HCC group compared to those in the LC, CHB and CN groups (P<0.01). Receiver operator characteristic analysis showed that measurement of serum hs-CRP could differentiate HCC from HBV-associated liver cirrhosis, as well as increase the accuracy of HCC diagnoses. Additionally, measurement of hs-CRP and AFP together improved diagnostic accuracy for HCC compared with either test alone. Serum hs-CRP could have potential as an effective diagnostic tool to complement AFP in diagnosing HCC and improving the identification of AFP-negative HCC in patients with HBV-associated liver cirrhosis. The present findings may facilitate the earlier diagnosis of hepatocellular carcinoma, permitting more effective treatment and a broader spectrum of treatment modalities for patients with advanced hepatic disease.

Encapsulating Peritoneal Sclerosis Occurring in a Hemodialysis Patient

Encapsulating peritoneal fibrosis (EPF) is a serious, uncommon complication of chronic peritoneal dialysis. However, it is rare in hemodialysis patients. EPF is characterized by peritoneal membrane inflammation followed by peritoneal membrane fibrosis and encapsulation. The etiology is unclear, but inflammation of the deteriorated peritoneum causes peritoneal fibrosis. We present a case of EPF that occurred in a 29-year-old man with hepatitis B-associated liver cirrhosis with ascites that was treated solely with hemodialysis. We managed this patient surgically and then medically with prednisolone. To our knowledge, this is the first such case in Korea, so we report this case with a literature review. (Korean J Med 2013;85:629-633)

Plasma gelsolin protein: a candidate biomarker for hepatitis B-associated liver cirrhosis identified by proteomic approach.

Despite the significant improvement in internal medicine and supportive therapy in recent years, liver fibrosis/cirrhosis remains a serious health issue in hepatitis B virus (HBV) infected patients. Invasive liver biopsy is presently the best means of diagnosing cirrhosis, but it carries a significant risk and has well recognised limitations such as sampling error, hence the importance in developing early diagnosis biomarkers. With this aim, we performed a pilot proteomic study to assess this as a strategy for plasma marker detection in patients suffering from HBV-associated liver cirrhosis. Plasma from eight chronic HBV-infection patients and from eight HBV-related cirrhotic patients were selected and proteome profiles were created by two-dimensional electrophoresis. The strategy included the use of ProteoMiner enrichment kit for the reduction of highly abundance proteins (e.g. albumin and IgG) prior to proteomic analyses with the goal to improve detection of novel candidate markers. One reproducible spot was found to be completely repressed in plasma samples from cirrhotic patients and mass spectrometry analysis identified this a specific variant of the gelsolin actin-depolymerizing factor. Though further investigations are needed, especially in term of clinical validation, to our knowledge this is the first time that gelsolin is proposed as potential biomarker in HBV-related liver pathologies. Our findings confirm the potential utility of gelsolin either as a prognostic marker or a replacement therapeutic agent to alleviate liver injury.

Lessons learned from 1,000 living donor liver transplantations in a single center: How to make living donations safe

Serious complications have occurred in a considerable proportion of living donors of liver transplants, but data from a single high-volume center has rarely been available. We analyzed the medical records of donors and recipients of the first 1,000 living donor liver transplants, performed at Asan Medical Center from December 1994 to June 2005, with a focus on donor safety. There were 107 pediatric and 893 adult transplants. The most common diagnoses were biliary atresia in pediatric recipients (63%) and hepatitis B-associated liver cirrhosis (80%) in adult recipients. Right lobe donors were strictly selected based on liver resection rate and steatosis. From 1,162 living donors, 588 right lobes, 6 extended right lobes, 7 right posterior segments, 464 left lobes, and 107 left lateral segments were obtained. Of these, 837 grafts were implanted singly, whereas 325, along with 1 cadaveric split graft, were implanted as dual grafts into 163 recipients. The 5-yr survival rates were 84.8% in pediatric recipients and 83.2% in adult recipients. There was no donor mortality, but 3.2% of donors experienced major complications. Until the end of 2001, the major donor complication rate was 6.7%, with most occurring in right liver donors. Since 2002, liver resection exceeding 65% of whole liver volume were avoided except for young donors with no hepatic steatosis, and the donor complication rate has been reduced to 1.3%. In conclusion, a majority of major living donor complications appear to be avoidable through the strict selection of living donor and graft type, intensive postoperative surveillance, and timely feedback of surgical techniques. Selection of right lobe graft should be very prudently considered if the donor right liver appears to be larger than 65% of the whole liver volume.

Hepatitis B-Associated Liver Cirrhosis as an Indication for Liver Transplantation

Fourteen HBsAg-positive patients received a liver transplant in Groningen. Two were HBeAg-positive and 12 HBeAg-negative. No anti-HBs immunoglobulin was given at the time. Both HBeAg-positive and 9 of 12 of the HBeAg-negative patients became HBsAg-positive again after transplantation. Virus titers were tested in eight patients. Two HBeAg-negative patients were HBV-DNA-negative at transplantation and are still HBV-DNA-negative one-and-half-years after transplantation, both by the branched DNA hybridization technique and by PCR (cut-off values 0.7 x 10(6) and 10(3) HBV genomes/ml, respectively). One patient who had a low HBV-DNA titer at transplantation remained PCR-positive thereafter, but became HBsAg-negative. All other patients were HBV-DNA-positive and had a recurrence that rapidly led to high HBV titers. The liver histology was characterized by fibrosis and cirrhosis, centrilobular cholestasis and high expression of HBsAg and HBcAg, but with little inflammatory infiltrate. We conclude from these results that without anti-HBs immunoglobulin prophylaxis there is a high rate of HBV recurrence after transplantation. The current policy is that patients who test negative in the HBV-DNA dot-blot assay (< 10(7) genomes/ml) are transplantation candidates and are treated with high-dose anti-HBs immunoglobulin after transplantation. HBV-DNA-positive patients (> 10(7) genomes/ml) remain poor candidates for liver transplantation, even with anti-HBs immunoprophylaxis.