Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Epidemiology,therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont,Italy

BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide.It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate.HCC patients have increasingly complex and constantly changing characteristics,thus up-to-date and comprehensive data are fundamental.AIM To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.METHODS In this retrospective study,we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at"Santa Croce e Carle"Hospital in Cuneo(Italy)between 1 January 2010 and 31 December 2019.To highlight possible changes in HCC patterns over the 10-year period,we split the population into two 5-year groups,according to the diagnosis period(2010-2014 and 2015-2019).RESULTS Of the 328 HCC patients who were included(M/F 255/73;mean age 68.9±11.3 years),154 in the first period,and 174 in the second.Hepatitis C virus infection was the most common HCC risk factor(41%,135 patients).The alcoholic etiology rate was 18%,the hepatitis B virus infection etiology was 5%,and the non-viral/non-alcoholic etiology rate was 22%.The Child-Pugh score distribution of the patients was:class A 75%,class B 21%and class C 4%.The average Mayo end-stage liver disease score was 10.6±3.7.A total of 55 patients(17%)were affected by portal vein thrombosis and 158(48%)by portal hypertension.The average nodule size of the HCC was 4.6±3.1 cm.A total of 204 patients(63%)had more than one nodule<3,and 92%(305 patients)had a non-metastatic stage of the disease.The Barcelona Clinic Liver Cancer(BCLC)staging distribution of all patients was:4%very early,32%early,23%intermediate,34%advanced,and 7%terminal.Average survival rate was 1.6±0.3 years.Only 20%of the patients underwent treatment.Age,presence of ascites,BCLC stage and therapy were predictors of a better prognosis(P<0.01).A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology(P<0.05)and alpha-fetoprotein(AFP)levels(P<0.01).CONCLUSION In this study analyzing patients with a new diagnosis of HCC between 2010-2019,hepatitis C virus infection was the most common etiology.Most patients presented with an advanced stage disease and a poor prognosis.When comparing the two 5-year groups,we observed a statistically significant difference only in global etiology(P<0.05)and AFP levels(P<0.01).

Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection:A systematic review

BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma(HCC)in people with cirrhosis.Of the 6 HCV genotypes(G1-G6),genotype-3 accounts for 17.9%of infections.HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings.Consequently,we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations.We searched Web of Science,Medline,EMBASE,and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings,1946-2023.RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates.Three thousand eight hundred and eighty-four records were screened with 3514 excluded.Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis.Of the seven studies,three studies were retrospective case-control trials,two retrospective cohort studies,one a prospective cohort study and one a cross-sectional study design.All were based in hospital settings with four in Pakistan,two in South Korea and one in the United States.The total number of participants were 9621 of which 167 developed HCC(1.7%).All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age(five-studies),with two studies each showing male sex,high alpha feto-protein,directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.CONCLUSION Although,studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease,HCC,and liver-related death,there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3.Only cirrhosis and age have demonstrated an association;however,the number of studies is very small,and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma

BACKGROUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its outcomes.However,after diagnosis of HCC,like other malignancies,the obesity paradox may exist where higher body mass index(BMI)may in fact confer a survival benefit.This is frequently observed in patients with advanced HCC and cirrhosis,who often present late with advanced tumor features and cancer related weight loss.AIM To explore the relationship between BMI and survival in patients with cirrhosis and HCC.METHODS This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers.Patient and tumor characteristics were extracted manually from medical records of each institutions'cancer registries.Patients were stratified according to BMI classes:<25 kg/m^(2)(lean),25-29.9 kg/m^(2)(overweight),and>30 kg/m^(2)(obese).Patient and tumor characteristics were compared according to BMI classification.We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria.A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC.RESULTS A total of 2548 patients with HCC were included in the analysis of which 11.2%(n=286)were classified as noncirrhotic.The three main BMI categories:Lean(n=754),overweight(n=861),and obese(n=933)represented 29.6%,33.8%,and 36.6%of the total population overall.Within each BMI class,the non-cirrhotic patients accounted for 15%(n=100),12%(n=94),and 11%(n=92),respectively.Underweight patients with a BMI<18.5 kg/m^(2)(n=52)were included in the lean cohort.Of the obese cohort,42%(n=396)had a BMI≥35 kg/m^(2).Out of 2262 patients with cirrhosis and HCC,654(29%)were lean,767(34%)were overweight,and 841(37%)were obese.The three BMI classes did not differ by age,MELD,or Child-Pugh class.Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients(71%,62%,49%,P<0.001).Lean patients had significantly larger tumors compared to the other two BMI classes(5.1 vs 4.2 vs 4.2 cm,P<0.001),were more likely outside Milan(56%vs 48%vs 47%,P<0.001),and less likely to undergo transplantation(9%vs 18%vs 18%,P<0.001).While both tumor size(P<0.0001)and elevated alpha fetoprotein(P<0.0001)were associated with worse survival by regression analysis,lean BMI was not(P=0.36).CONCLUSION Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria,reflecting cancer related cachexia from delayed diagnosis.Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit,but not overweight or obese BMI classifications.

Global trends in hepatitis C-related hepatocellular carcinoma mortality:A public database analysis(1999-2019)

BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].

Hepatitis E virus re-infection accelerates hepatocellular carcinoma development and relapse in a patient with liver cirrhosis:A case report and review of literature

BACKGROUND Hepatitis E virus(HEV)superinfection is a suspected promoting factor for hepatocellular carcinoma(HCC)in patients with chronic hepatitis and cirrhosis.However,to date,very few cases of HEV-related HCC have been reported.Nevertheless,the role of HEV re-infection in cirrhotic liver without other chronic hepatitis infections has rarely been explored.CASE SUMMARY A 53-year-old male farmer was diagnosed with liver cirrhosis and splenomegaly in August 2016,accompanied with negative HEV-IgM and positive HEV-IgG.No evidence of hepatitis B virus or hepatitis C virus infection was found.Since then the patient was evaluated for liver function and viral parameters every 3 mo.In June 2017,the patient presented severe fatigue with whole body itching and was diagnosed with HCC.Afterwards this patient experienced quick HCC development,progression,relapse,and metastasis in the following 8 mo,and presented persistent dual positivity of HEV-IgM and HEV-IgG.This patient had a long history of smoking and alcohol consumption.CONCLUSION This unique case invokes the importance of HEV surveillance and treatment among cirrhotic patients,HCC cases,and blood donors.

Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus:a retrospective cohort study

AIM To assess the incidence of hepatocellular carcinoma(HCC) in chronic liver disease due to hepatitis B virus(HBV) or hepatitis C virus(HCV) coinfected with human immunodeficiency virus(HIV).METHODS A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review.RESULTS Of 804 patients were included(399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger(36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected(P < 0.001). HCC was diagnosed in 36 patients(10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years(95%CI: 0.12-0.46 vs 0.47-1.05)(long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC. CONCLUSION In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Liver stiffness as a predictor of hepatocellular carcinoma behavior in patients with hepatitis C related liver cirrhosis

Background: Risk strati cation and prognostication of hepatocellular carcinoma (HCC) help to improve patient outcome. Herein we investigated the role of liver stiffness measurement (LSM) in the prediction of HCC behavior. Methods: Totally 121 na ve patients with HCC were included. HCC radiological evaluation and staging were done. LSM was measured using virtual touch quanti cation. Patients were divided into early to intermediate HCC (BCLC-0, A and B) and late HCC (BCLCC and D). HCC was treated according to the BCLC stage. HCC recurrence-free interval was estimated. Results: The mean LSM inside the tumor was signi cantly lower than the peri-tumoral area and the cirrhotic non-cancerous liver parts (P<0.001). In late HCCs stage, the mean LSM inside the tumor and in the peri-tumoral tissue was lower than the corresponding values in the early to intermediate HCCs stage (P<0.001). LSM inside the tumor and in the peri-tumoral tissue negatively correlated with serum AFP, tumor vascular invasion, and stage (P<0.05). The recurrence-free interval was directly correlated to LSM inside the tumor and inversely to LSM in cirrhotic non tumorous liver part. Kaplan-Meier analysis showed that the recurrence-free interval was signi cantly longer in patients with LSM inside the tumor of ≥1.25m/s compared to those with LSM inside the tumor of<1.25m/s. Conclusions: LSM can serve as a potential non-invasive predictor for HCC clinical behavior and the recurrence-free interval following loco-regional treatments.

Adjuvant hepatic chemotherapy after resection of solitary hepatocellular carcinoma associated with hepatitis B virus cirrhosis

BACKGROUND: Although resection is the major treatment for patients with hepatocellular carcinoma ( HCC), the high intrahepatic recurrence remains a cardinal cause of death. This study was undertaken to evaluate the effect of hepatic arterial infusion chemotherapy on the survival and recurrence of HCC patients with hepatitis B virus ( HBV) cirrhosis after resection. METHODS: Twenty-eight patients who had undergone placement of a hepatic arterial pump at the time of liver wedge resection for HCC from 1998 through 2004 were reviewed retrospectively. These patients aged 23-71 years had HBV cirrhosis (Child-Pugh class A or B). They were given floxuridine(FUDR) (250 mg), doxorubicin (10 mg) and mitomycin C (4 mg) alternatively every 2 or 3 days through arterial pumps for 8 cycles each year in the first two years after resection. Meanwhile, traditional Chinese herbal medicine was prescribed to the patients. When the leucocyte count was as low as 3 x 109/L or asparate aminotransferase (AST) level was significantly increased, the regimen of chemotherapy was delayed for the normalization of leucocyte count and AST level (below 80 U/L). RESULTS: Of the 28 patients, 23 received 8 or 16 cycles of the set regimen of chemotherapy. These patients are alive with no evidence of recurrence. Among them, 5,7, and 11 patients are alive beyond 5 years, 3 years, and 1 year respectively. In the remaining 5 patients, 3 who had had a HCC 10 cm or more in diameter showed tumor recurrence within 1 year, in whom, 8 cycles of chemotherapy were not completed because of their low leucocyte count (<3 × 109/L) and poor liver function. One patient who had received 8 cycles of chemotherapy demonstrated recurrence at 16 months after resection. One patient who had received 16 cycles of chemotherapy had intrahepatic recurrence at 58 months after surgery. No recurrence was observed in 17 patients who had received 16 cycles of chemotherapy. CONCLUSION: Adjuvant hepatic arterial chemotherapy may be feasible to improve the survival of patients after resection of solitary HCC associated with HBV cirrhosis.

Chemoprevention of hepatocellular carcinoma in patients with hepatitis C virus related cirrhosis

Interferon(IFN) therapy has been reported to decrease the risk of hepatocellular carcinoma(HCC) and improve survival by preventing liver-related deaths in patients with chronic hepatitis C virus(HCV) infection, while the role of IFN therapy on the natural history of hepatitis C related cirrhosis is still under debate. The ideal goal of therapy is to prevent the progression into end-stage disease. The use of IFN in patients with HCV compensated cirrhosis reduces the negative clinical evolution independently of the type of laboratoristic and virological response. In our experience, IFN therapy in HCV compensated cirrhosis is barely useful in prevention of HCC, as cirrhosis itself represents a risk of cancer.Some authors noted that IFN treatment reduces the risk of HCC independently of the virological response. It would probably be interesting to evaluate the efficacy of weekly low-dose pegylated(PEG)-IFN therapy in patients with HCV cirrhosis and to assess potential benefits of long-term PEG-IFN plus Ribavirin treatment.

Dermatomyositis associated with hepatocellular carcinoma in an elderly female patient with hepatitis C virus-related liver cirrhosis

A 79-year-old female patient with hepatitis C virusrelated liver cirrhosis was diagnosed as having hepatocellular carcinoma （HCC） with a diameter of 2.0 cm. She refused therapy for HCC. Nine months after the diagnosis, she developed dermatomyositis when the HCC enlarged to a diameter of 6.0 cm. She underwent therapy for dermatomyositis, and then transcatheter arterial chemoembolization for HCC. Although the manifestations of dermatomyositis improved and entire tumor necrosis was achieved, she died of pneumonia 2 mo after the treatment of HCC. HCC and/or chronic hepatitis C virus infection might be involved in the pathogenesis of dermatomyositis.

Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation

AIM to determine whether diabetes mellitus(DM) affects prognosis/recurrence after liver transplantation(Lt) for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent Lt with antiviral prophylaxis. Patient data were obtained from the China Liver transplant Registry(https://www.cltr.org/). to compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent Lt found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after Lt between the two groups were significant(P = 0.041), but recurrence-free survival rates were not(P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years(P = 0.002), the presence of vascular invasion(P = 0.096), tumors ≤ 3 cm(P = 0.047), two to three tumor nodules(P = 0.007), Child-Pugh grade B(P = 0.018), and preLt alanine aminotransferase levels between 40 and 80 IU/L(P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/m L(P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM(P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after Lt. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor Lt outcomes. Prevention strategies for HCC patients with DM are recommended.

Hepatitis B Virus in Cirrhosis and Primary Livers Cancers

Introduction: Hepatitis B virus (HBV) infection is a public health problem in sub-Saharan Africa, due to its frequency and progression to complications such as cirrhosis and/or hepatocellular carcinoma (HCC). Objective: To help improve the management of cirrhosis and hepatocellular carcinoma. Patients and Methods: This was a 34-month cross-sectional study conducted in the Hepato-Gastroenterology Department of the CHU de l’Amitié Sino-centra-fricaine in Bangui. It included patients of both sexes aged 18 years or older with a diagnosis of HBV-related cirrhosis and/or HCC. Results: During the study period, 1344 patients were admitted to hospital, 681 of them for chronic liver disease (51%). Among patients admitted for chronic liver disease, in particular cirrhosis and/or HCC, HBV was implicated in 288 cases (42.30%), of whom 170 (24.96%) met our inclusion criteria. These included 123 men (72.35%) and 47 women (27.65%). The sex ratio was 2.61. The mean age of our patients was 40 years (±11 years) with extremes of 18 and 76 years. Cirrhosis was observed in 101 cases (59.41%), HCC on cirrhosis in 59 cases (34.70%) and HCC in 10 cases (5.89%). Cirrhosis was classified as Child-Pugh B in 62 cases and C in 20 cases. HCC on cirrhosis was classified according to BCLC stage C in 7 cases and stage D in 52 cases. Conclusion: HBV is the leading cause of cirrhosis and HCC in the Central African Republic. Chronic liver disease is diagnosed at the advanced stage of the disease. Hence the importance of early detection, prevention through vaccination at birth, and management of infected patients.

Liver Transplantation Outcomes of HBV-,HCV-,and Alcohol-induced Hepatocellular Carcinoma in the United States:Analysis of National Inpatient Samples

Objective Liver transplantation is a current treatment option for hepatocellular carcinoma(HCC).The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation,including locoregional recurrence,distant metastasis,and in-hospital mortality,in HCC patients with concurrent hepatitis B infection,hepatitis C infection,or alcoholic cirrhosis.Methods This retrospective cohort study included HCC patients(n=2391)from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection,co-infection with hepatitis B and C,or alcoholic cirrhosis of the liver between 2005 and 2014.Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models.Results Liver cirrhosis was due to alcohol in 10.5%of patients,hepatitis B in 6.6%,hepatitis C in 10.8%,and combined hepatitis B and C infection in 24.3%.Distant metastasis was found in 16.7%of patients infected with hepatitis B and 9%of hepatitis C patients.Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease.Conclusion After liver transplantation,patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis.Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.

Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA

AIM To investigate the characteristics of newly established four hepatocellular carcinoma cell lines (SNU 739, SNU 761, SNU 878 and SNU 886) from Korean hepatocellular cancer patients. METHODS Morphologic and genetic studies were done. RESULTS All four lines grew as a monolayer with an adherent pattern, and their doubling times ranged from 20 to 29 hours. The viability rate was relatively high (88%-94%). Neither mycoplasmal nor bacterial contamination was present. The lines showed different patterns in fingerprinting analysis. The hepatitis B virus (HBV) DNA was integrated in the genomes of all four lines, and in all of them HBx, HBc and HBs transcripts were detected by reverse transcriptase PCR methods. Among the three cell lines used as control (Hep 3B, SK Hep1 and Hep G2), only Hep 3B showed HBx expression, and this line was used as a HBV integrated control. The RNA of albumin was detected in three lines (SNU 761, SNU 878 and SNU 886), that of transferrin in two lines (SNU 878, SNU 886), and that of IGF Ⅱ was detected in none of the cell lines. CONCLUSION These well characterized cell lines may be very useful for studying the biology of hepatocellular carcinoma in association with the hepatitis B virus.

Significance of hepatitis virus infection in the oncogenicinitiation of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.

WJG 20^(th) Anniversary Special Issues(1): Hepatocellular carcinoma Risk prediction of hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy

Chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC)is a major health problem in AsianPacific regions.Antiviral therapy reduces,but does not eliminate the risk of HCC.It would be a heavy financial burden in most low and middle economic countries if all CHB patients received antiviral therapy and HCC surveillance.Thus,there is a need for accurate risk prediction to assist prognostication,decisions on the need for antiviral therapy and HCC surveillance.A few wellestablished risk factors for HCC,namely advanced age,male gender,high viral load,cirrhosis etc.,are the core components of three HCC risk scores:CU-HCC,GAGHCC and REACH-B scores.These 3 scores were confirmed to be accurate in predicting HCC up to 10 years in treatment-na ve patients.Their validity and applicability have recently been demonstrated in a large cohort of entecavir treatment patients.A decrease in risk scores after antiviral therapy translates to a lower risk of HCC.These findings support the application of HCC risk scores in all CHB patients.Different levels of care and different intensities of HCC surveillance should be offered according to the risk profile of patients.Patients at risk of HCC should undergo regular HCC surveillance,even when they are receiving antiviral treatment.