A simple model to predict early recurrence of hepatocellular carcinoma after liver resection.

PURPOSE: Multiple studies have reported models for predicting early recurrence of hepatocellular carcinoma (HCC) after liver resection (LR). However, these models are too complex to use in daily practice. We aimed to develop a simple model. METHOD: We enrolled 1133 patients with newly diagnosed HCC undergoing LR. The Kaplan - Meier method and log-rank test were used for survival analysis and Cox proportional hazards analysis to identify prognostic factors associated with early recurrence (i.e., recurrence within two years after LR). RESULTS: Early recurrence was identified in 403 (35.1%) patients. In multivariate analysis, alpha-fetoprotein (AFP) 20-399 vs. < 20 ng/ml (HR = 1.282 [95% confidence interval = 1.002-1.639]; p = 0.048); AFP ≥ 400 vs. < 20 ng/ml (HR = 1.755 [1.382-2.229]; p < 0.001); 7th edition American Joint Committee on Cancer (AJCC) stage 2 vs. 1 (HR = 1.958 [1.505-2.547]; p < 0.001); AJCC stage 3 vs. 1 (HR = 4.099 [3.043-5.520]; p < 0.001); and pathology-defined cirrhosis (HR = 1.46 [1.200-1.775]; p < 0.001) were associated with early recurrence. We constructed a predictive model with these variables, which provided three risk strata for recurrence-free survival (RFS): low risk, intermediate risk, and high risk, with two-year RFS of 79%, 57%, and 35%, respectively (p < 0.001). CONCLUSION: We developed a simple model to predict early recurrence risk for patients undergoing LR for HCC.

A simple preoperative model to predict overall survival of patients undergoing liver resection for hepatocellular carcinoma ≥10 cm.

BACKGROUND: Studies have rarely reported on preoperative predictors of prognosis of patients undergoing liver resection (LR) for HCC ≥10 cm. We developed a simple model to predict overall survival (OS) of these patients. METHODS: We enrolled 305 patients with HCC ≥10 cm undergoing LR. Cirrhosis and imaging-defined AJCC stage were used to develop a preoperative model. Patients were divided into three groups based on the Kaplan-Meier estimator. RESULTS: Group 1 included patients with AJCC stage 1 and no cirrhosis (n = 86), group 2 those with AJCC stage 1 and cirrhosis plus those with AJCC stage 2 or 3 and no cirrhosis (n = 166), and group 3 those with AJCC stage 2 or 3 and cirrhosis (n = 51). The five-year OS of group 1, 2, and 3 was 55%, 32%, and 25%, respectively (p < 0.001). With group 1 as the reference, multivariate analysis of OS showed that group 2 (HR = 2.043; 95% CI = 1.332-3.134; p = 0.001) and group 3 (HR = 2.740; 95% CI = 1.645-4.564; p < 0.001) were independent predictors of OS. CONCLUSION: We developed a simple model to predict OS of patients undergoing LR for HCC ≥10 cm.

Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information.

BACKGROUND/PURPOSE: Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. METHODS: This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. RESULTS: The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. CONCLUSION: This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.

Identifying endemic areas and estimating the prevalence of hyperlipidemia in Taiwan's townships.

BACKGROUND/PURPOSE: This study aimed to evaluate geographic variations and differences in the prevalence of hypertriglyceridemia and hypercholesterolemia between Taiwan's townships. METHODS: The prevalence of hypertriglyceridemia and hypercholesterolemia was evaluated according to the geographic characteristics of the people in the Adult Preventive Service Program from 2009 to 2010. The prevalence of hypertriglyceridemia and hypercholesterolemia in 2009 and 2010 was used and divided into three groups. Then, all townships were classed as having a significantly high prevalence, low prevalence, or an undetermined prevalence. RESULTS: The mean prevalence of hypertriglyceridemia and hypercholesterolemia was 29.26% and 43.96%, respectively. Geographic variations were observed: 125 townships had a high prevalence of hypertriglyceridemia, 122 townships had a low prevalence of hypertriglyceridemia, 142 townships had a high prevalence of hypercholesterolemia, and 159 townships had a low prevalence. A higher prevalence of hypertriglyceridemia was noted in the aboriginal areas. CONCLUSION: Geographic variations exist in the prevalence of hypertriglyceridemia, and hypercholesterolemia. Our findings indicate that the prevention and treatment services in these high prevalence areas should be a priority.

Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus.

Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age- and sex-matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow-up. A panel of ten cancer-associated miRNAs was analyzed by quantitative real-time reverse-transcription polymerase chain reaction. Serum levels of miR-16, miR-122, miR-221, let-7b and miR-15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR-122, miR-let-7b and miR-15b levels increased significantly (p = 0.046, 0.043 and 0.044, respectively). As a single marker, α-fetoprotein (AFP) and miR-122 as well as let-7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let-7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p = 0.001). In conclusion, miR-122 and let-7b, which are upregulated in the serum of early-HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients.

Validation and modification of a proposed substaging system for patients with intermediate hepatocellular carcinoma.

BACKGROUND AND AIM: Based on up-to-seven criteria and Child-Pugh score, four substages of Barcelona Clinic Liver Cancer (BCLC) intermediate hepatocellular carcinoma (HCC) were proposed. The purpose of this study was to validate and modify this proposal. METHODS: Between January 2002 and February 2011, newly diagnosed intermediate HCC patients underwent transarterial embolization (TAE) were enrolled. Patients were stratified into four (B1-B4) substages and followed up until death or end of 2012. Patients' survivals and discriminatory ability of substaging systems were compared. RESULTS: Five-hundred and eighty patients were enrolled. There were 56.6%, 33.8%, 7.4%, and 2.2% in substage B1, B2, B3, and B4. The 5-year survival rate was 21.4%, 13.9%, 7.4%, and 7.7% with median survival time of 2.4, 1.3, 0.5, and 0.8 years (P < 0.001). In addition to substage B1-B4, α-fetoprotein (AFP) level was an independent factor associated with survival in multivariate analysis. According to AFP < or > 200 ng/mL, B1 was classified into B1a and B1b, and B2 into B2a and B2b. There were no differences in survivals between B1b and B2a (P = 0.174), and B2b and B3 (P = 0.785). Patients were re-classified into modified (m)B1 (B1a), mB2 (B1b + B2a), mB3 (B2b + B3). The modified substages (mB1-mB3) showed a more desirable substaging system. CONCLUSIONS: For BCLC intermediate HCC patients, substages B1-B4 were useful in predicting survival after TAE. However, modified substaging system provided better prognostic prediction.

Prognostic Factors of Survival From Intractable Oronasal Bleeding After Successful Transarterial Embolization.

PURPOSE: To evaluate the prognostic factors that influence the survival of patients with traumatic intractable oronasal bleeding treated by transarterial embolization (TAE). MATERIALS AND METHODS: Patients who received TAE for intractable oronasal bleeding in the National Taiwan University Hospital from 2002 through 2013 were included in the study. Retrospective reviews were undertaken to collect relevant clinical and neuroradiologic data that might be correlated with patients' survival. The Wilcoxon rank-sum test or Fisher exact test was adopted to analyze differences between the survival group and the mortality group. Odds ratios were estimated by univariate logistic regression. RESULTS: TAE successfully controlled the bleeding in 24 of 26 patients (92.3%) who had severe craniofacial injury in the 12-year period. Of the 24 patients with successful TAE, 13 patients were discharged alive from the hospital. The overall survival rate was 50% (13 of 26). Significantly higher initial Glasgow Coma Scale (GCS) score (P = .01) and lower Injury Severity Score (ISS; P < .01) were present in the survival group than in the mortality group by the Wilcoxon rank-sum test. Moreover, patients with an ISS of at least 30, a GCS score lower than 9, initial hemoglobin level lower than 10 g/dL, and computed tomographic (CT) findings of a brain midline shift had statistically higher odds ratios predicting mortality than their counterparts as estimated by univariate logistic regression. CONCLUSIONS: The results of this study showed that the combination of diagnostic angiography and therapeutic embolization is effective treatment for intractable oronasal bleeding in patients with severe craniofacial injury. The prognosis in patients who were rescued with successful TAE was statistically correlated with the severity of trauma and concomitant brain injury. An ISS of at least 30, a GCS score lower than 9, an initial hemoglobin level lower than 10, and CT findings of a brain midline shift were strong predictors for mortality.

A preoperative model to predict overall survival in patients with hepatoma undergoing resection.

BACKGROUND: We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR). METHODS: Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 â€‹+ â€‹(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6-7.9; high, >7.9. RESULTS: Multivariate analysis showed that radiographic TBS (low: referent; medium: HR â€‹= â€‹2.89; 95 â€‹% CI: 1.60-5.21; p â€‹< â€‹0.001; high, HR â€‹= â€‹7.60; 95 â€‹% CI: 3.80-15.2; p â€‹< â€‹0.001), AFP (<400 â€‹ng/mL: referent; ≧400 â€‹ng/mL: HR â€‹= â€‹1.67, 95 â€‹% CI: 1.11-2.52, p â€‹= â€‹0.014), and cirrhosis (absence: referent; presence: HR â€‹= â€‹1.88, 95 â€‹% CI: 1.30-2.72, p â€‹< â€‹0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623). CONCLUSIONS: We have developed a preoperative model that performs better in predicting OS than the BCLC system.

Patients undergoing liver resection for non-alcoholic fatty liver disease-related hepatocellular carcinoma and those for viral hepatitis-related hepatocellular carcinoma have similar survival outcomes.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan-Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p = 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p = 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p = 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

BACKGROUND: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. MATERIALS AND METHODS: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. RESULTS: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). CONCLUSION: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Validation of the 7th edition TNM staging system for hepatocellular carcinoma: an analysis of 8,828 patients in a single medical center.

BACKGROUND: Major modification of the 7th tumor-node-metastasis (TNM) staging system for hepatocellular carcinoma (HCC) was divided into 6th stage IIIA to 7th IIIA (multiple tumors, any>5 cm) and IIIB (tumors involving a major vessel). This study aimed to validate 6th and 7th TNM systems in prognostic prediction, then analyze the impact of time, Child-Pugh classification and treatment modalities in survival. METHODS: A total of 5,611 and 3,217 HCC patients were enrolled between 1986-2002 (past period) and 2003-2010 (recent period), respectively. The Akaike information criteria (AIC) within a Cox proportional hazard regression model were used to demonstrate the discriminatory ability for staging systems. RESULTS: The 1-, 3-, and 5-year survival rates of past and recent periods were 44.8, 24.9, 17.1%, and 65.5, 44.5, 34.6%, respectively (p<0.001). Rates of smaller HCC detection and received curative treatment were significantly higher in the recent period than in the past period (p<0.001). Survival rates were different in each Child-Pugh class (all p<0.001). Patients receiving curative treatment had highest survival rates, followed by non-curative treatment, and untreated patients (p<0.05). In both periods, significant differences in survival curves existed between each of the stages in the 6th and 7th TNM staging (all p<0.05), and also between IIIA and IIIB in the 7th TNM (p<0.001). The AIC of two periods in the 6th and 7th TNM systems were decreased, with 77,895 and 77,630, and 19,162 and 19,135, respectively. CONCLUSION: The 7th TNM provided better prognostic prediction than the 6th TNM after dividing into IIIA and IIIB. Survival rates of HCC have been improving in recent decades.

Alpha-Fetoprotein Combined with Radiographic Tumor Burden Score to Predict Overall Survival after Liver Resection in Hepatocellular Carcinoma.

We evaluated whether combining the radiographic tumor burden score (TBS) and alpha-fetoprotein (AFP) level could be used to stratify overall survival (OS) among hepatocellular carcinoma (HCC) patients after liver resection (LR). Patients who underwent LR for Barcelona Clinic Liver Cancer stage 0, A, or B HCC between 2011 and 2018 were enrolled. TBS scores were calculated using the following equation: TBS2 = (largest tumor size (in cm))2 + (tumor number)2. Among 743 patients, 193 (26.0%) patients had a low TBS (<2.6), 474 (63.8%) had a moderate TBS (2.6-7.9), and 75 (10.1%) had a high TBS (>7.9). Those with a TBS ≤ 7.9 and AFP < 400 ng/mL had a significantly better OS than those with a TBS > 7.9 and an AFP < 400 ng/mL (p = 0.003) or ≥ 400 ng/mL (p < 0.001). A multivariate analysis using TBS ≤ 7.9 and AFP < 400 ng/mL as the reference values showed that a TBS > 7.9 and an AFP < 400 ng/mL (hazard ratio (HR): 2.063; 95% confidence interval [CI]: 1.175-3.623; p = 0.012) or ≥ 400 ng/mL (HR: 6.570; 95% CI: 3.684-11.719; p < 0.001) were independent predictors of OS. In conclusion, combining radiographic TBSs and AFP levels could stratify OS among HCC patients undergoing LR.

Stationary Trend in Elevated Serum Alpha-Fetoprotein Level in Hepatocellular Carcinoma Patients.

A recent study from the US showed a decreasing trend in the elevated serum alpha-fetoprotein (AFP) level (i.e., ≥20 ng/mL) in hepatocellular carcinoma (HCC) patients at the time of diagnosis. Furthermore, advanced tumor stage and severe underlying liver disease were associated with elevated AFP levels. We aimed to evaluate this issue in an area endemic for hepatitis B virus (HBV). Between 2011 and 2020, 4031 patients were newly diagnosed with HCC at our institution. After excluding 54 patients with unknown AFP data, the remaining 3977 patients were enrolled in this study. Elevated AFP level was defined as ≥20 ng/mL. Overall, 51.2% of HCC patients had elevated AFP levels; this proportion remained stationary between 2011 and 2020 (51.8% vs. 51.1%). Multivariate analysis showed that female gender (odds ratio (OR) = 1.462; p < 0.001), tumor size per 10 mm increase (OR = 1.155; p < 0.001), multiple tumors (OR = 1.406; p < 0.001), Barcelona Clinic Liver Cancer stages B-D (OR = 1.247; p = 0.019), cirrhosis (OR = 1.288; p = 0.02), total bilirubin > 1.4 mg/dL (OR = 1.218; p = 0.030), and HBV- or hepatitis C virus (HCV)-positive status (OR = 1.720; p < 0.001) were associated with elevated AFP levels. In conclusion, a stationary trend in elevated serum AFP level in HCC patients has been noted in the past 10 years. Advanced tumor stage, severe underlying liver disease, viral etiology, and female gender are associated with elevated AFP levels in HCC patients.

A preoperative model for predicting early recurrence in patients undergoing resection for single hepatocellular carcinoma.

BACKGROUND AND AIM: The updated Barcelona Clinic Liver Cancer guidelines recommend liver resection (LR) for patients with single hepatocellular carcinoma (HCC) of any size. This study developed a preoperative model for predicting early recurrence in patients undergoing LR for single HCC. MATERIALS AND METHODS: We identified 773 patients undergoing LR for single HCC between 2011 and 2017 from the cancer registry database of our institution. Multivariate Cox regression analyses were performed to construct a preoperative model for predicting early recurrence, i.e., recurrence within 2 years of LR. RESULTS: Early recurrence was identified in 219 patients (28.3%). The final model of early recurrence included four predictive factors-alpha-fetoprotein level of ≥20 ng/mL, tumor size of >30 mm, Model for End-Stage Liver Disease score of >8, and cirrhosis. Preoperative application of this model provided three risk strata for recurrence-free survival (RFS): low risk, with 2-year RFS of 79.8% (95% confidence interval [CI]: 75.7-84.2%); intermediate risk, with 2-year RFS of 66.6% (95% CI: 61.1-72.6%); and high risk, with 2-year RFS of 51.1% (95% CI: 43.0-60.8%). CONCLUSION: We developed a preoperative model for predicting early recurrence after LR for single HCC. This model provides useful information for clinical decision-making.

Using the hazard function to evaluate hepatocellular carcinoma recurrence risk after curative resection.

Predicting recurrence patterns of hepatocellular carcinoma (HCC) can be helpful in developing surveillance strategies. This study aimed to use the hazard function to investigate recurrence hazard and peak recurrence time transitions in patients with HCC undergoing liver resection (LR). We enrolled 1204 patients with HCC undergoing LR between 2007 and 2018 at our institution. Recurrence hazard, patterns, and peak rates were analyzed. The overall recurrence hazard peaked at 7.2 months (peak hazard rate [pHR]: 0.0197), but varied markedly. In subgroups analysis based on recurrence risk factors, patients with a high radiographic tumor burden score (pHR: 0.0521), alpha-fetoprotein level ≥ 400 ng/ml (pHR: 0.0427), and pT3-4 (pHR: 0.0656) showed a pronounced peak within the first year after LR. Patients with cirrhosis showed a pronounced peak within three years after LR (pHR: 0.0248), whereas those with Barcelona Clinic Liver Cancer stage B (pHR: 0.0609) and poor tumor differentiation (pHR: 0.0451) showed multiple peaks during the 5-year follow-up period. In contrast, patients without these recurrence risk factors had a relatively flat hazard function curve. HCC recurrence hazard, patterns, and peak rates varied substantially depending on different risk factors of HCC recurrence.

Tumor necrosis as a predictor of early tumor recurrence after resection in patients with hepatoma.

BACKGROUND: Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. MATERIALS AND METHODS: Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features-tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis-were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping. RESULTS: Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. CONCLUSION: We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

Causes of Death among Patients with Hepatocellular Carcinoma According to Chronic Liver Disease Etiology.

This study was conducted to determine whether the causes of death among patients with hepatocellular carcinoma (HCC) differ according to chronic liver disease (CLD) etiology. Between 2011 and 2020, 3977 patients who were newly diagnosed with HCC at our institution were enrolled in this study. We determined whether the cause of death was HCC-related and non-HCC-related. For patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related causes > all negative. All negative was defined as negative for HCV, HBV, and alcohol-related causes. Among 3977 patients, 1415 patients were classified as HCV-related, 1691 patients were HBV-related, 145 patients were alcohol-related, and 725 patients were all negative. HCC-related mortality was the leading cause of death, irrespective of etiology. Among patients who underwent curative treatment, HCC-related mortality was the leading cause of death for patients in the HCV, HBV, and all-negative groups, but not for patients in the alcohol-related group. Among patients 75 years and older who underwent curative treatment, HCC-related mortality was the leading cause of death in the HCV but not HBV or all-negative groups. In conclusion, although most patients with HCC die due to HCC-related causes, non-HCC-related mortality represents a competing event in certain patient subgroups. The current study results underscore the importance of assessing and managing underlying comorbidities, particularly among patients with HCC at risk of non-HCC-related mortality.

Decreased anti-hepatitis C virus titer and associated factors in chronic hepatitis C patients after sustained virological response: a prospective study.

BACKGROUND AND AIM: Long-term trends of anti-hepatitis C virus (HCV) antibody titer and their associated factors in patients with sustained virological response (SVR) were investigated. METHODS: From May 1999 to July 2005, a total of 166 SVR consecutive patients (M/F: 86/80) were enrolled. Anti-HCV titer, samples to cut-off (S/CO) ratios, were measured with AxSYM HCV version 3.0. Their S/CO ratios were followed every 6 months after SVR and the patterns over time were identified by trajectory analyses. Changes of recombinant immunoblot assay (RIBA) pattern before treatment and end of follow-up were compared (n = 64). RESULTS: The mean duration of follow-up was 4.7 ± 1.5 years (median 4.3; range 3-9 years). The rates of S/CO ratios decreased annually (P < 0.001). Two of them (1.2%) achieved seroreversion. Trajectory groups included lower pretreatment S/CO ratios (LAB, n = 83), rapid decrease (RD, n = 62) and slow decrease (SD, n = 21) groups. Comparing LAB to RD group, odds ratio (OR) of increased platelet count per 1 unit and interferon regimen was 1.12 (95% confidence interval [CI] 1.04-1.20) and 2.17 (95% CI 1.04-4.52) respectively. Comparing SD to LAB and RD groups, the OR of advanced fibrotic stage, using mild fibrotic stage as a reference, was 4.33 (95% CI 1.49-12.63). Reaction strength of all four RIBA bands decreased significantly at the end of follow-up. CONCLUSIONS: Anti-HCV titers decreased annually during long-term follow-up after SVR. Higher pretreatment platelet count, interferon regimen and mild fibrosis were associated with decreased anti-HCV titers. However, only a few cases achieved seroreversion. All RIBA bands decreased significantly after long-term follow-up.

Community-based cross-sectional study: the association of lipids with hepatitis C seropositivity and diabetes mellitus.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is reported to be associated with or to cause type 2 diabetes mellitus (T2DM). Our study aimed to elucidate the role of triglyceride (TG) and cholesterol (CHOL) levels in the association between anti-HCV seropositivity and T2DM in an HCV-endemic area. METHODS: We analyzed a computerized dataset of 56 338 residents from a community-based comprehensive screening program in Tainan County in southern Taiwan. Fasting glucose, anti-HCV status, hepatitis B surface antigen (HBsAg) status, platelet counts, TG levels, CHOL levels, age, gender, and body mass index were included in the analyses. Multivariate logistic analysis was used to identify factors independently associated with T2DM. RESULTS: Older age, being overweight, thrombocytopenia, hypertriglyceridemia, hypercholesterolemia, anti-HCV seropositivity, and HBsAg seronegativity were common factors independently associated with diabetes. Among all models of multiple logistic regression analysis used for identifying factors independently associated with T2DM, anti-HCV seropositivity was only identified in the models that included either hypertriglyceridemia or hypercholesterolemia. When subjects were divided into hyperlipidemia (CHOL, > 200 or TG, > 150 mg/dL; n = 33 393) or non-hyperlipidemia subgroups (CHOL, < 200 and TG, < 150 mg/dL; n = 22 945), anti-HCV seropositivity was identified as an independent factor only in the non-hyperlipidemia subgroup. The odds ratio was 1.35, with a 95% confidence interval of 1.17-1.55. CONCLUSIONS: This study demonstrates that the lipid level is associated with the relationship between T2DM and anti-HCV seropositivity in non-hyperlipidemic individuals. However, the relationship between HCV and T2DM did not exist when the lipid level was not included in the analysis.

Alterations of Ocular Surface and Tear Film in Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

Purpose: Obstructive sleep apnea/hypopnea syndrome (OSA) results in repeated oxygen desaturation, repeated arousals, and episodic nocturnal activation of sympathetic nervous system during sleep. Untreated OSA is strongly associated with an increase of cardio- and cerebrovascular disorders, as well as the damages of ophthalmological microstructures. However, previous literature only simply studied the association between the ophthalmic disorders and OSA. In the present study, we first investigated the alterations of ocular surface and tear film non-invasively with the innovated corneal topographer in untreated OSA patients and normal control subjects. Furthermore, we analyzed in depth whether the correlations between OSA severity and ocular surface exams exist. Participants and Methods: Participants underwent a full-night polysomnography to determine OSA occurrence and severity. All participants subsequently received Ocular Surface Disease Index questionnaire and comprehensive ocular exams, including floppy eyelid syndrome (FES) assessment, oculus scan for tear meniscus height, non-invasive keratograph tear film breakup time (NIKBUT), and ocular surface redness, endothelial cell density, and corneal fluorescein staining. Results: One hundred eighty-one participants were prospectively enrolled in the study. FES was found in 11.5% of the normal control group and 60.0% of the severe OSA group (p=0.0005). There were significant differences in the first-NIKBUT (F-NIKBUT) (p < 0.0001), average-NIKBUT (A-NIKBUT) (p = 0.0007), and redness scores over the nasal bulbar (p = 0.032), temporal bulbar (p < 0.0001), nasal limbal (p = 0.014), and temporal limbal (p < 0.0001) areas among the four groups. F-NIKBUT and A-NIKBUT were significantly shorter in the moderate/severe OSA group (apnea/hypopnea index (AHI) ≥15) than in the normal/mild OSA group (AHI <15) (both p < 0.0001). The redness scores over the temporal bulbar (p < 0.0001) and temporal limbal (p < 0.0001) areas were also significantly different in these two OSA groups. Moreover, F-NIKBUT and A-NIKBUT negatively correlated with AHI. Nasal bulbar redness, temporal bulbar redness, nasal limbal redness, and temporal limbal redness positively correlated with AHI. Conclusion: OSA patients had higher occurrence of FES. The NIKBUT was significantly shorter, and the temporal conjunctival redness scores over bulbar and limbal areas were higher in the moderate/severe OSA group than in the normal/mild OSA group. NIKBUT and conjunctival hyperemia significantly correlated with the severity of untreated OSA.