Mayuko Kondo

Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma

BACKGROUND & AIMS Obesity defined by body mass index (BMI) significantly increases the risk of hepatocellular carcinoma (HCC). In contrast, not only obesity but also underweight is associated with poor prognosis in patients with HCC. Differences in body composition rather than BMI were suggested to be true determinants of prognosis. However, this hypothesis has not been demonstrated conclusively. METHODS We measured skeletal muscle index (SMI), mean muscle attenuation (MA), visceral adipose tissue index, subcutaneous adipose tissue index, and visceral to subcutaneous adipose tissue area ratios (VSR) via computed tomography in a large-scale retrospective cohort of 1257 patients with different stages of HCC, and comprehensively analyzed the impact of body composition on the prognoses. RESULTS Among five body composition components, low SMI (called sarcopenia), low MA (called intramuscular fat [IMF] deposition), and high VSR (called visceral adiposity) were significantly associated with mortality, independently of cancer stage or Child-Pugh class. A multivariate analysis revealed that sarcopenia (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.18-1.96; p=0.001), IMF deposition (HR, 1.34; 95% CI, 1.05-1.71; p=0.020), and visceral adiposity (HR, 1.35; 95% CI, 1.09-1.66; p=0.005) but not BMI were significant predictors of survival. The prevalence of poor prognostic body composition components was significantly higher in underweight and obese patients than in normal weight patients. CONCLUSIONS Sarcopenia, IMF deposition, and visceral adiposity independently predict mortality in patients with HCC. Body composition rather than BMI is a major determinant of prognosis in patients with HCC.

Increased serum autotaxin levels in hepatocellular carcinoma patients were caused by background liver fibrosis but not by carcinoma.

BACKGROUND Controversy exists as to whether autotaxin (ATX) may be importantly associated with pathophysiology of hepatocellular carcinoma (HCC). METHODS We evaluated serum ATX levels and its mRNA expression in consecutive 148 HCC patients treated with radiofrequency ablation (RFA) and 30 patients with hepatic resection. RESULTS Although increased serum ATX levels were observed in almost all the patients treated with RFA, they were not reduced after RFA. Furthermore, serum ATX levels were associated not with tumor burden but with the parameters predicting for liver fibrosis, such as liver stiffness values. Then, in surgically-treated patients, there was no significant correlation between serum ATX levels and ATX mRNA expression levels in HCC tissues. Notably, ATX mRNA expression levels in HCC tissues were not higher than those in peri-tumorous tissues. Finally, serum ATX levels in surgically-treated HCC patients were rather correlated with ATX mRNA expression levels in peri-tumorous tissues as well as with liver fibrosis stage. CONCLUSION The increase in serum ATX levels in HCC patients may not be caused by abundant ATX production in HCC tissues but by fibrosis in the background livers.

Impact of IL28B Genetic Variation on HCV-Induced Liver Fibrosis, Inflammation, and Steatosis: A Meta-Analysis

Background & Aims IL28B polymorphisms were shown to be strongly associated with the response to interferon therapy in chronic hepatitis C (CHC) and spontaneous viral clearance. However, little is known about how these polymorphisms affect the natural course of the disease. Thus, we conducted the present meta-analysis to assess the impact of IL28B polymorphisms on disease progression. Methods A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library. Integrated odds ratios (OR) were calculated with a fixed-effects or random-effects model based on heterogeneity analyses. Results We identified 28 studies that included 10,024 patients. The pooled results indicated that the rs12979860 genotype CC was significantly associated (vs. genotype CT/TT; OR, 1.122; 95%CI, 1.003–1.254; P = 0.044), and that the rs8099917 genotype TT tended to be (vs. genotype TG/GG; OR, 1.126; 95%CI, 0.988–1.284; P = 0.076) associated, with an increased possibility of severe fibrosis. Both rs12979860 CC (vs. CT/TT; OR, 1.288; 95%CI, 1.050–1.581; P = 0.015) and rs8099917 TT (vs. TG/GG; OR, 1.324; 95%CI, 1.110–1.579; P = 0.002) were significantly associated with a higher possibility of severe inflammation activity. Rs8099917 TT was also significantly associated with a lower possibility of severe steatosis (vs. TG/GG; OR, 0.580; 95%CI, 0.351–0.959; P = 0.034), whereas rs12979860 CC was not associated with hepatic steatosis (vs. CT/TT; OR, 1.062; 95%CI, 0.415–2.717; P = 0.901). Conclusions IL28B polymorphisms appeared to modify the natural course of disease in patients with CHC. Disease progression seems to be promoted in patients with the rs12979860 CC and rs8099917 TT genotypes.

Frequency of and Predictive Factors for Vascular Invasion after Radiofrequency Ablation for Hepatocellular Carcinoma

Background Vascular invasion in patients with hepatocellular carcinoma (HCC) is representative of advanced disease with an extremely poor prognosis. The detailed course of its development has not been fully elucidated. Methods We enrolled 1057 consecutive patients with HCC who had been treated with curative intent by radiofrequency ablation (RFA) as an initial therapy from 1999 to 2008 at our department. We analyzed the incidence rate of and predictive factors for vascular invasion. The survival rate after detection of vascular invasion was also analyzed. Results During a mean follow-up period of 4.5 years, 6075 nodules including primary and recurrent lesions were treated by RFA. Vascular invasion was observed in 97 patients. The rate of vascular invasion associated with site of original RFA procedure was 0.66% on a nodule basis. The incidence rates of vascular invasion on a patient basis at 1, 3, and 5 years were 1.1%, 5.9%, and 10.4%, respectively. Univariate analysis revealed that tumor size, tumor number, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein were significant risk predictors of vascular invasion. In multivariate analysis, DCP was the most significant predictor for vascular invasion (compared with a DCP of ≤100 mAu/mL, the hazard ratio was 1.95 when DCP was 101–200 mAu/mL and 3.22 when DCP was >200 mAu/mL). The median survival time after development of vascular invasion was only 6 months. Conclusion Vascular invasion occurs during the clinical course of patients initially treated with curative intent. High-risk patients may be identified using tumor markers.

Slight elevation of high-sensitivity C-reactive protein to predict recurrence and survival in patients with early stage hepatitis C-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is associated with chronic inflammation derived from various origins. We investigated whether high‐sensitivity C‐reactive protein (hsCRP) could predict recurrence and survival after curative treatment for early stage hepatitis C virus‐related HCC (C‐HCC).

Comparison of improved prognosis between hepatitis B‐ and hepatitis C‐related hepatocellular carcinoma

Treatment strategies for hepatocellular carcinoma (HCC) have been advanced. The aim of this study was to compare the change of the prognosis between hepatitis B‐related HCC (B‐HCC) and hepatitis C‐related HCC (C‐HCC) in the last two decades.

Impact of serum levels of interleukin‐6 and adiponectin on all‐cause, liver‐related, and liver‐unrelated mortality in chronic hepatitis C patients

Various inflammatory cytokines and adipokines have been implicated in hepatitis C virus (HCV)‐mediated liver disease, and interleukin‐6 (IL‐6) and adiponectin may play key roles. In addition, these factors may be associated with chronic hepatitis C (CHC)‐induced extrahepatic manifestations. However, little data are available on the role of these factors on future outcomes of CHC patients. This study aims to evaluate the impact of serum levels of IL‐6 and adiponectin on all‐cause mortality, liver‐related mortality, and liver‐unrelated mortality.

Cause-specific mortality associated with aging in patients with hepatocellular carcinoma undergoing percutaneous radiofrequency ablation.

Objective The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The aim of this study is to evaluate the efficacy of radiofrequency ablation (RFA) in elderly patients with HCC and to investigate cause-specific excess deaths associated with increasing number of elderly patients. Materials and methods We enrolled 1401 naive patients with HCC who were treated initially by RFA from 1999 to 2011. Patients below 75 years of age were categorized as ‘younger’ and those at least 75 as ‘elderly’. Differences in the demographic and laboratory data of these patients were assessed, along with Kaplan–Meier analysis of survival using the log-rank test. In addition, we assessed the causes of death, defined as liver related and liver unrelated, by competing risk analysis and risk factors for respective causes of death by a proportional subdistribution model. Results Overall, 353 patients were categorized as elderly. Elderly patients were more likely to be women, infected with hepatitis C virus, and score better in the Child–Pugh classification. The mortality at 5 years was lower in the elderly than in the younger patients (47.3 vs. 37.1%; P<0.001). Competing risk analysis showed a significant difference in liver-unrelated death (P<0.001) between the two groups, whereas there were no significant differences in liver-related death (P=0.64). By the proportional subdistribution model, age was a significant risk factor only for liver-unrelated death. Conclusion RFA provided satisfactory 5-year survival rates in elderly patients with HCC. The elderly tended to die from liver-unrelated causes.