ABSTRACT
Background@#Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. @*Methods@#A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]). @*Results@#Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). @*Conclusion@#The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.
ABSTRACT
Azathioprine is widely used for the treatment of Crohn’s disease (CD). Few cases from Western countries have reported idiopathic non-cirrhotic portal hypertension (NCPH) related to thiopurine therapy in patients with inflammatory bowel disease. Idiopathic NCPH is a rare hepatic condition with intrahepatic portal hypertension but no evidence of cirrhosis or chronic liver disease. Patients with idiopathic NCPH present with symptoms of portal hypertension such as thrombocytopenia, splenomegaly and esophageal varices. We report a case of idiopathic NCPH in a 51-year-old male patient with CD who had been taking azathioprine for 5 years. He was admitted due to esophageal variceal bleeding along with splenomegaly and thrombocytopenia. Evaluation of cirrhosis or chronic liver disease showed normal-range results as estimated by FibroScan evaluation, laboratory examination for autoimmune hepatitis or viral hepatitis, and liver biopsy. This case may suggest the need for careful monitoring for manifestations of portal hypertension in Asian patients with inflammatory bowel disease receiving thiopurine treatment.
ABSTRACT
Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.
ABSTRACT
Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
ABSTRACT
Background@#Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. @*Methods@#A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]). @*Results@#Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). @*Conclusion@#The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.
ABSTRACT
Azathioprine is widely used for the treatment of Crohn’s disease (CD). Few cases from Western countries have reported idiopathic non-cirrhotic portal hypertension (NCPH) related to thiopurine therapy in patients with inflammatory bowel disease. Idiopathic NCPH is a rare hepatic condition with intrahepatic portal hypertension but no evidence of cirrhosis or chronic liver disease. Patients with idiopathic NCPH present with symptoms of portal hypertension such as thrombocytopenia, splenomegaly and esophageal varices. We report a case of idiopathic NCPH in a 51-year-old male patient with CD who had been taking azathioprine for 5 years. He was admitted due to esophageal variceal bleeding along with splenomegaly and thrombocytopenia. Evaluation of cirrhosis or chronic liver disease showed normal-range results as estimated by FibroScan evaluation, laboratory examination for autoimmune hepatitis or viral hepatitis, and liver biopsy. This case may suggest the need for careful monitoring for manifestations of portal hypertension in Asian patients with inflammatory bowel disease receiving thiopurine treatment.
ABSTRACT
Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.
ABSTRACT
Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).
ABSTRACT
Purpose@#Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. @*Materials and Methods@#Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. @*Results@#Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). @*Conclusion@#High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.
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Background@#Mac-2 binding protein glycosylation isomer (M2BPGi) has been established as a non-invasive biomarker for liver fibrosis. We evaluated the diagnostic efficacy of M2BPGi compared with those of other liver fibrosis markers in liver fibrosis in non-alcoholic fatty liver disease (NAFLD). @*Methods@#We analyzed serum M2BPGi levels in 113 NAFLD patients. A pathologist graded liver fibrosis histopathologically. The diagnostic efficacies of serum M2BPGi and other liver fibrosis markers (aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, and NAFLD fibrosis score [NFS]) were evaluated using correlation, area under the ROC curve (AUC), logistic regression, and C-statistics. @*Results@#Serum M2BPGi level and other liver fibrosis markers showed a moderate correlation with fibrosis grade. The AUC values of M2BPGi were 0.761, 0.819, 0.866, and 0.900 for diagnosing fibrosis (F) > 0, F > 1, F > 2, and F > 3, respectively. Logistic regression analysis showed M2BPGi as the only independent factor associated with F > 2 and F > 3. Although C-statistics showed that NFS was the best diagnostic factor for F > 2 and F > 3, M2BPGi with NFS had an increased C-statistics value, indicating that it is a better diagnostic model. @*Conclusions@#The serum M2BPGi level increased with liver fibrosis severity and could be a good biomarker for diagnosing advanced fibrosis and cirrhosis in NAFLD patients. A well-controlled, prospective study with a larger sample size is needed to validate the diagnostic power of M2BPGi and other fibrosis markers in NAFLD.
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Background/Aims@#Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved. @*Methods@#A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed. @*Results@#Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P @*Conclusions@#This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.
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Background@#Liver cirrhosis has become a heavy burden not only for patients, but also for our society. However, little is known about the recent changes in clinical outcomes and characteristics of patients with cirrhosis-related complications in Korea. Therefore, we aimed to evaluate changes in characteristics of patients with liver cirrhosis in Daegu-Gyeongbuk province in Korea over the past 15 years. @*Methods@#We retrospectively reviewed the medical records of 15,716 liver cirrhotic patients from 5 university hospitals in Daegu-Gyeongbuk province from 2000 to 2014. The Korean Standard Classification of Diseases-6 code associated with cirrhosis was investigated through medical records and classified according to the year of first visit. @*Results@#A total of 15,716 patients was diagnosed with cirrhosis. A number of patients newly diagnosed with cirrhosis has decreased each year. In 2000, patients were most likely to be diagnosed with hepatitis B virus (HBV) cirrhosis, followed by alcoholic cirrhosis. There was a significant decrease in HBV (P < 0.001), but alcohol, hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD) showed a significant increase during the study period (alcohol, P = 0.036; HCV, P = 0.001; NAFLD, P = 0.001). At the time of initial diagnosis, the ratio of Child-Turcotte-Pugh (CTP) class A gradually increased from 23.1% to 32.9% (P < 0.001). The most common cause of liver-related hospitalization in 2000 was hepatocellular carcinoma (HCC) (25.5%); in 2014, gastrointestinal bleeding with esophageal and gastric varices (21.4%) was the most common cause. Cases of hospitalization with liver-related complication represented 76.4% of all cases in 2000 but 70.9% in 2014. Incidence rate of HCC has recently increased. In addition, HCC-free survival was significantly lower in CTP class A than in classes B and C. Finally, there was significant difference in HCC occurrence according to causes (P < 0.001). HBV and HCV cirrhosis had lower HCC-free survival than alcoholic and NAFLD cirrhosis. @*Conclusion@#In recent years, the overall number of cirrhosis patients has decreased. This study confirmed the recent trend in decrease of cirrhosis, especially of cirrhosis due to HBV, and the increase of HCV, alcoholic and NAFLD cirrhosis. Targeted screening for at-risk patients will facilitate early detection of liver diseases allowing effective intervention and may have decreased the development of cirrhosis and its complications.
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BACKGROUND/AIMS: Acoustic radiation force impulse (ARFI) elastography predicts the presence of esophageal varices (EVs). We investigated whether an ARFI-based prediction model can assess EV bleeding (EVB) risk in patients with cirrhosis. METHODS: The records of 262 patients with cirrhosis who underwent ARFI elastography and endoscopic surveillance at two institutions in 2008 to 2013 were retrospectively reviewed, and ARFI spleen diameter-to-platelet ratio scores (ASPS) were calculated. RESULTS: The median patient age (165 men, 97 women) was 56 years. The median ARFI velocity, spleen diameter, platelet count, and ASPS were 1.7 m/sec, 10.1 cm, 145×10⁹/L, and 1.16, respectively. During the median 38-month follow-up, 61 patients experienced EVB. Among all patients (179 without EVs and 83 with EVs), the cutoff value that maximized the sum of the sensitivity (73.1%) and specificity (78.4%) (area under receiver operating characteristic curve [AUROC], 0.824) for predicting EVB was 2.60. The cumulative EVB incidence was significantly higher in patients with ASPS ≥2.60 than in those with ASPS <2.60 (p<0.001). Among patients with EVs (n=83), 49 had high-risk EVs (HEVs), and 22 had EVB. The cumulative EVB incidence was significantly higher in HEV patients than in low-risk EV patients (p=0.037). At an ASPS of 4.50 (sensitivity, 66.7%; specificity, 70.6%; AUROC, 0.691), the cumulative EVB incidence was significantly higher in patients with a high ASPS than in those with a low ASPS (p=0.045). A higher ASPS independently predicted EVB (hazard ratio, 4.072; p=0.047). CONCLUSIONS: ASPS can assess EVB risk in patients with cirrhosis. Prophylactic management should be considered for patients with HEVs and ASPS ≥4.50.
Subject(s)
Humans , Male , Acoustics , Elasticity Imaging Techniques , Esophageal and Gastric Varices , Fibrosis , Follow-Up Studies , Hemorrhage , Incidence , Liver Cirrhosis , Platelet Count , Retrospective Studies , Risk Assessment , ROC Curve , Sensitivity and Specificity , Spleen , ViperidaeABSTRACT
BACKGROUND/AIMS@#Previous studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world.@*METHODS@#We enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end-of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure.@*RESULTS@#The mean age of patients was 59.5 ± 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure.@*CONCLUSIONS@#DCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events.
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BACKGROUND/AIMS: Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. METHODS: Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P < 0.0001), and week 240 (95.0% vs. 47.6%, P < 0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P < 0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P < 0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. CONCLUSIONS: Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.
Subject(s)
Humans , Alanine Transaminase , DNA , Hepatitis B virus , Hepatitis B , Hepatitis B, Chronic , Hepatitis , Hepatitis, Chronic , Incidence , LamivudineABSTRACT
BACKGROUND/AIMS: Periostin is an extracellular matrix protein and is known to be related to the metastatic potential and prognosis of cancer. However, few studies have investigated the expression level of periostin and its association with prognoses in hepatocellular carcinoma. Therefore, we analyzed periostin overexpression in hepatocellular carcinoma and its implication for prognoses. METHODS: We evaluated 149 patients who underwent surgical resection between 2006 and 2010. Tissue microarrays were constructed from hepatocellular carcinoma tissue and adjacent nontumor tissue, and immunohistochemistry was performed. RESULTS: A high periostin level was observed more frequently in cases of multiple tumors (odds ratio [OR], 2.826; 95% confidence interval [CI], 1.224 to 6.527; p=0.013), positive microvascular invasion (OR, 2.974; 95% CI, 1.431 to 6.181; p=0.003), and advanced stage disease (OR, 3.032; 95% CI, 1.424 to 6.452; p=0.003). Patients with high periostin expression had significantly (p=0.002) lower overall survival rates than those with low periostin expression (90.3%, 66.1%, and 56.2% vs 97.7%, 85.1%, and 77.5% at 1, 3, and 5 years). CONCLUSIONS: We found that a combination of periostin overexpression and microvascular invasion in hepatocellular carcinoma was correlated with a poor prognosis and can be a good prognostic marker for hepatocellular carcinoma.
Subject(s)
Humans , Carcinoma, Hepatocellular , Extracellular Matrix , Immunohistochemistry , Prognosis , Survival Rate , Tissue Array AnalysisABSTRACT
BACKGROUND/AIMS: Periostin is an extracellular matrix protein and is known to be related to the metastatic potential and prognosis of cancer. However, few studies have investigated the expression level of periostin and its association with prognoses in hepatocellular carcinoma. Therefore, we analyzed periostin overexpression in hepatocellular carcinoma and its implication for prognoses. METHODS: We evaluated 149 patients who underwent surgical resection between 2006 and 2010. Tissue microarrays were constructed from hepatocellular carcinoma tissue and adjacent nontumor tissue, and immunohistochemistry was performed. RESULTS: A high periostin level was observed more frequently in cases of multiple tumors (odds ratio [OR], 2.826; 95% confidence interval [CI], 1.224 to 6.527; p=0.013), positive microvascular invasion (OR, 2.974; 95% CI, 1.431 to 6.181; p=0.003), and advanced stage disease (OR, 3.032; 95% CI, 1.424 to 6.452; p=0.003). Patients with high periostin expression had significantly (p=0.002) lower overall survival rates than those with low periostin expression (90.3%, 66.1%, and 56.2% vs 97.7%, 85.1%, and 77.5% at 1, 3, and 5 years). CONCLUSIONS: We found that a combination of periostin overexpression and microvascular invasion in hepatocellular carcinoma was correlated with a poor prognosis and can be a good prognostic marker for hepatocellular carcinoma.
Subject(s)
Humans , Carcinoma, Hepatocellular , Extracellular Matrix , Immunohistochemistry , Prognosis , Survival Rate , Tissue Array AnalysisABSTRACT
BACKGROUND/AIMS: To determine factors predictive of discordance in staging liver fibrosis using liver biopsy (LB) and acoustic radiation force impulse (ARFI) elastography in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with CHB who underwent LB and ARFI elastography on the same day from November 2010 to March 2013 were prospectively recruited from three tertiary hospitals. RESULTS: We analyzed 105 patients (median age of 47 years). The F0-1, F2, F3, and F4 fibrosis stages were identified in 27 (25.7%), 27 (25.7%), 21 (20.0%), and 30 (28.6%) patients, respectively. The areas under the receiver operating characteristics curves for ARFI elastography in assessing ≥F2, ≥F3, and F4 was 0.814, 0.848, and 0.752, respectively. The discordance of at least one stage between LB and ARFI was observed in 68 patients (64.8%) and of at least two stages in 16 patients (15.2%). In a multivariate analysis, advanced fibrosis stage (F3-4) was the only factor that was negatively correlated with one-stage discordance (p=0.042). Moreover, advanced fibrosis stage was negatively (p=0.016) correlated and body mass index (BMI) was positively (p=0.006) correlated with two-stage discordance. CONCLUSIONS: Advanced fibrosis stage (F3-4) was a predictor of nondiscordance between LB and ARFI elastography; BMI also influenced the accuracy of ARFI elastography.
Subject(s)
Female , Humans , Male , Middle Aged , Body Mass Index , Elasticity Imaging Techniques/methods , Hepatitis B, Chronic/complications , Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , ROC Curve , Republic of KoreaABSTRACT
PURPOSE: The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study). MATERIALS AND METHODS: Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients. RESULTS: More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients. CONCLUSION: Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).
Subject(s)
Humans , Carcinoma, Hepatocellular , Diarrhea , Incidence , Korea , Life Change Events , Prospective Studies , SkinABSTRACT
BACKGROUND/AIMS: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. METHODS: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). RESULTS: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). CONCLUSIONS: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.