Ryo Nakagomi

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.

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.

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.

Drastically Reduced Neoplastic Seeding Related to Radiofrequency Ablation for Hepatocellular Carcinoma

Drastically Reduced Neoplastic Seeding Related to Radiofrequency Ablation for Hepatocellular Carcinoma

Serum levels of ferritin do not affect the prognosis of patients with hepatocellular carcinoma undergoing radiofrequency ablation

Background & aims Hepatic iron accumulation can accelerate liver injury in patients with various chronic liver diseases and lead to hepatocarcinogenesis. We elucidated the impact of serum levels of ferritin on the prognosis of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) in a large cohort. Methods We retrospectively analyzed 578 treatment-naïve HCC patients who underwent RFA. We divided our cohort into four groups by the quartile points of serum ferritin level: G1 (≤55 ng/mL, n = 148), G2 (56–130 ng/mL, n = 142), G3 (131–243 ng/mL, n = 144) and G4 (≥244 ng/mL, n = 144). We analyzed the recurrence and survival of patients using the Kaplan–Meier method. We also evaluated pathological iron deposition among patients with a solitary tumor smaller than 2 cm. Results The cumulative rates of overall recurrence and survival at 5 years were 81.6% and 66.3%, respectively. The serum levels of ferritin were correlated with pathological iron deposition. There were no significant differences in recurrence and survival rates according to serum levels of ferritin and pathological hepatic iron deposition. Conclusions Serum levels of ferritin do not affect the prognosis of HCC patients undergoing RFA.

Disappearance of Perihepatic Lymph Node Enlargement after hepatitis C viral eradication with direct acting antivirals

Perihepatic lymph node enlargement (PLNE) which has been shown to be negatively associated with hepatocellular carcinoma (HCC) occurrence is frequently observed in chronic liver disease; however, changes in the state of perihepatic lymph nodes after eradication of hepatitis C virus (HCV) have not been investigated yet. We aimed to evaluate this issue. We enrolled 472 patients with chronic HCV infection who achieved viral eradication with direct‐acting antivirals (DAA). We investigated whether the status of perihepatic lymph nodes changed before and after HCV eradication (primary endpoint). We also evaluated the association between PLNE and clinical findings such as liver fibrosis or hepatocellular injury before HCV eradication (secondary endpoint). Perihepatic lymph node enlargement was detected in 164 of 472 (34.7%) patients before DAA treatment. Surprisingly, disappearance of PLNE was observed in 23.8% (39 patients) of all PLNE‐positive patients after eradication of HCV. Disappearance of PLNE was not associated with baseline clinical parameters or changing rates of clinical findings before and after DAA treatment. At baseline, presence of PLNE was significantly associated with a lower serum HCV‐RNA level (P = .03), a higher serum AST level (P = .004) and a higher ALT level (P < .001) after adjustment for sex and age. In conclusion, PLNEs became undetectable after DAA treatment in 23.8% of PLNE‐positive patients. Further study with a longer follow‐up period is needed to clarify the clinical importance of this phenomenon especially in relationship with the risk of HCC development.

Impact of direct-acting antivirals on early recurrence of HCV-related HCC: comparison with interferon-based therapy

BACKGROUND & AIMS It remains controversial whether direct-acting antivirals (DAAs) accelerate the recurrence of hepatitis C-related hepatocellular carcinoma (HCC) after curative therapy. This study aimed to evaluate HCC recurrence after DAA treatment of chronic hepatitis C. METHODS We enrolled patients with a history of successful radiofrequency ablation treatment for hepatitis C-related HCC who received antiviral therapy with DAAs (DAA group: 147 patients) or with interferon (IFN)-based therapy (IFN group: 156 patients). We assessed HCC recurrence rates from the initiation of antiviral therapy using the Kaplan-Meier method and evaluated risk factors for HCC recurrence by multivariate Cox proportional hazard regression analysis. The recurrence pattern was categorized as follows: intrahepatic recurrence with a single tumor <2 cm (stage 0), a single tumor or up to 3 tumors ≤3 cm (stage A), multinodular (stage B), and extrahepatic metastasis or macrovascular invasion (stage C). RESULTS The recurrence rates at 1 and 2 years were 39% and 61% in the IFN group and 39% and 60% in the DAA group, respectively (p = 0.43). Multivariate analysis identified higher lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, a history of multiple HCC treatments, and a shorter interval between HCC treatment and initiation of antiviral therapy as independent risk factors for HCC recurrence. HCC recurrence in stage 0, A, B, and C was found in 56 (41%), 60 (44%), 19 (14%), and 1 (0.7%) patients in the IFN group and 35 (44%), 32 (40%), 11 (14%), and 2 (2.5%) patients in the DAA group, respectively (p = 0.70). CONCLUSIONS HCC recurrence rates and patterns after initiation of antiviral therapy did not differ between patients who received IFN-based therapy and DAA therapy. LAY SUMMARY We detected no significant difference in early hepatocellular carcinoma (HCC) recurrence rates and patterns between patients who received interferon-based and direct-acting antiviral therapy after HCC treatment. High lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, short recurrence-free period, and a history of multiple HCC treatments were independent risk factors for early HCC recurrence after the initiation of antiviral therapy.