Analysis of hepatitis B surface antigen (HBsAg) using high-sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays.

AIM: We investigated the utility of high-sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays. METHODS: Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut-off value, 0.05 IU/mL), the amount of HBsAg was re-examined by high-sensitivity HBsAg assays (cut-off value, 0.005 IU/mL). Cases negative for HBsAg in both assays were defined as consistent cases, and cases positive for HBsAg in the high-sensitivity HBsAg assay only were defined as discrepant cases. RESULTS: There were 55 (48.2%) discrepant cases, and the range of HBsAg titers determined by high-sensitivity HBsAg assays was 0.005-0.056 IU/mL. Multivariate analysis showed that the presence of nucleos(t)ide analog therapy, liver cirrhosis, and negative anti-HBs contributed to the discrepancies between the two assays. Cumulative anti-HBs positivity rates among discrepant cases were 12.7%, 17.2%, 38.8%, and 43.9% at baseline, 1 year, 3 years, and 5 years, respectively, whereas the corresponding rates among consistent cases were 50.8%, 56.0%, 61.7%, and 68.0%, respectively. Hepatitis B virus DNA negativity rates were 56.4% and 81.4% at baseline, 51.3% and 83.3% at 1 year, and 36.8% and 95.7% at 3 years, among discrepant and consistent cases, respectively. Hepatitis B surface antigen reversion was observed only in discrepant cases. CONCLUSIONS: Re-examination by high-sensitivity HBsAg assays revealed that HBsAg was positive in approximately 50% of cases. Cumulative anti-HBs seroconversion rates and HBV-DNA seroclearance rates were lower in these cases, suggesting a population at risk for HBsAg reversion.

Successful achievement of sustained virological response to triple combination therapy containing simeprevir in two patients with chronic hepatitis C who had failed asunaprevir:Daclatasvir combination therapy.

Patients 1 and 2 were treatment-naive women who had genotype 1b chronic hepatitis C. Both had IL-28B genotype TT, and amino acid substitutions of core 70 and 91 were both wild type. Search for the presence of resistance-associated variants (RAV) in non-structural (NS)3 and NS5A regions confirmed wild-type D168 and L31, along with Y93H, in both patients. These patients participated in a Japanese phase III clinical study of asunaprevir and daclatasvir at the age of 52 and 67 years, respectively, and were treated with the combination regimen for 24 weeks. However, both experienced post-treatment relapse, and then treated with triple combination therapy with simeprevir, pegylated interferon (IFN) and ribavirin at the age of 53 and 68 years, respectively, and achieved sustained virological response. A search for RAV prior to simeprevir treatment identified multiple resistance including D168E, Y93H and L31V in both patients. It has been demonstrated that, in many cases, a treatment failure with a combination of asunaprevir and daclatasvir results in acquisition of RAV in NS3 and NS5A regions and that drug-resistant mutants, particularly those in the NS5A region, survive for a long time. In these cases, direct-acting antivirals targeted towards the NS5A region may have a limited efficacy. The present case report is based on an idea that a regimen containing IFN with simeprevir could be a therapeutic option particularly for those who are likely to be highly sensitive and tolerable to IFN.

Response criteria of tolvaptan for the treatment of hepatic edema.

BACKGROUND: Although tolvaptan is an effective treatment for hepatic edema, there are no established criteria for assessment of the therapeutic effect. The present study evaluates the association between body weight change and clinical symptoms to identify an effective indicator of tolvaptan response. METHODS: The study comprised 460 patients. The first data set contained 147 patients with hepatic edema who received tolvaptan in Kagoshima Kouseiren Hospital, a representative institution of this study. From these data, an optimal cutoff value of body weight change, which accurately indicated symptom reduction, was identified. The response rates obtained based on the cutoff value were evaluated by receiver-operating characteristic (ROC) analysis and kappa coefficients. The kappa coefficient was then validated internally using the bootstrap method and externally using the validation data set of 313 patients from four other hospitals. RESULTS: A cutoff value for body weight loss of 1.5 kg/week produced the largest area under the ROC curve (0.961; sensitivity, 89.8%; specificity, 92.0%) and a high kappa coefficient (0.831). The correlation between symptom reduction and body weight loss of 1.5 kg/week was evaluated internally and externally, and the cutoff value was validated. CONCLUSIONS: The cutoff value of body weight change that most accurately reflected symptom reduction was 1.5 kg/week; this value is expected to be an effective indicator of response to tolvaptan in clinical practice.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin.

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was -3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only -1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV.

Endoscopic Color Doppler Ultrasonographic Evaluation of Gastric Varices Secondary to Left-Sided Portal Hypertension.

Gastric varices that arise secondary to the splenic vein occlusion can result in gastrointestinal hemorrhaging. Endoscopic color Doppler ultrasonography (ECDUS) was performed in 16 patients with gastric varices secondary to splenic vein occlusion. This study retrospectively evaluated the role of ECDUS in the diagnosis of gastric varices secondary to splenic vein occlusion. Thirteen patients had co-existing pancreatic diseases: 8 with chronic pancreatitis, 4 with cancer of the pancreatic body or tail and 1 with severe acute pancreatitis. Of the remaining 3 patients, 1 had myeloproliferative disease, 1 had advanced gastric cancer, and the third had splenic vein occlusion due to an obscure cause. The endoscopic findings of gastric varices were: variceal form (F) classified as enlarged tortuous (F2) in 12 cases and large, coil-shaped (F3) in 4 cases, and positive for erosion or red color sign of the variceal surface in 4 cases and negative in 12 cases. ECDUS color flow images of gastric variceal flow clearly depicted a round fundal region at the center, with varices expanding to the curvatura ventriculi major of the gastric body in all 16 cases. The velocities of F3 type gastric varices were significantly higher than those of the F2 type. The wall thickness of varices positive for erosion or red color sign was significantly less than the negative cases. I conclude that ECDUS color flow images of gastric variceal flow depicted specific findings of gastric varices secondary to splenic vein occlusion at the round fundal region at the center, with varices expanding to the curvatura ventriculi major of the gastric body.

[Antiviral therapy for patients with chronic hepatitis B with multi-drug resistance to nucleoside analogues].

In 18 of 547 patients who had received nucleoside analogue preparations for 1 year or more, multi-drug resistance was detected, after a median follow-up of 53 months. No patient showed liver failure related to multi-drug resistance acquisition. Multi-drug resistance was associated with entecavir (ETV) therapy in 7 lamivudine (LAM) -resistant patients, combination therapy with adefovir dipivoxil (ADV) in 8 LAM-resistant patients, LAM switching to ETV in 2 patients, and initial ETV administration in 1. For treatment, combination therapy with LAM and ADV was performed. In non-responders, combination therapy with ADV and ETV was employed. In all LAM- and ADV-resistant patients, and the HBV DNA level decreased to 3.0LC/ml or less. However, a similar decrease was noted in 7 (58.3%) of 12 LAM- and ETV-resistant patients. Of the 18 patients, 1 did not respond to combination therapy with ADV and ETV. Therapy with tenofovir disoproxil fumarate (TDF) was required.