Tenofovir disoproxil fumarate(TDF) is a potent nucleo-tide analogue that is recommended as first-line therapy for patients with chronic hepatitis B. The results of a longitudinal study of TDF treatment demonstrated no...Tenofovir disoproxil fumarate(TDF) is a potent nucleo-tide analogue that is recommended as first-line therapy for patients with chronic hepatitis B. The results of a longitudinal study of TDF treatment demonstrated no development of resistance. We observed one treatment-na?ve chronic hepatitis B(CHB) patient who developed TDF resistance after complete viral suppression during long-term TDF treatment. A 37-year-old HBe Ag-positive man received TDF 300 mg/d for 43 mo. The hepatitis B virus(HBV) DNA titer was 8 log_(10) copies/m L at baseline and became undetectable at 16 mo after treatment. However, the HBV DNA titer rebounded to 7.5 log_(10) copies/m L at 43 mo after treatment. We performed full sequencing to find mutation sites associated with virologic breakthrough. The results showed 9 mutation sites, most of which had not been well-known as mutation sites. We changed the therapy from tenofovir to entecavir with a regimen of 0.5 mg once daily. After 4 mo, the HBV DNA titer decreased to 267 copies/m L, and the liver enzyme levels were normalized.展开更多
AIM To evaluate the safety and efficacy of tenofovir disoproxil fumarate(TDF) as a first-line therapy in decompensated liver disease. METHODS We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treate...AIM To evaluate the safety and efficacy of tenofovir disoproxil fumarate(TDF) as a first-line therapy in decompensated liver disease. METHODS We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis group. We followed the patients for 12 mo and evaluated clinical outcomes, including biochemical, virological, and serological responses. We also evaluated changes in hepatic and renal function and compared the decompensated and compensated cirrhosis groups. RESULTS The 1-year complete virological response(CVR) and Hepatitis B e antigen(HBe Ag) seroconversion were seen in 70.2% and 14.2% in the decompensated cirrhosis group, respectively. The rates of HBe Ag seroconversion/loss and ALT normalization at month 12 were similar in both groups. TDF treatment was also effective for decreasing the level of hepatitis B virus(HBV) DNA in both groups, but CVR was higher in the compensated group(88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved Child-Turcotte-Pugh(CTP) and model for end-stage liver disease(MELD) scores in decompensated group(P < 0.001). Of the 57 decompensated patients, 39(68.4%) achieved CTP class A and 27(49.1%) showed improvement in the CTP score of 2 points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/d L increases in serum levels of creatinine in the decompensated and compensated cirrhosis group were 7.0% and 2.5%, respectively(P < 1.000).CONCLUSION TDF therapy in decompensated cirrhosis patients was effective for decreasing HBV DNA levels and improving hepatic function with relatively lower CVR than in compensated cirrhosis. Thus, physicians should carefully monitor not only renal function but also treatment responses when using TDF in decompensated cirrhosis patients.展开更多
Hepatocellular carcinoma(HCC)is a grave primary liver cancer that has a limited therapeutic option because it is generally diagnosed later in an advanced stage due to its aggressive biologic behavior.The early detecti...Hepatocellular carcinoma(HCC)is a grave primary liver cancer that has a limited therapeutic option because it is generally diagnosed later in an advanced stage due to its aggressive biologic behavior.The early detection of HCC has a great impact on the treatment efficacy and survival of patients at high risk for cancer.Potential host,environmental,and virus-related risk factors have been introduced.Hepatitis B virus(HBV)is a major cause of end-stage liver diseases such as liver cirrhosis or HCC in endemic areas,and its serologic or virologic status is considered an important risk factor.HCC risk prediction derived from the identification of major risk factors is necessary for providing adequate screening/surveillance strategies to high-risk individuals.Several risk prediction models for HBV-related HCC have been presented recently with simple,efficient,and readily available to use parameters applicable to average-or unknown-risk populations as well as high-risk individuals.Predictive scoring systems of risk estimation to assess HCC development can provide the way to an evidence-based clinical approach for cost-and effort-effective outcomes,capable of inducing a personalized surveillance program according to risk stratification.In this review,the concepts and perspectives of the risk prediction of HCC are discussed through the analysis of several risk prediction models of HBV-related HCC.展开更多
Primary hepatic neuroendocrine carcinoma(NEC) with concurrent occurrence of hepatocellular carcinoma(HCC) of the liver is very rare. Only 8 cases have been reported in the literature. Concurrent occurrence of HCC and ...Primary hepatic neuroendocrine carcinoma(NEC) with concurrent occurrence of hepatocellular carcinoma(HCC) of the liver is very rare. Only 8 cases have been reported in the literature. Concurrent occurrence of HCC and NEC in the liver is classified as combined type or collision type by histological distributional patterns; only 2 cases have been reported. Herein, we report a case of collision type concurrent occurrence of HCC and NEC, in which primary hepatic NEC was in only a small portion of the nodule, which is different from the 2 previously reported cases. A 72-year-old male with chronic hepatitis C was admitted to our hospital for a hepatic mass detected by liver computed tomography(CT) at another clinic. Because the nodule was in hepatic segment 3 and had proper radiologic findings for diagnosis of HCC, including enhancement in the arterial phase and wash-out in the portal and delay phases, the patient was treated with laparoscopic left lateral sectionectomy. The pathology demonstrated that the nodule was 2.5 cm and was moderately differentiated HCC. However, a 3 mm-sized focal neuroendocrine carcinoma was also detected on the capsule of the nodule. The tumor was concluded to be a collision type with HCC and primary hepatic NEC. After the surgery, for follow-up, the patient underwent a liver CT every 3 mo. Five multiple nodules were found in the right hepatic lobe on the follow-up liver CT 6 mo post-operatively. As the features of the nodules in the liver CT and MRI were different from that of HCC, a liver biopsy was performed. Intrahepatic recurrent NEC was proven after the liver biopsy, which showed the same pathologic features with the specimen obtained 6 mo ago. Palliative chemotherapy with a combination of etoposide and cisplatin has been administered for 4 months, showing partial response.展开更多
AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with ...AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d.The biochemical response,as assessed by serum alanine aminotransferase(ALT) activity,virologic response,as assessed by serum hepatitis B virus DNA(HBV DNA) titer,serologic response,as assessed by hepatitis B e antigen(HBeAg) status,and virologic breakthrough with genotypic mutations were assessed.RESULTS:Two-hundred and fifty-four patients [clevudine(n = 118) vs entecavir(n = 136)] were enrolled.In clevudine-treated patients,the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96(80.9% and 91.2% in the entecavir group,respectively),the mean titer changes in serum HBV DNA were-6.03 and-6.55 log 10 copies/mL(-6.35 and-6.86 log 10 copies/mL,respectively,in the entecavir group),and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1%(74.4% and 83.8%,respectively,in the entecavir group).These results were similar to those of entecavir-treated patients.The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine,which was similar to patients treated with entecavir(22.8% and 27.7%,respectively).The virologic breakthrough in the clevudine group occurred in 9(7.6%) patients at weeks 48 and 15(12.7%) patients at week 96,which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M.There was no virologic breakthrough in the entecavir group.CONCLUSION:In antiviral-naive CHB patients,longterm treatment outcomes of clevudine were not inferior to those of entecavir,except for virologic breakthrough.展开更多
The present study was conducted to investigate whether mitochondrial pathway of apoptosis is involved in cyclooxygenase-2 (COX-2) inhibitor-induced growth inhibition of hepatoma cells. The growth rate and pattern of N...The present study was conducted to investigate whether mitochondrial pathway of apoptosis is involved in cyclooxygenase-2 (COX-2) inhibitor-induced growth inhibition of hepatoma cells. The growth rate and pattern of NS-398 (selective COX-2 inhibitor)-treated Hep3B hepatoma cells were analyzed by microscopic examination, DNA fragmentation gel analysis and flow cytometry followed by the cleavage of down-stream caspase 3 and the release of cytosolic fraction of cytochrome c assessed by Western blot analysis. NS-398 induced the growth inhibition of hepatoma cells depending on the concentration of this COX-2 inhibitor and time sequence. Ladder patterned-DNA fragmentation and cytometric redistribution to sub-G1 phase in cell cycle were revealed in NS-398-induced growth inhibition of hepatoma cells. Cytochrome c was translocated from mitochondria to cytosol in time-dependent manner following NS-398 treatment to hepatoma cells. COX-2 inhibitor induces the growth inhibition of hepatoma cells via caspase-dependent, mitochondria-mediated intrinsic apoptosis pathway. These results strongly suggest the possibility of therapeutic implication of COX-2 inhibitor in HCC.展开更多
文摘Tenofovir disoproxil fumarate(TDF) is a potent nucleo-tide analogue that is recommended as first-line therapy for patients with chronic hepatitis B. The results of a longitudinal study of TDF treatment demonstrated no development of resistance. We observed one treatment-na?ve chronic hepatitis B(CHB) patient who developed TDF resistance after complete viral suppression during long-term TDF treatment. A 37-year-old HBe Ag-positive man received TDF 300 mg/d for 43 mo. The hepatitis B virus(HBV) DNA titer was 8 log_(10) copies/m L at baseline and became undetectable at 16 mo after treatment. However, the HBV DNA titer rebounded to 7.5 log_(10) copies/m L at 43 mo after treatment. We performed full sequencing to find mutation sites associated with virologic breakthrough. The results showed 9 mutation sites, most of which had not been well-known as mutation sites. We changed the therapy from tenofovir to entecavir with a regimen of 0.5 mg once daily. After 4 mo, the HBV DNA titer decreased to 267 copies/m L, and the liver enzyme levels were normalized.
基金Supported by the Catholic Medical Center Research Foundation program in 2014,No.5-2014-B0001-00176
文摘AIM To evaluate the safety and efficacy of tenofovir disoproxil fumarate(TDF) as a first-line therapy in decompensated liver disease. METHODS We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis group. We followed the patients for 12 mo and evaluated clinical outcomes, including biochemical, virological, and serological responses. We also evaluated changes in hepatic and renal function and compared the decompensated and compensated cirrhosis groups. RESULTS The 1-year complete virological response(CVR) and Hepatitis B e antigen(HBe Ag) seroconversion were seen in 70.2% and 14.2% in the decompensated cirrhosis group, respectively. The rates of HBe Ag seroconversion/loss and ALT normalization at month 12 were similar in both groups. TDF treatment was also effective for decreasing the level of hepatitis B virus(HBV) DNA in both groups, but CVR was higher in the compensated group(88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved Child-Turcotte-Pugh(CTP) and model for end-stage liver disease(MELD) scores in decompensated group(P < 0.001). Of the 57 decompensated patients, 39(68.4%) achieved CTP class A and 27(49.1%) showed improvement in the CTP score of 2 points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/d L increases in serum levels of creatinine in the decompensated and compensated cirrhosis group were 7.0% and 2.5%, respectively(P < 1.000).CONCLUSION TDF therapy in decompensated cirrhosis patients was effective for decreasing HBV DNA levels and improving hepatic function with relatively lower CVR than in compensated cirrhosis. Thus, physicians should carefully monitor not only renal function but also treatment responses when using TDF in decompensated cirrhosis patients.
文摘Hepatocellular carcinoma(HCC)is a grave primary liver cancer that has a limited therapeutic option because it is generally diagnosed later in an advanced stage due to its aggressive biologic behavior.The early detection of HCC has a great impact on the treatment efficacy and survival of patients at high risk for cancer.Potential host,environmental,and virus-related risk factors have been introduced.Hepatitis B virus(HBV)is a major cause of end-stage liver diseases such as liver cirrhosis or HCC in endemic areas,and its serologic or virologic status is considered an important risk factor.HCC risk prediction derived from the identification of major risk factors is necessary for providing adequate screening/surveillance strategies to high-risk individuals.Several risk prediction models for HBV-related HCC have been presented recently with simple,efficient,and readily available to use parameters applicable to average-or unknown-risk populations as well as high-risk individuals.Predictive scoring systems of risk estimation to assess HCC development can provide the way to an evidence-based clinical approach for cost-and effort-effective outcomes,capable of inducing a personalized surveillance program according to risk stratification.In this review,the concepts and perspectives of the risk prediction of HCC are discussed through the analysis of several risk prediction models of HBV-related HCC.
文摘Primary hepatic neuroendocrine carcinoma(NEC) with concurrent occurrence of hepatocellular carcinoma(HCC) of the liver is very rare. Only 8 cases have been reported in the literature. Concurrent occurrence of HCC and NEC in the liver is classified as combined type or collision type by histological distributional patterns; only 2 cases have been reported. Herein, we report a case of collision type concurrent occurrence of HCC and NEC, in which primary hepatic NEC was in only a small portion of the nodule, which is different from the 2 previously reported cases. A 72-year-old male with chronic hepatitis C was admitted to our hospital for a hepatic mass detected by liver computed tomography(CT) at another clinic. Because the nodule was in hepatic segment 3 and had proper radiologic findings for diagnosis of HCC, including enhancement in the arterial phase and wash-out in the portal and delay phases, the patient was treated with laparoscopic left lateral sectionectomy. The pathology demonstrated that the nodule was 2.5 cm and was moderately differentiated HCC. However, a 3 mm-sized focal neuroendocrine carcinoma was also detected on the capsule of the nodule. The tumor was concluded to be a collision type with HCC and primary hepatic NEC. After the surgery, for follow-up, the patient underwent a liver CT every 3 mo. Five multiple nodules were found in the right hepatic lobe on the follow-up liver CT 6 mo post-operatively. As the features of the nodules in the liver CT and MRI were different from that of HCC, a liver biopsy was performed. Intrahepatic recurrent NEC was proven after the liver biopsy, which showed the same pathologic features with the specimen obtained 6 mo ago. Palliative chemotherapy with a combination of etoposide and cisplatin has been administered for 4 months, showing partial response.
文摘AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d.The biochemical response,as assessed by serum alanine aminotransferase(ALT) activity,virologic response,as assessed by serum hepatitis B virus DNA(HBV DNA) titer,serologic response,as assessed by hepatitis B e antigen(HBeAg) status,and virologic breakthrough with genotypic mutations were assessed.RESULTS:Two-hundred and fifty-four patients [clevudine(n = 118) vs entecavir(n = 136)] were enrolled.In clevudine-treated patients,the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96(80.9% and 91.2% in the entecavir group,respectively),the mean titer changes in serum HBV DNA were-6.03 and-6.55 log 10 copies/mL(-6.35 and-6.86 log 10 copies/mL,respectively,in the entecavir group),and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1%(74.4% and 83.8%,respectively,in the entecavir group).These results were similar to those of entecavir-treated patients.The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine,which was similar to patients treated with entecavir(22.8% and 27.7%,respectively).The virologic breakthrough in the clevudine group occurred in 9(7.6%) patients at weeks 48 and 15(12.7%) patients at week 96,which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M.There was no virologic breakthrough in the entecavir group.CONCLUSION:In antiviral-naive CHB patients,longterm treatment outcomes of clevudine were not inferior to those of entecavir,except for virologic breakthrough.
文摘The present study was conducted to investigate whether mitochondrial pathway of apoptosis is involved in cyclooxygenase-2 (COX-2) inhibitor-induced growth inhibition of hepatoma cells. The growth rate and pattern of NS-398 (selective COX-2 inhibitor)-treated Hep3B hepatoma cells were analyzed by microscopic examination, DNA fragmentation gel analysis and flow cytometry followed by the cleavage of down-stream caspase 3 and the release of cytosolic fraction of cytochrome c assessed by Western blot analysis. NS-398 induced the growth inhibition of hepatoma cells depending on the concentration of this COX-2 inhibitor and time sequence. Ladder patterned-DNA fragmentation and cytometric redistribution to sub-G1 phase in cell cycle were revealed in NS-398-induced growth inhibition of hepatoma cells. Cytochrome c was translocated from mitochondria to cytosol in time-dependent manner following NS-398 treatment to hepatoma cells. COX-2 inhibitor induces the growth inhibition of hepatoma cells via caspase-dependent, mitochondria-mediated intrinsic apoptosis pathway. These results strongly suggest the possibility of therapeutic implication of COX-2 inhibitor in HCC.
