Shintaro Takaki

Factors contributing to ribavirin dose reduction due to anemia during interferon alfa2b and ribavirin combination therapy for chronic hepatitis C.

BackgroundRecent studies indicate that combination therapy with ribavirin and interferon alfa2b (IFNΑ2b) is effective for chronic hepatitis C virus (HCV) infection. However, reversible hemolytic anemia is a common side effect of this therapy.MethodsWe determined those factors that contribute to ribavirin dose reduction due to anemia during this treatment by using multiple logistic regression analysis in Japanese patients. The study included 123 patients with chronic hepatitis C (85 male, 38 female; mean age, 50 years; range, 20–70 years), who received 24-week combination therapy. All patients were treated with IFNΑ2b daily for 2 weeks, followed by three times weekly dosing for 22 weeks, with oral ribavirin twice daily, at a total daily dose of 600 or 800 mg.ResultsOf the 123 patients, 34 patients required dose reduction of ribavirin, and 78 patients required no dose reduction. Overall, 20 patients discontinued. On univariate analysis, reduction of the ribavirin dose correlated significantly with pretreatment hemoglobin (Hb) levels of less than 14 g/dl, female sex, and patient age 55 years or older. On multivariate analysis, pretreatment Hb of less than 14 g/dl level and age 55 years or older were significantly associated with ribavirin dose reduction. The hazard ratios were 3.56 (95% confidence interval [CI], 1.48–8.53) for pretreatment Hb levels of less than 14 g/dl, and 2.50 (95% CI, 1.05–5.94) for age 55 years or more.ConclusionsBecause patient age of 55 years or more, and Hb levels of less than 14 g/dl are significant factors that influence ribavirin-induced hemolytic anemia, more careful monitoring is necessary during combination therapy for patients with these risk factors.

The long-term outcome of patients with bleeding gastric varices after balloon-occluded retrograde transvenous obliteration

BackgroundThe purpose of our study was to evaluate the long-term outcome and complications of balloon-occluded retrograde transvenous obliteration (B-RTO) in patients with hemorrhage from gastric fundal varices.MethodsThirty-four consecutive patients with bleeding from gastric varices who were treated with B-RTO were enrolled in this study between December 1994 and September 2005 (urgent cases, n = 12; elective cases, n = 22). The long-term outcome, complications, and various liver functions were evaluated.ResultsComplete obliteration was achieved in 31 of 34 (91%) patients with an acute bleeding episode. In one of the remaining patients, there was a technical failure, and the other two had only partial obliteration. The two patients with partial obliteration did not obtain hemostasis. Thus, the rate of hemostasis was 94% (31/33). Gastric varices disappeared in all patients with complete obliteration during the treatment. The rate of gastric variceal eradication was 91%. Variceal rebleeding from esophageal varices occurred in three patients. The rate of rebleeding was 10% (3/31). Rebleeding from gastric varices was not observed after complete obliteration. None of the patients showed worsening of their Child-Pugh score. Although the 5-year cumulative worsening rate of esophageal varices was 52%, neither portal hypertensive gastropathy nor ectopic varices were observed. The patients with worsening esophageal varices were successfully treated with an endoscopic procedure. The 5-year survival rate was 68%.ConclusionsB-RTO is useful for treatment of bleeding gastric varices, achieving high eradication of gastric varices, a low rebleeding rate, and a fairly good prognosis with improved hepatic function.

Recent trend of clinical features in patients with hepatocellular carcinoma

Aim:  In this study, we evaluated the clinical characteristics of hepatocellular carcinoma (HCC) because the etiology of HCC has been changing recently.

Percutaneous radiofrequency ablation as first‐line treatment for small hepatocellular carcinoma: Results and prognostic factors on long‐term follow up

Background and Aims:  We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first‐line treatment.

Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma

To compare the tumor control and safety of stereotactic body radiation therapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) for small, solitary, and hypervascular hepatocellular carcinoma (HCC) with TACE alone.

Evaluation of the mRECIST and α-fetoprotein ratio for stratification of the prognosis of advanced-hepatocellular-carcinoma patients treated with sorafenib.

Objective: To compare the assessment of response and prognosis of patients to sorafenib treatment by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP). Methods: Sixty-six patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib were enrolled in this retrospective study. The response to treatment was evaluated by RECIST, mRECIST and changes in AFP and DCP. Results: The median survival time of all patients was 8.6 months. The median time to radiological progression was 3.3 months. The response rates [complete response (CR) + partial response (PR)] by RECIST and mRECIST were 3.0 and 9.0%, respectively, while the disease control rates [CR + PR + stable disease (SD)] were 50 and 50%, respectively. Assessment by mRECIST of overall survival provided a better stratification of the patients according to the response to treatment (p = 0.009) than RECIST (p = 0.09). Assessment of overall survival by a change in AFP ratio of ≤1 at 8 weeks was better than that of >1 at 8 weeks (p = 0.002). The DCP ratio was not useful for assessment of overall survival. Multivariate analysis identified mRECIST response (CR + PR + SD; p = 0.001), AFP ratio at 8 weeks (≤1; p = 0.046) and Child-Pugh A before treatment (p = 0.012) as significant and independent determinants of survival. The combination of AFP ratio at 8 weeks, assessment by mRECIST and Child-Pugh score before treatment allows stratification of prognosis of patients treated with sorafenib. Conclusion: The combination of mRECIST and AFP ratio is useful for the assessment of prognosis of patients with advanced HCC treated with sorafenib.

Pretreatment predictor of response, time to progression, and survival to intraarterial 5-fluorouracil/interferon combination therapy in patients with advanced hepatocellular carcinoma

BackgroundSeveral studies have reported survival benefits of combination therapy with intraarterial 5-fluorouracil (5-FU) and subcutaneous interferon (IFN) α for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We investigated the pretreatment predictive factors of early response, time to progression (TTP), and survival in response to intraarterial 5-FU/IFN combination therapy.MethodsPatients with nonresectable HCC and variable PVTT grades (without PVTT to PVTT in the trunk) received intraarterial 5-FU/IFN combination therapy (n = 55).ResultsAfter two courses of the combination therapy, 1 (2%), 15 (27%), 16 (29%), 12 (22%), and 11 (20%) of 55 patients showed complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or had dropped out (DO), respectively, when their early response to treatment was assessed. Univariate analysis identified only hepatitis C virus (HCV) antibody positivity as having significantly influenced the early response (P = 0.028) and TTP (P = 0.021). Multivariate analysis identified performance status (P = 0.003) and HCV antibody positivity (P = 0.007) as significant and independent determinants of survival. PVTT grade did not influence early response, TTP, or survival. The survival rate was significantly higher in patients who achieved CR or PR than in those that assessed as SD or PD, or DO (P < 0.0001, each).ConclusionsHCV antibody positivity may be a significant pretreatment predictor of early response, TTP, and survival of patients with advanced HCC treated with 5-FU/IFN. CR or PR as the early response to the combination therapy might indicate a more favorable prognosis in patients with advanced HCC. PVTT grade did not seem to influence the efficacy of combination therapy.

FDG positron emission tomography/computed tomography for the detection of extrahepatic metastases from hepatocellular carcinoma

Aims:  To compare the efficacy of positron emission tomography (PET) computed tomography (CT), multi‐detector helical computed tomography (MDCT) and bone scintigraphy for the detection of extrahepatic metastases in patients with hepatocellular carcinoma (HCC).

Utility of controlled attenuation parameter measurement for assessing liver steatosis in Japanese patients with chronic liver diseases

Steatosis is a common histological feature of chronic liver disease, especially alcoholic and non‐alcoholic fatty liver disease, as well as chronic hepatitis C. A recent study showed that evaluating the controlled attenuation parameter (CAP) with transient elastography was an efficient way of non‐invasively determining the severity of hepatic steatosis. The objective of this study was to prospectively evaluate the utility of CAP for diagnosing steatosis in patients with chronic liver disease.

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma according to Child-Pugh classification.

We compared the treatment response, survival, and safety to hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) according to Child–Pugh (CP) score.