Yoshimichi Chuganji

Proton Beam Therapy for Hepatocellular Carcinoma: A Retrospective Review of 162 Patients

Purpose: We present results of patients with hepatocellular carcinoma (HCC) treated with proton beam therapy. Experimental Design: We reviewed 162 patients having 192 HCCs treated from November 1985 to July 1998 by proton beam therapy with or without transarterial embolization and percutaneous ethanol injection. The patients in the present series were considered unsuitable for surgery for various reasons, including hepatic dysfunction, multiple tumors, recurrence after surgical resection, and concomitant illnesses. The median total dose of proton irradiation was 72 Gy in 16 fractions over 29 days. Results: The overall survival rate for all of the 162 patients was 23.5% at 5 years. The local control rate at 5 years was 86.9% for all 192 tumors among the 162 patients. The degree of impairment of hepatic functions attributable to coexisting liver cirrhosis and the number of tumors in the liver significantly affected patient survival. For 50 patients having least impaired hepatic functions and a solitary tumor, the survival rate at 5 years was 53.5%. The patients had very few acute reactions to treatments and a few late sequelae during and after the treatments. Conclusions: Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic functions, and coexisting intercurrent diseases.

A new, effective and safe therapeutic option using proton irradiation for hepatocellular carcinoma

BACKGROUND/AIMS Conventional radiation is almost useless for hepatocellular carcinoma (HCC) because of the severe adverse effects of the irradiation to the accompanying liver cirrhosis. In contrast, the proton beam has Bragg peak, which limits distribution of the beam. The aim of this study was to prove the usefulness of proton irradiation for HCC. METHODS The proton irradiation was performed in 32 nodular lesions in 24 patients with HCC who had unresectable tumors or serious complications; the proton irradiation was performed either as monotherapy (15 lesions) or as combination therapy to insufficient Lipiodol-targeted chemotherapy (Kodama Co. Ltd., Tokyo, Japan) (17 lesions). The energy was 250 MeV, and 50-87 Gy (76.5 +/- 9.5, mean +/- SD) in total was irradiated for a time period of 17-69 days. RESULTS After 1 year, size reduction was seen in 12 out of 13 lesions (92%) in the monotherapy group and 9 out of 9 lesions (100%) in the combination therapy group; after 2 years, size reduction was seen 4 out of 5 lesions (80%) in the monotherapy group and 5 out of 5 lesions (100%) in the combination therapy group. Local tumor control has being assured for 2 years of the observation, which is continuing for another 2 years. None of the patients have experienced any serious adverse effects. CONCLUSIONS These results show that proton irradiation is a new, safe, and effective therapeutic option in cases of HCC, even in patients with unresectable tumors or those with serious complications.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients with genotype 1b chronic hepatitis C

From a pharmacokinetic viewpoint, the use of ombitasvir/paritaprevir/ritonavir, one of the standards of care for genotype 1b chronic hepatitis C in Japan, could be possible in patients with impaired renal function. The aim of this study was to assess the efficacy and safety of this combination that have not yet been addressed in patients undergoing dialysis.

Daclatasvir and asunaprevir for genotype 1b chronic hepatitis C patients with chronic kidney disease

To evaluate the efficacy and safety of daclatasvir and asunaprevir combined therapy in genotype 1b chronic hepatitis C patients with non‐dialysis chronic kidney disease (CKD).

Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin

Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non‐TT. Among such treatment‐refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non‐TT.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir combination therapy for genotype 1b chronic hepatitis C patients complicated with chronic kidney disease: Ombitasvir/paritaprevir/ritonavir for CHC patients with CKD

The aim of this study was to clarify the effects and safety of ombitasvir/paritaprevir/ritonavir (OBT/PTV/r) therapy in genotype 1b chronic hepatitis C patients with non‐dialysis chronic kidney disease (CKD).

Centrilobular zonal necrosis as a hallmark of a distinctive subtype of autoimmune hepatitis

Background and aim Centrilobular zonal necrosis (CZN) is a known histological variant of autoimmune hepatitis (AIH). However, the significance of CZN is yet to be fully elucidated. This study aimed to determine whether CZN is a hallmark of a distinctive subtype of AIH. Methods Histological changes in the centrilobular zones of liver biopsies from 113 AIH patients were assessed by a single pathologist and classified into three categories: typical zonal necrosis defined as CZN (15 patients); other necroinflammatory change (NIC; 24 patients); and absence of necrosis (non-NIC; 74 patients). The clinicopathological features and immunogenetic background of CZN patients were then assessed. Results The clinicopathological features of AIH with CZN were distinct from other types of AIH, including a higher frequency of acute onset, lower frequency of antinuclear antibodies, lower antinuclear antibody titers, lower serum immunoglobulin G levels, lower grade interface hepatitis, less prominent lymphoplasmacytic infiltration, and lower AIH score. Increased and decreased frequencies of HLA-DR9 and HLA-DR4, respectively, were identified as immunogenetic features of AIH with CZN. Conversely, the clinicopathological characteristics of AIH with NIC were similar to those of non-NIC AIH, including the majority of the AIH patients. The therapeutic outcomes of AIH with CZN were excellent when precise diagnoses were made without delay. Conclusion The clinicopathological features and immunogenetic background of AIH with CZN differed from AIH without CZN. CZN may be a hallmark of a distinct subtype of AIH.

Analysis of factors predicting the response to tolvaptan in patients with liver cirrhosis and hepatic edema: Factors predicting the response to tolvaptan

This study aimed to clarify the factors predictive of treatment response to tolvaptan (V2‐receptor antagonist) for cirrhotic patients with hepatic edema in a real‐world setting.

Treatment effects and predictors of a 24-week course of interferon α-2b plus ribavirin combination therapy for patients with chronic hepatitis C

Background and Aims:  In chronic hepatitis C patients with genotype 1b and a high viral load, the sustained virological response (SVR) rate remained as low as 2‐3% with conventional interferon (IFN) monotherapy, but improved to more than 20% with IFN α‐2b plus ribavirin combination therapy. This study examined the therapeutic effects and predictors of this combination therapy.

Laparoscopic observation of liver colored with indocyanine green in chronic hepatitis. I. Improved sensitivity for diagnosis of fibrosis

We investigated the significance of intravenous injection of indocyanine green during laparoscopic examination in chronic hepatitis. The presence or absence of bridging fibrosis was estimated during laparoscopy from the pattern of lobular markings before and after indocyanine green coloration. Laparoscopy without indocyanine green predicted the presence of bridging fibrosis in biopsy specimens with a low sensitivity of 0.42 (specificity, 0.8). After intravenous injection of indocyanine green, lobular markings became clearer and the sensitivity of laparoscopy in the diagnosis of bridging fibrosis was markedly increased (sensitivity, 0.89; specificity, 0.8). These results indicate that the indocyanine green coloration method improves the correspondence between laparoscopy and liver biopsy in evaluating the severity of chronic hepatitis.