DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells.

BACKGROUND: Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated. METHODS: The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells. RESULTS: Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown-induced cell migration and invasion of gastric cancer cells. CONCLUSIONS: Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.

Activated Integrated Stress Response Induced by Salubrinal Promotes Cisplatin Resistance in Human Gastric Cancer Cells via Enhanced xCT Expression and Glutathione Biosynthesis.

The integrated stress response (ISR) pathway is essential for adaption of various stresses and is related to mitochondrion-to-nucleus communication. Mitochondrial dysfunction-induced reactive oxygen species (ROS) was demonstrated to activate general control nonderepressible 2 (GCN2)⁻eukaryotic translation initiation factor 2α (eIF2α)⁻activating transcription factor-4 (ATF4) pathway-mediated cisplatin resistance of human gastric cancer cells. However, whether or how ISR activation per se could enhance chemoresistance remains unclear. In this study, we used eIF2α phosphatase inhibitor salubrinal to activate the ISR pathway and found that salubrinal reduced susceptibility to cisplatin. Moreover, salubrinal up-regulated ATF4-modulated gene expression, and knockdown of ATF4 attenuated salubrinal-induced drug resistance, suggesting that ATF4-modulated genes contribute to the process. The ATF4-modulated genes, xCT (a cystine/glutamate anti-transporter), tribbles-related protein 3 (TRB3), heme oxygenase 1 (HO-1), and phosphoenolpyruvate carboxykinase 2 (PCK2), were associated with a poorer prognosis for gastric cancer patients. By silencing individual genes, we found that xCT, but not TRB3, HO-1, or PCK2, is responsible for salubrinal-induced cisplatin resistance. In addition, salubrinal increased intracellular glutathione (GSH) and decreased cisplatin-induced lipid peroxidation. Salubrinal-induced cisplatin resistance was attenuated by inhibition of xCT and GSH biosynthesis. In conclusion, our results suggest that ISR activation by salubrinal up-regulates ATF4-modulated gene expression, increases GSH synthesis, and decreases cisplatin-induced oxidative damage, which contribute to cisplatin resistance in gastric cancer cells.

Impact of Steatosis on Prognosis of Patients with Early-Stage Hepatocellular Carcinoma After Hepatic Resection.

BACKGROUND: It is still unclear whether steatosis determines the prognosis of patients with hepatocellular carcinoma (HCC). This study aimed to compare the clinical manifestations and outcomes between early-stage HCC patients with and without steatosis after hepatic resection. METHODS: We enrolled 188 patients who underwent hepatic resection for HCC within the Milan criteria. After surgery, fibrosis, steatosis, lobular inflammation, portal inflammation, and ballooning in the background liver were assessed. Factors related to prognosis after surgery were analyzed by multivariate analysis. RESULTS: Seventy-four patients (39.4 %) had steatosis. Patients with steatosis had larger body mass index, higher fasting glucose levels, and higher rates of ballooning than those without steatosis. After a median follow-up period of 69.8 months, 73 patients died. The cumulative survival rates at 5 years were 57.8 and 75.6 % for patients with and without steatosis, respectively (p = 0.008). Multivariate analysis disclosed that an age of > 65 years [hazard ratio (HR) 1.996, p = 0.009], platelet count of <10(5)/mm(3) (HR 2.198, p = 0.005), indocyanine green retention rate at 15 min of >10 % (HR 2.037, p = 0.022), multinodularity (HR 2.389, p = 0.004), and steatosis (HR 1.773, p = 0.023) were independent risk factors associated with poor overall survival after resection. The impact of steatosis on postsurgical prognosis was more apparent in patients without cirrhosis. CONCLUSIONS: The presence of steatosis in the background liver was associated with a poor prognosis in early-stage HCC patients after hepatic resection, especially for noncirrhotic patients.

A comparison of clinical manifestations and prognoses between patients with hepatocellular carcinoma and Child-Pugh scores of 5 or 6.

The objective of this work is to compare the outcomes between the Child-Pugh score 5 (A5 group) and Child-Pugh score 6 (A6 group) in patients with hepatocellular carcinoma (HCC). Whether HCC patients with A5 and A6 groups have different prognoses is still obscure. We enrolled 2462 consecutive treatment-naive HCC patients from 2007 to 2012. Among them, 1486 patients had Child-Pugh grade A, including 1016 in the A5 group and 470 in the A6 group. Factors in the prognoses were analyzed by multivariate analysis. Compared with those in the A6 group, patients in the A5 group were younger, had higher proportions of tumors within the Milan criteria, and more of them underwent curative therapies. The cumulative survival rates at 5 years were 51.3% and 37.1% for patients in the A5 and A6 groups, respectively (P < 0.001). Multivariate analysis showed that the independent risk factors associated with poor overall survival were nonhepatitis C virus carrier, serum albumin ≤ 4 g/dL, aspartate aminotransferase > 45 U/L, α-fetoprotein > 20 ng/mL, multinodularity, tumor size > 3 cm, vascular invasion, and noncurative therapies, but not the Child-Pugh numeric score. The Child-Pugh numeric score had a significant prognostic effect only in patients who had tumors beyond the Milan criteria and received noncurative therapies. HCC patients with A5 group had a better overall survival rate than those with A6 group due to the early tumor stage and higher rate of receiving curative treatments. Tumor factors and treatment modalities were more important than the Child-Pugh numeric score.

Differential roles of serum hepatitis B virus DNA and hepatitis B surface antigen level in predicting virological breakthrough in patients receiving lamivudine therapy.

BACKGROUND AND AIM: The role of serum hepatitis B surface antigen (HBsAg) level in determining virological breakthrough (VB) for patients with hepatitis B virus (HBV) infection receiving lamivudine remains unclear. The study aimed to evaluate the impact of serum HBsAg levels on VB among patients receiving lamivudine therapy, especially in a setting of low HBV viral load. METHODS: Two hundred sixty-eight consecutive treatment-naïve patients who underwent lamivudine therapy for chronic hepatitis B were enrolled. Factors in terms of VB were analyzed by multivariate analysis. RESULTS: After a median treatment duration of 67.1 weeks, 102 patients had VB. Multivariate analysis showed that positive hepatitis B e antigen (HBeAg) (hazard ratio 2.165, P = 0.026) and HBV DNA levels ≥ 2000 IU/mL after 6 months of lamivudine therapy (hazard ratio 5.236, P = 0.001) were independent risk factors predicting VB. The cumulative VB rates stratified by HBeAg-positive and -negative at 3 years were 44.7% and 26.3%, respectively. At 3 years, the cumulative VB rates stratified by the HBV DNA < 2000 and ≥ 2000 IU/mL after 6 months of therapy were 25.5% and 79.4%, respectively. For HBeAg-positive patients with serum HBV DNA < 2000 IU/mL after 6 months of therapy, baseline HBsAg levels ≥ 20,000 IU/mL was the only risk factor associated with VB. CONCLUSIONS: For chronic hepatitis B patients treated with lamivudine, serum HBV DNA level > 2000 IU/mL after 6 months of therapy could predict subsequent VB. In patients with lower on-treatment viral load, baseline serum HBsAg level is associated with the emergence of VB, especially for those with serum positive HBeAg.

The Influence of Hepatitis B Viral Load and Pre-S Deletion Mutations on Post-Operative Recurrence of Hepatocellular Carcinoma and the Tertiary Preventive Effects by Anti-Viral Therapy.

BACKGROUND: Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial. AIMS: To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors. METHODS: A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels, mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence. RESULTS: After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >10(6) copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence. CONCLUSIONS: Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.

Comparison of prognosis by viral etiology in patients with hepatocellular carcinoma after radiofrequency ablation.

UNLABELLED: BACKGROUND; Radiofrequency ablation (RFA) has been performed as a first line curative treatment modality for patients with hepatocellular carcinoma (HCC) within the Milan criteria currently. However, prognosis of hepatitis B- and hepatitis C-related HCC after RFA remains debatable. This study aimed to assess the impact of viral etiology on the prognosis of HCC patients undergoing RFA. MATERIAL AND METHODS: One hundred and ninety-two patients with positive serum HBV surface antigen (HBsAg) and negative serum antibody against HCV (anti-HCV) were enrolled as the B-HCC group and 165 patients with negative serum HBsAg and positive anti-HCV as the C-HCC group. Post-RFA prognoses were compared between the two groups using multivariate and propensity score matching analyses. RESULTS: The B-HCC group had higher male-to-female ratio and better liver functional reserve than the C-HCC group. After a median follow-up of 23.0 ± 22.7 months, 55 patients died and 189 patients had tumor recurrence after RFA. The cumulative five-year survival rate was 75.9% and 69.5% in the B-HCC and C-HCC groups, respectively (p = 0.312), while the five-year recurrence-free survival rate was 19.0% and 26.6%, respectively (p = 0.490). After propensity-score matching, the B-HCC group still had comparable overall survival rate (p = 0.679) and recurrence-free survival rate (p = 0.689) to the C-HCC group. For 132 patients with Barcelona-Clinic Liver Cancer stage 0, the five-year overall survival and recurrence-free survival rates were also comparable between the two groups (p = 0.559 and p = 0.872, respectively). CONCLUSION: Viral etiology is not essential for determining outcome in HCC patients undergoing RFA.

Milan criteria, multi-nodularity, and microvascular invasion predict the recurrence patterns of hepatocellular carcinoma after resection.

AIMS: This study aims to evaluate the risk factors for tumor recurrence beyond the Milan criteria (MC) for patients with hepatocellular carcinoma (HCC) after surgical resection (SR) in which salvage liver transplantation is relatively contraindicated. METHODS: A total of 447 patients who underwent SR for HCC were enrolled consecutively. Among them, 248 and 199 patients were within the Milan criteria and beyond the Milan criteria (BMC group), respectively. Overall survival, recurrence, and disease-free survival were analyzed by multivariate analysis. RESULTS: After a median follow-up of 34.4 months, 130 patients died. Microvascular invasion, higher Edmondson stage of tumor cell differentiation, BMC group, and no anti-viral therapy were associated with poor overall survival. Multi-nodularity, higher Edmondson stage, BMC group, and no anti-viral therapy were independent risk factors for tumor recurrence, while BMC group and no anti-viral therapy were independent risk factors for disease-free survival. The Milan criteria, multi-nodularity, and microvascular invasion were used to stratify the patients into low-, medium-, and high-risk groups for tumor recurrence outside the MC and showed statistical significance (low vs. medium, p = 0.011; low vs. high, p < 0.001; medium vs. high, p = 0.009). CONCLUSIONS: The combination of the MC, multi-nodularity, and microvascular invasion predict the post-operative recurrence of HCC and may provide a roadmap for further treatment.

Prognostic significance of computed tomography scan-derived splenic volume in hepatocellular carcinoma treated with radiofrequency ablation.

GOALS: To evaluate the clinical implication of splenic volume measured by computed tomography (CT) scan in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). BACKGROUND: Splenomegaly is an important sign of portal hypertension and poor liver function in patients with advanced liver disease. But whether it could predict the prognosis of patients with HCC is still obscure. STUDY: We enrolled 161 treatment-naive HCC patients. Splenomegaly was defined as splenic volume >300 mL by CT scan and its impact on prognosis was analyzed. Moreover, noninvasive serum markers were validated to predict splenomegaly. RESULTS: A total of 78 patients were with splenomegaly, while the remaining 83 patients had normal splenic volume at the time of receiving RFA. After a median follow-up of 38.1±20.8 months, 41 patients died. The cumulative 5-year survival rates were 54.8% and 77.8% in patients with splenomegaly and in those with normal splenic volume, respectively (P=0.003). By multivariate analysis, age 65 years and older, serum albumin levels ≤3.5 g/dL, and splenic volume >300 mL were independent risk factors associated with poor overall survival after RFA. For predicting splenomegaly by noninvasive serum markers, platelet count yielded the highest area under the curve from corresponding receiver operating curves with a level of 0.868 at a cut-off value of 11,7000/mm(3). CONCLUSIONS: HCC patients with splenomegaly measured by CT scan have relatively poorer liver functional reserve than those with normal splenic volume. Splenomegaly is an independent risk factor predicting overall survival for patients with small HCC undergoing RFA.

Citrus reticulata peel improves patient tolerance of low-volume polyethylene glycol for colonoscopy preparation.

BACKGROUND: Adequate adjuncts help to reduce the volume of polyethylene glycol-electrolyte lavage solution (PEG-ELS) needed, to ameliorate patient discomfort, and to improve colonic visibility during colonoscopy. This study aimed to assess the effect of Citrus reticulata peel (CRP) as an adjunct to low-volume PEG for colonic preparation. METHODS: A total of 1092 health examination examinees received colonoscopy during the study period. After excluding those who refused to participate and those who did not meet our criteria, 212 examinees were enrolled into this study. They were divided into the PEG group and the PEG + CRP group according to their date of examination. All examinees received 2 L of PEG-ELS one day before colonoscopy. The PEG + CRP group also received additional CRP in the form of a "buccal tablet" between drinks. Tolerance and adverse events were assessed by questionnaire, while the quality of bowel preparation for colonoscopy was scored by an endoscopist. RESULTS: There were 107 examinees in the PEG group and 105 examinees in the PEG + CRP group. The demographic characteristics of the examinees were comparable between these two groups. Examinees in the PEG + CRP group had a trend of better colonic visibility than those in the PEG group (p = 0.056). Moreover, examinees in the PEG + CRP group had higher rate of acceptable taste (p = 0.015) and lower rate of difficulty swallowing (p = 0.001). The incidences of adverse events including vomiting (p = 0.045), bloating (p = 0.035), and difficulty sleeping (p < 0.001) were also significantly lower in the PEG + CRP group. CONCLUSION: Compared with conventional colonic preparation, the application of CRP as an adjunct could improve examinees' tolerance, decrease the incidence of adverse events, and maintain the quality of colonic cleansing.

Efficacy of non-selective ß-blockers as adjunct to endoscopic prophylactic treatment for gastric variceal bleeding: a randomized controlled trial.

BACKGROUND & AIMS: Gastric variceal obturation (GVO) therapy is the current treatment of choice for gastric variceal bleeding (GVB). However, the efficacy of non-selective ß-blockers (NSBB) in the secondary prevention of GVB is still debatable. This study aimed at evaluating the efficacy of additional NSBB to repeated GVO in the secondary prevention of GVB. METHODS: From April 2007 to March 2011, 95 patients with GVB after primary hemostasis using GVO were enrolled. Repeated GVO were performed until GV eradication. Forty-eight and 47 patients were randomized into the GVO alone group (Group A) and the GVO+NSBB group (Group B), respectively. Primary outcomes in terms of re-bleeding and overall survival were analyzed by multivariate analysis. RESULTS: After a mean follow-up of 18.10 months in group A, 26 patients bled and 20 died. In group B, 22 patients bled and 22 died after a mean follow-up of 20.29 months. The overall re-bleeding and survival rates analyzed by the Kaplan-Meier method were not different between the two groups (p=0.336 and 0.936, respectively). The model of end-stage liver disease (MELD) score and main portal vein thrombosis (MPT) were independent determinants of re-bleeding while MPT and re-bleeding were independent factors of mortality by time-dependent Cox-regression model. Asthenia was the most common adverse event and was higher in group B (p<0.001). CONCLUSIONS: Adding NSBB therapy to repeated GVO provides no benefit for the secondary prevention of bleeding and mortality in patients with GVB.

Younger hepatocellular carcinoma patients have better prognosis after percutaneous radiofrequency ablation therapy.

GOALS: To evaluate the impact of age on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). BACKGROUND: Whether age plays an important role in the outcomes of HCC after RFA remains controversial. STUDY: Two hundred fifty-eight consecutive treatment naive HCC patients who underwent RFA were enrolled. Patients aged ≤ 65 years (n = 100) were defined as the younger group and those aged > 65 years (n = 158) were the elderly group. Their clinicopathologic features and prognosis were compared. RESULTS: Younger patients had a higher male-to-female ratio, higher prevalence of hepatitis B virus, and smaller tumor size than elder patients. After median follow-up of 28.5 ± 18.7 months, 45 patients died. The cumulative 5-year survival rates were 81.3% and 65.4% in younger and elder HCC patients, respectively (P = 0.008). Multivariate analysis disclosed that age > 65 years, serum albumin level ≤ 3.7 g/dL, prothrombin time international normalized ratio > 1.1, α-fetoprotein (AFP) > 20 ng/mL, and no antiviral therapy after RFA were independent risk factors associated with poor overall survival. Besides, there were 163 patients with tumor recurrence after RFA. Multivariate analysis showed that age > 65 years, platelet count ≤ 10/mm, AFP > 20 ng/mL, multinodularity, and tumor size > 2 cm were the independent risk factors predicting recurrence. CONCLUSIONS: Both liver functional reserve (serum albumin level, prothrombin time international normalized ratio, platelet count, and antiviral therapy) and tumor factors (tumor size, number, and AFP level) were crucial in determining post-RFA prognosis in HCC patients. Moreover, younger HCC patients have better overall survival and lower recurrence rate after RFA compared with elder patients.

The effect of age on the long-term prognosis of patients with hepatocellular carcinoma after resection surgery: a propensity score matching analysis.

OBJECTIVE: The effect of age on the clinicopathologic manifestations of hepatocellular carcinoma (HCC) and on the survival rate in patients with HCC after resection surgery remains controversial. We aim to compare the clinicopathological features and prognoses between younger and older patients with HCC undergoing resection. DESIGN: Retrospective review. SETTING: A tertiary medical center. PATIENTS: We enrolled 1074 consecutive patients with HCC who were undergoing a partial hepatectomy. Patients who were 55 years of age or younger were defined as the younger group (n = 374), and patients who were older than 55 years of age were defined as the older group (n = 700). MAIN OUTCOME MEASURES: The postoperative prognoses of the younger and older groups using multivariate analysis and propensity score matching analysis. RESULTS: The younger patients had better liver functional reserve but more aggressive tumor factors than did the older patients. After a median follow-up of 41.0 months, 543 patients died. The cumulative 10-year survival rates were 41.3% in younger patients and 28.8% in the older patients (P = .02). However, using both multivariate analysis and propensity score matching analysis, we failed to demonstrate that age was an independent risk factor associated with overall survival. Besides, there were 643 patients with tumor recurrence after surgery. Using both multivariate analysis and propensity score matching analysis, we found that the incidence of tumor recurrence in younger patients was comparable to that in the older patients. CONCLUSIONS: Age is not a risk factor to determine the prognosis of patients with HCC who underwent resection. Older patients with HCC who have good liver functional reserve are encouraged to receive resection surgery.

Risk factors for long-term prognosis in hepatocellular carcinoma after radiofrequency ablation therapy: the clinical implication of aspartate aminotransferase-platelet ratio index.

OBJECTIVE: Percutaneous radiofrequency ablation (RFA) is one of the first-line curative therapies for hepatocellular carcinoma (HCC), but factors affecting the prognosis remain unclear. This study aimed to evaluate the prognostic factors associated with the prognosis in patients with HCC undergoing RFA. METHODS: The study enrolled 190 treatment-naïve patients with HCC (<5 cm). Factors were analyzed in terms of overall survival and recurrence. RESULTS: After a median follow-up of 30.7±17.5 months, 41 patients died and 149 patients were alive. Of the 112 patients who developed tumor recurrence, 61 had local recurrence and 51 had distant intrahepatic recurrence. The 5-year overall survival rate and recurrence rate were 65.5 and 73.6%, respectively. Factors associated with overall mortality were, age older than 65 years (P=0.019), aspartate aminotransferase-to-platelet ratio index (APRI) of more than 1 (P=0.015), prothrombin time international normalized ratio of more than 1.1 (P=0.013), multinodularity (P=0.024), and Child-Pugh grade B (P=0.036). Besides, multivariate analysis disclosed that APRI of more than 1 (P=0.002), multinodularity (P<0.001), and tumor size of more than 2 cm (P=0.002) predicted higher incidence of developing recurrence after RFA. Factors determining local recurrence were, age older than 65 years (P=0.030), APRI of more than 1 (P=0.003), multinodularity (P=0.019), and tumor size of more than 2 cm (P=0.015), whereas only APRI of more than 1 (P=0.013) and multinodularity (P<0.001) were independent risk factors predictive of intrahepatic distant metastasis. CONCLUSION: Both multinodularity and APRI are associated with overall survival and recurrence for patients with HCC after RFA therapy. Consequently, APRI seems to serve as a feasible marker for predicting the prognosis of patients with small HCC undergoing RFA.

Survival rates are comparable after radiofrequency ablation or surgery in patients with small hepatocellular carcinomas.

BACKGROUND & AIMS: Differences in efficacy of radiofrequency ablation (RFA) and surgical resection (SR) are not clear for patients with hepatocellular carcinoma (HCC). METHODS: From 2002 to 2007, 419 patients with HCCs ≤5 cm were enrolled consecutively in the study. Among these patients, 190 and 229 patients received RFA and SR, respectively, as their first treatment. Factors were analyzed in terms of overall survival and recurrence by multivariate analysis and propensity score matching analysis. RESULTS: The SR group had younger age, a higher male-to-female ratio, higher prevalence of hepatitis B virus, lower prevalence of hepatitis C virus, better liver function reserve, and larger tumor size than the RFA group. The cumulative 5-year overall survival rates were 79.3% in the SR group and 67.4% in the RFA group. During the follow-up period, tumors recurred in 244 patients in a median time of 14.5 ± 15.7 months. Before propensity-score matching, the RFA group had shorter overall survival time (P = .009) and higher tumor recurrence rate (P < .001) than the SR group. After matching, RFA was comparable to SR in overall survival time (P = .519), but the RFA group still had a greater incidence of tumor recurrence (P < .001). In patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 HCC, RFA was as effective as SR for overall survival time and recurrence. CONCLUSIONS: Patients with small HCCs have a higher rate of tumor recurrence following RFA than surgery, but overall survival rates are comparable between therapies. RFA is as effective as surgery in patients with BCLC stage 0 HCC.

Comparative analysis of noninvasive models to predict early liver fibrosis in hepatitis B e Antigen-negative Chronic Hepatitis B.

BACKGROUND: Portal or bridging fibrosis is an indication for antiviral treatment in patients with chronic hepatitis B (CHB). An early marker predictive of liver fibrosis in hepatitis B e antigen (HBeAg)-negative CHB patients can alert clinicians to plan for treatment before disease progression. GOALS: To predict early and significant liver fibrosis (Ishak score ≥2) in HBeAg-negative CHB by validating several noninvasive markers derived from CHC. STUDY: One hundred seventy-seven consecutive treatment-naive HBeAg-negative CHB patients who underwent liver biopsy were divided into a training group (n=121) and a validation group (n=56). Factors associated with liver fibrosis were analyzed. RESULTS: Multivariate analysis identified Lok's model ≥0.87, cirrhosis discriminant score greater than 4, and positive alanine aminotransferase ratio platelet score as independent factors associated with liver fibrosis in the training group. The area under the receiver operating characteristic curve revealed that Lok's model was better than cirrhosis discriminant score in predicting liver fibrosis in both the training and the validation groups. In patients with hepatitis B virus DNA greater than 2000 IU/mL or greater than 20,000 IU/mL, Lok's model showed equal prediction value (area under the receiver operating characteristic curve 0.709 and 0.704, respectively). Lok's model could also discriminate high and low hepatitis B virus DNA loads. In general, liver biopsy can be avoided in one-third (58 of 177) of patients by Lok's model. CONCLUSIONS: Lok's model ≥0.87 can be an early marker of liver fibrosis in HBeAg-negative CHB patients. Lok's model has clinical applications not only for CHC, but also for HBeAg-negative CHB.

Immunoglobulin G antibody against Helicobacter pylori is an accurate test for atrophic gastritis.

BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) is the most commonly used serologic test for Helicobacter pylori. This study aimed to investigate the effects of age and atrophic gastritis on the diagnostic accuracy of an immunoglobulin G (IgG) antibody test against H. pylori in adults. METHODS: One hundred and seventy dyspeptic patients (age range, 20-70 years) were evaluated. H. pylori infection was diagnosed when culture or both urease and histological tests were positive. Serum pepsinogen-I (P-I) and pepsinogen-II (P-II) levels were measured. Atrophic gastritis was defined when P-I < or = 70 microg/L and P-I/P-II < or = 3. A quantitative ELISA test (HEL-pTEST II) was used for IgG antibodies against H. pylori. RESULTS: The H. pylori prevalence rate was 62.1%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ELISA were 93.5%, 94.4%, 95.6%, 91.9%, and 93.9% in patients aged < 45 years, and 100%, 81.3%, 94.3%, 100%, and 95.6% in patients aged > or = 45 years, respectively. Twenty-six patients had atrophic gastritis. There was 100% sensitivity and 86.7% specificity in atrophic gastritis and 96.5% sensitivity and 91.9% specificity in non-atrophic gastritis. CONCLUSION: The quantitative ELISA test is a good noninvasive test even in older age groups and is a suitable test in patients with atrophic gastritis due to its excellent sensitivity.

Correlation between clinical indication for treatment and liver histology in HBeAg-negative chronic hepatitis B: a novel role of alpha-fetoprotein.

BACKGROUND: It is unclear whether clinical indication for antiviral treatment is in agreement with histological indication in HBeAg-negative chronic hepatitis B (CHB). This study aimed to clarify this relationship and identify factors associated with liver histology. PATIENTS AND METHODS: We investigated 152 consecutive, treatment-naïve, HBeAg-negative CHB patients who had undergone liver biopsies at a tertiary medical centre in Taiwan. Clinical indications for treatment included a serum alanine aminotransferase level more than twice the upper limit of normal and an hepatitis B virus DNA level > 2000 IU/ml. Factors associated with the histological indication (Ishak's grade > or = 7 and/or stage > or = 2) were analysed. RESULTS: The association between the clinical and the histological indications was significant (P=0.011). However, the agreement was poor (kappa value=0.197). In patients satisfying the clinical indication, age > 52 years [odds ratio (OR)=2.669, P=0.042], serum alpha-fetoprotein (AFP) level > 7 ng/ml (OR=7.070, P<0.001) and platelet count < 130 x 10(9)/L (OR=11.720, P=0.025) were identified to be independent factors associated with histological indication. In patients who did not satisfy the clinical indication, multivariate analysis revealed that only an AFP level > 7 ng/ml (OR=10.345, P=0.021) was independently associated with histological indication. Combining the clinical indication and/or AFP level > 7 ng/ml to predict liver histology, the sensitivity and the negative predictive value could improve from 86 to 94.4% and 66.7 to 81% respectively. CONCLUSION: AFP level is associated with liver histology in HBeAg-negative CHB. Serum AFP level can serve as a surrogate indicator to identify patients who need antiviral treatment.

Core antigen expression is associated with hepatic necroinflammation in e antigen-negative chronic hepatitis B patients with low DNA loads.

Intrahepatic hepatitis B virus (HBV) core antigen (HBcAg) is a hallmark of viral replication in hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B (CHB). The aim of this study was to evaluate the role of HBcAg in HBeAg-negative CHB. One hundred six HBeAg-negative CHB patients who underwent ultrasonographically guided liver biopsy were reviewed for their HBV DNA load and clinical and histological data. Factors associated with the expression of intrahepatic HBcAg were analyzed. Among the patients, 35 (33%) were positive for HBcAg by immunohistostaining. In patients whose HBV DNA loads were higher than 10(7) copies (cp)/ml, nearly one-half (52%) had detectable HBcAg. Compared with HBcAg-negative patients, HBcAg-positive patients had higher serum alanine transaminase (ALT) and HBV DNA levels and more-severe hepatic necroinflammation. High serum ALT level (>160 U/liter) and HBV viral load were the determinants of HBcAg expression in multivariate analysis. Large amounts of HBcAg expression were frequently detected in patients with high DNA loads, and the patterns of HBcAg distribution were not related to histological activity or HBV DNA levels. In patients with lower HBV DNA loads, the expression of HBcAg was the key factor associated with active hepatic necroinflammation (hazard ratio = 11.25; 95% confidence interval [CI], 1.42 to 89.26; P = 0.022). In conclusion, the expression of HBcAg is not frequent in HBeAg-negative CHB. The expression of intrahepatic HBcAg indicates active hepatic necroinflammation, even in patients with low HBV DNA load. Both HBV viral load and HBcAg expression have implications in the pathogenesis of HBeAg-negative CHB.