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Risk score model for the development of hepatocellular carcinoma in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B.

Won SOHN ; Ju Yeon CHO ; Ji Hoon KIM ; Jung Il LEE ; Hyung Joon KIM ; Min Ah WOO ; Sin Ho JUNG ; Yong Han PAIK

Clinical and Molecular Hepatology.2017;23(2):170-178. doi:10.3350/cmh.2016.0086

BACKGROUND/AIMS: This study aimed to develop and validate a risk prediction model for the development of hepatocellular carcinoma (HCC) in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B (CHB). METHODS: We investigated 2,061 Korean treatment-naïve patients with CHB treated with entecavir as an initial therapy. A risk score model for HCC development was developed based on multivariable Cox regression model in a single center (n=990) and was validated using the time-dependent area under the receiver operating characteristic curve (AUROC) in three other centers (n=1,071). The difference of HCC development among risk groups (low, intermediate, and high) categorized by risk score was also investigated. RESULTS: The cumulative incidence rates of HCC at 5 years were 11.2% and 8.9% in the testing and validation cohorts, respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC-RESCUE) is formulated as (age+15×gender [female=0 / male=1]+23×cirrhosis [absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82, 0.81, and 0.81, respectively, in the validation cohort. A significant difference of HCC development in each risk group was determined by the 5-year HCC risk score in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%; high risk group, 41.2%, p<0.001). CONCLUSIONS: The study presents a new risk score model with a good ability to predict HCC development and determine high risk patients for HCC development consisting of readily available clinical factors in treatment-naïve CHB patients receiving entecavir.
Antiviral Agents ; Carcinoma, Hepatocellular* ; Cohort Studies ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Incidence ; Risk Assessment ; ROC Curve

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Clinical features and outcomes of patients with hepatocellular carcinoma complicated with bile duct invasion.

Jihyun AN ; Kwang Sun LEE ; Kang Mo KIM ; Do Hyun PARK ; Sang Soo LEE ; Danbi LEE ; Ju Hyun SHIM ; Young Suk LIM ; Han Chu LEE ; Young Hwa CHUNG ; Yung Sang LEE

Clinical and Molecular Hepatology.2017;23(2):160-169. doi:10.3350/cmh.2016.0088

BACKGROUND/AIMS: Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion. METHODS: A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. RESULTS: The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively). CONCLUSIONS: The survival of HCC patients with bile duct invasion at initial diagnosis is generally poor. However, aggressive treatments for HCC such as resection or biliary drainage may be beneficial therapeutic options for patients with preserved liver function.
Bile Ducts* ; Bile* ; Carcinoma, Hepatocellular* ; Diagnosis ; Drainage ; Drug Therapy ; Humans ; Jaundice, Obstructive ; Liver ; Liver Neoplasms ; Portal Vein ; Prognosis ; Retrospective Studies ; Survival Rate ; Thrombosis

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Clinical impact of the early alanine amininotransferase flare during tenofovir monotherapy in treatment-naïve patients with chronic hepatitis B.

Hee Yeon SEO ; Han Ah LEE ; Soon Young KO ; Joon Ho WANG ; Jeong Han KIM ; Won Hyeok CHOE ; So Young KWON

Clinical and Molecular Hepatology.2017;23(2):154-159. doi:10.3350/cmh.2016.0067

BACKGROUND/AIMS: Little is known about the effect of early flares on response during first-line tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB). The aim of this study was to investigate the incidence and outcome of early alanine aminotransferase (ALT) flare in treatment-naive patients with CHB during long-term TDF monotherapy. METHODS: One hundred eighty-one treatment-naive CHB patients were treated with a 300-mg once-daily dose of TDF for more than 12 weeks. Virological markers of hepatitis B virus (HBV) and biochemical data were measured at baseline and every 4-12 weeks during the therapy. The proportion of patients with undetectable HBV DNA level (< 100 copies/mL) was noted. RESULTS: The median age was 48.3 years and 122 patients (67.4%) were men. Hepatitis B envelope antigen (HBeAg) was positive in 101 patients (55.8%). No patient had cirrhosis. The median follow-up duration was 45 weeks (12-155 weeks). ALT flare (>5 × upper limit of the normal range) occurred in seven patients (3%) without viral breakthrough within the first 8 weeks after the start of TDF monotherapy. Among them, six patients were HBeAg-positive and one patient was HBeAg-negative. All cases of early ALT flares resolved within 4 weeks and virologic response was observed in all patients without interruption or discontinuation of treatment. CONCLUSIONS: Continuous TDF monotherapy was effective and safe in treatment-naive patients with CHB who experienced early ALT flares followed by a decrease in HBV DNA level.
Alanine Transaminase ; Alanine* ; DNA ; Fibrosis ; Follow-Up Studies ; Hepatitis B ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Incidence ; Male ; Tenofovir*

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Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis.

Oidov BAATARKHUU ; Hye Won LEE ; Jacob GEORGE ; Dashchirev MUNKH-ORSHIKH ; Baasankhuu ENKHTUVSHIN ; Sosorbaram ARIUNAA ; Mohammed ESLAM ; Sang Hoon AHN ; Kwang Hyub HAN ; Do Young KIM

Clinical and Molecular Hepatology.2017;23(2):147-153. doi:10.3350/cmh.2016.0055

BACKGROUND/AIMS: Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. METHODS: The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. RESULTS: Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. CONCLUSIONS: Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.
Cohort Studies ; Hepacivirus ; Hepatitis A virus ; Hepatitis A* ; Hepatitis B ; Hepatitis B virus ; Hepatitis C ; Hepatitis D ; Hepatitis Delta Virus ; Hepatitis Viruses ; Hepatitis* ; Humans ; Incidence ; Infection Control ; Liver Diseases ; Male ; Mongolia* ; Prevalence ; Risk Factors ; Superinfection

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Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin family member 1B and susceptibility to hepatitis B virus related hepatocellular carcinoma.

Mingkuan SU ; Jianfeng GUO ; Jiancheng HUANG

Clinical and Molecular Hepatology.2017;23(2):138-146. doi:10.3350/cmh.2016.0083

BACKGROUND/AIMS: The association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC. METHODS: The results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study. RESULTS: The 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.’s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent. CONCLUSIONS: The results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship.
Alleles ; Carcinoma, Hepatocellular* ; Case-Control Studies ; Cohort Studies ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Kinesin* ; Polymorphism, Single Nucleotide ; Population Characteristics

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A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function.

Hyun YANG ; Hyun Young WOO ; Soon Kyu LEE ; Ji Won HAN ; Bohyun JANG ; Hee Chul NAM ; Hae Lim LEE ; Sung Won LEE ; Do Seon SONG ; Myeong Jun SONG ; Jung Suk OH ; Ho Jong CHUN ; Jeong Won JANG ; Angelo LOZADA ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON

Clinical and Molecular Hepatology.2017;23(2):128-137. doi:10.3350/cmh.2016.0071

BACKGROUND/AIMS: Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS) of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). METHODS: A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. RESULTS: The median number of MET cycles was two (1-15). The OS values for the MET group and sorafenib group were 158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014) and Child-Pugh class B (HR=1.856, P=0.008). CONCLUSIONS: MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.
Administration, Metronomic ; alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Drug Therapy* ; Humans ; Liver* ; Portal Vein ; Thrombosis

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Is alanine aminotransferase flare-up in nucleos(t)ide analogue treatment of chronic hepatitis B a promising, rather than a devastating, sign?.

Nae Yun HEO

Clinical and Molecular Hepatology.2017;23(2):125-127. doi:10.3350/cmh.2017.0106

No abstract available.
Alanine Transaminase* ; Alanine* ; Hepatitis B ; Hepatitis B, Chronic* ; Hepatitis, Chronic*

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Can metronomic chemotherapy be an alternative to sorafenib in advanced hepatocellular carcinoma?.

Do Young KIM

Clinical and Molecular Hepatology.2017;23(2):123-124. doi:10.3350/cmh.2017.0107

No abstract available.
Carcinoma, Hepatocellular* ; Drug Therapy*

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Life-sustaining treatment and palliative care in patients with liver cirrhosis - legal, ethical, and practical issues.

Dong Joon KIM ; Moon Seok CHOI

Clinical and Molecular Hepatology.2017;23(2):115-122. doi:10.3350/cmh.2017.0018

With the enactment of the ‘Act on Decisions on Life-Sustaining Treatment for Patients in Hospice and Palliative Care or at the End of Life’ (Act No. 14013) in Korea, there is growing concern about the practicality of this law. In this review, we discuss definitions, ethics, and practical issues related to this law.
End Stage Liver Disease ; Ethics ; Hospices ; Humans ; Jurisprudence ; Korea ; Liver Cirrhosis* ; Liver* ; Palliative Care*

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Radioembolization for the treatment of hepatocellular carcinoma.

Hyo Cheol KIM

Clinical and Molecular Hepatology.2017;23(2):109-114. doi:10.3350/cmh.2017.0004

Transarterial radioembolization (TARE) with yttrium 90 (⁹⁰Y), an intra-arterial procedure performed by interventional radiologists, has begun being utilized in managing hepatocellular carcinoma (HCC) in Korea. There are two available TARE products: glass and resin microspheres with different physical characteristics. All patients undergoing TARE must be assessed with clinical examination and laboratory tests as well as a thorough angiographic evaluation. TARE is safe and effective in the treatment of unresectable HCC, as it has longer time-to-progression, greater ability to downsize tumors for liver transplantation, less post-embolization syndrome, and shorter hospitalization compared with chemoembolization. TARE can also serve as an alternative to ablation, surgical resection, portal vein embolization, and sorafenib. The utility of TARE continues to expand with new insights in interventional oncology.
Carcinoma, Hepatocellular* ; Glass ; Hospitalization ; Humans ; Korea ; Liver Transplantation ; Microspheres ; Portal Vein ; Yttrium

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