Chronic hepatitis B infection is a major public health challenge. With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for ≥6 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial/ functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use.
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Background/Aims We investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg).
Methods Serum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36, and 48 of treatment. Patients were followed up thereafter and serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU.
Results Twenty-eight hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients (median, 38.2 years old; 71.9% male) were recruited with median follow-up duration of 17.1 years (interquartile range, 12.8–18.2). For the entire cohort, 22/64 (34.4%) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR (5.49 vs. 4.32 log copies/mL, respectively; P=0.016). The area under the receiver-operating-characteristic curve (AUROC) for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% confidence interval [CI], 0.661–0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs. reduction of 2.98 log U/mL; P=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI, 0.596–0.982).
Conclusions Early on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.
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Backgrounds/Aims The purpose of this study was to evaluate the cost-effectiveness of 1 year and up to 5 years of antiviral treatment for chronic hepatitis B (CHB). Methods: Two ten-health-state Markov models were developed for CHB patients. The proportion of patients remaining alive in each health state, and healthcare costs and quality-adjusted life years (QALYs) were determined during annual cycles of these Markov models. The total healthcare costs, life years, and QALYs over the 40-year time horizon of the model were calculated. The perspectives of the cost-effectiveness analysis were the Korean healthcare system and the healthcare needs of the CHB patient. Results: Short-course therapy with α-interferon or 1-year treatment with pegylated interferon α-2a, lamivudine (LMV), or adefovir (ADV) had limited impact on disease progression. In contrast, either LMV-ADV or ADV-LMV as rescue medication administered for 5 years resulted in a more sustained decrease in the rate of disease progression. The cost-effectiveness threshold in Korea was estimated to be approximately 25,000,000 South Korean won. LMV administered for 1 year is cost-effective in comparison with no treatment for both HBeAg-positive and HBeAg-negative CHB patients, but longer duration antiviral therapies administered for up to 5 years in CHB patients were found to be highly cost-effective by international standards. Conclusions: Antiviral treatment of CHB with LMV or ADV for up to 5 years using the alternative antiviral agent as rescue medication appears to be a cost-effective strategy for both HBeAg-positive and HBeAg-negative CHB patients in Korea. Economic evaluation of antiviral therapies should be studied further and updated, particularly for newer agents. (Korean J Hepatol 2008;15: 25-41)
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Ki Tae Yoon, M.D.1,2, Jong Won Choi, M.D.1,2, Jun Yong Park, M.D.1,2,
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Korean J Hepatol 2008;14(3):360-370. Published online September 30, 2008
Background/Aims Advanced hepatocellular carcinoma (HCC) with multiple lung metastases has a poor
prognosis with no effective treatment having been established. This study evaluated the outcomes of systemic
chemotherapy for advanced HCC with multiple lung metastases. Methods: Between January 2000 and
December 2006, 68 patients were diagnosed with HCC presenting with multiple lung metastases. Sixteen
patients in the terminal stage, such as Child-Pugh grade ‘C’ or an Eastern Cooperative Oncology Group
performance status exceeding grade 2, were excluded from the analysis. The following treatment modalities
were applied: 26 patients received primary tumor treatment (transarterial chemoembolization or intra-arterial
chemotherapy) with systemic chemotherapy, 10 patients received primary treatment only, 8 patients received
systemic chemotherapy only, and 8 patients received highly supportive care. The treatment responses and
median survival times for the modalities were analyzed and compared. Results: The median age of the 52
analyzed patients (45 males) was 52.4 years. The most common etiology of HCC was chronic hepatitis B virus
infection (n=44, 84.6%) followed by hepatitis C virus infection (n=2, 3.8%), with the etiology being unknown
in 6 cases (11.5%). The treatment modality had no significant effect on the treatment response rate (P=0.432)
or median survival time (133, 66, 74, and 96 days for primary tumor treatment with systemic chemotherapy,
primary tumor treatment only, systemic chemotherapy only, and highly supportive care, respectively; P=0.067).
Conclusions We found that systemic chemotherapy was not effective in treating HCC presenting with
multiple lung metastases. Improving the effectiveness of systemic treatment and selecting patients who would
benefit from such treatment remains a major challenge. (Korean J Hepatol 2008;14:360-370)
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Background/Aims Hepatitis C virus (HCV)-associated cirrhosis is an increasingly frequent indication for liver transplantation (LT). However, HCV recurrence is universal and this immediately occurs following LT, which endangers both the graft and patient survival. We investigated the frequency of posttransplant recurrence of HCV infection and the patient-graft survival, and we analyzed the responses to ribavirin and interferon therapy in the patients with recurrent HCV infection after living donor liver transplantation (LDLT). Methods: We retrospectively reviewed the clinical outcomes of 39 HCV-associated cirrhosis patients who underwent LDLT at Asan Medical Center between August 1992 and June 2006. In this study, the diagnosis of recurrent HCV was made on the basis of increased transaminases and serum HCV RNA levels greater than 10 million IU/mL because protocol liver biopsy was not performed. Results: HCV recurrence was seen in 26 of the 39 LDLT patients (66.7%). 86.7% of recurrence occurred within the first postoperative year. Antiviral treatment was used for all patients with recurrence of HCV. None of the 10 patients receiving ribavirin alone and 9 of 16 patients who received combination therapy with pegylated interferon alpha-2a plus ribavirin became HCV RNA negative and they remained persistently negative during the median follow-up of 24.9 months. Our data indicates that there is no significant factor influencing HCV recurrence except for the recipient`s age. The 2-year patient survival for the HCV patients with HCC and those patients without HCC were 81.2% and 81.3%, respectively (P=0.85) and the 2-year graft survival rates were 81.2% and 68.2%, respectively (P=0.29). No patient died from HCV recurrence during the follow-up period. Conclusions: Combination therapy with ribavirin and interferon appears to improve the outcome of recurrent HCV infected patients after LDLT. (Korean J Hepatol 2007;13:543-555)
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Kyung Woo Park, M.D.1, Joong-Won Park, M.D., Tae Hyun Kim, M.D., Jun Il Choi, M.D.,
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Korean J Hepatol 2007;13(4):530-543. Published online December 20, 2007
Background/Aims We investigated the five-year survival outcomes of a large cohort of hepatocellular carcinoma (HCC) patients who were treated at a single institute, and this is a follow-up study of a previous report. Methods: Nine hundred four HCC patients who were treated at the National Cancer Center Korea were enrolled and they were followed till February 2007. Results: The mean age of the patients was 56.0 years and 731 patients were male. Six hundred seventy-seven (74.9%) patients died and the overall 5-year survival rate (5-YSR) was 23.9%. The 5-YSRs of the patients with modified UICC stage I, II and III were 61.2%, 54.4% and 18.4%, respectively, and the median survival time was 4.3 and 3.7 months for the stage IVa and IVb patients, respectively. For the analysis of the treatment modality, surgical resection showed significantly better outcomes for the five-year survival as compared with transcatheter arterial chemoembolization (TACE) for Child-Pugh A patients with modified UICC stage I or II disease (80.1% vs 52.8%, respectively, P<.001), or stage III disease (60.7% vs 17.0%, respectively, P<.001). For patients with advanced stage IVb disease, TACE, systemic chemotherapy and radiotherapy increased the median survival period more than conservative management for the Child-Pugh class A patients. The serum alpha-fetoprotein level, portal vein tumor thrombosis, the Child-Pugh class, the tumor stage, the tumor type and symptoms were related to the prognosis. Conclusions: This study presented, for the first time, the 5-YSRs of a cohort of HCC patients. (Korean J Hepatol 2007;13:530-542)
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Phase I Dose-Escalation Study of Proton Beam Therapy for Inoperable Hepatocellular Carcinoma Tae Hyun Kim, Joong-Won Park, Yeon-Joo Kim, Bo Hyun Kim, Sang Myung Woo, Sung Ho Moon, Sang Soo Kim, Young-Hwan Koh, Woo Jin Lee, Sang Jae Park, Joo-Young Kim, Dae Yong Kim, Chang-Min Kim Cancer Research and Treatment.1970; 47(1): 34. CrossRef
Background/Aims Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. Methods: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. Results: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. Conclusions: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine. (Korean J Hepatol 2007;13:503-512)
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Ja Kyung Kim, M.D.1,2,3, Hyun Woong Lee, M.D.1,2,3, Beom Kyung Kim, M.D.1,
Kwang Hyub Han, M.D.1,2,3, Chae Yoon Chon, M.D.1,2,3, Young Myoung Moon, M.D.1,2,3,
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Korean J Hepatol 2007;13(3):387-395. Published online September 20, 2007
Background/Aims Hepatocellular carcinoma (HCC) with an extension to the inferior vena cava (IVC) or right atrium is uncommon, and its prognosis remains unclear due to the few case reports. In order to elucidate the natural history and treatment outcome, this study investigated advanced HCC patients with an IVC invasion or atrial tumor thrombus. Methods: Between November 1987 and June 2004, a total of 41 patients were diagnosed as having HCC with IVC or right atrial involvement using the new imaging techniques including a two-dimensional echocardiography. Those patients were stratified into the untreated ‘control group’ (n=17) and ‘treated group’ (n=24). The clinical features, treatment outcome and prognosis including patient survival were analyzed. Results: The mean age of the total patients was 55 years (male:female, 33:8). The most common cause of HCC was a hepatitis B virus infection (85.4%), followed by a hepatitis C virus infection (7.4%). According to the Child-Pugh classification, 24 patients were Child-Pugh class A (58.5%), 15 were Child-Pugh class B (36.6%), and 2 were Child-Pugh class C (4.9%). Lung metastases were identified in 10 patients (24.5%). The treatment modalities of the treated group included 11 systemic chemotherapy regimens (5-FU and cisplatin), 10 transarterial chemotherapy regimens, 2 chemoradiation procedures and 1 hepatic resection. The overall survival was 3.0 months (range, 1-29 months). The 6 month survival rate was 23.5% (4/17) in the control group and 29.2% (7/24) in the treated group. The 12 months survival rate was 0% (0/17) and 25.0% (6/24), respectively. Independent prognostic factor affecting the survival was whether or not any treatment had been carried out. Conclusions: Although the prognosis of advanced HCC with IVC invasion or a right atrial tumor thrombi is poor, treatment might improve the survival rate. (Korean J Hepatol 2007;13: 387-395)
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Risk Factors for Patients with Stage IVB Hepatocellular Carcinoma and Extension into the Heart: Prognostic and Therapeutic Implications Chung Hwan Jun, Da Woon Sim, Sang Ho Kim, Hyoung Ju Hong, Min Woo Chung, Sung Bum Cho, Chang Hwan Park, Young Eun Joo, Hyun Soo Kim, Sung Kyu Choi, Jong Sun Rew Yonsei Medical Journal.2014; 55(2): 379. CrossRef
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Dong Hoon Lee, M.D.2, Ho Jong Chun, M.D.2, Byung Gil Choi, M.D.2
Korean J Hepatol 2007;13(3):378-386. Published online September 20, 2007
Background/Aims The treatment efficacy for advanced hepatocellular carcinoma is poor. This study examined the efficacy and toxicity of 3-dimensional conformal radiotherapy (3D-CRT) in combination with transarterial chemolipiodolization (TACL) for a huge hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: From March 2001 to November 2004, 49 patients with advanced HCC with PVTT (size>8 cm, modified UICC stage IVa) were enrolled in this retrospective study. Twenty two patients underwent more than 2 cycles of TACL (adriamycin 50 mg/m2, cisplatin 60 mg/m2, 5-fluorouracil 200 mg/m2 every 4-6 weeks) without 3D-CRT, while 27 patients underwent consecutive TACL with 3D-CRT (40-45 Gy for 4-5 weeks) that was started one week after the 1st TACL. The response was assessed by a computed tomography (CT) and the serum alpha-fetoprotein (AFP) level at 1-2 month intervals. Results: The objective response rates in the TACL group and TACL with 3D-CRT group were 18% and 48% at 3 months (P=0.051), and 10.5% and 42% at 6 months (P=0.024) respectively. The median survival time was 13 months and 13.5 months in TACL and TACL with 3D-CRT groups, respectively (P=0.502). The treatment response was better in the TACL with 3D-CRT group but there was no significant difference in survival between the two groups. Most toxicities in the two groups were mild, not exceeding grade 1 according to the WHO criteria. Conclusions: For patients with a huge HCC with PVTT, TACL with 3D-CRT achieved some meaningful clinical benefit. Prospective controlled trials will be needed to confirm the real benefit of TACL combined with 3D-CRT. (Korean J Hepatol 2007;13:378-386)
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Sang Hoon Ahn, M.D., Kwang-Hyub Han, M.D., Young Hoon Youn, M.D.,Myoung Hwan Kim, M.D.,
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Do Yun Lee, M.D.* and Jong Tae Lee, M.D.*
Background/Aims The study proposed to evaluate the efficacy of anticancer drugs of intraarterial chemoinfusion and investigate prognostic factors influencing survival. Methods: A total of 127 patients diagnosed as having advanced hepatocellular carcinoma(HCC) of same stage (TNM stage IVa) from 1996 to 1998 were examined. Two intraarterial infusion chemotherapeutic regimens were employed: Adriamycin(Group I) and Cisplatin(Group II). Results: Overall survival was significantly diffrent(10.0 vs 5.7months) and favored Group I. By the univariate analysis, significant prognostic factors included: age, portal vein thrombosis(PVT), size(>5cm) and type of tumor, response rate (size & -fetoprotein) at 3 months after therapy, level of albumin, alkaline phosphatase, and total bilirubin. After repeated therapy, Group I showed better survival (14.0 vs 7.9 months), but there was no statistical difference in survival rate between two groups in the case of large size, PVT, and diffuse type. Conclusion: Group I showed better survival than Group II in advanced HCC of TNM stage IVa. But, considering prognostic factors, there was no significant difference in survival rate between two groups except small size or nodular type of HCC. TNM classification of stage IVa should be reconsidered to include prognostic factors influencing survival rate such as PVT, size and type of HCC.
Background/Aims Combination therapy with peginterferon and ribavirin is a standard therapy for western patients with chronic hepatitis C; however, its efficacy remains unclear in East Asian patients. We evaluated the efficacy and safety of administering peginterferon alfa-2a plus ribavirin in native Korean patients with chronic hepatitis C. Methods: Seventy-five patients with detectable HCV RNA (52.0% male, median age: 50.8 years) were eligible for the study. The patients were treated with peginterferon alfa-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks (for genotype non-1, n=46) or 1000-1200 mg/day for 48 weeks (for genotype 1, n=29). The early virologic response (EVR), the end of treatment virologic response (ETVR), the sustained virologic response (SVR), the biochemical response and the adverse event were analyzed. Results: EVR was seen in 86.2% of the patients with genotype 1. The ETVR was 58.6% in the genotype 1 group and 84.8% in the genotype non-1 group (P=0.02). The overall SVR was 70.7%: 55.2% in the genotype 1 group and 80.4% in the non-1 group (P=0.04). The sustained biochemical response was 64.0%. Multivariate analysis showed that the baseline HCV RNA level (Odds ratio: 0.045, 95% CI: 0.011-0.183, P<0.001) and genotype (Odds ratio: 0.247, 95% CI: 0.063-0.969, P=0.045) had an independent effect on the SVR. Neutropenia, anemia, flu-like symptoms and itching were the common adverse events. Aggravated liver function led to discontinuation of therapy for six patients. Dose modification in twenty-nine patients was effective without producing a significant reduction of the SVR. Conclusions: Our data suggest that the efficacy of peginterferon plus ribavirin therapy in Koreans is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C patients. The baseline HCV RNA level and the genotype can be significant factors influencing the SVR. (Korean J Hepatol 2006;12:31-40)
Background/Aims: Lamivudine is an effective therapy in chronic hepatitis B patients, but the emergence of resistant hepatitis B virus (HBV) mutants is a major concern. This study was performed to investigate whether serum viral DNA levels during lamivudine therapy are related with viral breakthrough in patients with chronic HBV infection. Methods: This study consisting of 103 patients was performed retrospectively and prospectively. Follow-up duration was 24 months after lamivudine therapy. Serum HBV DNA levels were quantified by PCR-based assay every 6 months. Results: Cumulative rate of viral breakthrough was 0%, 19.4%, 36%, and 48.5% in 6, 12, 18, and 24 months respectively. The rate of viral breakthrough in 24 months increased as serum HBV DNA levels increased at 6 months. When serum HBV DNA levels were 2-3 log10, 3-4 log10, 4-5 log10, and 5 log10 copies/mL or more, the breakthrough rates were significantly higher than that of the HBV DNA level less than 2 log10 copies/mL. The relative risks were 1.10, 1.93, 2.69, 3.21 respectively (P<0.001). The viral breakthrough rate also increased as serum HBV DNA levels at 12 months increased. When the HBV DNA levels were 2-3 log10, 3-4 log10, 4-5 log10, and 5 log10 copies/ mL or more, the breakthrough rate were significantly higher than those of HBV DNA level less than 2 log10 copies/mL. The relative risks were 2.42, 4.35, 3.73, 2.61, respectively (P=0.002). Conclusions: The serum HBV DNA levels at 6 months and 12 months during lamivudine therapy can be closely correlated with the rate of viral breakthrough in 24 months. (Korean J Hepatol 2006;12:173-183)
Background/Aims Gastric variceal bleeding is a severe complication of cirrhosis, and it has a high mortality rate. This study was conducted to evaluate the efficacy of n-butyl-2-cyanoacrylate injection therapy for patients suffering with gastric variceal bleeding. Methods: A total of 86 patients diagnosed with gastric variceal bleeding underwent endoscopic n-butyl-2-cyanoacrylate (HistoacrylⓇ) injection therapy at our department between April, 2002 and July, 2005, with a mean follow-up period of 44 weeks (range: 2 to 136 weeks). The initial hemostasis rate and the rebleeding rate of endoscopic sclerotherapy were analyzed. Also, the cumulative survival rate was analyzed according to the status of hepatocellular carcinoma and hyponatremia, the MELD score, the Child-Pugh score and the amount of injected HistoacrylⓇ. Results: The initial hemostasis rate of HistoacrylⓇ injection therapy was 93% and the 1 month rebleeding rate was 16.1%. The total number of session for treating the initial hemostasis was 1.2±0.4 and the total volume of HistoacrylⓇ was 2.7±1.2 mL. The cumulative rebleeding-free rates for the patients treated by the HistoacrylⓇ injection method at 1 month, 12 months and 34 months period were 95.1%, 83.2% and 74%, respectively. The cumulative survival rates were 78.3% at 1 month, 61.9% at 12 months and 54.6% at 34 months, respectively. No thromboembolic phenomenon occurred. According to the Cox’s proportional hazards analysis, only the MELD score (<15) was an independent predicting factor for survival of the patients with gastric variceal bleeding. Conclusions: Endoscopic sclerotherapy using n-butyl-2-cyanoacrylate was a safe and effective hemostatic method for patients with gastric variceal bleeding. Also, the MELD score (<15) contributed to predicting survival of the patients with gastric variceal bleeding.
Background/Aims Sclerosing hepatocellular carcinoma (HCC) is an unusual subtype of HCC that is
characterized by an embedded dense fibrous stroma in the tubular neoplastic structures. We aimed to
assess the surgical approaches and outcomes of sclerosing HCC. Methods: We retrospectively analyzed
the clinicopathologic features of 6 patients with sclerosing HCC who underwent surgical treatment at Asan
Medical Center between July 1989 and December 2005. Results: Six HCC patients with sclerosing HCC were
diagnosed out of the total 1390 HCC patients (0.43%) during the study period. The mean age was 58 years and
4 patients were male. Weight loss and abdominal pain were the most common symptoms. The serum calcium
and phosphorus levels were normal in all the patients. All of them were hepatitis B surface antigen-positive,
but none was positive for hepatitis C. All the lesions were solitary. The tumor size ranged from 45 to 150 mm
in diameter (median size: 81 mm). We performed right trisegmentectomy (n=1), central bisegmentectomy (n=1),
right anterior segmentectomy (n=1), ex-vivo resection and autotransplantation (n=1) and right posterior
segmentectomy (n=2). The median overall survival and disease free-survival periods were 24 months and 9.5
months, respectively. Conclusions: The incidence of sclerosing HCC was very low. Sclerosing HCC was often
not correctly diagnosed before an operation, but performing resection prolonged the patients’ survival and their
prognosis was not worse than that for ordinary HCC. Our experience implicates that aggressive surgical
treatment for sclerosing HCC is beneficial for patient survival. (Korean J Hepatol 2006;12:412-419)
Adefovir dipivoxil (ADV) is effective in the treatment of chronic hepatitis patients with wild type and lamivudine-resistant hepatitis B virus. The occurrence of viral resistance to long-term adefovir therapy is rare, the cumulative rates of resistance were 0%, 3%, 11%, 18%, and 28% at 1, 2, 3, 4, and 5 years of therapy, respectively. The emergence of adefovir resistant mutant in patients with lamivudine resistance is more common than in treatment-naive patients. Two major mutations of adefovir resistance are rtN236T and rtA181V/T. Other mutations in the HBV polymerase (rtP237H, rtN238T/D, rtV84M, rtS85A, rtV214A, rtQ215S) reduce sensitivity to adefovir, but the significance of these mutations is unclear. The adefovir mutations slightly decrease adefovir susceptibility in vitro, suggesting mild clinical course after the occurrence of adefovir resistance. However, some patients show viral rebound and hepatic decompensation. Lamivudine, entecavir, and tenofovir are used currently for salvage therapy in patients with adefovir resistance. To reduce adefovir resistance, combination therapy with adefovir and lamivudine in patients with lamivudine resistance may be a treatment option. (Korean J Hepatol 2006;12:484-492)
Backgrounds/Aims Although the survival rate after surgical resection of peripheral cholangiocarcinoma is
low, surgical resection is only potentially curative therapy. The aim of this study is to evaluate
clinicopathological factors affecting survival after surgical resection of peripheral cholangiocarcinoma. Methods:
Between February 1990 and December 2005, surgical intervention with curative intent was performed on 318
patients and 292 patients underwent resection. We retrospectively analyzed survival data of 318 patients and
clinicopathological factors affecting survival by reviewing the medical record. Results: Among the 292 cases
of resection, curative resection with tumor-free margin (R0) has been resulted in 221 cases. The 1-, 3-, 5- and
10-year survival rate of R0 resection were 74.9, 46.9, 36.9 and 15.2%, respectively. The survival rate of patient
undergoing R0 resection was significantly better than that of R1, R2 or nonresection. Multivariate analysis
showed that curative resectability, macroscopic type of tumor and lymph node metastasis were statically
significant independent prognostic factors. Conclusions: The survival after surgical resection of peripheral
cholangiocarcinoma depends on curability of surgical resection, macroscopic type of tumor and status of lymph
node. Particullary in R0 resection for intraductal growth type without lymph node metastasis, there is great
chance for long-term survival. Surgical resection attaining tumor free margin should be attempted if liver
function and general condition of patient are acceptable for hepatectomy. (Korean J Hepatol 2007;13:208-221)
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