Tae Nyeun Kim

Risk assessment for the development of hepatocellular carcinoma: according to on-treatment viral response during long-term lamivudine therapy in hepatitis B virus-related liver disease.

BACKGROUND & AIMS To assess the risk for the development of hepatocellular carcinoma (HCC) according to the underlying liver status and on-treatment viral response during long-term lamivudine therapy in patients with hepatitis B virus-related liver disease. PATIENTS AND METHODS Between March 1997 and February 2005, a total of 872 patients were treated with lamivudine for more than one year. Between 1983 and 1998, a total of 699 patients were enrolled as historical controls. RESULTS For patients with compensated cirrhosis, HCC occurred in 4.9% (5/103) of cases with sustained viral suppression (persistently <141,500 copies/ml), 11.8% (20/170) in cases with viral breakthrough, and 19.4% (7/36) in cases with a suboptimal response (persistently 141,500 copies/ml): the mean follow-up was 5.1+/-2.7, 5.4+/-2.3, and 3.7+/-1.8 years, respectively. For the control group, HCC developed in 25.0% (37/148) of the cases during a mean follow-up of 6.1+/-4.3 years. Thus, the annual incidence of HCC was 0.95%, 2.18%, 5.26%, and 4.10% in patients with sustained viral suppression, viral breakthrough, suboptimal response, and the control group, respectively. The cumulative incidence of HCC in patients with sustained viral suppression was significantly lower than in patients with a suboptimal response and the controls (p=0.002 and p=0.005, respectively). In patients without cirrhosis and with decompensated cirrhosis, the preventive effects of lamivudine on the development of HCC were not observed (p=0.446 and p=0.123, respectively). CONCLUSION Lamivudine therapy reduced the incidence of HCC in patients with compensated cirrhosis when the viral suppression was sustained.

Association between acid suppressive therapy and spontaneous bacterial peritonitis in cirrhotic patients with ascites

Abstract Objective. Proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) therapy may cause intestinal bacterial overgrowth and translocation. Therefore, acid suppressive therapy may increase the risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. Material and methods. A total of 176 cirrhotic patients with ascites who underwent diagnostic paracentesis between September 2004 and April 2009 were included in the analysis. Patients with gastrointestinal hemorrhage and/or antibiotic therapy within 2 weeks prior to hospital admission were excluded. SBP was defined as ≥250/mm3 polymorphonuclear white blood cells with or without a positive culture from the ascitic fluid. Eighty-three patients (mean age 56.1 years, 63 males) had SBP and 93 (mean age 54.7 years, 75 males) did not. Results. On the multivariate analysis, a Child–Pugh class C (OR = 2.890, 95% CI 1.443–5.786; p = 0.003), high MELD scores (≥20, OR = 3.540, 95% CI 1.155–10.849; p = 0.027), and PPI use (OR = 3.443, 95% CI 1.164–10.188; p = 0.025) were risk factors for SBP. H2RA was not associated with SBP. Conclusions. PPI use, as well as Child–Pugh class C and high MELD scores, was an independent risk factor for the development of SBP in cirrhotic patients with ascites. Further prospective studies are warranted to clarify this issue.

A case of severe hypophosphatemia related to adefovir dipivoxil treatment in a patient with liver cirrhosis related to hepatitis B virus

Adefovir dipivoxyl (ADV) effectively suppresses hepatitis B virus (HBV) replication but exhibits nephrotoxicity with severe hypophosphatemia when administered at a high dosage. This is the first report of severe hypophosphatemic osteomalacia induced by ADV at 10 mg/day. A 42-year-old man with HBV-related chronic liver disease presented with generalized bone pain, especially in the left ankle. He had been taking ADV for more than 1.5 years following a clinical breakthrough due to lamivudine-resistant HBV. Aggravating severe hypophosphatemia and elevated serum alkaline phosphatase levels with high bone fraction had been noted after 6 months of ADV therapy. Bone densitometry, simple bone X-rays, and a whole-body bone scan demonstrated osteoporosis and multiple areas with hot uptake, especially in the left ankle. All the image findings and symptoms improved after correcting the hypophosphatemia.

S-1 and Gemcitabine as an Outpatient-based Regimen in Patients with Advanced or Metastatic Pancreatic Cancer

OBJECTIVE The standard beneficial chemotherapy proved for patients with pancreatic cancer is a regimen containing gemcitabine. Novel oral fluoropyrimidine, S-1, can be added to gemcitabine to improve the efficacy of chemotherapy and to provide better convenience for patients. We aimed to evaluate the efficacy and safety of S-1 plus gemcitabine combination chemotherapy as a first-line treatment in patients with locally advanced or metastatic pancreatic cancer. METHODS Patients with histologically confirmed, bidimensionally measurable advanced/metastatic pancreatic cancer were eligible for the study. Chemotherapy consisted of S-1 (30 mg/m(2) p.o. bid from Day 1 to 14) and gemcitabine (1000 mg/m(2) on Days 8 and 15) every 3 weeks based on the results of a previously reported Phase I trial. Treatment was repeated until disease progression or unacceptable toxicity occurred. RESULTS From January 2005 to August 2007, 22 patients were enrolled. Median age was 62 years (range, 50-73). Nineteen patients (86.3%) had metastases and of these, 11 patients (57.9%) had multiple liver metastases. The overall response rate was 27.3% (95% CI, 8.7-45.9), with a partial response in six patients, stable disease in nine (40.9%) and progressive disease in seven (31.8%). With a median follow-up of 25.4 months, the median time to progression and overall survival were 4.6 (95% CI, 2-7.2 months) and 8.5 months (95% CI, 6.8-10.1 months), respectively, and 1-year survival rate was 27.3%. S-1 plus gemcitabine was well tolerated. Grade 3/4 hematological adverse events were neutropenia (9.1/9.1%) and anemia (4.5/0%). Non-hematological adverse events were mainly gastrointestinal events. Twenty patients (91%) received chemotherapy on an outpatient basis. CONCLUSIONS Combination chemotherapy of S-1 plus gemcitabine appears to be active and well tolerated as first-line treatment in patients with advanced/metastatic pancreatic cancer.

High-dose radiotherapy with intensity-modulated radiation therapy for advanced hepatocellular carcinoma.

AIMS AND BACKGROUND We report the results of intensity-modulated radiotherapy for patients with advanced hepatocellular carcinoma who were not candidate for local ablative therapies, transarterial chemoembolization or hepatic arterial infusion chemotherapy. METHODS AND STUDY DESIGN Between 2003 and 2008, 27 patients were treated with high-dose radiotherapy (median dose, 50.4 Gy). The equivalent sphere size of tumors was 11.4 ± 2.6 cm. Nineteen and 8 patients were Child-Pugh class A and B, respectively. Eighteen patients had thromboses in large veins. Six patients were treated with radiotherapy as the initial treatment modality, and 21 patients received other treatments before radiotherapy. RESULTS The overall response rate was 44.4% (1 pathologic complete response and 11 partial responses). The primary failure pattern was intrahepatic disease progression. Until the last follow-up, the primary liver masses and vein thromboses did not progress in 63.6% and 60.0% of the patients, respectively. The median progression-free survival and overall survival after radiotherapy rate were 3 and 5 months, respectively. Based on univariate analyses, response, Child-Pugh classification, and vein thrombosis were significant factors for overall survival, and tumor response, tumor size, vein thrombosis, and multiplicity were significant factors for progression-free survival. Tumor response was the only significant prognostic factor for overall survival and progression-free survival based on multivariate analyses. CONCLUSIONS Radiotherapy with intensity-modulated radiotherapy achieved a good response rate in patients with advanced hepatocellular carcinoma, and patients who had a good response lived longer than patients who did not have a good response.