Safety of direct oral anticoagulants compared to warfarin in cirrhotic patients with atrial fibrillation

Background/Aims@#The safety of direct oral anticoagulants (DOACs) compared with warfarin in patients with both nonvalvular atrial fibrillation (AF) and clinically confirmed liver cirrhosis (LC) has not been well studied. We compared the risk of a major bleeding event between DOAC and warfarin treatments in this patient population. @*Methods@#A total of 238 cirrhotic patients with AF were retrospectively analyzed. The major bleeding event risk was compared between DOAC- and warfarin-treated groups. The median follow-up duration was 5.6 years. @*Results@#Among the 238 study patients with LC and AF, 128 (53.8%) received DOACs and 110 (46.2%) received warfarin. The mean patient age was 68.8 years, and 78.2% were men. A major bleeding event occurred in 10 and 20 patients in the DOAC and warfarin groups, respectively, most commonly caused by gastrointestinal bleeding (70.0%). The cumulative risk of major bleeding did not differ between the groups by log-rank test (p = 0.12). This finding did not change when using 60 propensity score-matched pairs. A multivariable Cox regression model indicated that the concomitant use of antiplatelet agents (adjusted hazard ratio [aHR], 2.06; 95% confidence interval [CI], 1.00 to 4.30; p = 0.048) and presence of esophageal or gastric varices confirmed by endoscopic examination (aHR, 2.31; 95% CI, 1.03 to 5.17; p = 0.04) were associated with major bleeding in the entire cohort. @*Conclusions@#A major bleeding event risk is not increased by DOAC compared with warfarin treatment. Antiplatelet agent use and varices are independently associated with a higher risk of major bleeding during anticoagulation.

Comparison of surgical resection versus transarterial chemoembolization with additional radiation therapy in patients with hepatocellular carcinoma with portal vein invasion

BACKGROUND/AIMS: Portal vein invasion (PVI) is a poor prognostic factor in patients with hepatocellular carcinoma (HCC). We intended to compare the effects of surgical resection and transarterial chemoembolization (TACE) with additional radiation therapy (RT) in HCC patients with PVI. METHODS: The subjects comprised 43 patients who underwent surgical resection for HCC with PVI without previous treatment and another 43 patients who received TACE followed by RT (TACE+RT) as initial treatment who were matched for Child-Pugh class, tumor size, and extent of PVI. Disease progression and death after the treatment were examined, and progression-free survival (PFS) and overall survival (OS) were compared between groups. Predisposing factors affecting OS were analyzed using univariate and multivariate analyses in HCC patients with PVI. RESULTS: The subjects (Age [51, 24-74; median, range], Sex [81/13; male/female], Etiology [78/1/15; hepatitis B virus {HBV}/ hepatitis C virus {HCV}/non-HBV and non-HCV]) were followed for a median of 17 (2-68) months. There were no differences in clinical or tumor characteristics between the resection and TACE+RT groups. The cumulative PFS was not significantly different between groups. The median PFS was 5.6 and 4.0 months in the resection and TACE+RT groups, respectively. However, the cumulative OS was significantly longer in patients treated with resection than in those treated with TACE+RT (P=0.04). The median OS was 26.9 and 14.2 months in the resection and TACE+RT groups, respectively. Univariate and multivariate analyses revealed that surgical resection was an independent predictive factor for better survival outcome. CONCLUSIONS: Surgical resection might be an effective treatment in HCC patients with PVI.

Methionine Adenosyltransferase 1: A Proteomic Surrogate Marker of Early Hepatocellular Carcinoma in Cirrhotic Patients

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.

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

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.

Fibroblast growth factor receptor isotype expression and its association with overall survival in patients with hepatocellular carcinoma

BACKGROUND/AIMS: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. METHODS: Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis. RESULTS: FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set. CONCLUSIONS: FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.

No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients

BACKGROUND/AIMS: There are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients. METHODS: This was a retrospective cohort study of 156 patients with chronic hepatitis C virus (HCV) infection who received combination treatment of PEG-IFN plus RBV. Blood samples from these patients were analyzed to identify the IL28B SNPs at rs12979860, rs12980275, rs8099917, and rs8103142. Association analyses were performed to evaluate the relationships between each IL28B SNP and SVRs. RESULTS: Seventy six patients with HCV genotype 1 and 80 with genotype non-1 were enrolled. The frequencies of rs12979860 CC and CT genotypes were 90.4% and 9.6%, respectively; those of rs12980275 AA and AG genotypes were 87.2% and 12.8%, respectively; those of rs8099917 TT and TG genotypes were 92.3% and 7.7%, respectively; and those of rs8103142 TT and CT genotypes were 90.4% and 9.6%, respectively. Among the patients with HCV genotype 1, the SVR rates were 69.7% and 80.0% for rs12979860 CC and CT, respectively (P=0.71). Among the HCV genotype non-1 patients, SVR rates were 88.0% and 100% for rs12979860 CC and CT (P=1.00), respectively. CONCLUSIONS: Genotypes of the IL28B SNP that are known to be favorable were present in most of the Korean patients with chronic hepatitis C in this study. Moreover, the IL28B SNP did not influence the SVR rate in either the HCV genotype 1 or non-1 patients. Therefore, IL28B SNP analysis might be not useful for the initial assessment, prediction of treatment outcomes, or treatment decision-making of Korean chronic hepatitis C patients.

Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma

BACKGROUND/AIMS: The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored. RESULTS: The interleukin-1-beta-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues. CONCLUSIONS: The prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.

A Case of Hemolytic Uremic Syndrome after Transarterial Chemoembolization with Cisplatin / 대한내과학회지

Hemolytic uremic syndrome (HUS) is a rare disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. These characteristics are related to the formation of platelet-rich microthrombi in the microvasculature. HUS is associated with a variety of etiologies, including cisplatin. Previously reported HUS cases after cisplatin administration were almost always related to systemic combination chemotherapy that included cisplatin. Transarterial chemoembolization (TACE) is commonly used in treatment of hepatocellular carcinoma, and most centers in Korea use cisplatin. A 70-year-old female with hepatocellular carcinoma was treated with TACE including cisplatin and subsequently developed clinical and laboratory findings compatible with HUS.

High effectiveness of peginterferon alfa-2a plus ribavirin therapy in Korean patients with chronic hepatitis C in clinical practice

BACKGROUND/AIMS: Identifying the impact of a patient's ethnicity on treatment responses in clinical practice may assist in providing individualized treatment regimens for chronic hepatitis C (CHC). The effectiveness of standard peginterferon plus ribavirin therapy and the need for triple combination therapy with protease inhibitors in Koreans remain matters of debate. These issues were investigated in the present study. METHODS: The clinical data of 272 treatment-naive Korean CHC patients who were treated in a community-based clinical trial (Clinical Trial group; n=51) and in clinical practice (Cohort group; n=221), were analyzed and compared. All were treated with standard protocols of peginterferon alfa-2a plus ribavirin therapy. RESULTS: For patients with hepatitis C virus (HCV) genotype 1, the sustained virological response (SVR) rates in the Clinical Trial and Cohort groups were 81% (21/26) and 55% (58/106), respectively, by intention-to-treat (ITT) analysis (P=0.02), and 100% (13/13) and 80% (32/40), respectively, in treatment-adherent patients (P=0.18). For patients with HCV genotype 2, the SVR rates in these two groups were 96% (24/25) and 88% (101/115), respectively, by ITT analysis (P=0.31). Adherence and treatment duration were independent predictors of SVR for genotypes 1 and 2, respectively (P<0.01 for each). Korean patients with CHC achieved high SVR rates with peginterferon alfa-2a plus ribavirin in both the clinical trial and clinical practice settings. CONCLUSIONS: Measures to raise adherence to standard therapy in clinical practice may improve the SVR rates in these patients as effectively as adding protease inhibitors, thus obviating the need for the latter.

Applicability of the BCLC staging system to patients with hepatocellular carcinoma in Korea: analysis at a single center with a liver transplant center / 대한간학회지

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) staging system is logical for the staging and treatment of hepatocellular carcinoma (HCC) because it was based on survival data. This study evaluated the applicability of the BCLC staging system and reasons for divergence from BCLC-recommended treatments in Korean HCC patients. METHODS: One hundred and sixty consecutive HCC patients were prospectively enrolled. Treatments were generally recommended according to the guideline of the American Association for the Study of Liver Diseases, but patients were also informed about alternative treatments. The final decision was made with patient agreement, and was based on the doctor's preferences when a patient was unable to reach a decision. RESULTS: There were 2 (1%), 101 (64%), 20 (12.5%), 34 (21.5%), and 3 (1%) patients with very early-, early-, intermediate-, advanced-, and terminal-stage disease, respectively. Only 64 patients (40%) were treated according to BCLC recommendations. The treatment deviated from BCLC recommendations in 68% (69/101) and 79% (27/34) of patients with early and advanced stage, respectively. The main causes of deviation were refusal to undergo surgery, the presence of an indeterminate malignancy nodule, the absence of a suitable donor, or financial problems. CONCLUSIONS: Donor shortage, financial problems, the relatively limited efficacy of molecular targeting agents, and the presence of an indeterminate nodule were the main causes of deviation from BCLC recommendations. Even after excluding cases in which decisions were made by patient preference, only 66% of the HCC patients were treated according to BCLC recommendations. Treatment guidelines that reflect the Korean situation are mandatory for HCC patients.

Osler-Weber-Rendu disease presenting with hepatocellular carcinoma: radiologic and genetic findings / 대한간학회지

This is a case report of a 68-year-old man with hepatocellular carcinoma (HCC) accompanied by hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, and hepatic vascular malformation. HHT is an autosomal dominant disorder of the fibrovascular tissue that is characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. HHT is caused by mutation of the genes involved in the signaling pathway of transforming growth factor-beta, which plays an important role in the formation of vascular endothelia1. Hepatic involvement has been reported as occurring in 30-73% of patients with HHT. However, symptomatic liver involvement is quite rare, and the representative clinical presentations of HHT in hepatic involvement are high-output heart failure, portal hypertension, nodular regenerative hyperplasia, and symptoms of biliary ischemia. Some cases of HCC in association with HHT have been reported, but are very rare. We present herein the characteristic radiologic and genetic findings of HHT that was diagnosed during the evaluation and treatment of HCC.

Could HBx Protein Expression Affect Signal Pathway Inhibition by Gefitinib or Selumetinib, a MEK Inhibitor, in Hepatocellular Carcinoma Cell Lines?

Hepatitis B virus X (HBx) protein has been known to play an important role in development of hepatocellular carcinoma (HCC). The aim of this study is to find out whether HBx protein expression affects antiproliferative effect of an epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor and a MEK inhibitor in HepG2 and Huh-7 cell lines. We established HepG2 and Huh-7 cells transfected stably with HBx gene. HBx protein expression increased pERK and pAkt expression as well as beta-catenin activity in both cells. Gefitinib (EGFR-TK inhibitor) inhibited pERK and pAkt expression and beta-catenin activity in both cells. Selumetinib (MEK inhibitor) reduced pERK level and beta-catenin activity but pAkt expression was rather elevated by selumetinib in these cells. Reduction of pERK levels was much stronger with selumetinib than gefitinib in both cells. The antiproliferative efficacy of selumetinib was more potent than that of gefitinib. However, the antiproliferative effect of gefitinib, as well as selumetinib, was not different between cell lines with or without HBx expression. Signal pathway activation by HBx might not be strong enough to attenuate the antiproliferative effect of EGFR-TK inhibitor. Future experiments are needed to understand the role of HBx protein expression in HCC treatment using molecular targeting agent.

Mutations within the interferon sensitivity determining region in Korean patients infected with hepatitis C virus genotype 1b / 대한간학회지

BACKGROUND/AIMS: The treatment response to interferon could differ with mutations in the interferon-sensitivity-determining region (ISDR) in patients infected with hepatitis C virus (HCV) genotype-1b (HCV-Ib). We examined the pattern of ISDR mutations and analyzed whether the number of amino acid substitutions influences the treatment response to peginterferon plus ribavirin in chronic hepatitis or cirrhotic patients infected with HCV-Ib. METHODS: The study population comprised 52 patients who visited Seoul Asan Medical Center and Seoul National University Bundang Hospital from January 2006 to December 2008 and who received peginterferon alpha-2a (n=37) or -2b (n=15) plus ribavirin, and whose serum was stored. We analyzed the early virologic response, end-of-treatment response, and sustained virologic response (SVR), and examined the ISDR using direct sequencing. RESULTS: The proportions of patients with ISDR mutation types of wild (0 mutations), intermediate (1-3 mutations), and mutant (> or =4 mutations) were 50.0%, 42.3%, and 7.7%, respectively, and the corresponding SVR rates were 63%, 50%, and 67% (p>0.05). The SVR rates were 59.4% and 50.0% in patients with or =2 mutations, respectively (p>0.05). On univariate analysis, age was the only predictive factor for SVR (p=0.016). The pretreatment HCV RNA titer tended to be lower in those with SVR, but without statistical significance (p=0.069). CONCLUSIONS: The frequency of ISDR mutations was low in our cohort of Korean patients infected with HCV-Ib. Therefore, ISDR mutations might not contribute to the response to treatment with peginterferon plus ribavirin.

Cholestyramine resin for erythropoietic protoporphyria with severe hepatic disease: a case report / 대한간학회지

Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by mutations in the gene encoding the enzyme ferrochelatase. In EPP, deficient ferrochelatase activity leads to the excessive production and biliary excretion of protoporphyrin (PP). The major clinical features of EPP are photosensitivity and hepatobiliary disease that may progress to severe liver disease, that are caused by the toxicity of PP. EPP-related liver disease has been treated medically or surgically including liver transplantation. We described a 20-year-old male with severe liver disease who was diagnosed with EPP based on clinical and laboratory findings. He was treated with cholestyramine resin. Six months after the treatment, he was doing well without any abdominal pain or photosensitivity.

Prognostic value of serum osteopontin in hepatocellular carcinoma patients treated with transarterial chemoembolization / 대한간학회지

BACKGROUND/AIMS: Osteopontin (OPN) is overexpressed in hepatocellular carcinoma (HCC) with postoperative recurrence or extrahepatic metastasis. However, its prognostic value in patients treated with transarterial chemoembolization (TACE) is unclear. We investigated the utility of serum OPN levels and changes therein as prognostic markers in HCC patients who have received TACE. METHODS: Forty-six patients with HCC were enrolled. Serum OPN levels were measured before and 4 weeks after TACE. Serum biochemistry and computed tomography (CT) scans were analyzed. We evaluated baseline serum OPN levels and subsequent changes therein in relation to tumor responses and cumulative survival rates following TACE. A decreasing pattern was defined as a decrease after TACE of more than 10% relative to baseline levels. A "responder" was defined as a patient who exhibited a tumor necrosis rate of higher than 50% on the follow-up CT scan. RESULTS: Higher initial serum OPN levels were associated with a large tumor, portal vein invasion, and an advanced tumor stage. Patients who had lower initial serum OPN levels and those who exhibited decreasing patterns after TACE tended to have more favorable tumor responses (P=0.043 and 0.055, respectively) and exhibited better cumulative survival rates (P=0.036 and 0.030, respectively). However, the initial serum OPN level and subsequent changes in serum OPN levels were not independent predictors for survival on multivariate analysis. CONCLUSIONS: Serum OPN levels were significantly higher in patients with advanced HCC. In addition, HCC patients with low pretreatment serum OPN levels and those for whom serum OPN declined following TACE exhibited better tumor responses and survived for longer.

Hepatic myelopathy as a presenting neurological complication in patients with cirrhosis and spontaneous splenorenal shunt / 대한간학회지

Hepatic myelopathy is a rare complication of chronic liver disease that is associated with extensive portosystemic shunts. The main clinical feature of hepatic myelopathy is progressive spastic paraparesis in the absence of sensory or sphincter impairment. Early and accurate diagnosis of hepatic myelopathy is important because patients with early stages of the disease can fully recover following liver transplantation. Motor-evoked potential studies may be suitable for the early diagnosis of hepatic myelopathy, even in patients with preclinical stages of the disease. Here we describe two patients who presented with spastic paraparesis associated with a spontaneous splenorenal shunt and without any previous episode of hepatic encephalopathy. One patient experienced improved neurologic symptoms after liver transplantation, whereas the other patient only received medical treatment, which did not prevent the progression of spastic paraparesis.

A Case of Acute Hepatitis A Complicated by Guillain-Barre Syndrome / 대한간학회지

We report here a case of acute hepatitis A, which was complicated by Guillain-Barr? syndrome (GBS). A 32-year old male admitted to our hospital with the symptoms of acute hepatitis and was diagnosed to have acute hepatitis A with positive IgM anti hepatitis A virus antibody. On 9th day after the onset of jaundice, acute progressive, ascending, symmetric motor paralysis were developed and eventually respiratory failure ensued. Cerebrospinal fluid analysis showed albumino-cytologic dissociation and nerve conduction velocity test suggested a polyradiculopathy. He was diagnosed to have GBS and treated with intravenous immunoglobulin and required a ventilatory support. After 90 hospital days, he recovered in ambulatory condition with the aid of crutches. The clinical course, prognosis and the outcome of neuropathic symptoms of GBS following acute hepatitis A were relatively poor in our case.

Clinical Outcome after Living Donor Liver Transplantation in Patients with Hepatitis C Virus-associated Cirrhosis / 대한간학회지

BACKGROUND AND 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.

Nine Cases of Sporadic Acute Hepatitis E in Korea / 대한간학회지

Hepatitis E virus is an enterically transmitted virus that causes endemic cases of acute hepatitis in many countries in Africa, and Southeast and Central Asia. Sporadic cases of acute hepatitis E also have been reported in developed countries. In non-endemic areas, most of the sporadic cases of hepatitis E are introduced from the endemic areas. Until now, only three cases of acute hepatitis E have been reported in Korea. Recently, we experienced nine cases of acute hepatitis, in which serologic studies showed positive of IgM anti-HEV. We report these as cases of acute hepatitis E. These cases suggest that HEV infection occurs sporadically in Korea and should be considered as a cause of cryptogenic acute hepatitis.

Clinical Features of Fulminant Hepatic Failure in a Tertiary Hospital with a Liver Transplant Center in Korea / 대한간학회지

BACKGROUND/AIMS: Striking geographic differences have been noted in the etiology of fulminant hepatic failure (FHF). The prognosis of patients with FHF who do not receive liver transplantation in a timely manner is quite dismal. This study intended to identify the etiology and outcome of FHF in Korean adults and to examine the role of urgent living-donor liver transplantation (LDLT) for treating this unique situation. METHODS: We identified all the adult FHF patients who were referred to our unit between 1999 and 2004. FHF was defined as severe acute hepatitis complicated by the rapid development of hepatic encephalopathy within 8 weeks of the initial symptoms in the patients without a previous history of liver disease. RESULTS: One hundred fourteen patients (47 males and 67 females) were identified. The mean age was 39.5+/-15.3 years. Drugs were the most common cause (28.1%) of FHF (herbal medications, 9.6%), and acute viral infection accounted for 23.7% (HBV accounted for 15.8%). Indeterminate etiologies were noted in 34%. The 90-day survival rate of the nontransplant group was only 15%. Fourteen patients received liver transplants (13 right-lobe LDLT, 1 cadaveric whole liver), and 12 of these (85.7%) survived and showed good graft function during 22 months of median follow-up. CONCLUSIONS: Although the causes of FHF in Korea were diverse, HBV infection and herbal medications were responsible for a significant proportion of the cases. Since urgent LDLT improved the overall survival rate of patients with FHF, this should be considered as an important treatment option for patients suffering with FHF.