Clinical Effect of Lenvatinib Re-Administration after Transcatheter Arterial Chemoembolization in Patients with Intermediate Stage Hepatocellular Carcinoma.

The present study clarified the prognosis of intermediate-stage hepatocellular carcinoma (HCC) patients who received lenvatinib (LEN) followed by transcatheter arterial chemoembolization (TACE) on demand. We retrospectively evaluated 88 intermediate-stage HCC patients who received LEN. The median age was 74 (range: 47-92) years old, 67 patients were male, and 82 were classified as Child-Pugh A. LEN was administered until disease progression or discontinuation due to adverse events (AEs). The mean duration of LEN treatment was 7.0 months. The response and disease control rates were 51.1% and 89.8%, respectively. The median progression-free survival and overall survival (OS) after the initiation of LEN were 6.8 months and 29.9 months, respectively. The OS in patients for whom LEN was re-administered after TACE (TACE-LEN) was better than that in patients who received other therapies (e.g., only TACE, TACE-other therapy, or only other therapy) even with propensity score matching (p = 0.008). A Cox proportional hazard analysis showed that TACE-LEN was most strongly associated with the OS (hazard ratio: 0.083, 95% confidence interval: 0.019-0.362, p = 0.001). LEN was administered for approximately 11.1 months after TACE. In intermediate-stage HCC patients who can tolerate LEN without discontinuation due to AEs, TACE-LEN may prolong the prognosis.

Features of patients who developed hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C Virus.

BACKGROUND: The features of hepatitis C virus patients with a sustained virologic response (SVR) who developed hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) therapy are unclear. METHODS: The study population included 1494 DAA-SVR patients without a history of HCC. The cumulative carcinogenesis rate after the end of treatment (EOT) and factors related to HCC were analyzed. RESULTS: Sixty (4.0%) patients developed HCC during a median observation period of 47.6 months. At four years, the cumulative carcinogenesis rate was 4.7%. A Cox proportional hazards analysis showed that age ≥73 years (hazard ratio [HR]: 2.148), male sex (HR: 3.060), hyaluronic acid (HA) ≥75 ng/mL (HR: 3.996), alpha-fetoprotein at EOT (EOT-AFP) ≥5.3 ng/mL (HR: 4.773), and albumin at EOT (EOT-Alb) <3.9 g/dL (HR: 2.305) were associated with HCC development. Especially, EOT-AFP ≥5.3 ng/mL was associated with HCC development after 3 years from EOT (HR: 6.237). Among patients who developed HCC, AFP did not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. Of these 5 factors, EOT-AFP ≥5.3 ng/mL was scored as 2 points; the others were scored as 1 point. The 4-year cumulative carcinogenesis rate for patients with total scores of 0-2, 3-4, and 5-6 points were 0.6%, 11.9%, and 27.1%, respectively (p<0.001). CONCLUSIONS: EOT-AFP ≥5.3 ng/mL is useful for predicting HCC development after an SVR. However, AFP does not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. The combination of EOT-AFP, age, sex, HA, and EOT-Alb is important for predicting carcinogenesis.

Changes in body composition and low blood urea nitrogen level related to an increase in the prevalence of fatty liver over 20 years: A cross-sectional study.

AIM: Qualitative body composition (BC) change, characterized by the combination of visceral fat gain and muscle loss, is drawing attention as a risk factor for fatty liver (FL). The present study aimed to describe trends in BC change and its association with FL in the Japanese population. METHODS: Data from medical checkups carried out on 56 639 Japanese participants every 5 years from 1997 to 2017 were analyzed. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated using body mass index and body fat percentage. Subjects were divided into two groups according to deviations from the correlation line of FMI and FFMI as the reference: FMI-predominant BC and FFM-dominant BC. Fatty liver was determined using abdominal ultrasonography. RESULTS: The prevalence of FL significantly increased from 27.3% to 42.7% in men and from 18.0% to 25.5% in women. The prevalence of FMI predominance significantly increased from 33.6% to 43.9% in men and from 29.1% to 47.0% in women. Fat mass index predominance was independently associated with FL in men and women (odds ratio: 1.96 and 1.94, respectively). Serum blood urea nitrogen level was inversely associated with FL in men and women (0.958 and 0.961, respectively) and significantly decreased from 15.8 to 14.9 mg/dl in men and from 15.1 to 14.0 mg/dl in women. CONCLUSIONS: Increasing FMI-predominant BC and decreasing serum blood urea nitrogen level could account for the increase in the prevalence of FL over 20 years. We believe that these factors stem from current lifestyle habits in Japan.

Efficacy of rifaximin, a poorly absorbed rifamycin antimicrobial agent, for hepatic encephalopathy in Japanese patients.

AIM: Rifaximin is recommended as treatment for hepatic encephalopathy (HE) that targets intestinal bacterial flora. Although combined use with synthetic disaccharides is the standard of care worldwide, the therapeutic effects of rifaximin for overt encephalopathy (OHE) in Japanese patients have not been examined sufficiently. We examined the therapeutic effects of rifaximin for OHE in Japanese patients. METHODS: A total of 76 patients who developed OHE of West Haven grade II or higher at least once within the 12 months before starting rifaximin were included. Blood ammonia levels and the incidence of OHE during the 12 months before and after starting rifaximin therapy were compared in a before-and-after study. Rifaximin efficacy and predictors of efficacy were also examined. RESULTS: Post-treatment blood ammonia levels were significantly lower than pretreatment levels. The mean annual number of OHE incidents and intravenous branched-chain amino acid preparations used per patient were significantly lower after starting rifaximin therapy (2.51 vs. 0.76 times/year, p < 0.001; and 71.9 vs. 20.7 preparations/year, p = 0.003, respectively). The cumulative incidence of hospitalizations associated with HE significantly decreased after rifaximin therapy (hazard ratio 0.187; p < 0.001). The efficacy rate, defined as the proportion of patients without OHE during the administration of rifaximin for 1 year after starting rifaximin therapy, was 65.8%. Serum albumin ≥2.7 g/dl was an independent predictor of efficacy. CONCLUSION: Rifaximin was associated with decreased blood ammonia levels, lower incidence of OHE, and fewer hospitalizations in Japanese patients with HE. In addition, serum albumin level was an important predictor on efficacy of rifaximin.

Impact of acute kidney injury on prognosis and the effect of tolvaptan in patients with hepatic ascites.

BACKGROUND: In hepatic cirrhosis, ascites and acute kidney injury (AKI) portend poor prognosis. We examined the incidence and characteristics of AKI in patients with hepatic ascites and the impact of diuretics on AKI onset. METHODS: This study included 337 patients with hepatic ascites treated with oral diuretics during September 2013-June 2019. Incidence of AKI, cumulative survival by AKI status, and prognostic factors were investigated. Patients were divided into those treated with tolvaptan (TLV) [TLV group (n = 244)] and those not treated with TLV [control group (n = 93)]. After propensity score matching, the incidence of AKI and changes in renal function and doses of diuretics were compared. RESULTS: The incidence of AKI overall was 35% (n = 118). Patients with AKI had a significantly worse survival than those without AKI (P = 0.001), indicating that AKI is an independent prognostic factor for hepatic ascites (P = 0.025). After adjustment for background factors in the two groups (n = 77 each), the TLV group had a significantly lower incidence of AKI (27.6% vs. 44.7%, P = 0.028). While renal function worsened with higher natriuretic agent doses in the control group, no significant change was observed in the TLV group, suggesting that TLV is an independent prognostic factor for AKI onset. CONCLUSIONS: Our study suggests that concomitant AKI significantly worsens survival in Japanese patients with hepatic ascites, and TLV and natriuretic agent combination therapy might lead to an excellent synergistic therapeutic effect of hepatic ascites and inhibition of AKI onset.

Hypovascular tumors developed into hepatocellular carcinoma at a high rate despite the elimination of hepatitis C virus by direct-acting antivirals.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) exert high anti-HCV activity and are expected to show anti-inflammatory effects associated with HCV elimination. Furthermore, hepatocellular carcinoma (HCC) is known to dedifferentiate from hypovascular tumors, such as dysplastic nodules or well-differentiated HCC, to hypervascular tumors. We therefore explored whether or not DAAs can suppress the growth and hypervascularization of hypovascular tumors. METHODS: We enrolled 481 patients with HCV genotype 1 infection who were treated with Daclatasvir and Asunaprevir therapy. Of these, 29 patients had 33 hypovascular tumors, which were confirmed by contrast-enhanced MRI or CT before therapy. We prospectively analyzed the cumulative incidence of HCC, i.e. the growth or hypervascularization of hypovascular tumors, and compared the HCC development rates between patients with hypovascular tumors and those without any tumors. RESULTS: The mean size of the hypovascular tumors was 11.3 mm. Twenty seven of 29 patients who achieved an SVR had 31 nodules, 19 of 31 nodules (61.3%) showed tumor growth or hypervascularization, and 12 (38.7%) nodules showed no change or improvement. The cumulative incidence rates of tumor growth or hypervascularization were 19.4% at 1 year, 36.0% at 2 years, 56.6% at 3 years, and 65.3% at 4 years. Among the patients who achieved a sustained virologic response, the cumulative HCC development rates of patients with hypovascular tumors was significantly higher than in those without any tumors. A Cox proportional hazard analysis showed that a history of HCC therapy, the presence of a hypovascular tumor, and AFP >4.6 ng/mL at the end of treatment were independent risk factors for HCC development. CONCLUSION: Hypovascular tumors developed into HCC at a high rate despite the elimination of HCV by DAAs. As patients with hypovascular tumors were shown to have a high risk of HCC development, they should undergo strict HCC surveillance.

Viral and host factors are associated with retreatment failure in hepatitis C patients receiving all-oral direct antiviral therapy.

AIM: Direct-acting antiviral (DAA) therapy for hepatitis C virus is associated with high sustained virologic response rates. However, patients for whom DAA therapy fails acquire resistance-associated substitutions (RASs). We therefore evaluated the efficacy of DAA retreatment and factors associated with retreatment failure. METHODS: Non-structural 5A RASs were investigated at the start of DAA therapy and at treatment failure in 64 patients with hepatitis C virus genotype 1b for whom DAA combination therapy had failed. A total of 59 patients were introduced to DAA retreatment. The factors associated with retreatment failure were investigated. RESULTS: A total of 20 of 43 (46.5%) daclatasvir + asunaprevir-treated patients with virologic failure had no RASs at baseline, and three (15%) acquired P32 deletion RASs. Four of seven sofosbuvir/ledipasvir-treated patients with virologic failure had more than two RASs of NS5A at baseline. The sustained virologic response rates on retreatment were as follows: sofosbuvir/ledipasvir, 81.8%; with elbasvir + grazoprevir, 0%; and glecaprevir/pibrentasvir, 87.5%. Patients for whom sofosbuvir/ledipasvir or elbasvir + grazoprevir failed achieved sustained virologic response with glecaprevir/pibrentasvir. Two of three patients for whom glecaprevir/pibrentasvir retreatment failed had Q24/L28/R30 and A92K RASs; the other had P32 deletion RAS at baseline. Interestingly, 10 of 11 patients with retreatment failure had the interleukin (IL)-28B single-nucleotide polymorphism (SNP) minor allele. A multivariate analysis showed that the IL28B SNP minor allele (P = 0.005, odds ratio 28.291) was an independent risk factor for retreatment failure. CONCLUSIONS: In addition to viral factors (e.g. Q24, L28, R30, and A92 or P32 deletion RASs), host factors (e.g. IL28B SNP) are associated with DAA retreatment failure.

Nonalcoholic fatty liver disease is associated with both subcutaneous and visceral adiposity: A cross-sectional study.

Nonalcoholic fatty liver disease (NAFLD) is recognized as a hepatic manifestation of metabolic syndrome because of the association with visceral obesity. However, the association between NAFLD and subcutaneous fat accumulation remains unclear.The study population included 3197 participants in regular health checkups, who were both hepatitis B virus surface antigen and hepatitis C virus antibody-negative, and consumed <20 g of alcohol per day. They were divided according to 4 quantiles of subcutaneous fat area (SFA) and visceral fat area (VFA) on computed tomography. Fatty liver was diagnosed using ultrasonography (FL-US).The prevalence of FL-US increased across the SFA categories, even after adjusting for the VFA, in both men (P < .001) and women (P < .001). This significant association between FL-US and the SFA was already detected from the second SFA quantile. It is noteworthy that the mean body mass index (BMI) of the subjects in the second quantile was 23.7 kg/m in men and 22.6 kg/m in women. Independent positive associations were observed between alanine aminotransferase elevation, and both the SFA and VFA in men, while gamma glutamyl transpeptidase elevation was independently associated with the VFA, but not the SFA, in both men and women. Similarly, the components of metabolic syndrome were independently associated with the VFA, but were less strongly associated (or not associated at all) with the SFA.This cross-sectional study suggests that NAFLD is independently associated with both visceral and subcutaneous adiposity ab initio, which is a characteristic that distinguishes NAFLD from other components of metabolic syndrome.

Effect of tolvaptan on the prognosis of patients with hepatic ascites.

AIM: Despite accumulating evidence concerning the efficacy of tolvaptan in the treatment of body fluid retention or hyponatremia, the effect of tolvaptan on the prognosis of patients with hepatic ascites has not been fully investigated. METHODS: A total of 628 patients with hepatic ascites who were treated with diuretics (furosemide, spironolactone, or tolvaptan) between 2007 and 2017 were enrolled and divided into two groups: those who received tolvaptan (original tolvaptan group, n = 278) and those who did not (original control group, n = 350). The cumulative survival rates between the groups were compared and the factors associated with survival in patients with hepatic ascites were identified using a Cox regression analysis. In addition, propensity score matching was applied in patients who started conventional diuretics for new-onset hepatic ascites after September 2013 (pre-matching tolvaptan group, n = 177; pre-matching control group, n = 63), and the cumulative survival rates were compared between the post-matching tolvaptan and control groups. RESULTS: The survival rate was significantly higher in the tolvaptan group than the control group (P = 0.005), and tolvaptan therapy was identified as an independent factor associated with survival (hazard ratio 0.721 for death relative to control, P < 0.001). The propensity score-matched comparison also showed a significantly higher survival rate in the tolvaptan group (n = 51) than in the control group (n = 51) (P = 0.009). CONCLUSIONS: This study suggests that tolvaptan might improve the prognosis of patients with hepatic ascites.

The co-existence of NS5A and NS5B resistance-associated substitutions is associated with virologic failure in Hepatitis C Virus genotype 1 patients treated with sofosbuvir and ledipasvir.

OBJECTIVE: The present study aimed to reveal the factors associated with virologic failure in sofosbuvir and ledipasvir (SOF/LDV)-treated patients, and identify baseline NS5A or NS5B resistance-associated substitutions (RASs). METHODS: Four hundred ninety-three patients with Hepatitis C Virus (HCV) genotype 1b infection were treated with SOF/LDV; 31 had a history of interferon (IFN)-free treatment with daclatasvir and asunaprevir. The effect of baseline RASs on the response to SOF/LDV therapy was analyzed. RESULTS: Overall, a sustained virologic response at 12 weeks (SVR12) was achieved in 476 patients (96.6%). The SVR12 rates in the patients with IFN-free treatment-naïve and retreatment were 97.6% and 80.6%, respectively. HCV elimination was not achieved in 17 patients, 11 (including 5 with IFN-free retreatment) of whom had virologic failure. Eight patients had coexisting NS5A RASs of Q24, L28 and/or R30, L31, or Y93 and one patient had coexisting NS5A RASs of P32L and A92K. Interestingly, 10 and 8 patients had NS5B A218S and C316N RAS respectively. According to a multivariate analysis, coexisting NS5A RASs, NS5A P32 RAS, NS5B A218 and/or C316 RASs, and γ-glutamyltranspeptidase were associated with virologic failure. In the naïve patients, all patients without NS5B A218 and/or C316 RAS achieved an SVR12. Notably, the SVR12 rates of patients with coexisting NS5A and NS5B RASs were significantly lower (83.3%). CONCLUSIONS: Although SOF/LDV therapy resulted in a high SVR12 rate, coexisting NS5A and NS5B RASs were associated with virologic failure. These results might indicate that the coexisting baseline RASs influence the therapeutic effects of SOF/LDV.

Response criteria of tolvaptan for the treatment of hepatic edema.

BACKGROUND: Although tolvaptan is an effective treatment for hepatic edema, there are no established criteria for assessment of the therapeutic effect. The present study evaluates the association between body weight change and clinical symptoms to identify an effective indicator of tolvaptan response. METHODS: The study comprised 460 patients. The first data set contained 147 patients with hepatic edema who received tolvaptan in Kagoshima Kouseiren Hospital, a representative institution of this study. From these data, an optimal cutoff value of body weight change, which accurately indicated symptom reduction, was identified. The response rates obtained based on the cutoff value were evaluated by receiver-operating characteristic (ROC) analysis and kappa coefficients. The kappa coefficient was then validated internally using the bootstrap method and externally using the validation data set of 313 patients from four other hospitals. RESULTS: A cutoff value for body weight loss of 1.5 kg/week produced the largest area under the ROC curve (0.961; sensitivity, 89.8%; specificity, 92.0%) and a high kappa coefficient (0.831). The correlation between symptom reduction and body weight loss of 1.5 kg/week was evaluated internally and externally, and the cutoff value was validated. CONCLUSIONS: The cutoff value of body weight change that most accurately reflected symptom reduction was 1.5 kg/week; this value is expected to be an effective indicator of response to tolvaptan in clinical practice.

New resistance-associated substitutions and failure of dual oral therapy with daclatasvir and asunaprevir.

BACKGROUND: Daclatasvir (DCV) and asunaprevir (ASV) combination therapy has been primarily used in patients without NS5A L31 or Y93 resistance-associated substitutions (RASs) before treatment. We examined the characteristics of patients without these baseline RASs who did not achieve hepatitis C virus eradication with DCV and ASV combination therapy and identified new baseline NS5A RASs that are closely associated with failure of combination therapy. METHODS: Three hundred thirty-five patients with hepatitis C virus genotype 1 infection with no NS5A L31, NS5A Y93, and NS3 D168 RASs before DCV and ASV combination therapy and no history of protease inhibitor therapy were enrolled. All RASs were evaluated by direct sequencing. RESULTS: Sustained virologic response at 12 weeks (SVR12) was achieved in 297 patients (89%). Patients with NS5A Q24, L28, and/or R30 RASs or concomitant NS5A F37 and Q54 RASs had a significantly lower SVR12 rate than patients without these RASs (70% vs 92%, p < 0.001 and 79% vs 92%, p = 0.002 respectively). Multivariate analysis showed that NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs were significantly associated with virologic failure. The SVR12 rate in patients without NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs was 96.2% (202/210). CONCLUSIONS: In patients without NS5A L31 or Y93 RASs, the presence of NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs at the baseline was associated with failure of DCV and ASV combination therapy. The coexistence of baseline RASs other than NS5A L31 and Y93 may affect the therapeutic effectiveness of DCV and ASV combination therapy.

Efficacy of vasopressin V2 receptor antagonist tolvaptan in treatment of hepatic edema.

AIM: Tolvaptan, an oral active vasopressin V2 receptor antagonist, is widely used for hepatic edema in Japan, but its clinical benefits have yet to be fully clarified. The present study evaluated the efficacy of tolvaptan in hepatic edema. METHODS: The efficacy and treatment regimen of tolvaptan were evaluated in 150 patients with hepatic edema by analyzing the initial (day 14) and long-term (day 90) responses to the drug and their predictive factors. All patients were divided into good (Child-Pugh classification B, and absent of advanced hepatocellular carcinoma) and poor hepatic condition groups, and the response rates were compared between the two groups. RESULTS: The initial response rate was 62%, and the long-term response rate was 47%. The assessment of predictive factors for response to tolvaptan showed that serum creatinine and C-reactive protein levels were important predictors of initial response, and that hepatic conditions, such as the Child-Pugh score or presence of hepatocellular carcinoma, as well as initial response, were significant predictors of long-term response. In addition, both the initial and long-term response rates and the cumulative survival rate were found to be higher in the good hepatic condition group than in the poor hepatic condition group, respectively (71% vs. 57%, P = 0.113; 62% vs. 39%, P = 0.009; log-rank test, P < 0.001). CONCLUSION: These results suggest that tolvaptan may provide high response rates when used early in the course of hepatic edema, or when both hepatic and renal functions are still retained, leading to an improved disease prognosis.

Increasing prevalence of diabetes mellitus in association with fatty liver in a Japanese population.

BACKGROUND: The prevalence of diabetes mellitus (DM) has been increasing. The present study was carried out to examine the relationship between this increase and fatty liver. METHODS: Japanese participants who underwent regular health examinations in 1991, 1996, 2001, 2006, and 2011 were enrolled. Fatty liver was diagnosed using ultrasonography. DM was defined as requiring the use of medication for DM, having a fasting blood glucose level ≥ 126 mg/dl, or hemoglobin A1c level ≥ 6.5 %. RESULTS: Logistic regression analysis on data from 11,235 participants (6,882 men and 4,271 women) in 2011 revealed that the association between fatty liver and DM was independent of age, body composition, and other confounders [odds ratio (OR) 1.97, 95 % confidence interval (95 % CI) 1.66-2.32 in men, and OR, 3.12; 95 % CI, 2.29-4.26 in women]. In 2006, 5,318 participants did not have DM and were able to be followed up in 2011. Fatty liver in 2006 was an independent predictor of DM in 2011 [OR 1.73 (95 % CI 1.20-2.50) in men, 4.13 (2.16-8.10) in women]. The prevalence of DM increased significantly during the 20-year period examined among both men (6.0, 8.9, 10.0, 10.8, 12.0 %, P < 0.001) and women (3.3, 4.5, 4.2, 4.1, 5.1 %, P = 0.004), accompanied with an increased prevalence of fatty liver among both men (10.8, 26.3, 33.8, 36.7, and 38.0 %, P < 0.001) and women (6.5, 16.7, 22.2, 21.3, and 20.8 %, P < 0.001). CONCLUSION: Fatty liver independently predicts both present and future DM. Fatty liver may play an important role in the recent increases in the prevalence of DM.

Fatty liver in men is associated with high serum levels of small, dense low-density lipoprotein cholesterol.

AIMS: Our study addressed potential associations between fatty liver and small, dense low-density lipoprotein cholesterol (sd-LDL-C) levels using a cross-sectional analysis. METHODS: We enrolled 476 male subjects. Serum sd-LDL-C concentrations were determined using precipitation assays. RESULTS: Subjects were divided into four groups based on triglyceride (TG) and LDL-C levels: A, TG < 150 mg/dl and LDL-C < 140 mg/dl; B, TG < 150 mg/dl and LDL-C ≥ 140 mg/dl; C, TG ≥ 150 mg/dl and LDL-C < 140 mg/dl; and D, TG ≥ 150 mg/dl and LDL-C ≥ 140 mg/dl. sd-LDL-C levels and the prevalence of fatty liver were significantly higher in groups B, C, and D than in group A. Subjects were also categorized into four groups based on serum sd-LDL-C levels; the prevalence of fatty liver significantly increased with increasing sd-LDL-C levels. Additionally, logistic regression analysis revealed an independent association between sd-LDL-C concentrations and fatty liver using such potential confounders as obesity and hyperglycemia as variables independent of elevated TG or LDL-C levels. CONCLUSIONS: Fatty liver is a significant determinant of serum sd-LDL-C levels independent of the presence of obesity or hyperglycemia. Fatty liver may alter hepatic metabolism of TG and LDL-C, resulting in increased sd-LDL-C levels.

Alcohol drinking patterns and the risk of fatty liver in Japanese men.

BACKGROUND: Alcohol is considered to be a major cause of fatty liver (FL). In contrast, however, recent investigations have suggested that moderate alcohol consumption is protective against FL. To clarify the role of alcohol consumption in FL development, we examined the association between drinking patterns and FL prevalence. METHODS: We enrolled 9,886 male participants at regular medical health checks. Each subject's history of alcohol consumption was determined by questionnaire. The subjects were classified according to alcohol consumption as non-, light, moderate, and heavy drinkers (0, <20, 20-59, and ≥60 g/day, respectively). FL was defined by ultrasonography. Independent predictors of FL were determined by logistic regression analysis. RESULTS: The prevalence of FL displayed a "U-shaped curve" across the categories of daily alcohol consumption (non-, 44.7%; light, 39.3%; moderate, 35.9%; heavy drinkers, 40.1%; P < 0.001). The prevalence of FL was associated positively with body mass index and other obesity-related diseases and inversely with alcohol consumption (light, odds ratio [OR] 0.71, 95% confidence interval [CI] 0.59-0.86; moderate, OR 0.55, CI 0.45-0.67; heavy, OR 0.44, CI 0.32-0.62) as determined by multivariate analysis after adjusting for potential confounding variables. In addition, examination of drinking patterns (frequency and volume) revealed that the prevalence of FL was inversely associated with the frequency of alcohol consumption (≥21 days/month) (OR 0.62, CI 0.53-0.71) but not with the volume of alcohol consumed. CONCLUSIONS: Our observations suggest that alcohol consumption plays a protective role against FL in men, and consistent alcohol consumption may contribute to this favorable effect.

Sorafenib and hepatic arterial infusion chemotherapy for unresectable advanced hepatocellular carcinoma: A comparative study.

Sorafenib is a kinase-targeted drug that has high efficacy for advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine whether sorafenib is more effective than hepatic arterial infusion chemotherapy (HAIC) for HCC. Twenty patients treated with sorafenib (sorafenib group) initiated at 800 mg/day and 45 patients treated with HAIC (HAIC group) for unresectable Child-Pugh A advanced HCC were investigated retrospectively. The treatment effect was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). As a result, the overall response rate was significantly lower in the sorafenib group than in the HAIC group (P=0.03), while the disease control and survival rates did not differ between the two groups. In the sorafenib group, treatment was discontinued in 19 patients, including 12 due to side effects. In subgroups of patients treated with sorafenib, the survival rate was significantly lower in patients (n=11) administered sorafenib for <60 days compared to those (n=9) treated for ≥60 days. A shorter treatment period (<60 days) was an independent risk factor for unfavorable survival [hazard ratio (HR), 3.34; 95% confidence interval (CI), 1.45-7.66 vs. HAIC], while survival in patients treated with sorafenib for ≥60 days did not differ from those treated with HAIC (HR, 0.79; 95% CI, 0.27-2.34). In conclusion, the disease control and survival rates of patients treated with sorafenib for advanced HCC were comparable to such rates in patients treated with HAIC. However, the prognosis was poor when long-term sorafenib treatment was not possible due to side effects, demonstrating the importance of patient selection for sorafenib treatment.

[Evaluation of transhepatic artery chemotherapy for highly advanced hepatocellular carcinoma].

We conducted transhepatic arterial infusion chemotherapy (TAI) was on 62 patients with highly advanced hepatocellular carcinoma without distant metastases and therapeutic outcome was compared with 18 who were untreated. TAI significantly prolonged the survival of the patients, and was the most important prognostic factor on multivariate analysis. The following 3 regimens for trans-arterial injection were compared: A, a combination of a bolus hepatic artery injection of 3 agents (cisplatin, mitomycin-C and epirubicin)+low dose 5-fluorouracil+cisplatin (FP); B, low-dose FP alone; and C, bolus intrahepatic artery injection of the above 3 agents combined without FP. Regimen A yielded in the most effective survival rate, with an efficacy rate of 41.6% and a CR of about 20%. These results indicate that TAI is an effective therapeutic modality, and the dose FP combined with a bolus intrahepatic arterial infusion may improve outcomes in advanced liver cancer.

Association between changes in body composition and the increasing prevalence of fatty liver in Japanese men.

AIM: Prevalence of fatty liver is increasing. In this study, to elucidate the factor that contributes most to recent increases in prevalence of fatty liver, we determined the independent predictors for the onset of fatty liver and compared these predictors between 2000 and 2005. METHODS: Japanese persons, aged 30-74 years, who participated in regular health checks at Kagoshima Kouseiren Medical Health Care Center (10 336 persons in 2000 and 11 011 persons in 2005) were enrolled in the study. Diagnosis of fatty liver was performed by ultrasonography. Body fat percentage (BFP) was determined using a bipedal bioimpedance instrument. RESULTS: The prevalence of fatty liver has increased between 2000 and 2005 in men (33.3 vs 38.5% in 2000 vs 2005, respectively, P < 0.0001), but not in women (21.3 vs 21.0%, P = 0.8101). Logistic regression analysis revealed that both body mass index (BMI) and BFP are independent predictors of fatty liver in both men and women. BMI did not change in either men (23.4 +/- 2.9 vs 23.8 +/- 3.0 kg/m(2), P = 0.0528) or women (22.8 +/- 3.1 vs 22.8 +/- 3.3 kg/m(2), P = 0.9862) during the survey period. In contrast, BFP increased in men (20.6 +/- 4.7 vs 22.3 +/- 5.0 kg/m(2), P = 0.0003), but not in women (27.4 +/- 5.5 vs 28.4 +/- 5.9 kg/m(2), P = 0.3993). There was no significant change in triglycerides and glucose levels. CONCLUSION: These results suggest that altered body composition, particularly increased BFP without an increase in BMI, has developed in men and is strongly associated with the increasing prevalence of fatty live amongst Japanese men.