Effect of L-carnitine on quality of life in covert hepatic encephalopathy: a randomized, double-blind, placebo-controlled study

Background/Aims@#L-carnitine is potentially beneficial in patients with hepatic encephalopathy (HE). We aimed to evaluate the impact of L-carnitine on the quality of life and liver function in patients with liver cirrhosis and covert HE. @*Methods@#We conducted an investigator-initiated, prospective, multi-center, double- blind, randomized phase III trial in patients with covert HE. A total of 150 patients were randomized 1:1 to L-carnitine (2 g/day) or placebo for 24 weeks. Changes in quality of life and liver function were assessed at 6 months. The model for end-stage liver disease (MELD), the 36-Item Short Form Survey (SF-36), the psychometric hepatic encephalopathy score (PHES), and the Stroop Test were evaluated in all patients. @*Results@#The total SF-36 score significantly improved in the L-carnitine group after 24 weeks (difference: median, 2; interquartile range, 0 to 11; p < 0.001); however, these values were comparable between the two groups. Furthermore, there was a significant ordinal improvement in PHES scores among patients with minimal HE who were in the L-carnitine group (p = 0.007). Changes in the total carnitine level also positively correlated with improvements in the Stroop test in the L-carnitine group (color test, r = 0.3; word test, r = 0.4; inhibition test, r = 0.5; inhibition/switching test, r = 0.3; all p < 0.05). Nevertheless, the MELD scores at week 24 did not differ between the groups. @*Conclusions@#Twenty-four weeks of L-carnitine supplementation was safe but ineffective in improving quality of life and liver function.

Nonalcoholic Fatty Liver Disease and Endoplasmic Reticulum Stress / 대한내과학회지

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem with comorbidities including obesity and dyslipidemia. Although the manifestations of NAFLD range from simple steatosis to non-alcoholic steatohepatitis, these may potentially give rise to liver cirrhosis and hepatocellular carcinoma. However, the mechanisms underlying NAFLD, and the factors that determine the individual risk of disease progression, remain poorly known. The most obvious clinicopathological characteristic of NAFLD is hepatic lipid accumulation and subsequent inflammation. In hepatocytes, the endoplasmic reticulum (ER) is a critical site of protein synthesis, detoxification, lipid and glucose metabolism, and Ca2+ homeostasis; the ER is involved in NAFLD pathogenesis. Hepatic accumulation of lipids stresses the ER; this activates the unfolded protein response (UPR), which is classically viewed as an adaptive pathway that maintains ER homeostasis. Recent studies have revealed that UPR sensors regulate hepatic steatosis and the cellular response to lipotoxic stress. Therefore, the basic mechanisms of ER stress and UPR induction are of great interest for understanding the pathogenesis of NAFLD. The present review focuses on the roles played by ER stress and the UPR in NAFLD pathogenesis.

Impact of COVID-19 on Gastroenterology Fellowship Training / 대한소화기학회지

Background/Aims@#The coronavirus disease 2019 (COVID-19) outbreak caused numerous social and cultural changes, but few studies focused on their effects on gastroenterology (GI) fellowship training. This study evaluated the impact of COVID-19 on GI fellowship training. @*Methods@#A web-based questionnaire was sent out to GI fellows in Korea between 15 February and 15 March 2021. The questionnaire included questions regarding the characteristics of GI fellows, perception of COVID-19 outbreak, impact of COVID-19 outbreak, and telemedicine on the education of a GI fellowship. @*Results@#Among 111 answers, 94 respondents were analyzed. The GI fellows were provided with sufficient information about the COVID-19 outbreak (74.7%), well educated, and provided with personal protective equipment use (74.7% and 83.9%, respectively).On the other hand, outpatient schedule and volume decreased in 25.5% and 37.8% of respondents, respectively. Moreover, endoscopy sessions and volume decreased in 51.1% and 65.6% of respondents, respectively. As a result, 78.9% of respondents were concerned that the COVID-19 outbreak adversely affected their education. Telemedicine utilization was introduced during the COVID-19 outbreak, but only 20.0% and 10.6% of respondents agreed that telemedicine has benefits from the patient’s and doctor’s perspectives, respectively. In addition, only 25.9% of respondents were willing to continue telemedicine if adequately reimbursed, and 68.2% of respondents were concerned that it adversely affected their education. @*Conclusions@#The COVID-19 outbreak has adversely affected GI fellowship training in Korea for outpatient clinics, gastrointestinal endoscopy, educational conferences, and telemedicine. This study highlights that GI fellowship training needs more attention in the COVID-19 outbreak.

Nonalcoholic Fatty Liver Disease and Endoplasmic Reticulum Stress / 대한내과학회지

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem with comorbidities including obesity and dyslipidemia. Although the manifestations of NAFLD range from simple steatosis to non-alcoholic steatohepatitis, these may potentially give rise to liver cirrhosis and hepatocellular carcinoma. However, the mechanisms underlying NAFLD, and the factors that determine the individual risk of disease progression, remain poorly known. The most obvious clinicopathological characteristic of NAFLD is hepatic lipid accumulation and subsequent inflammation. In hepatocytes, the endoplasmic reticulum (ER) is a critical site of protein synthesis, detoxification, lipid and glucose metabolism, and Ca2+ homeostasis; the ER is involved in NAFLD pathogenesis. Hepatic accumulation of lipids stresses the ER; this activates the unfolded protein response (UPR), which is classically viewed as an adaptive pathway that maintains ER homeostasis. Recent studies have revealed that UPR sensors regulate hepatic steatosis and the cellular response to lipotoxic stress. Therefore, the basic mechanisms of ER stress and UPR induction are of great interest for understanding the pathogenesis of NAFLD. The present review focuses on the roles played by ER stress and the UPR in NAFLD pathogenesis.

Impact of COVID-19 on Gastroenterology Fellowship Training / 대한소화기학회지

Background/Aims@#The coronavirus disease 2019 (COVID-19) outbreak caused numerous social and cultural changes, but few studies focused on their effects on gastroenterology (GI) fellowship training. This study evaluated the impact of COVID-19 on GI fellowship training. @*Methods@#A web-based questionnaire was sent out to GI fellows in Korea between 15 February and 15 March 2021. The questionnaire included questions regarding the characteristics of GI fellows, perception of COVID-19 outbreak, impact of COVID-19 outbreak, and telemedicine on the education of a GI fellowship. @*Results@#Among 111 answers, 94 respondents were analyzed. The GI fellows were provided with sufficient information about the COVID-19 outbreak (74.7%), well educated, and provided with personal protective equipment use (74.7% and 83.9%, respectively).On the other hand, outpatient schedule and volume decreased in 25.5% and 37.8% of respondents, respectively. Moreover, endoscopy sessions and volume decreased in 51.1% and 65.6% of respondents, respectively. As a result, 78.9% of respondents were concerned that the COVID-19 outbreak adversely affected their education. Telemedicine utilization was introduced during the COVID-19 outbreak, but only 20.0% and 10.6% of respondents agreed that telemedicine has benefits from the patient’s and doctor’s perspectives, respectively. In addition, only 25.9% of respondents were willing to continue telemedicine if adequately reimbursed, and 68.2% of respondents were concerned that it adversely affected their education. @*Conclusions@#The COVID-19 outbreak has adversely affected GI fellowship training in Korea for outpatient clinics, gastrointestinal endoscopy, educational conferences, and telemedicine. This study highlights that GI fellowship training needs more attention in the COVID-19 outbreak.

Efficacy and Safety of Daclatasvir and Asunaprevir in Patients with Hepatitis C Virus Genotype 1b Infection on Hemodialysis

BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)

Cardiac diastolic dysfunction predicts poor prognosis in patients with decompensated liver cirrhosis

BACKGROUND/AIMS: Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cardiac dysfunction in patients with liver cirrhosis (LC). However, the effect of LVDD on survival has not been clarified, especially in decompensated LC. METHODS: We prospectively enrolled 70 patients with decompensated LC, including ascites or variceal bleeding, at Daejeon St. Mary's Hospital from April 2013 to April 2015. The cardiac function of these patients was evaluated using 2D echocardiography with tissue Doppler imaging. The diagnosis of LVDD was based on the American Society of Echocardiography guidelines. The primary endpoint was overall survival. RESULTS: Forty-four patients (62.9%) had LVDD. During follow-up (22.3 months), 18 patients died (16 with LVDD and 2 without LVDD). The survival rate was significantly lower in patients with LVDD than in those without LVDD (31.1 months vs. 42.6 months, P=0.01). In a multivariate analysis, the Child-Pugh score and LVDD were independent predictors of survival. Moreover, patients with a ratio of early filling velocity to early diastolic mitral annular velocity (E/e') ≥ 10 (LVDD grade 2) had lower survival than patients with E/e' ratio < 10. CONCLUSIONS: The presence of LVDD is associated with poor survival in patients with decompensated LC. Therefore, it may be important to monitor and closely follow LVDD patients.

Efficacy and safety of sofosbuvir plus ribavirin for Korean patients with hepatitis C virus genotype 2 infection: A retrospective multi-institutional study

BACKGROUND/AIMS: Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. METHODS: We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. RESULTS: A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. CONCLUSIONS: A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.

Drop metastasis from hepatocellular carcinoma after percutaneous radiofrequency ablation therapy

No abstract available.

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

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.

Recurrent acute portal vein thrombosis in liver cirrhosis treated by rivaroxaban

Cirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may aggravate portal hypertension, and it can lead to hepatic decompensation. The international guideline recommends for anticoagulation treatment to be maintained for at least 3 months in all patients with acute PVT. Low-molecular-weight-heparin and changing to warfarin is the usual anticoagulation treatment. However, warfarin therapy is problematic due to a narrow therapeutic window and the requirement for frequent dose adjustment, which has prompted the development of novel oral anticoagulants for overcoming these problems. We report a 63-year-old female who experienced complete resolution of recurrent acute PVT in liver cirrhosis after treatment with rivaroxaban.

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Combination transarterial chemoembolization and radiofrequency ablation therapy for early hepatocellular carcinoma

BACKGROUND/AIMS: We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone. METHODS: This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC < or = 5.0 cm or up to three HCCs < or = 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43). RESULTS: The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively). CONCLUSIONS: TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment.

High-level Expression of Interleukin-17 and C-reactive Protein Predicts Tumor Progression in Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is the standard locoregional treatment in patients with unresectable hepatocellular carcinoma (HCC). Angiogenesis and inflammation play important roles in tumor growth in HCC. In this study, we evaluated the associations between the levels of growth factors and inflammatory markers and clinical prognosis in patients with unresectable HCC treated with TACE. METHODS: The clinical outcomes of 58 HCC patients treated with TACE at the Catholic Medical Centers from January, 2012 to February 2015 were evaluated. Baseline levels of the growth factors vascular endothelial growth factor, fibroblast growth factor, platelet-derived growth factor, and hepatocyte growth factor and the inflammatory cytokines interleukin (IL)-17 and high sensitivity C-reactive protein (hs-CRP) were compared with the treatment outcomes. The primary endpoint was time to progression (TTP); the secondary endpoint was overall survival (OS). RESULTS: During the 20.8 months of follow-up, TTP was significantly delayed in patients with low levels of hs-CRP (≤0.15) and IL-17 (≤0.94) and a maximal tumor diameter ≤5 cm (P=0.010, P=0.015, and 0.048, respectively). Patients with HCC with low hs-CRP and IL-17 levels had a longer survival than that of those with high hs-CRP levels and IL-17 (35.1 vs. 22.5 months, P=0.000; 41 vs. 21.8 months, P=0.000, respectively). However, any baseline growth factors were not significantly correlated with TTP and OS. CONCLUSIONS: Elevated IL-17 and hs-CRP may be predictive of a poor outcome in patients with HCC treated with TACE. A better understanding of this relationship will require further investigation of the immune mechanisms underlying tumor progression.

Comparative Study between Metronomic Chemotherapy and Transarterial Chemoembolization in Patients with Child-Pugh Class B Advanced Hepatocellular Carcinoma

BACKGROUND/AIMS: Metronomic (MET) chemotherapy is a treatment characterized by frequent infusion of low doses of chemotherapeutic agent without extended break. The aim of this study is to evaluate the efficacy of MET chemotherapy compared with transarterial chemoembolization (TACE) in patients with child B class advanced hepatocellular carcinoma (HCC). METHODS: Seventy-three patients with child B class advanced HCC were analyzed between April, 2007 and August, 2013 according to two treatment groups: (i) MET chemotherapy group (n=43, Epirubicin 35 mg/body surface area [BSA] every 4 weeks, and cisplatin 15 mg/BSA and 5-fluorouracil 50 mg/BSA weekly for 3 weeks) via an implantable port system with 1 week break. (ii) TACE group (n=30, Adriamycin 20-50 mg) every 4 weeks. Primary endpoint was overall survival (OS). RESULTS: The median survival times in the MET and TACE groups were 4.5 months and 3.1 months, respectively. The overall survival rate showed significantly better in the MET treatment group than in the TACE group (P=0.039). When the factors affecting patient OS were analyzed, MET chemotherapy (P=0.038, hazard ratio {HR} 0.538 [95% confidence interval {CI} 0.299-0.967]) was independently associated with OS. Larger maximal tumor size, extrahepatic metastasis and advanced stage also were significant factors for OS (P=0.009, HR 1.064 [95% CI 1.014-16.064]; P=0.014, HR 2.120 [95% CI 1.164-3.861]; P=0.019, HR 2.046 [95% CI 1.125-3.720], respectively). CONCLUSIONS: MET chemotherapy showed survival benefit than TACE in patients with child class B advanced HCC. Therefore, MET chemotherapy may be considered as a treatment option for advanced HCC with poor liver function.

Newer treatments for advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The only curative treatment modalities for HCC are surgery, percutaneous ablation, and liver transplantation. Unfortunately, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options are needed for patients with advanced HCC. The current standard treatment for patients with advanced HCC, according to the Barcelona Clinic Liver Cancer staging system, is the multikinase inhibitor sorafenib. Other alternative therapies are required, due to the limited treatment response to, and tolerance of, this molecular target agent. Clinical trials of hepatic artery infusion chemotherapy, radioembolization, and multimodal treatments have shown favorable results in advanced HCC patients. This article introduces new treatment modalities for advanced HCC and discusses future therapeutic possibilities.

DC Bead Transarterial Chemoembolization Is Effective in Hepatocellular Carcinoma Refractory to Conventional Transarteral Chemoembolization: A Pilot Study

BACKGROUND/AIMS: To determine if hepatocellular carcinoma refractory to conventional transarterial chemoembolization (TACE) responds to TACE with DC beads. METHODS: Between July 2008 to June 2010, 435 patients underwent TACE. Of these, 10 patients who had tumors refractory to conventional TACE and who thus were treated with TACE with DC beads were enrolled in this study. The treatment response after TACE with DC beads was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the Response Evaluation Criteria in Cancer of the Liver (RECICL). RESULTS: Ten tumors were treated in 10 patients. Using the mRECIST and the RECICL, a complete response was observed in four (40%) of the tumors, and six tumors (60%) showed a partial response. Eight (80%) out of 10 HCCs showed delayed enhancement patterns upon angiography, and better responses were observed in these cases following DC bead treatment. The adverse effects of treatment with DC beads became tolerable. CONCLUSIONS: TACE with DC beads was effective for HCCs refractory to conventional TACE, and this treatment elicited a better response, especially when the tumors were small and showed a delayed enhancement pattern upon angiography.

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. METHODS: One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8+/-13.5 years, mean+/-SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. RESULTS: According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis > or =2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. CONCLUSIONS: Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.

Adult Living Donor Liver Transplantation Using Hepatitis B Core Antibody-Positive Grafts in Korea, a Hepatitis B-endemic Region

BACKGROUND/AIMS: The exclusion of hepatitis B core antibody (HBcAb)-positive donors from liver transplants (LTs) due to the risk of transmitting hepatitis B virus (HBV) does not appear to be practical in Korea, where hepatitis B is endemic. This study assessed the risk of de novo HBV infection in hepatitis B surface antigen (HBsAg)-negative LT recipients receiving a liver from HBcAb-positive donors. METHODS: Of 341 adult living donor LTs conducted at our institution between March 2001 and September 2008, 176 donors (51.6%) were HBcAb-positive, and 26 HBcAb-positive grafts were transplanted to HBsAg-negative recipients. The median follow-up time after LT was 41.9 months. RESULTS: Without anti-HBV prophylaxis, 2 out of 26 (7.7%) HBsAg-negative recipients who received grafts from HBcAb-positive donors developed de novo HBV infection 20 and 85 months after LT. These patients had been negative for all HBV serologic markers before transplantation. In both cases, there were no abnormalities in liver function tests upon diagnosis of de novo HBV infection. CONCLUSIONS: De novo HBV infection from HBcAb-positive donors after LT does not appear to be of great concern in terms of the number of cases in Korea because high risk patients who are HBV-negative comprise only a small proportion of the recipients. However, HBV-naive LT recipients still carry the risk of developing de novo HBV infection as in non-HBV endemic areas.

Frequency of Killer Cell Immunoglobulin-like Receptors (KIRs) in Korean Patients with Chronic HCV Infection

Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea.