Disease Progression in Chronic Hepatitis B Patients under Long-Term Antiviral Therapy

BACKGROUND/AIMS: We investigated factors associated with the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients during long-term oral nucleos(t)ide analog (NA) therapy. METHODS: This retrospective study included 524 naive CHB patients who received oral NA therapy for more than 48 weeks between January 2003 and December 2007. The primary outcome was 5-year cumulative probability of disease progression and HCC development. Disease progression was defined as cirrhosis development, cirrhotic complications, HCC or liver-related mortality. RESULTS: For the 524 patients, the cumulative probabilities of disease progression and HCC development at 1, 2, 3, 4 and 5 years were 1.1%, 6.3%, 9.0%, 11.6%, and 16.2% and 0.2%, 1.8%, 3.6%, 5.8%, and 9.3%, respectively. In multivariate analysis, age >50 years (hazard ratio [HR], 1.05) and cirrhosis (HR, 2.95) were significant factors for disease progression. Similarly, age >50 years (HR, 1.05), family history of HCC (HR, 5.48), and cirrhosis (HR, 17.16) were significant factors for HCC development. Importantly, longer duration (>12 months) of maintained virological response (<20 IU/mL) reduced the risks of disease progression (HR, 0.19) and HCC development (HR, 0.09). CONCLUSIONS: Longer duration of maintained virological response significantly reduces the risk of disease progression or HCC development in CHB patients undergoing long-term oral NA therapy.

A Rare Case of Chronic Diarrhea

No abstract available.

Parthenolide Sensitizes Human Colorectal Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand through Mitochondrial and Caspase Dependent Pathway

BACKGROUND/AIMS: Combination therapy utilizing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in conjunction with other anticancer agents, is a promising strategy to overcome TRAIL resistance in malignant cells. Recently, parthenolide (PT) has proved to be a promising anticancer agent, and several studies have explored its use in combination therapy. Here, we investigated the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. METHODS: HT-29 cells (TRAIL-resistant) were treated with PT and/or TRAIL for 24 hours. The inhibitory effect on proliferation was detected using the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining, cell cycle analysis, and Hoechst 33258 staining were used to assess apoptotic cell death. Activation of an apoptotic pathway was confirmed by Western blot. RESULTS: Treatment with TRAIL alone inhibited the proliferation of HCT 116 cells in a dose-dependent manner, whereas proliferation was not affected in HT-29 cells. Combination PT and TRAIL treatment significantly inhibited cell growth and induced apoptosis of HT-29 cells. We observed that the synergistic effect was associated with misregulation of B-cell lymphoma 2 (Bcl-2) family members, release of cytochrome C to the cytosol, activation of caspases, and increased levels of p53. CONCLUSION: Combination therapy using PT and TRAIL might offer an effetive strategy to overcome TRAIL resistance in certain CRC cells.

Clinical Features and Risk Factors for Severe Complications among Patients with Acute Hepatitis A Virus Infection in The Jeonbuk Province of Korea / 대한소화기학회지

BACKGROUND/AIMS: The frequency of symptomatic acute HAV infections in adulthood are increasing in Korea. This study analyzes the clinical severity in patients with acute HAV infection and investigates risk factors associated with three severe complications: prolonged cholestasis, acute kidney injury, and acute liver failure. METHODS: We performed a retrospective analysis of 726 patients diagnosed from January 2006 to December 2010 at three tertiary hospitals in Jeonbuk Province, Republic of Korea with acute HAV infection. RESULTS: In the group of 726 patients, the mean age was 30.3 years, 426 (58.6%) were male, and 34 (4.7%) were HBsAg positive. Severe complications from acute HAV infection occurred as follows: prolonged cholestasis in 33 (4.6%), acute kidney injury in 17 (2.3%), and acute liver failure in 16 (2.2%). Through multivariate analysis, age > or =40 years (OR 2.63, p=0.024) and peak PT (INR) > or =1.5 (OR 5.81, p=0.035) were found to be significant risk factors for prolonged cholestasis. Age > or =40 years (OR 5.24, p=0.002) and female gender (OR 3.11, p=0.036) were significant risk factors for acute kidney injury. Age > or =40 years (OR 6.91, p=0.002), HBsAg positivity (OR 5.02, p=0.049), and peak total bilirubin (OR 1.11, p=0.001) were significant risk factors for acute liver failure. CONCLUSIONS: Age > or =40 years, female gender, HBsAg positivity, peak PT (INR) > or =1.5, and peak total bilirubin were significant risk factors for severe complications in acute HAV infections.

Hemorrhagic fever with renal syndrome and coexisting hantavirus pulmonary syndrome

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease with fever, hemorrhage and renal failure caused by hantavirus infection. Hantavirus induces HFRS or hantavirus pulmonary syndrome (HPS). HPS progression to a life-threatening pulmonary disease is found primarily in the USA and very rarely in South Korea. Here, we report a case of HFRS and coexisting HPS.