Aspartate aminotransferase to platelet ratio index and sustained virologic response are associated with progression from hepatitis C associated liver cirrhosis to hepatocellular carcinoma after treatment with pegylated interferon plus ribavirin.

BACKGROUND: The aim of this study was to evaluate the clinically significant predictors of hepatocellular carcinoma (HCC) development among hepatitis C virus (HCV) cirrhotic patients receiving combination therapy. PATIENTS AND METHODS: One hundred and five compensated cirrhosis patients who received pegylated interferon plus ribavirin between January 2005 and December 2011 were enrolled. All the patients were examined with abdominal sonography and liver biochemistry at baseline, end of treatment, and every 3-6 months posttreatment. The occurrence of HCC was evaluated every 3-6 months posttreatment. RESULTS: A total of 105 patients were enrolled (mean age 58.3±10.4 years). The average follow-up time for each patient was 4.38 years (standard deviation 1.73 years; range 1.13-9.27 years). Fifteen (14.3%) patients developed HCC during follow-up period. Thirteen of them had high baseline aspartate aminotransferase to platelet ratio index (APRI) (ie, an APRI >2.0). Multivariate analysis showed that those without sustained virologic response (SVR) (hazard ratio [HR] 5.795; 95% confidence interval [CI] 1.370-24.5; P=0.017) and high APRI (HR 5.548; 95% CI 1.191-25.86; P=0.029) had a significantly higher risk of HCC occurrence. The cumulative incidence of HCC was significantly higher (P=0.009) in patients without SVR (3-year cumulative incidence 21.4%; 95% CI 7.4%-35.5%; 5-year cumulative incidence 31.1%; 95% CI 11.2%-51.1%) compared to those with SVR (3- and 5-year cumulative incidence 6.2%; 95% CI 0%-1.3%). Further, the cumulative incidence of HCC was significantly higher (P=0.006) in patients with high APRI (3-year cumulative incidence 21.8%; 95% CI 8.2%-35.3%; 5-year cumulative incidence 30.5%, 95% CI 11.8%-49.3%) compared to those with low APRI (3- and 5-year cumulative incidence 4.2%, 95% CI 0%-1.0%). CONCLUSION: In HCV-infected cirrhotic patients who received combination therapy, APRI and SVR are the two major predictors of HCC development.

Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C.

OBJECTIVE: We studied the effect of sustained virologic response (SVR) after treatment with pegylated-interferon (PEG-IFN) plus ribavirin on the development of liver cirrhosis in elderly patients with chronic hepatitis C (CHC). PATIENTS AND METHODS: This retrospective study enrolled 145 elderly CHC patients (aged ≥65 years) who were treatment-naïve and were treated with PEG-IFN plus ribavirin for 6 months between January 2005 and December 2011. Abdominal sonography was performed and liver biochemistry was studied at baseline, at the end of treatment, and every 3-6 months thereafter. The development of liver cirrhosis and related complications was evaluated at the follow-ups. The aspartate aminotransferase-to-platelet ratio index was used as a noninvasive maker for fibrosis. RESULTS: The mean patient age was 69.1±3.3 years, and the average follow-up time was 5.5 years (standard deviation: 2.5 years, range: 1.1-12.3 years). Ninety-five patients (65.5%) achieved SVR, and 26 (17.9%) discontinued treatment. Twenty-seven patients (18.6%) developed liver cirrhosis after treatment. Patients without SVR had significantly greater risk of liver cirrhosis than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312-8.761, P=0.012). The difference in 3-year cumulative incidence of liver cirrhosis was 24.8% greater for patients without SVR (35.2%, 95% CI: 13.0-57.5, P=0.012) compared with those with SVR (10.4%, 95% CI: 3.1-17.7). There was a trend of a higher baseline aspartate aminotransferase-to-platelet ratio index score in patients who progressed to liver cirrhosis compared with those who did not progress (2.1±1.2 vs 1.6±1.3, P=0.055), but the difference failed to reach significance by Cox regression (adjusted HR: 1.285, 95% CI: 0.921-1.791, P=0.14). CONCLUSION: An SVR following PEG-IFN combination treatment can reduce the risk of liver cirrhosis in elderly CHC patients.

Peginterferon alfa-2a is associated with elevations in alanine aminotransferase at the end of treatment in chronic hepatitis C patients with sustained virologic response.

BACKGROUND: The purpose of this study was to investigate the incidence and demographic/clinical factors of alanine aminotransferase (ALT) abnormalities at the end of treatment (EOT) in chronic hepatitis C (CHC) patients with sustained virologic response (SVR). METHODS AND FINDINGS: Seven hundred naïve CHC patients who underwent combination treatment between January 2003 and December 2010 were included in the study. The patients with SVR and serum ALT>upper limit of normal (ULN) at the EOT were further analyzed. The effects of clinical characteristics, treatment regimen, and virologic variables were evaluated by logistic regression. Of the 700 included patients, 488 (69.7%) achieved an SVR after treatment, and 235 (33.6%) had serum ALT levels>ULN at the EOT. Of those 488 patients, 137 (28.1%) had abnormal ALT values at the EOT. A multivariate analysis showed that the occurrence of ALT abnormalities at the EOT was significantly associated with pegylated interferon (PEG-IFN) alfa-2a (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.45-3.45; P<0.001), baseline fatty liver (OR, 1.76; 95% CI, 1.16-2.76; P = 0.007), and baseline liver cirrhosis (OR, 2.35; 95% CI, 1.35-4.09; P = 0.002). CONCLUSIONS: Use of PEG-IFN-alfa-2a, fatty liver, and cirrhosis are important factors associated with EOT-ALT abnormality in CHC patients receiving combination therapy that achieve an SVR. PEG-IFN-alfa-2a-related EOT-ALT elevation will become normal at the end of follow-up, but fatty liver and cirrhosis-related ALT elevation will not be resolved.

Nonparametric estimation of sojourn time distributions for truncated serial event data--a weight-adjusted approach.

In follow-up studies, survival data often include subjects who have had a certain event at recruitment and may potentially experience a series of subsequent events during the follow-up period. This kind of survival data collected under a cross-sectional sampling criterion is called truncated serial event data. The outcome variables of interest in this paper are serial sojourn times between successive events. To analyze the sojourn times in truncated serial event data, we need to confront two potential sampling biases arising simultaneously from a sampling criterion and induced informative censoring. In this study, nonparametric estimation of the joint probability function of serial sojourn times is developed by using inverse probabilities of the truncation and censoring times as weight functions to accommodate these two sampling biases under various situations of truncation and censoring. Relevant statistical properties of the proposed estimators are also discussed. Simulation studies and two real data are presented to illustrate the proposed methods.

Prognostic factors for the survival of Taiwanese breast cancer patients.

BACKGROUND: The incidence of breast cancer is increasing rapidly in Taiwan. Prognostic factors for survival in Taiwanese breast cancer patients have not been comprehensively studied. METHODS: Registry records of 979 newly diagnosed breast cancer patients who received initial therapy at National Taiwan University Hospital from January 1991 to December 1995 were linked to the national mortality file from 1991 to 1997 using the citizen ID of each patient. The effects of potential prognostic factors were assessed using Cox's regression model. Five-year survival rates of common characteristics were predicted according to the model. RESULTS: Among the 979 patients, 174 died within the 7-year study period (163 died from breast cancer). The overall 5-year survival rate was 81% (95% confidence interval, CI = 78-84%). The adjusted hazard ratio (HR) of mortality for patients aged at least 50 years versus patients aged less than 50 years was 1.49 (95% CI = 1.08-2.05); the HR of mortality for tumors of at least 5 cm in diameter versus those less than 2 cm was 2.45 (95% CI = 1.33-4.51); the HR of mortality for positive versus negative nodes was 3.65 (95% CI = 2.33-5.71); and the HR of mortality for pathology of infiltrating ductal carcinoma versus other types was 2.63 (95% CI = 1.32-5.27). Five-year survival rates for patients without node involvement were higher than 90% regardless of tumor size, while those for patients with positive nodes were significantly lower, except for patients with tumors of less than 2 cm in diameter. CONCLUSIONS: Patients who had a small tumor and involvement of fewer nodes, and who were younger, had a higher probability of survival. Node involvement was more important than tumor size in the prediction of survival.