Factors associated with the decrease in hepatitis B surface antigen titers following interferon therapy in patients with chronic hepatitis B: Is interferon and adefovir combination therapy effective?

The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36.7±8.5 years; 27 males and 8 females) were enrolled in this study. Of the 35 patients, 21 patients received pegylated IFN monotherapy and 14 patients received IFN and adefovir (ADV) combination therapy. We examined the factors associated with reductions in the HBsAg titer of >1.0 log IU/ml from the initial HBsAg titer to the end of treatment and to 24 weeks after treatment. Although 13 patients (37%) had a reduction in HBsAg of >1.0 IU/ml at the end of treatment, it was only maintained to 24 weeks after treatment in 7 patients (20%). The HBV core-related antigen (HBcrAg) titer before treatment was significantly higher in patients with a decrease in HBsAg at the end of treatment than in patients without a decrease in HBsAg (6.56±0.78 vs. 5.30±1.66 log IU/ml, P<0.05). Moreover, an increase in alanine aminotransferase (ALT) of >2 times from baseline occurred significantly more frequently in patients with a decrease in HBsAg (62 vs. 14%, P<0.05). The proportion of patients with a decrease in HBsAg was significantly greater in patients who received IFN monotherapy than in patients who received IFN and ADV combination therapy (43 vs. 29%, P<0.05). The present results revealed that the HBcr antigen titer before therapy and an on-treatment elevation of ALT (indicative of host instruction flare) are important factors associated with a decrease in HBsAg titers after IFN-based therapy. The efficacy of IFN and ADV combination therapy was not apparent in terms of a reduction in the HBsAg titer.

[Comparison of garenoxacin and levofloxacin for the prophylaxis of febrile neutropenia].

Placebo-controlled randomized trials have demonstrated that prophylactic levofloxacin (LVFX) significantly reduced the incidence of febrile neutropenia (FN) in patients receiving chemotherapy for advanced solid tumors. Garenoxacin (GRNX) has been reported to be more effective than LVFX against gram-positive bacteria especially Streptococcus pneumoniae. Against this background we conducted a study to compare the efficacy and safety of GRNX with that of LVFX for the prophylaxis of FN. We retrospectively analyzed 127 patients at high risk for FN who were administered GRNX or LVFX for the prophylaxis of FN that occurred during chemotherapy for advanced solid tumors. Our primary outcome of interest was the incidence of febrile episodes. Secondary outcomes included evidence of bacterial infection and infection focus when febrile episodes were observed; adverse drug reactions and mortality were also evaluated. Febrile episodes were observed in 2 patients administered GRNX and 7 patients administered LVFX (p=0.044). Definitive pathogenic bacteria and infection focus could not be identified in any patient with febrile episodes and all cases of fever resolved simultaneously with the recovery from neutropenia. We observed 4 cases of rashes and 3 cases of liver dysfunction in the GRNX group and 2 cases of rashes and 2 cases of liver dysfunctions were observed in the LVFX group(not statistically significant in both the groups). No severe adverse effects or deaths were associated with either of these drugs. These results suggest that GRNX is useful for the prophylaxis of FN.

Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer.

BACKGROUND: Little is known about acute upper gastrointestinal (GI) complications associated with gemcitabine-concurrent proton radiotherapy (GPT) for inoperable pancreatic cancer. We investigated acute GI complications following GPT in patients with inoperable pancreatic cancer using small-bowel endoscopy. METHODS: This prospective single center observational study was conducted at the Hyogo Ion Beam Medical Center from January 2010 to January 2012. Ninety-one patients who had clinically and medically inoperable pancreatic cancer treated by GPT were analyzed. Endoscopic examinations were performed before and after GPT to clarify the incidence rates of radiation-induced ulcers, GI hemorrhage, and GI perforation associated with GPT. RESULTS: Post-treatment endoscopic examinations revealed that 45 (49.4 %) patients had radiation-induced ulcers in the stomach and duodenum. Of those, many ulcerative lesions were found in the lower stomach (51 %) and horizontal part of the duodenum (39 %), regardless of the primary tumor site in the pancreas. Neither GI hemorrhage, nor perforation, was found in post-treatment endoscopy examinations. CONCLUSION: Approximately half of the patients treated with GPT for inoperable pancreatic cancer exhibited radiation-induced ulcers in the stomach and duodenum.

[Small bowel obstruction and gastric ulceration resulting from rice cake ingestion -computed tomography diagnosis in eight patients-].

Here we report the cases of eight patients who developed small bowel obstruction and/or gastric ulcers after ingesting rice cake, the traditional Asian food, and were managed conservatively. This report adds to the existing literature on gastrointestinal disorders induced by rice cake ingestion, which are characterized by gastrointestinal obstruction, perforation, and ulceration and are occasionally accompanied by peritonism. These conditions tend to occur in 50-60-year-old males who wear dentures or eat rapidly. Therapeutically, hard rice cake remnants in the upper gastrointestinal tract can be broken up by endoscopic snaring and can be detected by computed tomography as homogeneous high-density material at approximately 145 (range:120-206) Hounsfield units.

Therapeutic effects of mosapride citrate and lansoprazole for prevention of aspiration pneumonia in patients receiving gastrostomy feeding.

BACKGROUND: Aspiration pneumonia is an emerging problem in patients receiving gastrostomy feeding. This study is designed to clarify the therapeutic effects of mosapride citrate and lansoprazole for prevention of aspiration pneumonia in patients receiving gastrostomy feeding. METHODS: The study subjects were 119 patients with dysphasia who required gastrostomy feeding. They were randomly assigned to the control (without medication), lansoprazole (15 mg, 1/day), and mosapride (5 mg, 3/day) groups. The number of days with fever (≥37.8 °C), vomiting, and antibiotics administration, as well as the occurrence of pneumonia were investigated during the 6-month observation period. RESULTS: The incidence of pneumonia during the observation period was significantly lower in the mosapride group as compared to the control (7/38 vs. 16/40, p = 0.038) and lansoprazole (vs. 20/41, p = 0.005) groups. The mosapride group also showed a significant decrease in days with fever and antibiotics administration as compared to the other groups. Multivariate analysis revealed that the presence of hiatal hernia was a significant risk factor and administration of mosapride was a significant preventive factor for pneumonia. CONCLUSION: Mosapride has a preventive effect on occurrence of pneumonia in patients receiving gastrostomy feeding.

[Cisplatin administration for outpatients with short hydration of less than four hours].

BACKGROUND: The administration of cisplatin (CDDP)-containing regimens for outpatients has been popularized with the development of supportive care such as antiemetics. Currently, the number of chemotherapies available for outpatients has increased for many kinds of cancer, and administration with a shorter duration is desirable even in CDDP-containing regimens. METHODS: Between January 2008 and October 2011, we retrospectively evaluated 22 outpatients who received B 50mg/m² of cisplatin with a short hydration of within 4 hours. We instructed the patients to drink water(1, 000mL/day) on days 2 and 3 instead of receiving a drip infusion. The first course of chemotherapy was usually introduced on admission, and subsequent courses were administered in outpatient clinics. RESULTS: Thirteen cases of lung cancer, eight with gastric cancer, and one with esophageal cancer, were retrospectively evaluated. Thirteen CDDP+S-1 regimens, four CDDP+gemcitabine regimens, and five other types of regimens were administered. The median dose of CDDP was 60mg/m² (range, 50-75mg/m²), the median amount of drip infusion was 1, 600 mL (range, 1, 350-2, 000mL), and the median duration of drip infusion was 4 hours (range 3-4 hours). The decision to use antiemetics and diuretics was made on a case-by-case basis. The average creatinine level before the initiation of a CDDP-containing regimen was 0. 778±0. 212mg/dL, and the lebel four weeks after completion of the regimen was 0. 847±0. 200mg/dL. Among these 22 patients, 20 completed cisplatin-containing regimens. However, cisplatin was reduced in one patient due to renal dysfunction, and the cisplatin regimen was interrupted in one patient due to intolerable nausea and vomiting. CONCLUSIONS: CDDP administration at doses of 50-60mg/m² for outpatients was suggested to be safe with optimal patient selection, a total duration of administration of less than four hours, and with 2, 000 mL of hydration on day 1 and without drip infusion from day 2.

Mutations in non-structural 5A and rapid viral response to pegylated interferon-α-2b plus ribavirin therapy are associated with therapeutic efficacy in patients with genotype 1b chronic hepatitis C.

For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with <5 aa mutations in IRRDR (30%) or no mutation in ISDR (29%). Multivariate analysis revealed that rapid viral response (RVR) (odds ratio, 18.1) and mutations of ≥6 in IRRDR (odds ratio, 15.5) were significantly associated with SVR. In conclusion, mutations in the NS5A region, particularly in patients with ≥6 aa mutations in IRRDR were strongly associated with a therapeutic response to pegylated IFN and ribavirin combination therapy.

Medroxyprogesterone acetate for refractory emesis in cisplatin-treated patients.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing side effects in systemic chemotherapies. Recently, several effective agents have been developed to prevent CINV, and CINV can be prevented in 70%-80% of patients receiving chemotherapies. Conversely, 20%-30% of patients still suffer from CINV despite recommended optimal antiemetic preventions. Refractory emesis is defined as emesis occuring despite the use of antiemetic prophylaxis during the previous cycle of chemotherapy. Salvage treatments for refractory emesis are necessary, but there are few effective treatments at present. We consider medroxyprogesterone acetate to be a potentially promising agent for refractory emesis. We encountered three cases in which medroxyprogesterone acetate was extremely effective for refractory emesis induced by cisplatin-containing chemotherapy.

A phase I/II study of gemcitabine-concurrent proton radiotherapy for locally advanced pancreatic cancer without distant metastasis.

PURPOSE: We conducted the study to assess the feasibility and efficacy of gemcitabine-concurrent proton radiotherapy (GPT) for locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Of all 50 patients who participated in the study, 5 patients with gastrointestinal (GI)-adjacent LAPC were enrolled in P-1 (50 Gy equivalent [GyE] in 25 fractions) and 5 patients with non-GI-adjacent LAPC in P-2 (70.2 GyE in 26 fractions), and 40 patients with LAPC regardless of GI-adjacency in P-3 (67.5 GyE in 25 fractions using the field-within-a-field technique). In every protocol, gemcitabine (800 mg/m(2)/week for 3 weeks) was administered concurrently. Every patient received adjuvant chemotherapy including gemcitabine after GPT within the tolerable limit. RESULTS: The median follow-up period was 12.5 months. The scheduled GPT was feasible for all except 6 patients (12%) due to acute hematologic or GI toxicities. Grade 3 or greater late gastric ulcer and hemorrhage were seen in 5 patients (10%) in P-2 and P-3. The one-year freedom from local-progression, progression-free, and overall survival rates were 81.7%, 64.3%, and 76.8%, respectively. CONCLUSION: GPT was feasible and showed high efficacy. Although the number of patients and the follow-up periods are insufficient, the clinical results seem very encouraging.

Comparisons of symptoms reported by elderly and non-elderly patients with GERD.

BACKGROUND: The characteristics of symptoms reported by elderly patients with gastroesophageal reflux disease (GERD) have not been fully investigated. We performed this study to clarify these characteristics in elderly patients with GERD. METHODS: The study subjects were 340 Japanese patients with symptoms of heartburn and/or acid regurgitation. All patients were investigated by upper gastrointestinal endoscopy, and were asked about the presence of atypical GERD symptoms, such as an epigastric burning sensation, epigastralgia, epigastric discomfort, and abdominal fullness, as well as the time of day when bothersome symptoms occurred. RESULTS: Of the 340 patients, 161 were elderly (≥65 years old) and 179 were non-elderly (age <65 years). There were 158 patients without esophageal mucosal breaks, 147 with low-grade reflux esophagitis (RE; Los Angeles classification grade A or B), and 35 with high-grade reflux esophagitis (LA grade C or D). Elderly patients with RE reported typical reflux symptoms at the same frequency as the non-elderly patients, whereas elderly patients without mucosal breaks reported typical symptoms more frequently than the non-elderly patients without mucosal breaks. Both elderly and non-elderly patients with different types of GERD reported that their symptoms occurred most frequently during the postprandial period. CONCLUSION: Elderly patients with GERD tend to show typical GERD symptoms frequently at the typical post-prandial time points in a day, irrespective of the presence of esophageal mucosal breaks.

Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a prospective study.

BACKGROUND: Previous exposure to hepatitis B virus (HBV) and occult HBV infection may have an important role in the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease related to hepatitis C virus (HCV). OBJECTIVE: To prospectively study the association between antibody to hepatitis B core antigen (anti-HBc) and clinical outcomes in patients with HCV-related chronic liver disease. DESIGN: Prospective observational study. SETTING: Kyoto University Hospital and 14 regional core hospitals in Japan. PARTICIPANTS: 872 patients with chronic HCV infection (597 with chronic hepatitis and 275 with cirrhosis). MEASUREMENTS: Incidence of HCC on follow-up (from 1995 to 2005). RESULTS: Only 846 of the 872 enrolled patients were followed. Hepatocellular carcinoma occurred in 237 of 846 patients (28.0%) during follow-up. Among patients with cirrhosis, HCC was diagnosed in 85 of 141 patients (60.3%) with anti-HBc and 58 of 129 patients (45.0%) without HBV-related serologic markers. Of 224 patients with chronic hepatitis who had interferon monotherapy, 92 (41.1%) had sustained or transient disappearance of HCV RNA. None of the anti-HBc-negative patients who had a virologic response to interferon therapy developed HCC, whereas cancer was diagnosed in 4 of 37 anti-HBc-positive patients (10.8%) with a virologic response to interferon. On multivariate analysis using a Cox proportional hazards model, anti-HBc-positive results on serologic testing was an independent risk factor in patients with cirrhosis (incidence rate ratio, 1.58 [95% CI, 1.12 to 2.22]). LIMITATIONS: The study included only 1 assessment of smoking and alcohol consumption at study entry and did not precisely determine the duration of smoking or alcohol use. CONCLUSIONS: Anti-HBc-positive results on serologic testing are a marker of high risk for HCC among patients with HCV-related cirrhosis. Interferon therapy might be less effective in preventing HCC among patients with chronic hepatitis C who are anti-HBc-positive than in those with chronic hepatitis C who are anti-HBc-negative.

Complete or near-complete nucleotide sequences of hepatitis E virus genome recovered from a wild boar, a deer, and four patients who ate the deer.

Zoonosis has been implicated in hepatitis E virus (HEV) transmission. We examined wild boar living in a forest of Hyogo prefecture, Japan, and found HEV RNA in three of seven boars. A full-genome HEV isolate from one of them was revealed to be 99.7% identical to a previous isolate from a wild deer hunted in the same forest and to those from four patients who contracted hepatitis E after eating raw meat of the deer. These findings suggest an interspecies HEV transmission between boar and deer in their wild life, and that both animals might serve as an infection source for human beings as suggested previously.

Consumption of uncooked deer meat as a risk factor for hepatitis E virus infection: an age- and sex-matched case-control study.

It was reported previously food-borne transmission of hepatitis E virus (HEV) to humans from deer meat. The present study attempted to clarify whether eating uncooked deer meat is a major epidemiological risk factor for HEV infection in Kasai, a city in western Japan. In total, 45 volunteer subjects with experience of eating raw deer meat were enrolled. An equivalent number of people from the same area who had never eaten raw deer meat served as controls. The subjects and controls had comparable age and sex distributions. Serum anti-HEV IgG and anti-hepatitis A virus (HAV) IgG levels were measured in all 90 volunteers. There was no significant difference in age, overseas travel history, or rate of anti-HAV antibody positivity between the subjects and controls. Eight (17.7%) of the subjects but only one (2.2%) of the controls had measurable serum anti-HEV IgG levels (P = 0.014). Anti-HAV prevalence did not differ between the anti-HEV-positive and negative groups. The results suggest that eating uncooked deer meat is an epidemiological risk factor for HEV infection in the studied area. In countries such as Japan where deer meat is sometimes eaten raw, attention must be paid to this route of HEV infection.

Zoonotic transmission of hepatitis E virus from deer to human beings.

Zoonosis has been suggested for hepatitis E virus (HEV) infection, but so far is based only on indirect evidence. We experienced a series of cases of HEV infection among people who had eaten uncooked deer meat 6-7 weeks before. On testing, a left over portion of the deer meat, kept frozen to eat in the future, was positive for HEV RNA, whose nucleotide sequence was identical to those from the patients. Patients' family members who ate none or very little of the deer meat remained uninfected. These findings provide direct evidence for HEV infection to be a zoonosis.