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.

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.

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.

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.

An atypical extrahepatic metastasis of the distal phalanx from hepatocellular carcinoma.

A 49-year-old woman presented with severe swelling and pain of the left little finger, which had exacerbated rapidly, in October 2006. The patient had a history of hepatocellular carcinoma and metastatic lung cancer. She had undergone partial hepatectomy for the hepatocellular carcinoma in September 2001 and pulmonary resection for metastatic lung cancer in November 2005. Roentgenogram of the hand on admission showed complete destruction of the distal phalanx of the left little finger. The final pathological result of the tissue obtained by disarticulation was an extrahepatic metastasis of hepatocellular carcinoma. Extrahepatic metastasis from primary hepatocellular carcinoma to the hand is very rare and only four cases have been reported in the literature. All the patients with extrahepatic metastases from the primary hepatocellular carcinoma to the hand had poor prognoses, but the patient presented in this article exhibited an unusual clinical course. The patient is still alive 1 year after the diagnosis of extrahepatic bone metastasis of the distal phalanx.

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.

Outcome of patients with hepatitis C virus-related single, small hepatocellular carcinoma.

To clarify the cumulative recurrence-free interval and survival rate with hepatitis C virus (HCV)-related single, small hepatocellular carcinoma (HCC), we studied 32 patients with surgical resection, 61 with ablation therapy and 28 with transcatheter chemoembolization (TACE). A log-rank test revealed that there were no significant differences in the recurrence-free interval (p = 0.08) and survival (p = 0.279) between the resection and the ablation groups. Univariate analysis using the Cox proportional hazards regression model showed initial treatment (p = 0.0051) was associated with recurrence-free interval. Platelet count (p = 0.009), indocianine green retention rate at 15 minutes (p = 0.003), Child-Pugh classification (p = 0.001), serum albumin level (p = 0.0012) and serum total bililubin (p = 0.015) were associated with survival. Hence patients with HCV-related single, small HCC should be treated according to their hepatic reserve.

Outcome of patients with hepatitis C virus-related hepatocellular carcinoma occurring after interferon therapy.

To determine whether previous IFN therapy for chronic hepatitis C (HCV) infection influences the outcome of patients with hepatocellular carcinoma (HCC), 143 patients were enrolled in this study. Of 143 patients, 48 had received previous IFN therapy (IFN group) and the remaining 95 had not (untreated group). We estimated distant intrahepatic recurrence-free intervals and disease-specific survivals of the two groups by the Kaplan-Meier method and analyzed the difference by the log-rank test. Factors determining distant intrahepatic recurrence-free interval and disease-specific survival were studied by univariate and multivariate analysis using Cox proportional hazards regression model. The proportion of patients with single tumors was significantly higher in the IFN group (p = 0.026). The IFN group showed a significantly higher distant intrahepatic recurrence-free interval (p = 0.001) and disease-specific survival (p = 0.003). Moreover, multivariate analysis indicated that previous IFN therapy for chronic HCV infection was a significant independent factor for distant intrahepatic recurrence-free interval and disease-specific survival. These results indicate that previous IFN therapy reduces multicentric hepatocarcinogenesis of HCV-related HCC and improves the patients' survival.