Rapid re-emergence of YMDD mutation of hepatitis B virus with hepatic decompensation after lamivudine retreatment.

Lamivudine has a high rate of antiviral resistance. Sequential treatment of anti-hepatitis B virus (HBV) is commonly used for lamivudine resistance. We report 4 cases of patients with rapid redetection of HBV mutants during the lamivudine retreatment. The four patients received lamivudine as an initial treatment of HBV and adefovir and lamivudine as a rescue therapy consecutively. HBV-DNA level, YMDD mutations and adefovir -resistant mutations (RFMP) were tested every 3 mo during the sequential treatment. All the patients showed YMDD mutations during the initial lamivudine therapy. After adefovir therapy for lamivudine resistance, they showed viral breakthrough. Adefovir was switched to lamivudine, however, it did not induce viral suppression at all, rather increased HBV-DNA with rapid reemergence of the YMDD mutations. All the patients had ALT flares, and hepatic decompensation occurred in two patients. After switching to adefovir combined with entecavir or lamivudine for a rescue therapy, the patients had reduction in HBV-DNA and ALT improvement. These cases demonstrated that lamivudine retreatment of patients with preexposed lamivudine resistance leads to rapid reemergence of YMDD mutation with significant viral rebounds and subsequent hepatic decompensation. Sequential administration of lamivudine in patients with a prior history of YMDD mutation should be abandoned.

Removal of press-through-packs impacted in the upper esophagus using an overtube.

Foreign bodies in the upper esophagus should be removed as soon as possible to avoid serious complications. However, removals of foreign bodies in the upper esophagus are very difficult, especially if they have sharp edges, such as press-through-packs (PTPs). We experienced four cases of the impacted PTPs in the upper esophagus which was successfully extracted endoscopically with the overtube. Because two edges of PTPs were so firmly impacted in the esophageal wall in all cases, the PTPs were not movable in the upper esophagus. However, after insertion of the overtube, PTPs became movable and were successfully extracted and no serious complications occurred after extraction of PTPs. In one case, insertion of the overtube rapidly expanded the upper esophagus and PTP progressed to the gastric cavity and it could be extracted with the endoscopic protector hood. The endoscopic removal with the overtube was a simple, safe and effective technique for the removal of the impacted PTPs in upper esophagus.

A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus.

BACKGROUND: The standard-of-care regimen for chronic hepatitis C virus (HCV) infection in Korea, pegylated-interferon-alpha plus ribavirin, is poorly tolerated. Ledipasvir/sofosbuvir is a two-drug, fixed-dose combination tablet approved in the USA, European Union, and Japan for chronic genotype 1 HCV infection. METHODS: This single-arm, phase IIIb study (NCT02021656) investigated the efficacy and safety of ledipasvir/sofosbuvir fixed-dose combination tablet for 12 weeks in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 HCV with or without compensated cirrhosis. RESULTS: The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 99 % (92/93), with rates of 100 % (46/46) and 98 % (46/47) in treatment-naïve and treatment-experienced patients, respectively. There were no on-treatment failures. One patient relapsed after the end of treatment. The most common treatment-emergent adverse events were headache (8 %, 7/93) and fatigue (6 %, 6/93). There were no grade 3 or 4 adverse events, seven grade 3 laboratory abnormalities, and one premature discontinuation of study treatment (due to nonserious mouth ulceration). None of the three reported serious adverse events were related to treatment. CONCLUSIONS: These data suggest that 12 weeks of ledipasvir/sofosbuvir is effective and well tolerated in treatment-naïve and treatment-experienced Korean patients with chronic genotype 1 HCV infection.

How good is cola for dissolution of gastric phytobezoars?

AIM: To evaluate the efficacy of cola treatment for gastric phytobezoars, including diospyrobezoars. METHODS: A total of 17 patients (range: 48 to 78 years) with symptomatic gastric phytobezoars treated with cola and adjuvant endoscopic therapy were reviewed. Three liters of cola lavage (10 cases) or drink (7 cases) were initially used, and then endoscopic fragmentation was done for the remnant bezoars by using a lithotripsy basket or a polypectomy snare. The overall success of dissolving a gastric phytobezoars with using three liters of cola and the clinical and endoscopic findings were compared retrospectively between four cases of complete dissolution by using only cola and 13 cases of partial dissolution with cola. RESULTS: After 3 L of cola lavage or drinking, a complete dissolution of bezoars was achieved in four patients (23.5%), while 13 cases (76.5%) were only partially dissolved. Phytobezoars (4 of 6 cases) were observed more frequently than diospyrobezoars (0 of 11) in the group that underwent complete dissolution (P = 0.006). Gender, symptom duration, size of bezoar and method of cola administration were not significantly different between the two groups. Twelve of 13 patients with residual bezoars were completely treated with a combination of cola and endoscopic fragmentation. CONCLUSION: The rate of complete dissolution with three liters of cola was 23.5%, but no case of diospyrobezoar was completely dissolved using this method. However, pretreatment with cola may be helpful and facilitate endoscopic fragmentation of gastric phytobezoars.

Humoral and cellular immune responses to influenza vaccine in patients with advanced cirrhosis.

Influenza vaccine has been shown to successfully reduce influenza- and pneumonia-associated hospitalizations and deaths. Yet in liver cirrhosis, influenza vaccines have received little attention in determining the potential benefits. Thus, we undertook this study to evaluate the humoral and cellular immune responses to vaccination against influenza in patients with advanced cirrhosis. We measured interferon (IFN)-gamma secretion response and hemagglutinin inhibition (HI) of antibody titer from pre- and post-vaccination blood samples in 80 cirrhotic patients (Child-Pugh class B or C) and 80 healthy, age-matched subjects. Although the patients with advanced cirrhosis showed similar humoral immune response against influenza vaccination compared to the healthy controls, cell-mediated immunity showed different results according to the remnant liver function.

Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection.

Variants in the amino acid composition of the primary antibody-binding site of hepatitis B surface antigen (HBsAg) have been identified in a number of populations with chronic hepatitis B virus (HBV) infection. Direct sequencing of amplified or cloned PCR products, solid phase detection of sequence-specific PCR products (SP-PCR), and limiting dilution cloning PCR (LDC-PCR) were compared to determine their sensitivity in detecting differing concentrations of HBsAg variants. LDC-PCR had the greatest sensitivity and could detect HBsAg variants at a concentration of 0.1% of the total viral population. HBsAg variants were detected in 51% of infants with chronic HBV infection acquired after postexposure prophylaxis, and more than half of the variants were detected only by the most sensitive methods.