Prophylaxis against hepatitis B virus recurrence after liver transplantation: A registry study

AIM: To evaluate the prophylactic efficacy of hepatitis B immunoglobulin(HBIG) in combination with different nucleos(t)ide analogues.METHODS: A total of 5333 hepatitis B surface antigenpositive patients from the China Liver Transplant Registry database were enrolled between January 2000 and December 2009. Low-dose intramuscular(im) HBIG combined with one nucleos(t)ide analogue has been shown to be very cost-effective in recent reports. Hepatitis B virus(HBV) prophylactic outcomes were compared based on their posttransplant prophylactic protocols [group A(n = 4684): im HBIG plus lamivudine; group B(n = 491): im HBIG plus entecavir; group C(n = 158): im HBIG plus adefovir dipivoxil]. We compared the related baseline characteristics among the three groups, including the age, male sex, Meld score at the time of transplantation, Child-Pugh score at the time of transplantation, HCC, pre-transplantation hepatitis B e antigen positivity, pre-transplantation HBV deoxyribonucleic acid(HBV DNA) positivity, HBV DNA at the time of transplantation, pre-transplantation antiviral therapy, and the duration of antiviral therapy before transplantation of the patients. We also calculated the 1-, 3- and 5-year survival rates and HBV recurrence rates according to the different groups. All potential risk factors were analyzed using univariate and multivariate analyses.RESULTS: The mean follow-up duration was 42.1 ± 30.3 mo. The 1-, 3- and 5-year survival rates were lower in group A than in groups B(86.2% vs 94.4%, 76.9% vs 86.6%, 73.7% vs 82.4%, respectively, P 0.001) and C(86.2% vs 92.5%, 76.9% vs 73.7%, 87.0% vs 81.6%, respectively, P 0.001). The 1-, 3-and 5-year posttransplant HBV recurrence rates were significantly higher in group A than in group B(1.7% vs 0.5%, 3.5% vs 1.5%, 4.7% vs 1.5%, respectively, P = 0.023). No significant difference existed between groups A and C and between groups B and C with respect to the 1-, 3- and 5-year HBV recurrence rates. Pretransplant hepatocellular carcinoma, high viral load and posttransplant prophylactic protocol(lamivudine and HBIG vs entecavir and HBIG) were associated with HBV recurrence.CONCLUSION: Low-dose intramuscular HBIG in combination with a nucleos(t)ide analogue provides effective prophylaxis against posttransplant HBV recurrence, especially for HBIG plus entecavir.     

Neutrophil-lymphocyte ratio predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation

AIM:To determine whether an elevated neutrophillymphocyte ratio(NLR)is negatively associated with tumor recurrence in patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)after liver transplantation(LT),and to determine the optimal predictive NLR cut-off value.METHODS:The data of HCC patients who had undergone LT came from the China Liver Transplant Registry database.We collected data from 326 liver cancer patients who had undergone LT at our medical center.We divided the patients into groups based on their NLRs(3,4 or 5).We then compared the clinicopathological data and long-time survival between these groups.Meanwhile,we used receiver operating characteristic analysis to determine the optimal NLR cut-off.RESULTS:Of 280 HCC patients included in this study,263 were HBV positive.Patients with an NLR<3 and patients with an NLR≥3 but<4 showed no significant differences in overall survival(OS)(P=0.212)or disease-free survival(DFS)(P=0.601).Patients with an NLR≥4 but<5 and patients with an NLR≥5also showed no significant differences in OS(P=0.208)or DFS(P=0.618).The 1-,3-and 5-year OS rates of patients with an NLR<4 vs an NLR≥4 were 87.8%,63.8%and 61.5%vs 73.9%,36.7%and 30.3%,respectively(P<0.001).The 1-,3-and 5-year DFS rates of patients with an NLR<4 vs NLR≥4 were 83.9%,62.9%and 60.7%vs 64.9%,30.1%and 30.1%,respectively(P<0.001).Univariate and multivariate analyses demonstrated that three factors,including NLR≥4(P=0.002),were significant predictors of tumor recurrence in HCC patients after LT.CONCLUSION:A preoperative elevated NLR significantly increased the risk for tumor recurrence in HCC patients after LT.     

Antiviral drug resistance increases hepatocellular carcinoma: A prospective decompensated cirrhosis cohort study

AIM:To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.METHODS:Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort.With two years of follow-up,198patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.RESULTS:Among the antiviral treatment patients,162had a complete virological response(CVR),and 36 were drug-resistant(DR).The two-year cumulative incidence of hepatocellular carcinoma(HCC)in the DR patients(30.6%)was significantly higher than that in both the CVR patients(4.3%)and the control group(10.3%)(P<0.001).Among the DR patients in particular,the incidence of HCC was 55.6%(5/9)in those who failed rescue therapy,which was extremely high.The rtA181T mutation was closely associated with rescue therapy failure(P=0.006).The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline(8.9±2.3 vs 6.0±1.3,P=0.043).CONCLUSION:This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients,especially in those who failed rescue therapy.     

Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients

AIM: To identify the prevalence of pre-S2 start codon mutations and to assess their association with liver disease progression. METHODS: The mutations were identified by direct sequencing from 73 asymptomatic carriers, 66 chronic hepatitis (CH), 66 liver cirrhosis (LC) and 63 hepatocellular carcinoma (HCC) patients. Statistical significances were determined using Fisher's exact test, χ 2 test, and t -test analyses whenever appropriate. Pre-S mutation as a risk factor for advanced liver disease was estimated by unconditional logistic regression model adjusted with age, sex, and hepatitis B e antigen (HBeAg). P 0.05 was considered significant. RESULTS: Mutation of the hepatitis B virus (HBV) pre-S2 start codon was found in 59 samples from 268 subjects (22.0%), with higher prevalence in patients with cirrhosis 27/66 (40.9%) followed by HCC 18/63 (28.6%), chronic hepatitis 12/66 (18.2%) and asymptomatic carriers 2/73 (2.7%) (P 0.001). Logistic regression analysis showed that pre-S2 start codon mutation was an independent factor for progressive liver disease. Other mutations, at T130, Q132, and A138, were also associated with LC and HCC, although this was not statistically significant when adjusted for age, sex, and HBeAg. The prevalence of pre-S2 start codon mutation was higher in HBV/B than in HBV/C (23.0% vs 19.1%), whilst the prevalence of T130, Q132, and A138 mutation was higher in HBV/C than in HBV/B. The prevalence of pre-S2 start codon mutation was higher in LC (38.9%) and HCC (40.0%) than CH (5.6%) in HBeAg(+) group, but it was similar between CH, LC and HCC in HBeAg(-) group. CONCLUSION: Pre-S2 start codon mutation was higher in Indonesian patients compared to other Asian countries, and its prevalence was associated with advanced liver disease, particularly in HBeAg(+) patients.     

Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome

AIM: To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC).METHODS: Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 ± 11.2 vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.     

Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis

AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir(0.5 mg) in Chinese nucleosidenaive patients with cirrhosis.METHODS: A total of 204 nucleoside-naive patients with compensated(n = 96) or decompensated(n = 108) hepatitis B virus(HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital(Jilin University, Changchun, China) who were treated with entecavir(0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment(baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level 500 copies/m L, the association of interleukin-28 B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ2 test.RESULTS: At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level 500 copies/m L. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype(CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pughclass A disease was significantly increased at week 240(68%) from the baseline(47%; P 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240(25%) from the baseline(39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points(7.11 ± 1.80 vs 3.53 ± 1.35, P 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points(5.58 ± 0.50 vs 4.32 ± 0.81, P 0.01).CONCLUSION: Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.     

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period.RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 10⁹/L vs 63.3 ± 15.7 × 10⁹/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation.CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.     

Independent Predictors of Mortality and Resource Utilization in Viral Hepatitis Related Hepatocellular Carcinoma

IntroductionHepatitis B (HBV) and C viruses (HCV) are important causes of hepatocellular carcinoma (HCC). Our aim was to assess mortality and resource utilization of patients with HCC-related to HBV and HCV.Material and methodsNational Cancer Institute's Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (2001-2009) was used. Medicare claims included patient demographic information, diagnoses, treatment, procedures, ICD-9 codes, service dates, payments, coverage status, survival data, carrier claims, and Medicare Provider Analysis and Review (MEDPAR) data. HCC related to HBV/HCV and non-cancer controls with HBV/HCV were included. Pairwise comparisons were made by t-tests and chisquare tests. Logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals (CIs) were used.ResultsWe included 2,711 cases of HCC (518 HBV, 2,193 HCV-related) and 5,130 non-cancer controls (1,321 HBV, 3,809 HCV). Between 2001-2009, HCC cases related to HBV and HCV increased. Compared to controls, HBV and HCV patients with HCC were older, more likely to be male (73.2% vs 48.9% and 57.1% vs. 50.5%), die within one-year (49.3% vs. 20.3% and 52.2% vs. 19.2%), have decompensated cirrhosis (44.8% vs. 6.9% and 53.9% vs. 10.4%) and have higher inpatient ($60.471 vs. $47.223 and $56.033 vs. $41.005) and outpatient charges ($3,840 vs. $3,328 and $3,251 vs. $2,096) (all P < 0.05). In two separate multivariate analyses, independent predictors of one-year mortality were older age, being male and the presence of decompensated cirrhosis.ConclusionsThe rate of viral hepatitis-related HCC is increasing. Mortality and resource utilization related to HBV and HCV-related HCC is substantial.     

Liver resection in hepatitis B related-hepatocellular carcinoma: Clinical outcomes and safety in elderly patients

AIM:To compare the morbidity and mortality in young and elderly hepatocellular carcinoma(HCC)patients undergoing liver resection.METHODS:We retrospectively enrolled 1543 consecutive hepatitis B(HBV)-related HCC patients undergoing elective hepatic resection in our cohort,including 207elderly patients(≥65 years)and 1336 younger patients(<65 years).Patient characteristics and clinical outcomes after liver resection were compared between the two groups.RESULTS:Elderly patients had more preoperative comorbidities and lower alanine aminotransferase and aspartate aminotransferase levels.Positive rates for hepatitis B surface antigen(P<0.001),hepatitis B e antigen(P<0.001)and HBV DNA(P=0.017)were more common in younger patients.Overall complications and their severity classified using the Clavien system were similarin the two groups(33.3%vs 29.6%,P=0.271).Elderly patients had a higher rate of postoperative cardiovascular complications(3.9%vs 0.6%,P=0.001),neurological complications(2.9%vs 0.4%,P<0.001)and mortality(3.4%vs 1.2%,P=0.035),and had more hospital stay requirement(13 d vs 12 d,P<0.001)and more intensive care unit stay(36.7%vs 27.8%,P=0.008)compared with younger patients.However,postoperative hepatic insufficiency was more common in the younger group(7.7%vs 3.4%,P=0.024).CONCLUSION:Hepatectomy can be safely performed in elderly patients.Age should not be regarded as a contraindication to liver resection with expected higher complication and mortality rates.     

Management of hepatitis C infection before and after liver transplantation

Chronic hepatitis C (CHC) is the most common indication for liver transplantation (LT). Aggressive treatment of hepatitis C virus (HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon (IFN)-based regimens can be used in dual-agent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals (e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free anti-HCV therapy for pre- and post-LT remains high.     

Latent hepatitis B is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C

AIM:To study the potential association between hepatocellular carcinoma(HCC)in patients with chronic hepatitis C(CHC),cirrhosis and latent hepatitis B(LHB)infection,defined as the absence of detectable serum hepatitis B surface antigen(HBsAg)and the presence of hepatitis B core antibody(HBcAb).METHODS:This retrospective analysis is comprised of 185 cirrhotic patients with HCC who were hepatitis C virus antibody(HCV Ab)(+)and HBsAg(-)at Wayne State University between 1999 and 2008.From these,108 patients had HCV polymerase chain reaction confirmation of viremia while the remaining(77)were considered to have CHC on the basis of a positive HCV Ab and the absence of any other cause of liver disease.Controls were drawn from our institutional database from the same time period and consisted of 356 HBsAg(-)age,race and gender matched patients with HCV RNA-confirmed CHC and without evidence of HCC.A subgroup of controls included 118matched patients with liver cirrhosis.χ2test and t test were used for data analysis.RESULTS:Seventy-seven percent of patients in all3 groups were African Americans.Patients with HCC had a significantly higher body mass index(P=0.03),a higher rate of co-infection with human immunodeficiency virus(HIV)(P=0.05)and a higher prevalence of alcohol abuse(P=0.03)than the controls.More patients with HCC had LHB than controls(78%vs39%,P=0.01).Sixty three percent of patients with HCC were both hepatitis B surface antigen(HBsAb)(-)and HBcAb(+)compared to 23%of controls(P<0.01).When compared to cirrhotic controls,the frequency of HBcAb(+)remained higher in patients with HCC(78%vs 45%,P=0.02).Patients with HCC were more likely to be both HBsAb(-)and HBcAb(+)than the cirrhotic controls(63%vs 28%,P=0.01).Although not statistically significant,100%of CHC and HIV coinfected patients with HCC(n=11)were HBcAb(+)when compared to controls(44%;n=9).CONCLUSION:These data suggest that LHB occurs at a significantly increased frequency in patients with CHC and HCC than in patients with CHC without HCC.     

Different pre-S deletion patterns and their association with hepatitis B virus genotypes

AIMTo investigate the associations of different types of pre-S deletions with hepatitis B virus (HBV) genotypes.METHODSThe sequences of the pre-S region, basal core promoter (BCP) mutation, and precore (PC) mutation were examined through direct DNA sequencing or clonal analysis and sequencing in 273 HBV carriers, namely 55 asymptomatic carriers, 55 carriers with chronic hepatitis (CH), 55 with liver cirrhosis (LC), 53 with liver cirrhotic hepatocellular carcinoma (LC-HCC), and 55 with noncirrhotic HCC. A total of 126 HBV carriers (46.2%) harbored pre-S deletions. The DNA sequences of pre-S deletion mutants from 43 age-matched genotype B (HBV/B)-infected carriers and 43 age-matched genotype C (HBV/C)-infected carriers were further examined, aligned, and compared.RESULTSNo significant difference was observed in the mean age distribution (P = 0.464), male sex (P = 0.805), viral load (P = 0.635), or BCP mutation (P = 0.117) between the HBV/B and HBV/C groups. However, the rate of PC mutation was significantly higher in the HBV/B-infected carriers than in the HBV/C-infected carriers (P = 0.003). Both genotypes exhibited a high rate of deletion in the C-terminal half of the pre-S1 region and N-terminus of the pre-S2 region (86.0% and 79.1% in the HBV/B group; 69.8% and 72.1% in the HBV/C group, respectively). Epitope mapping showed that deletion in several epitope sites was frequent in both genotypes, particularly pS1-BT and pS2-B2. Conversely, the rate of pS2-B1 deletion was significantly higher in the HBV/B group (72.1% vs 37.2%, P = 0.002), and the rate of pS2-T deletion was significantly higher in the HBV/C group (48.8% vs 25.6%, P = 0.044). Functional mapping showed that the rate of deletion in three functional sites (the nucleocapsid binding site, start codon of M, and site for viral secretion) located in the N-terminus of the pre-S2 region was significantly higher in the HBV/B group (P < 0.05). One type of N-terminus pre-S1 deletion mutant with deletion of the start codon of the L protein was frequently observed in the HBV/C group (20.9% vs 9.3%, P = 0.228), particularly in the LC patients (42.9% vs 12.5%). Different patterns of pre-S deletions were also found between the HBV/B and HBV/C groups according to different clinical outcomes. In CH patients, deletion in the site for polymerized human serum albumin was more frequent in the HBV/B group (88.9% vs 36.4%, P = 0.028). In the LC-HCC patients, the rate of deletion in the pre-S2 region was significantly higher in the HBV/B group than in the HBV/C group (P < 0.05).CONCLUSIONHBV/B- and HBV/C-infected carriers exhibit different patterns of pre-S deletion, which may be associated with the progression of liver diseases.     

Prognostic Significance of Serum Galectin-3 Levels in Patients with Hepatocellular Cancer and Chronic Viral Hepatitis

Background/Aim:

Galectins affect diverse physiological and pathophysiological processes such as development, inflammation, and tumor growth. We aimed to compare serum galectin-3 levels in three patient groups with chronic hepatitis B and C virus (HBV, HCV), cirrhosis secondary to HBV or HCV, and hepatocellular carcinoma (HCC) secondary to HBV or HCV and evaluate the role of galectin-3 during HCC progression.

Patients and Methods:

Nineteen patients with hepatocellular cancer, 22 patients with cirrhosis, and 24 patients with chronic hepatitis B and C were included in this study. Serum galectin-3 levels in different liver diseases were assessed by enzyme-linked immunosorbent assay.

Results:

The mean galectin-3 levels were 4.61 ng/mL (±2.32) in HCC patients, 5.68 ng/mL (±2,2) in cirrhotic patients, 1.98 ng/mL (±1.50) in chronic viral hepatitis group. There were no statistical differences between HCC and cirrhotic patients (P = 0.5), but lower in chronic hepatitis group statistically compared with cirrhosis and HCC (P < 0.001, P = 0.002, respectively). In case of cirrhotic patients, galectin-3 levels were significantly higher in patients with cirrhosis secondary to HCV compared with HBV (P = 0.03). When we evaluated galectin-3 levels in HCC patients, it was found to be 3.92 ng/mL in HCC secondary to hepatitis B and 5.37 ng/mL in HCC secondary to hepatitis C.

Conclusion:

Serum galectin-3 levels in patients with chronic HBV or HCV may guide us about progression to cirrhosis or HCC and prognosis of the disease. Especially, galectin-3 levels may be more pronounced in case of HCV.     

Suppressive effects of entecavir on hepatitis B virus and hepatocellular carcinoma

Background and Aim: We investigated the efficacy and effectiveness of entecavir in hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients. Methods: We enrolled 231 nucleoside‐naïve chronic hepatitis B (CHB) patients primarily treated with entecavir 0.5 mg/day for at least 6 months in our institution. Of these, 71 patients had HCC at the start of entecavir treatment (HCC group) and 160 did not (non‐HCC group). We compared antiviral responses to entecavir in the two groups, and evaluated the effects of entecavir on the clinical outcomes of curatively‐treated HCC patients. Results: The HCC and non‐HCC groups had similar cumulative rates of HBV‐DNA negativity, alanine aminotransferase normalization, and hepatitis e antigen loss in year 2 (100% vs 95.4%, 94.7% vs 97.3%, and 40.8% vs 41.8%, respectively; P > 0.05). Entecavir treatment for 12 months decreased mean Model for End‐Stage Liver Disease scores in patients with cirrhosis and HCC (7.2 vs 5.6, P < 0.001). Of the 71 HCC patients, 16 underwent curative therapies concurrently with entecavir; hepatectomy in six and radiofrequency ablation in 10, and the 55 remaining patients received transarterial chemoembolization or conservative treatment. In a subgroup of 16 HCC patients receiving curative treatments, patients who became serum HBV DNA negative by week 24 had better overall survival (P = 0.039), but not recurrence‐free survival (P = 0.961), than those who did not. Conclusions: First‐line entecavir monotherapy is comparably effective in CHB patients with and without HCC, and improves hepatic function in HBV‐related HCC patients. An early virological response to entecavir is prognostic of improved survival following curative therapy against HBV‐related HCC.     

Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations

AIM: To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mu-tations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis. METHODS: We investigated 264 liver cirrhosis pa-tients who were not treated with antiviral drugs, in-cluding 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe poly-merase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ2 test and unconditional logistic regression analysis. RESULTS: In the HCC group, genotype C strains, spon-taneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains,spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The dif-ferences in genotype C strains, spontaneous YMDD mu-tations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ2=15.441, P=0.000; χ2=11.983, P=0.001; P=0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC oc-curred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P=0.000). Unconditional logistic regres-sion analysis revealed that patients infected by geno-type C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P=0.013, 95%CI: 1.540-39.264). CONCLUSION: Genotype C strains with spontaneous YMDD mutations ar     

Diagnostic value of PIVKA-Ⅱ and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein(AFP) and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) in chronic hepatitis B(CHB).METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma(HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic(AUROC) curves of PIVKA-Ⅱ, AFP and their combination were calculated and compared.RESULTS: The optimal cutoff values for PIVKA-Ⅱ and AFP were 40 m AU/m L and 10 ng/m L, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-Ⅱ and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-Ⅱ and AFP were not significantly different(0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-Ⅱ was significantly better than that of AFP in patients with cirrhosis(0.870 vs 0.812, P = 0.042). When PIVKA-Ⅱ and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-Ⅱ alone for the differentiation of HCC from nonmalignant CHB(P 0.05), especially when cirrhosis was present(P 0.05).CONCLUSION: Serum PIVKA-Ⅱ might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.     

Association between HBs Ag quantification and the risk of hepatocellular carcinoma in patients treated with tenofovir disoproxil fumarate or entecavir

This study evaluated the clinical implications of hepatitis B surface antigen quantification (qHBs Ag) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and identified the association between qHBs Ag and the risk of hepatocellular carcinoma (HCC) in these patients.Between January 2007 and December 2018, the qHBs Ag and clinical data of 183 CHB patients who initially received ETV (n = 45, 24.6%) or TDF (n = 138, 75.4%) were analyzed.The mean follow-up period of the 183 CHB patients was 45.3 months, of which 59 (32.2%) patients showed a reduction in qHBs Ag by >50% after 1 year of antiviral treatment (ETV or TDF). The HCC development (P = .179) or qHBs Ag reduction (P = .524) were similar in the ETV and TDF groups. Patients with a ≥50% decrease in qHBs Ag had a significantly lower incidence of HCC or decompensated cirrhosis complications (P = .005). Multivariate analysis showed that a >50% reduction of qHBs Ag (hazard ratio 0.085, P = .018) and the presence of cirrhosis (hazard ratio 3.32, P = .016) were independent factors predicting the development of HCC.Patients whose qHBs Ag value decreased >50% at 1 year after antiviral treatment for CHB showed a significant decrease in HCC or decompensated cirrhosis events. A reduction in qHBs Ag could be used as a predictive factor of HCC development or critical complications in CHB patients treated with TDF or ETV.     

Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients

AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma.METHODS: Thirty-nine patients (mean age 55 years, males: 32) with decompensated liver cirrhosis and refractory ascites were enrolled. All patients received a combination of tolvaptan (15 mg/d for 5-14 d) and diuretics (40-80 mg/d of furosemide and 80-160 mg/d of spironolactone). The etiology of cirrhosis included hepatitis B (69.2%), hepatitis C (7.7%) and alcohol-induced (23.1%). Changes in the urine excretion volume, abdominal circumference and edema were assessed. The serum sodium levels were also measured, and adverse events were recorded. A follow-up assessment was conducted 1 mo after treatment with tolvaptan.RESULTS: Tolvaptan increased the mean urine excretion volume (1969.2 ± 355.55 mL vs 3410.3 ± 974.1 mL, P < 0.001), and 89.7% of patients showed improvements in their ascites, 46.2% of whom showed significant improvements. The overall efficacy of tolvaptan in all patients was 89.7%; the efficacies in patients with hepatocellular carcinoma and hepatorenal syndrome were 84.2% and 77.8%, respectively. The incidence of hyponatremia was 53.8%. In patients with hyponatremia, the serum sodium levels increased after tolvaptan treatment (from 128.1 ± 4.22 mEq/L vs 133.1 ± 3.8 mEq/L, P < 0.001). Only mild drug-related adverse events, including thirst and dry mouth, were observed.CONCLUSION: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis.     

Hépatite Delta : épidémiologie,diagnostic, histoire naturelle et traitements

Hepatitis B virus is a small enveloped RNA virus, which replicates independently but requires the hepatitis B virus (HBV) to provide the envelope proteins necessary for the assembly of its own viral particles. Approximately 5% of chronic hepatitis B virus carriers are infected with HDV. HBV vaccination remains the best preventive treatment for HDV. All HBV patients should be screened for HDV (anti-HDV serology). In case of positive HDV serology, HDV replication (HDV RNA) should be investigated using a sensitive and specific technique. Hepatitis Delta is often complicated by cirrhosis and hepatocellular carcinoma (HCC). For this reason, every patient with Delta cirrhosis should be screened for HCC by abdominal ultrasound every 6 months. The historical treatment was based on PEG-IFN with many side effects. A new treatment has been approved, Bulevirtide (Hepcludex®) an HDV/HBV entry inhibitor, for any patient with chronic hepatitis Delta infection (CHD) with active replication (except in decompensated cirrhosis), at a dose of 2 mg/day by subcutaneous injection. The exact duration on-treatment is unknown, thus treatment should be continued if clinical benefit is observed.     

Hepatitis B vaccination in patients with inflammatory bowel disease

AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD).METHODS: This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination.RESULTS: About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313).CONCLUSION: The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.