Naoto Fujiwara

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.

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).

Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma.

Background To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. Materials and Methods We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors’ institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions. Results There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10th, 20th, and 30th examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10th exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections. Conclusion Repeated exposures to iodinated contrast media increase the risk of adverse reaction.

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.

Family history is an independent risk factor for the progression of gastric atrophy among patients with Helicobacter pylori infection

Background and aim Risk factors for progression of gastric atrophy have not been fully elucidated. The aim of this study was to evaluate the risk factors for the development of atrophic gastritis in patients with Helicobacter pylori (H. pylori ) infection. Methods We reviewed 206 H. pylori-infected patients retrospectively. Endoscopic gastric atrophy was classified into closed- and open-type. We conducted univariate and multivariate logistic regression analyses on the contribution of age, sex, body mass index, past history of cancer, the first-degree family history of gastric cancer, habitual smoking and alcohol drinking, and endoscopic findings of gastric ulcer or duodenal ulcer for open-type gastric atrophy. Results On multivariate analysis, age (odds ratio = 1.079, 95% confidence interval = 1.048–1.11, p < 0.001), family history of gastric cancer (odds ratio = 3.967, 95% confidence interval = 1.414–10.6, p = 0.006) and duodenal ulcer (odds ratio = 0.834, 95% confidence interval = 0.711–0.977, p = 0.024) were the factors independently associated with open-type gastric atrophy. Conclusions A first-degree family history of gastric cancer, absence of duodenal ulcer, and old age were independent risk factors for the progression of gastric atrophy among H. pylori-infected patients. Careful examination with upper gastrointestinal endoscopy is necessary in patients with such risk factors.

Impact of serum ferritin level on hepatocarcinogenesis in chronic hepatitis C patients

To elucidate the impact of the serum ferritin level, a surrogate indicator of hepatic iron accumulation, on hepatocarcinogenesis in chronic hepatitis C patients.

Serum Alpha-Fetoprotein Has High Specificity for the Early Detection of Hepatocellular Carcinoma After Hepatitis C Virus Eradication in Patients.

Abstract Alpha-fetoprotein (AFP) has not played a large role in the surveillance of hepatocellular carcinoma due to inadequate sensitivity and specificity for active chronic hepatitis or cirrhosis. The aim of this study was to evaluate the diagnostic accuracy of AFP in small hepatocellular carcinomas after hepatitis C virus eradication to determine the optimal cutoff value. We conducted a case–control study of 29 cases and 58 controls, matched for age, gender, and platelet counts. The AFP cutoff was 5 ng/mL in patients after hepatitis C virus eradication and 17 ng/mL in those without hepatitis C virus eradication. The areas under the receiver operating characteristic curve were 0.86 (95% confidence interval, 0.76–0.96) in patients after hepatitis C virus eradication and 0.83 (95% confidence interval, 0.74–0.91) in those without hepatitis C virus eradication. In patients after hepatitis C virus eradication, the sensitivity and specificity of AFP levels were 24.1% and 100%, respectively, using a cutoff value of 17 ng/mL. Using a lower cutoff value of 5 ng/mL, the sensitivity increased to 75.9%, although the specificity decreased to 89.0%. AFP is a specific tumor marker for the diagnosis of hepatocellular carcinoma after hepatitis C virus eradication when using the optimal cutoff value of 5 ng/mL.

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.