-Hsu Hung

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 >106 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.

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, &agr;-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 ⩽105/mm3, 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.

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.

Updated thresholds for serum alanine aminotransferase level in a large-scale population study composed of 34 346 subjects

The sensitivity of current upper limit of normal (ULN) of serum alanine aminotransferase (ALT) levels for detecting chronic liver disease has been challenged recently.

Efficacy of non-selective β-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 β-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.

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.

Natural history and prognostic factors of primary biliary cirrhosis in Taiwan: a follow‐up study up to 18 years

Purpose: The natural history of primary biliary cirrhosis (PBC) has been little studied in Asia. We conducted a Taiwanese cohort study on the natural history of PBC and analysed the prognostic factors.

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 Loks 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 Loks 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, Loks model showed equal prediction value (area under the receiver operating characteristic curve 0.709 and 0.704, respectively). Loks 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 Loks model. Conclusions Loks model ≥0.87 can be an early marker of liver fibrosis in HBeAg-negative CHB patients. Loks model has clinical applications not only for CHC, but also for HBeAg-negative CHB.

Predictive value of aspartate aminotransferase to alanine aminotransferase ratio for hepatic fibrosis and clinical adverse outcomes in patients with primary biliary cirrhosis.

Background The aspartate aminotransferase to alanine aminotransferase ratio (AAR) was seldom applied for fibrosis assessment in primary biliary cirrhosis (PBC) patients. Goals To validate the AAR for evaluating hepatic fibrosis, disease severity, and prognosis in patients with PBC. Study Ninety-two consecutive PBC patients were retrospectively evaluated to validate the AAR for assessing the severity of liver function, the degrees of hepatic fibrosis, and predicting outcomes. Results AAR showed modest correlations to Mayo score, model for end-stage liver disease score, and Child-Pugh score (r2=0.156, P<0.001; r2=0.084, P=0.005; r2=0.142, P<0.001, respectively) in evaluating the severity of liver function. For 46 patients who underwent liver biopsy, 35 were in early stage fibrosis and the other 11 were in advanced fibrosis. AAR was significantly higher in patients with advanced fibrosis than those with early fibrosis (mean±standard deviation; 1.40±0.44 vs. 0.98±0.65, P=0.001). The AAR yielded the highest area under the receiver operating curve of 0.847 than Mayo score, model for end-stage liver disease score, and Child-Pugh score in predicting advanced fibrosis. During a median follow-up of 44.5 months, 24 patients expired and 68 patients were alive. Patients with an AAR of 1 or less had significantly better prognosis than their counterparts (P=0.043). Conclusions AAR is a simple and reliable marker to assess liver function and hepatic fibrosis as well as to predict outcomes in PBC patients.

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/mm3. 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.