Pui-Ching Lee

Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma ☆

BACKGROUND/AIMS Hepatitis B virus (HBV) levels correlate with the development of hepatocellular carcinoma (HCC), but the role of viral load in HCC recurrence after tumor resection remains unclear. Herein we aimed to investigate the role of viral load in HCC recurrence following tumor resection. METHODS From 1990 to 2002, 193 HBV-related HCC patients who underwent tumor resection in Taipei Veterans General Hospital were enrolled. Serum HBV DNA level and mutations were analyzed for association with early and late recurrence, together with other clinical variables. RESULTS During a follow-up of 58.2+/-44 months, 134 patients had HCC recurrence. Multivariate analysis showed that multinodularity (Hazard ratio [HR], 95% confidence interval [CI]; 2.232, 1.021-4.878), macroscopic venous invasion (4.693, 1.645-13.391), AFP >20 ng/ml (3.891, 1.795-8.475), and cut margin <or= 1cm (3.333, 1.487-7.470) were correlated with early recurrence (within two years of operation) of HCC. In addition, multivariate analysis determined that Ishak hepatic inflammatory activity >6 (4.658, 1.970-11.017), multinodularity (3.266, 1.417-7.526), ICG-15 >10% (2.487, 1.095-5.650) and HBV DNA level >10(6) copies/ml (2.548, 1.040-6.240) were significantly associated with late recurrence (>two years after resection). Patients with high viral loads tended to have higher Ishak inflammatory (7.00+/-3.07 vs. 5.33+/-2.96, p=0.001) and fibrosis scores (4.17+/-2.01 vs. 3.20+/-2.41, p=0.007) than those with lower loads. CONCLUSIONS Tumor factors were associated with early HCC recurrence while high viral loads and hepatic inflammatory activity were associated with late recurrence. Pre- and post-operative antiviral and anti-inflammatory therapies may be crucial in reducing late recurrence.

A new prognostic model for hepatocellular carcinoma based on total tumor volume: The Taipei Integrated Scoring system

BACKGROUND & AIMS The currently used staging systems for hepatocellular carcinoma (HCC) are not satisfactory. The optimal prognostic model for HCC is still under intense debate. This study aimed to propose a new staging system for HCC based on total tumor volume (TTV) and to compare it with the currently used systems. METHODS A total of 2030 HCC patients undergoing different treatment strategies were retrospectively analyzed. TTV was defined as the sum of the volume of each tumor [(4/3)x3.14x(radius of tumor in cm)(3)]. The discriminatory ability of the TTV-based staging system and the four current systems, including the Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging system, and Tokyo system, was examined by comparing the Akaike information criterion (AIC) using the Cox proportional hazards model. RESULTS A higher TTV correlated well with the decreased survival in HCC patients (p<0.001). Among the 12 TTV-based staging systems, the TTV-Child-Turcotte-Pugh (CTP)-alpha-fetoprotein (AFP) combination provided the lowest AIC value. The TTV-CTP-AFP model consistently showed a better prognostic ability in comparison to the current four staging systems. In 936 HCC patients receiving curative treatment, the TTV-CTP-AFP model provided the second best predictive accuracy following the CLIP score. Alternatively, in 1094 patients undergoing non-curative treatment, the TTV-CTP-AFP model exhibited the smallest AIC value. CONCLUSIONS TTV may be a feasible tumoral prognostic predictor for HCC. In this single-hospital study that included patients with early to advanced cancer stages, the TTV-CTP-AFP model provides the best prognostic ability among 12 TTV-based and currently used staging systems.

Selecting an optimal staging system for hepatocellular carcinoma: comparison of 5 currently used prognostic models.

Selecting an appropriate staging system is crucial to predict the outcome of patients with hepatocellular carcinoma (HCC). The optimal prognostic model for HCC is under intense debate. This study investigated the prognostic ability of the 5 currently used staging systems, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Japan Integrated Scoring (JIS) system, tumor‐node‐metastasis (TNM), and Tokyo score, for HCC.

Model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor and its correlation with portal pressure in patients with liver cirrhosis

Background: The models for end‐stage liver disease (MELD) and serum sodium (SNa) are important prognostic markers in cirrhosis. A novel index, MELD to SNa ratio (MESO), was developed to amplify the opposing effect of MELD and SNa on outcome prediction.

Comparison of percutaneous acetic acid injection and percutaneous ethanol injection for hepatocellular carcinoma in cirrhotic patients: a prospective study.

Background: Ultrasound-guided percutaneous ethanol injection (PEI) and percutaneous acetic acid injection (PAI) are effective in the treatment of hepatocellular carcinoma (HCC). We conducted a prospective study to compare the therapeutic efficacy of both these methods. Methods: Sixty-three patients were treated by PAI using 50% acetic acid and 62 by PEI using pure ethanol. There were no significant baseline differences in age, sex, Child-Pugh class, tumour size and number, or other clinico-biochemical parameters between the two groups. Results: During a follow-up period of 24 ± 9 (range 6-38) months, 19 (30%) of the PAI group and 21 (34%) of the PEI group died ( P r = r 0.704). The 1- and 3-year survival rates were 84% and 51% for the PAI group and 81% and 46% for the PEI group ( P r = r 0.651). The corresponding tumour recurrence rates were 51% and 74% for the PAI group, and 54% and 64% for the PEI group ( P r = r 0.787). The treatment sessions were 3.9 ± 1.6 and 6.2 ± 2.3 for the PAI and PEI groups, respectively, in each treatment cycle ( P r = r 0.008). A multivariate analysis using the Cox regression model revealed that ascites (relative risk (RR) 3.1, 95% confidence interval (CI) 1.5-6.3, P r = r 0.002), large (>3 r cm) or multinodular HCCs (RR 2.4, 95% CI 1.1-5.4, P r = r 0.04), and development of tumour recurrence (RR 7.0, 95% CI 3.1-16.0, P r < r 0.001) were independent, poor prognostic factors in both groups. Conclusions: PAI and PEI are equally effective in the treatment of HCC. PAI has the advantage of fewer treatment sessions in each treatment course. Careful pretreatment patient selection may improve survival.BACKGROUND Ultrasound-guided percutaneous ethanol injection (PEI) and percutaneous acetic acid injection (PAI) are effective in the treatment of hepatocellular carcinoma (HCC). We conducted a prospective study to compare the therapeutic efficacy of both these methods. METHODS Sixty-three patients were treated by PAI using 50% acetic acid and 62 by PEI using pure ethanol. There were no significant baseline differences in age, sex, Child-Pugh class, tumour size and number, or other clinico-biochemical parameters between the two groups. RESULTS During a follow-up period of 24 +/- 9 (range 6-38) months, 19 (30%) of the PAI group and 21 (34%) of the PEI group died (P = 0.704). The 1- and 3-year survival rates were 84% and 51% for the PAI group and 81% and 46% for the PEI group (P = 0.651). The corresponding tumour recurrence rates were 51% and 74% for the PAI group, and 54% and 64% for the PEI group (P = 0.787). The treatment sessions were 3.9 +/- 1.6 and 6.2 +/- 2.3 for the PAI and PEI groups, respectively, in each treatment cycle (P = 0.008). A multivariate analysis using the Cox regression model revealed that ascites (relative risk (RR) 3.1, 95% confidence interval (CI) 1.5-6.3, P = 0.002), large (>3 cm) or multinodular HCCs (RR 2.4, 95% CI 1.1-5.4, P = 0.04), and development of tumour recurrence (RR 7.0, 95% CI 3.1-16.0, P < 0.001) were independent, poor prognostic factors in both groups. CONCLUSIONS PAI and PEI are equally effective in the treatment of HCC. PAI has the advantage of fewer treatment sessions in each treatment course. Careful pretreatment patient selection may improve survival.

Proposal of a modified Child-Turcotte-Pugh scoring system and comparison with the model for end-stage liver disease for outcome prediction in patients with cirrhosis.

The model for end‐stage liver disease (MELD) has a better predictive accuracy for survival than the Child‐Turcotte‐Pugh (CTP) system and has been the primary reference for organ allocation in liver transplantation. The CTP system, with a score range of 5–15, has a ceiling effect that may compromise its predictive power. In this study, we proposed a refined CTP scoring method and investigated its predictive ability. An additional point was given to patients with serum albumin < 2.3 g/dL, bilirubin > 8 mg/dL or prothrombin time prolongation > 11 seconds. The modified CTP system, containing class D, was compared to the MELD and original CTP system in 436 patients. There was a significant correlation between the MELD and modified CTP score (ρ=0.59, P< 0.001). Using mortality as the endpoint, the area under receiver operating characteristic curve for modified CTP system was 0.895 compared with 0.872 for MELD (P=0.450) and 0.809 for original CTP system (P < 0.001) at 3 months; the area was 0.890, 0.837 and 0.756, respectively (P=0.051 and < 0.001, respectively) at 6 months. The risk ratio per unit increase for the modified CTP score was 2.7 and 3.08 at 3 and 6 months respectively (P < 0.001). In conclusion, the modified CTP system can be proposed as an alternative prognostic model for cirrhotic patients. By extending the score range according to the influence of the laboratory‐derived variables, the modified CTP system has a better performance than the original system and is as efficient as the MELD for outcome prediction. Liver Transpl 12:65–71, 2006.

Incidence and risk factors for acute renal failure in patients with hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective study

Abstract: Background: Transarterial chemoembolization (TACE) is effective for hepatocellular carcinoma (HCC). Considerable amounts of radiocontrast agent are used for TACE and may induce renal dysfunction.

Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study.

Objective and design Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis; however, factors associated with the development of cirrhosis have been incompletely studied. A total of 516 patients with chronic hepatitis B were followed up longitudinally to determine their outcome. Methods The clinical and pathological features were compared between those with and without cirrhosis occurrence. The risk factors were analysed, and the probability of the development of cirrhosis was estimated. Results During a mean follow‐up period of 5.7 ± 3.4 years (range 1‐17 years), cirrhosis occurred in 71 patients, with a calculated annual incidence of 2.4%. Older age (> 45 years) at entry, male gender, persistent hepatitis (> 1.5‐fold rise of serum alanine aminotransferase levels for at least one year) and diabetes mellitus were identified as independent risk factors of cirrhosis in a multivariate analysis (odds ratios 8.0, 19.3, 2.0 and 5.2, respectively; P values all < 0.05). A logistic regression equation was used to predict the probability of cirrhosis occurrence, which was as high as 76.6% when all risk factors were present. Acute exacerbation or super‐infection by hepatitis C or D viruses were not significant predictors. Patients with subsequent cirrhosis had higher initial hepatic histological necro‐inflammatory activities when compared to age‐ and sex‐matched non‐cirrhotic controls (Knodells scores: 8.2 ± 2.4 versus 6.0 ± 4.1, P < 0.05). Conclusions Patients who were elderly, male, diabetic or had a history of persistent and histologically severe hepatitis were at increased risks of liver cirrhosis. Aggressive anti‐viral therapy may be needed for these patients and they should be closely monitored for HBV‐related late complications. Eur J Gastroenterol Hepatol 12:687‐693

Comparison of recurrence after hepatic resection in patients with hepatitis B vs. hepatitis C-related small hepatocellular carcinoma in hepatitis B virus endemic area.

Abstract: Purpose: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are two important factors in the development of hepatocellular carcinoma (HCC). The carcinogenic mechanism of HBV and HCV is considered to be different. It is interesting to compare the recurrence after hepatic resection in patients with small HCC who were infected with HBV or HCV.

Diabetes mellitus is a risk factor for hepatic decompensation in patients with hepatocellular carcinoma undergoing resection: a longitudinal study.

OBJECTIVES:Patients with hepatocellular carcinoma (HCC) frequently have diabetes mellitus (DM) due to coexisting liver cirrhosis. The aim of this study was to assess the long-term impact of DM on the hepatic regenerative ability of HCC patients undergoing surgical resection.METHODS:We retrospectively studied 245 HCC patients (210 male; age, 61 ± 13 yr) with well-preserved liver functions undergoing resection. Forty (16%) of them were diabetic and were controlled with hypoglycemic agents. The Child-Pugh scoring system was used to evaluate the postoperative liver regeneration ability. The endpoint was the occurrence of hepatic decompensation, defined as a sustained increase in the Child-Pugh score of 2 or more points or the development of tumor recurrence.RESULTS:Seventy-five patients (31%) developed hepatic decompensation during a follow-up period of 27 ± 18 months (range, 3–75). DM (p= 0.001), large (>3 cm) tumor size (p= 0.044), and age > 65 yr (p= 0.058) were the factors associated with hepatic decompensation in univariate analysis. Multivariate Cox regression model analysis confirmed that DM (relative risk [RR] = 2.3, 95% CI = 1.4–3.7, p= 0.001) and tumor size > 3 cm (RR = 1.7, 95% CI = 1.1–2.7, p= 0.046) were independent prognostic predictors associated with the occurrence of hepatic decompensation; the respective 3- and 5-yr cumulative rates were 53% and 64% versus 27% and 50% for diabetic and nondiabetic patients, and 24% and 41% versus 38% and 60% for patients with small (≤3 cm) versus large (>3 cm) tumors.CONCLUSION:HCC patients with DM or large tumor size are at a cumulative increased risk for postoperative hepatic decompensation.