Takehiko Abe

Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C.

We evaluated the synergistic effect of zinc supplementation on the response to interferon (IFN) therapy in patients with intractable chronic hepatitis C in a pilot study using natural IFN‐α with or without zinc. No clinical differences were observed between patients treated with IFN alone (n=40) and IFN with polaprezinc (IFN + Zn, n=35). All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum. Ten million units of natural IFN‐α was administered daily for 4 weeks followed by the same dose every other day for 20 weeks. In the IFN + Zn group, patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24‐week IFN course. No additional side‐effects of polaprezinc were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side‐effects. Complete response (CR) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy. Incomplete response (IR) was normal liver enzyme and positive serum HCV RNA. Both of them were evaluated at the 6 months after the completion of the treatment. Patients with higher levels of serum HCV (more than 5 × 105 copies/mL) had little response in both treatment groups. Patients with moderate amount of HCV (105 to 4.99 × 105/mL) showed high response rates in combination group (CR: 11/27, 40.7%; CR + IR 15/27, 64.3%), better than IFN alone (CR: 2/15, 18.2%; CR + IR: 2/15, 18.2%). Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group. Our results indicate that zinc supplementation enhances the response to interferon therapy in patients with intractable chronic hepatitis C.

Emergency balloon-occluded retrograde transvenous obliteration for gastric varices.

BackgroundWe evaluated the efficacy of emergency balloon-occluded retrograde transvenous obliteration (B-RTO) performed within 24 h after initial hemostasis for the prevention of rebleeding from ruptured gastric varices.MethodsFrom December 1995 to March 2003, 11 patients who had undergone B-RTO within 24 h after the control of gastric variceal bleeding at Maebashi Red Cross Hospital were investigated. They were followed up for complete eradication, recurrence of varices, and rebleeding. Efficacy was determined by endoscopic examination and computed tomography.ResultsThe 4 patients with acute bleeding from ruptured gastric varices were treated with endoscopic therapy—endoscopic variceal ligation (EVL) in 2 patients, and clipping treatment in 2. Initial hemostasis was achieved in all 4; the other 7 patients had already stopped bleeding at endoscopy. After hemostasis was achieved, emergency B-RTO was immediately performed within 24 h and was successful in all 11 patients. Ten (90.9%) of the 11 gastric varices were obliterated and the other 1 (9.1%) was diminished in size. During the mean follow-up period of 1136 days, no rebleeding or recurrence as found. Four patients died during the follow-up period, but none died from variceal bleeding. Survival rates were 90.9% and 70.7%, respectively, at 1 year and 3 years. In 6 patients, development of esophageal varices appeared during the follow-up period, all of which were controlled by usual endoscopic therapy. No severe side effects were found after the B-RTO treatment.ConclusionsEmergency B-RTO is an effective treatment for the prevention of rebleeding from ruptured gastric varices.

Long-term outcome of interferon-alpha-induced autoimmune thyroid disorders in chronic hepatitis C.

Abstract: Background: Autoimmune thyroid disorders are among the well‐known adverse effects of interferon‐α (IFN‐α) therapy in patients with chronic hepatitis C. However, there are few reports regarding the long‐term outcome of this complication. We aimed to evaluate the natural history of IFN‐α‐induced autoimmune thyroid disorders with long‐term follow‐up.

Accidental transmission of HCV and treatment with interferon

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work‐related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunodeficiency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2–3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV‐injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.

Hepatocellular Carcinoma in Young Adults: The Clinical Characteristics, Prognosis, and Findings of a Patient Survival Analysis

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, HCC is rare in young Japanese patients and the clinical features of young patients with HCC have not yet been fully studied. This study was designed to determine the clinical characteristics and prognosis of patients with HCC who are younger than aged 40 years. A retrospective analysis was performed for patients newly diagnosed with HCC and observed from January 1990 to December 2003 at our hospitals. Patients younger than aged 40 years at the diagnosis of HCC were defined as the young group and were reviewed. There were 20 patients (16 males) with HCC who were younger than aged 40 years. The mean age at diagnosis was 33.6 (range, 20–39) years. Fifteen of 20 patients were positive for hepatitis B surface antigen (HBsAg) and 2 patients were positive for hepatitis C virus antibody. According to the Child-Pugh grading, the liver function was relatively good in all patients. Because most of the patients did not receive periodic follow-up, this disease often was discovered at an advanced stage, usually after the appearance of some symptoms. Although intensive treatment was performed for such young patients, the survival was nevertheless poor. Most patients died from this cancer within 1 year. However, one patient who received periodic follow-up and also was in relatively good physical condition had a better prognosis, and he survived for 88 months. Young patients with HCC tended to have a poor prognosis because of advanced stage of HCC, despite a well-preserved liver function and aggressive treatment. Screening for HCC and an early diagnosis is needed for such patients to demonstrate an improved prognosis, especially for HBsAg-positive patients.

Evaluation of twice-daily administration of interferon-beta for chronic hepatitis C.

To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN‐β twice per day was evaluated. Thirty‐eight patients with chronic hepatitis C (26 males and 12 females, aged 25–67 years) were included. Patients were treated with a new protocol that included twice‐daily treatment with IFN‐β. Three million units (MU) of IFN‐β was administered twice daily every day for 4 weeks followed by 10 MU of IFN‐α2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN‐β, 148 MU; IFN‐α2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor® assay. Twenty‐one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml–1 (1 MEq ml–1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml–1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml–1 HCV RNA, four of 15 (26.7%) responded to IFN. Two‐thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non‐responders. Proteinuria was frequently observed as an adverse effect of twice‐daily administration of IFN‐β. The combination of twice‐daily administration of IFN‐β for 4 weeks followed by IFN‐α showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low. Thus, the HCV RNA titre 2 weeks after starting therapy with IFN was useful for predicting the eventual response to IFN.

Safety and efficacy of balloon‐occluded transcatheter arterial chemoembolization using miriplatin for hepatocellular carcinoma

Balloon‐occluded transcatheter arterial chemoembolization (B‐TACE) using a microballoon catheter was performed to administrate miriplatin, and the early therapeutic efficacy and safety of the procedure were evaluated.

Hepatocellular carcinoma complicated by hemothorax.

Abstract: Although hemoperitoneum is a well-known cause of death induced by rupture of hepatocellular carcinoma (HCC), hemothorax caused by rupture of HCC has not been adequately described. We report here a 64-year-old woman who died of bleeding from pleural wall metastasis of HCC. She presented with liver failure and sudden-onset hypotension, and on the same day, she died of hypovolemic shock associated with liver failure. Autopsy revealed HCC metastatic to the lungs and right pleura and 2 l of bloody pleural effusion in the right side. The cut surface of the metastatic nodule in the right pleura was filled with coagulated blood and necrotic tissue. We concluded that the pleural metastasis had ruptured and caused the right hemothorax. We discuss reported cases of HCC complicated by hemothorax.

Spleen stiffness correlates with the presence of ascites but not esophageal varices in chronic hepatitis C patients.

Although spleen stiffness has recently been identified as potential surrogate marker for portal hypertension, the relationship between spleen stiffness and portal hypertension has not been fully elucidated. We attempted to determine the relationship between the liver or spleen stiffness and the presence of ascites or esophageal varices by acoustic radiation force impulse (ARFI) imaging. A total of 33 chronic hepatitis C (CHC) patients (median age 68; range 51–84) were enrolled. We evaluated the relationship between the liver or spleen stiffness and indicators of portal hypertension as well as clinical and biochemical parameters. Fourteen healthy volunteers were used for validating the accuracy of AFRI imaging. The liver and spleen stiffness increased significantly with progression of liver disease. A significant positive correlation was observed between the liver and spleen stiffness. However, spleen stiffness, but not liver stiffness, was significantly associated with the presence of ascites (P < 0.05), while there was no significant association between the spleen stiffness and spleen index/presence of esophageal varices in CHC patients. The area under the receiver operating characteristic curve based on the spleen stiffness was 0.80. In conclusion, spleen stiffness significantly correlates with the presence of ascites but not esophageal varices in CHC patients.

Simple liver cyst with spontaneous regression.

We report a-55-year-old woman with spontaneous regression of simple liver cyst. The size of the cyst gradually became reduced without any treatment, and a reduction in diameter from 77 mm to 10 mm was observed after 8 years of follow-up. Spontaneous regression of congenital cysts of the liver in an adult seems to be very rare, and its mechanism is discussed.