Inflammation scores predict survival for hepatitis B virus-related hepatocellular carcinoma patients after transarterial chemoembolization

AIM:To compare the prognostic ability of inflammation scores for patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)undergoing transarterial chemoembolization(TACE).METHODS:Data of 224 consecutive patients who underwent TACE for unresectable HBV-related HCC from September 2009 to November 2011 were retrieved from a prospective database.The association of inflammation scores with clinicopathologic variables and overall survival(OS)were analyzed,and receiver operating characteristic curves were generated,and the area under the curve(AUC)was calculated to evaluate the discriminatory ability of each inflammation score and staging system,including tumor-node-metastasis,Barcelona Clinic Liver Cancer,and Cancer of the Liver Italian Program(CLIP)scores.RESULTS:The median follow-up period was 390 d,the one-,two-,and three-year OS were 38.4%,18.3%,and 11.1%,respectively,and the median OS was 390d.The Glasgow Prognostic Score(GPS),modifed GPS,neutrophil-lymphocyte ratio,and Prognostic Index were associated with OS.The GPS consistently had a higher AUC value at 6 mo(0.702),12 mo(0.676),and24 mo(0.687)in comparison with other inflammation scores.CLIP consistently had a higher AUC value at6 mo(0.656),12 mo(0.711),and 24 mo(0.721)in comparison with tumor-node-metastasis and Barcelona Clinic Liver Cancer staging systems.Multivariate analysis revealed that alanine aminotransferase,GPS,and CLIP were independent prognostic factors for OS.The combination of GPS and CLIP(AUC=0.777)was superior to CLIP or GPS alone in prognostic ability for OS.CONCLUSION:The prognostic ability of GPS is superior to other inflammation scores for HCC patients undergoing TACE.Combining GPS and CLIP improved the prognostic power for OS.     

Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) with typical cutaneous manifestations. It has been proposed that DM may be caused by autoimmune responses to viral infections, and previous studies have also shown that an association between DM and malignancy. However, chronic hepatitis B virus (HBV) infection associated with DM and hepatocellular carcinoma (HCC) is rarely encountered. The authors report a case of DM and HCC in a patient with a HBV infection. A 58-year-old man presented erythematous skin rashes on a sun-exposed area of 2 year’s duration, and recent proximal muscle weakness. His medical history revealed that he had a chronic HBV infection. A diagnosis of DM relies on proximal muscle weakness, elevated muscle enzymes, myopathic changes (demonstrated by electromyography), muscle biopsy evidence of myositis, and its characteristic cutaneous findings. A Liver mass in the left lobe visualized by abdominal computed tomography was confirmed histologically as HCC. This case suggests that DM associated with HCC might be caused by a HBV infection.     

Meta-learning algorithm development to predict outcomes in patients with hepatitis C virus-related hepatocellular carcinoma

Background and study aimsPrediction of prognosis and treatment outcomes for patients with hepatocellular carcinoma (HCC) is complex for most patients. Machine learning predictive analysis can be used to explore the rich information in electronic health records to discover hidden patterns and relationships. We aimed to develop a noninvasive algorithm for predicting outcome treatment options for patients with HCC.Patients and methodsThis cross-sectional study included 1298 patients with Hepatitis C virus-related HCC attending an HCC multidisciplinary clinic, Kasr Al-Aini Hospital, Cairo University, between 2009 and 2016. Using machine learning analysis, we constructed Reduced Error Pruning (REP) decision tree algorithms and applied Auto-WEKA to select the best classifier out of 39 algorithms.ResultsThe REP-tree algorithm predicted HCC management outcomes with a recall (sensitivity) of 0.658 and a precision (specificity) of 0.653 using only routine data. 854 (65.8%) instances were correctly identified, and 444 (34.2%) instances were incorrectly classified. Out of 31 attributes, liver decompensation was selected by REP-tree as the best predictor of HCC outcome (root node). With Auto-WEKA, the random subspace classifier was chosen as the best predictive algorithm with a recall (sensitivity) of 0.750 and a precision (specificity) of 0.75. There were 974 (75%) correctly classified instances and 324 (25%) incorrectly classified instances, which was better than REP-tree.ConclusionMachine learning analysis explores data to discover hidden patterns and trends and enables the development of models to predict HCC treatment outcomes utilizing simple laboratory data. The random subspace classifier predicted the outcome more accurately than REP-tree.     

Orthotopic liver transplantation for patients with hepatitis B virus-related liver disease

Fifty-nine patients with prior hepatitis B virus infection underwent orthotopic liver transplantation. During the first 2 mo, mortality was not significantly different in the hepatitis B virus-infected group (25.5%) vs. a hepatitis B virus-immune control group (21%). Beyond 2 mo, the mortality, rate of graft loss, need for retransplantation and incidence of abnormal liver function were significantly higher in the hepatitis B virus-infected group. Treatment of the hepatitis B virus infection was attempted with passive immunization, combined active and passive immunization, alpha-interferon or nothing. The clinical outcome was not significantly influenced by any of these therapies. However, of the patients who lived more than 60 days, 6 of 22 treated with active plus passive immunization were cleared of HBsAg, something achieved once in 16 patients treated with alpha-interferon, never in 3 patients with passive immunization only and once in 4 patients with no therapy. In patients with recurrent hepatitis B virus infection, the pace of hepatitis development in the graft appeared to be accelerated, and this was particularly striking in patients who underwent multiple retransplantations at progressively shorter intervals. None of the patients who became HBsAg-negative had HBeAg preoperatively.     

Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) worldwide due to the high prevalence of HCV infection and the high rate of HCC occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence has been observed during the past decades in most industrialized countries, partly related to the growing number of patients infected by HCV. HCC is currently the main cause of death in patients with HCV-related cirrhosis, a fact that justifies screening as far as curative treatments apply only in patients with small tumors. As a whole, treatment options are similar in patients with cirrhosis whatever the cause. Chemoprevention could be also helpful in the near future. It is strongly suggested that antiviral treatment of HCV infection could prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained virological response is obtained.     

Spontaneous fungal peritonitis in patients with hepatitis B virus-related liver disease

Spontaneous bacterial peritoneal infections is recognized as a very common complication of cirrhotic ascites, but isolation of fungus in pure culture from ascitic fluid is relatively rare, even more so in the human immunodeficiency virus (HIV)-negative or nonimmunocompromised hosts. We describe two patients of spontaneous fungal peritonitis where the isolate was Cryptococcus neoformans. Both cases suffered from hepatitis B virus (HBV) infection. The clinical and laboratory profiles of both patients were similar to those of conventional spontaneous bacterial peritonitis. We suggest that it would be prudent to heighten clinical suspicion for fungal peritonitis in such cases.     

Clinical features of hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of cancer death,and chronic hepatitis B is a serious worldwide problem.The epidemiology of HCC is distinctive.Hepatitis B virus (HBV) plays a major role in hepatocarcinogenesis.Prevention of HBV-related HCC is a key issue in current hepatology.This paper describes the prevention and clinical features of HBVrelated HCC,along with a short review of the disease.     

Human liver tissue metabolic profiling research on hepatitis B virus-related hepatocellular carcinoma

AIM: To select characteristic endogenous metabolites in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients and to identify their molecular mechanism and potential clinical value. METHODS: An ultra performance liquid chromatography and linear trap quadrupole-Orbitrap XL-mass spectrometry platform was used to analyze endogenous metabolites in the homogenate of central tumor tissue, adjacent tissue and distant tissue obtained from 10 HBV-related HCC patients. After pretreatment with Mzmine software, including peak detection, alignment and normalization, the acquired data were treated with Simca-P+software to establish multivariate statistical analysis based on a pattern recognition technique and characteristic metabolites highly correlated with changing trends in metabolic profiling were selected and further identified. RESULTS: Based on data acquired using Mzmine software, a principal component analysis model (R2X = 66.9%, Q2 = 21.7%) with 6 principal components and an orthogonal partial least squares discriminant analy-sis model (R2X = 76.5%, R2Y = 93.7%, Q2 = 68.7%) with 2 predicted principal components and 5 orthogonal principal components were established in the three tissue groups. Forty-nine ions were selected, 33 ions passed the 2 related samples nonparametric test (P < 0.05) and 14 of these were further identified as characteristic metabolites that showed significant differences in levels between the central tumor tissue group and distant tumor tissue group, including 9 metabolites (L -phenylalanine, glycerophosphocholine, lysophosphatidylcholines, lysophosphatidylethanolamines and chenodeoxycholic acid glycine conjugate) which had been reported as serum metabolite biomarkers for HCC diagnosis in previous research, and 5 metabolites (betasitosterol, quinaldic acid, arachidyl carnitine, tetradecanal, and oleamide) which had not been reported before. CONCLUSION: Characteristic metabolites and metabolic pathways highly related to HCC pathogenesis and progression are identified through     

Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma

Chronic hepatitis B virus(HBV) infection is a critical risk factor for the carcinogenesis and progression of hepatocellular carcinoma(HCC). It promotes HCC development by inducing liver fibrogenesis, genetic and epigenetic alterations, and the expression of active viral-coded proteins. Effective antiviral treatments inhibit the replication of HBV, reduce serum viral load and accelerate hepatitis B e antigen serum conversion. Timely initiation of antiviral treatment is not only essential for preventing the incidence of HCC in chronic hepatitis B patients, but also important for reducing HBV reactivation, improving liver function, reducing or delaying HCC recurrence, and prolonging overall survival of HBV-related HCC patients after curative and palliative therapies. The selection of antiviral drugs, monitoring of indicators such as HBV DNA and hepatitis B surface antigen, and timely rescue treatment when necessary, are essential in antiviral therapies for HBVrelated HCC.     

Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma

Approximately 350 million people worldwide are chronically infected by hepatitis B virus (HBV). HBV causes severe liver diseases including cirrhosis and hepatocellular carcinoma (HCC). In about 25% of affected patients, HBV infection proceeds to HCC. Therefore, the mechanisms by which HBV affects the host cell to promote viral replication and its pathogenesis have been the subject of intensive research efforts. Emerging evidence indicates that both autophagy and microRNAs (miRNAs) are involved in HBV replication and HBV-related hepatocarcinogenesis. In this review, we summarize how HBV induces autophagy, the role of autophagy in HBV infection, and HBV-related tumorigenesis. We further discuss the emerging roles of miRNAs in HBV infection and how HBV affects miRNAs biogenesis. The accumulating knowledge pertaining to autophagy and miRNAs in HBV replication and its pathogenesis may lead to the development of novel strategies against HBV infection and HBV-related HCC tumorigenesis.     

Long noncoding RNAs in hepatitis B virus-related hepatocellular carcinoma

AIM: To study the expression of long noncoding RNAs (lncRNAs) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).METHODS: The lncRNA profiles between HBV-related HCC tissues and corresponding normal liver tissues were generated using microarray analysis. Datasets were analyzed using multiple algorithms to depict alterations in gene expression on the basis of gene ontology (GO), pathway analysis, and lncRNA levels.RESULTS: The microarray revealed that 1772 lncRNAs and 2508 mRNAs were differently expressed. The pathway analysis demonstrated that the cell cycle, cytokine-cytokine receptor interaction, chemokine signaling pathway, and phosphoinositide 3-kinase-protein kinase B signaling pathway may play important roles in HCC. Several GO terms, such as cell cycle, DNA replication, immune response, and signal transduction, were enriched in gene lists, suggesting a potential correlation with HBV-related HCC. The upregulated large intergenic noncoding RNA ULK4P2 was physically combined with enhancer of zeste homolog 2. Therefore, the lncRNAs may participate in regulating HBV-related HCC.CONCLUSION: lncRNAs play important roles in HCC, future studies should verify whether large intergenic noncoding ULK4P2 functions by combining with enhancer of zeste homolog 2 in HCC.     

Prevention and surveillance of hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) infection in approximately 50% of cases, although the oncogenic mechanisms of HBV are not well understood. Vaccination for HBV has successfully lowered the rates of both HBV infection and HCC. Once chronic HBV infection is established, the objective of antiviral treatment is to prevent disease progression to liver cirrhosis or HCC, or both. Studies have found HBV DNA level to be a strong predictor for the development of cirrhosis and HCC, irrespective of the status of viral and biochemical factors. This article reviews recent clinical trials evaluating sustained viral suppression with interferon alfa and lamivudine. The results support the need to reduce viral load as an important therapeutic goal. For HCC not prevented by these measures, surveillance using ultrasonography and serum alpha-fetoprotein assay every 3 to 6 months is able to detect HCC at an earlier stage and allows curative therapy with survival benefit.     

Antiviral efficacy of lamivudine versus entecavir in patients with hepatitis B virus-related advanced hepatocellular carcinoma

Background and Aim: Little information is available about the antiviral efficacy of lamivudine (LAM) and entecavir (ETV) in patients with hepatitis B virus (HBV)‐related advanced hepatocellular carcinoma (HCC). Thus, we compared the antiviral efficacy of LAM and ETV in these patients. Methods: The medical records of 134 antiviral therapy‐naïve patients with HBV‐related advanced HCC (modified Union for International Cancer Control [UICC] Tumor, Nodes, and Metastases [TNM] stages III–IV) treated between January 2005 and September 2009 were reviewed. After HCC diagnosis, 87 (64.9%) and 47 (35.1%) patients received LAM and ETV, respectively. Results: The mean age of patients (115 men, 19 women) was 53 years. Sixty‐five (48.5%) and 69 (51.5%) patients had TNM stages III and IV HCC, respectively. Treatment outcomes during follow‐up, including virologic, biochemical, and serologic responses and appearance of antiviral resistance, were similar in the LAM and ETV groups (all P > 0.05). Multivariate analysis identified Child–Pugh class, α‐fetoprotein, and TNM stage as independent predictors of overall survival (all P < 0.05). Antiviral agent type (LAM vs ETV) did not influence overall survival (median 9.6 months in LAM vs 13.6 months in ETV group; P = 0.493). HCC treatment was not interrupted due to HBV flare up in any patient. Conclusions: The antiviral efficacy of LAM and ETV was similar and the type of antiviral agent did not influence overall survival in patients with HBV‐related advanced HCC. Thus, LAM, which is less expensive than ETV in Korea, might be sufficient to control HBV in these patients.     

Perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis with hepatocellular carcinoma

Liver cirrhosis is reportedly one of the conditions preceding peripheral-type intrahepatic cholangiocarcinoma but not hilar/perihilar cholangiocarcinoma. Herein, we report a case of perihilar cholangiocarcinoma arising in a hepatitis C virus-related cirrhotic liver. The patient was a 69-year-old man. He was diagnosed with hepatitis C virus-related chronic hepatitis at the age of 56 years, and 9 years later, multiple hepatocellular carcinomas were detected by imaging modalities. Despite treatments, including chemotherapy, he died of hepatic failure at the age of 69 years. At autopsy, in addition to multiple nodules of hepatocellular carcinoma, we found a white mucinous and fibrous tumor spreading from the hepatic hilum to the periphery along the left lateral segmental bile ducts in the advanced cirrhotic liver. This tumor was histologically a cholangiocarcinoma that involved mainly the peribiliary glands and showed variable cystic dilation, suggesting that it might have been derived from these peribiliary glands. Immunohistochemically, the cholangiocarcinoma cells were positive for cytokeratin 7 and mucin core protein 1, and negative for cytokeratin 20 and mucin core protein 2. Hilar/perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis has rarely been reported. This case warrants further studies to clarify the possible involvement of hepatitis C virus in tumorigenesis of hilar/perihilar cholangiocarcinoma.