Drug induced hypersensitivity syndrome by triple therapy of peginterferon alpha2b, ribavirin and telaprevir in patient with double positive for HBV and HCV.

Sixty year-old male positive for both HCV-RNA and HBsAg was treated by triple therapy of peginterferon alpha2b, ribavirin and telaprevir. Eight weeks after the beginning of the therapy, the patient developed drug induced hypersensitivity syndrome (DIHS) with general erythema multiforme and 64 times anti-HHV6 antibody elevation. Sixty milligram of prednisolone was administered with gradual dose reduction and the skin lesion was improved. HBV-DNA and transaminase elevated one week after the steroid induction and entecavir improved them. DIHS itself and the aggravation of hepatitis B by corticosteroid should be kept in mind in cases with dual infection of HBV and HCV treated by antivirals including telaprevir.

Interactions among pulmonary surfactant, vernix caseosa, and intestinal enterocytes: intra-amniotic administration of fluorescently liposomes to pregnant rabbits.

Although vernix caseosa is known to be a natural biofilm at birth, human pulmonary surfactant commences to remove the vernix from fetal skin into the amniotic fluid at gestational week 34, i.e., well before delivery. To explain this paradox, we first produced two types of fluorescently labeled liposomes displaying morphology similar to that of pulmonary surfactant and vernix caseosa complexes. We then continuously administered these liposomes into the amniotic fluid space of pregnant rabbits. In addition, we produced pulmonary surfactant and vernix caseosa complexes and administered them into the amniotic fluid space of pregnant rabbits. The intra-amniotic infused fluorescently labeled liposomes were absorbed into the fetal intestinal epithelium. However, the liposomes were not transported to the livers of fetal rabbits. We also revealed that continuous administration of micelles derived from pulmonary surfactants and vernix caseosa protected the small intestine of the rabbit fetus from damage due to surgical intervention. Our results indicate that pulmonary surfactant and vernix caseosa complexes in swallowed amniotic fluid might locally influence fetal intestinal enterocytes. Although the present studies are primarily observational and further studies are needed, our findings elucidate the physiological interactions among pulmonary, dermal-epidermal, and gastrointestinal developmental processes.

Optimal follow-up time to determine the sustained virological response in patients with chronic hepatitis C receiving pegylated-interferon and ribavirin.

BACKGROUND AND AIM: This study evaluated whether the assessment of hepatitis C virus (HCV)-RNA at 12 weeks (FW+12) post-treatment follow-up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real-time polymerase chain reaction (PCR) HCV assay. METHODS AND RESULTS: Two hundred and twenty-two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg-IFN) and ribavirin were administered for 24-72 weeks based on the genotype and viral load. Serum HCV-RNA was measured using real-time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty-eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load. CONCLUSION: The assessment of serum HCV-RNA FW+12, using the highly sensitive real-time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV-RNA FW+12 may be effective in most patients.

Ectopic varices rupture in the gastroduodenal anastomosis successfully treated with N-butyl-2-cyanoacrylate injection.

The term "ectopic varices" is used to describe dilated portosystemic collateral veins in unusual locations other than the gastroesophageal region. We recently experienced a rare case of ectopic varices that developed in the gastroduodenal anastomosis after subtotal gastrectomy. A 70-year-old male with liver cirrhosis due to hepatitis C virus infection was admitted for hematemesis and tarry stool. He had received a subtotal gastrectomy with the Billroth-I method for gastric ulcer at 46 years of age. Although emergency endoscopy revealed esophageal and gastric fundal varices, there were no obvious bleeding points. After removal of the coagula, ectopic varices and a fibrin plug were observed on the gastroduodenal anastomosis. During the observation, blood began to spurt from the fibrin plug. N-butyl-2-cyanoacrylate with lipiodol injection succeeded in hemostasis. Splenic angiography showed gastric varices feeding from a short gastric vein and the posterior gastric vein. The blood flow around the bleeding point, as indicated by lipiodol deposition, had decreased, and no feeding vein was observed. Endoscopic and angiographic findings are shown and the treatment for such lesions is discussed.

Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C: a randomized controlled clinical trial.

AIM: To study the therapeutic effect of interferon (IFN) and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection. METHODS: A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFN-alpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defined as negative HCV-RNA in the serum 6 mo after treatment. RESULTS: There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P<0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P=0.019). CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.

Solitary mandibular metastasis as an initial manifestation of hepatocellular carcinoma.

Oral metastases from hepatocellular carcinoma are very rare. We encountered a case of hepatocellular carcinoma with a solitary metastasis to the mandible as an initial manifestation. The patient was a 76-year-old man who was admitted for left mandibular swelling. A biopsy specimen of mandible was suspected to be a metastatic tumor. The histological findings, abdominal computed tomography, bone scintigraphy, and F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed it to be a solitary metastasis from hepatocellular carcinoma. As a result, he was diagnosed to have liver cirrhosis due to a hepatitis C virus infection and hepatocellular carcinoma with a solitary metastasis to the mandible. The primary lesion was treated with transcatheter arterial embolization (TAE), and the metastasis to the mandible was surgically resected. The patient survived for 9 months after treatment without recurrence.

Metastasis of hepatocellular carcinoma to the supramaxillary gingiva and right ventricle.

We describe a rare double metastasis of hepatocellular carcinoma to the supramaxillary gingiva and papillary muscle of the right ventricle. The patient was a 72-year-old woman who underwent three sessions of transcatheter arterial embolization for the primary lesions. Control of bleeding from the supramaxillary gingival metastasis was difficult by conservative treatment such as compression with gauze soaked in epinephrine. Therefore, radiotherapy was performed, but it failed to control the bleeding. The patient subsequently died due to hepatic failure. Autopsy revealed metastases of hepatocellular carcinoma to the papillary muscle of the right ventricle and paraaortic lymph node in the abdomen in addition to the supramaxillary gingival metastasis. Histopathological examination showed moderately differentiated hepatocellular carcinoma of both the primary site and metastatic sites to the gingiva and the heart and poorly differentiated in the paraaortic lymph node.

A retrospective cohort study of partial splenic embolization for antiviral therapy in chronic hepatitis C with thrombocytopenia.

BACKGROUND: Although partial splenic embolization (PSE) is reportedly effective prior to interferon (IFN)-based therapy, the number of subjects in these studies is small, and the appropriate candidates and disease prognosis remain unknown. METHODS: PSE was performed in 30 patients with advanced hepatitis C who could not receive IFN-based therapy because of thrombocytopenia, platelet counts of ≤100,000/mm(3), and hypersplenism. Also, we compared 25 PSE-treated patients with 23 PSE-untreated patients with thrombocytopenia receiving pegylated IFN (PEG-IFN)-alpha 2b plus ribavirin over the same period. RESULTS: PSE significantly increased platelet and leukocyte counts. PSE was well tolerated with no severe complications. All the patients could receive IFN-based therapy. Discontinuation of therapy in the total cohort of PSE-treated patients was not due to thrombocytopenia. Although PSE did not significantly increase the sustained virological response (SVR) rate, it significantly maintained higher platelet counts throughout the observation period and increased the percentage of patients with 100% adherence to PEG-IFN in the total controlled study population and in subjects with genotype 2. In PSE-treated patients with genotype 2, a trend towards increased SVR was noted. Four patients developed hepatocellular carcinoma (HCC) at a median of 14.5 months after PSE, even though two of these patients had achieved an SVR. CONCLUSIONS: IFN-based therapy following PSE had an advantage in the maintenance of higher platelet counts, and PSE possibly caused an increase in adherence to PEG-IFN. Although patients with genotype 2 might be better candidates for PSE, further evaluation is needed. Careful follow-up of PSE-treated patients, even though they may have achieved an SVR, is needed to detect HCC.