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.

Background/Aims: The hepatic venous pressure gradient (HVPG) reflects portal hypertension, but its measurement is invasive. Transient elastography (TE) is a noninvasive method for evaluating liver stiffness (LS). We investigated the correlation between the value of LS, LS to platelet ratio (LPR), LS-spleen diameter-to-platelet ratio score (LSPS) and HVPG according to the etiology of cirrhosis, especially focused on alcoholic cirrhosis. Methods: Between January 2008 and March 2017, 556 patients who underwent HVPG and TE were consecutively enrolled. We evaluated LS, LPR, and LSPS according to the etiology of cirrhosis and analyzed their correlations with HVPG. Results: The LS value was higher in patients with alcoholic cirrhosis than viral cirrhosis based on the HVPG (43.5 vs. 32.0 kPa, P<0.001). There were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups, and the areas under the curves for the LPR and LSPS in subgroups according to HVPG levels were not superior to that for LS. In alcoholic cirrhosis, the LS cutoff value for predicting an HVPG ≥10 mmHg was 32.2 kPa with positive predictive value (PPV) of 94.5% and 36.6 kPa for HVPG ≥12 mmHg with PPV of 91.0%. Conclusions The LS cutoff value should be determined separately for patients with alcoholic and viral cirrhosis. In alcoholic cirrhosis, the LS cutoff values were 32.2 and 36.6 kPa for predicting an HVPG ≥10 and ≥12 mmHg, respectively. However, there were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups.

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is performed for single hepatocellular carcinoma (HCC) that are not eligible for surgery or ablation therapy. We investigated the clinical outcomes of patients with a single HCC ≤ 5 cm treated with TACE. METHODS: This study analyzed 175 consecutive patients who underwent TACE as an initial treatment for single HCC ≤ 5 cm. Predictive factors for complete response (CR), recurrence after CR, and overall survival (OS) were evaluated. RESULTS: Total 119 patients (68%) achieved CR after TACE. Tumor size < 3 cm and hepatitis B virus infection were significant predictors of CR (p < 0.05). Recurrent HCC was detected in 73 patients (61.3%) after CR. Age > 65 years and absence of liver cirrhosis were predictive factors for non-recurrence after CR (p < 0.05). The OS for all patients was 80.7 ± 5.6 months, and the 1-, 3-, and 5-year OS rates were 88.1%, 64.8%, and 49.9%, respectively. In multivariate analysis for OS, CR (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.292 to 0.747) and Child class A (HR, 0.390; 95% CI, 0.243 to 0.626) were significant factors. The OS for the CR and Child class A group were 92 and 93.6 months, respectively, and that of the non-CR and Child B, C group were 53.3 and 50.7 months, respectively (p < 0.001). CONCLUSIONS TACE can be a valid treatment in patients with a single HCC ≤ 5 cm not suitable for curative treatment, especially in patients with Child class A and CR after TACE.

The aim of this study was to validate a new paper and pencil test battery to diagnose minimal hepatic encephalopathy (MHE) in Korea. A new paper and pencil test battery was composed of number connection test-A (NCT-A), number connection test-B (NCT-B), digit span test (DST), and symbol digit modality test (SDMT). The norm of the new test was based on 315 healthy individuals between the ages of 20 and 70 years old. Another 63 healthy subjects (n = 31) and cirrhosis patients (n = 32) were included as a validation cohort. All participants completed the new paper and pencil test, a critical flicker frequency (CFF) test and computerized cognitive function test (visual continuous performance test [CPT]). The scores on the NCT-A and NCT-B increased but those of DST and SDMT decreased according to age. Twelve of the cirrhotic patients (37.5%) were diagnosed with MHE based on the new paper and pencil test battery. The total score of the paper and pencil test battery showed good positive correlation with the CFF (r = 0.551, P < 0.001) and computerized cognitive function test. Also, this score was lower in patients with MHE compared to those without MHE (P < 0.001). Scores on the CFF (32.0 vs. 28.7 Hz, P = 0.028) and the computer base cognitive test decreased significantly in patients with MHE compared to those without MHE. Test-retest reliability was comparable. In conclusion, the new paper and pencil test battery including NCT-A, NCT-B, DST, and SDMT showed good correlation with neuropsychological tests. This new paper and pencil test battery could help to discriminate patients with impaired cognitive function in cirrhosis (registered at Clinical Research Information Service [CRIS], https://cris.nih.go.kr/cris, KCT0000955).
Cognition ; Cohort Studies ; Diagnosis* ; Fibrosis ; Healthy Volunteers ; Hepatic Encephalopathy* ; Humans ; Information Services ; Korea* ; Liver Cirrhosis ; Neuropsychological Tests ; Reproducibility of Results

BACKGROUND/AIMS: To investigate the predictive factors for complete response (CR) and recurrence after CR in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). METHODS: Among 691 newly diagnosed HCC patients, 287 were treated with TACE as a first therapy. We analyzed the predictive factors for CR, recurrence after CR, and overall survival (OS). RESULTS: Eighty-one patients (28.2%) achieved CR after TACE, and recurrence after CR was detected in 35 patients (43.2%). In multivariate analyses, tumor size (≤5 cm) and single nodularity were predictive factors for CR, with hazard ratios (HRs) of 0.35 (p=0.002) and 0.41 (p<0.001), respectively. Elevated serum α-fetoprotein (AFP) (>20 ng/mL) level and multinodularity exhibited significant relationships with recurrence after CR, with HRs of 2.220 (p=0.026) and 3.887 (p<0.001), respectively. Tumor size (>5 cm), multinodularity, elevated serum AFP (>20 ng/mL) level, Child-Turcotte-Pugh score (B and C), and portal vein thrombosis were significant factors for OS. CONCLUSIONS: In patients treated with TACE as a first therapy, tumor size (≤5 cm) and single nodularity were predictive factors for CR, and multinodularity and elevated serum AFP (>20 ng/mL) levels were predictive factors for recurrence after CR. These factors were also significant for OS.
Carcinoma, Hepatocellular* ; Chemoembolization, Therapeutic ; Humans ; Multivariate Analysis ; Recurrence* ; Venous Thrombosis

Hepatocellular carcinoma (HCC) is the 2nd most common cause of cancer related death in Korea and well-known malignancy with poor prognosis. Sorafenib is the first-line molecular targeted agent in patients with extra-hepatic spread of HCC. However, complete response is extremely rare in patients treated with sorafenib and the disease control rate is only 43%. We report a 53-year-old man with advanced HCC with pulmonary metastasis who showed complete response by cytotoxic chemotherapy with doxorubicin and cisplatin with relatively tolerable adverse effects after failure of treatment with sorafenib.
Carcinoma, Hepatocellular* ; Cisplatin ; Doxorubicin ; Drug Therapy* ; Humans ; Korea ; Middle Aged ; Neoplasm Metastasis* ; Prognosis

BACKGROUND/AIMS: The predictive role of contrast-enhanced ultrasonography (CEUS) before performing transarterial chemoembolization (TACE) has not been determined. We assessed the possible predictive factors of CEUS for the response to TACE. METHODS: Seventeen patients with 18 hepatocellular carcinoma (HCC) underwent TACE. All of the tumors were studied with CEUS before TACE using a second-generation ultrasound contrast agent (SonoVue(R), Bracco, Milan, Italy). The tumor response to TACE was classified with a score between 1 and 4 according to the remaining enhancing-tumor percentage based on modified response evaluation criteria in solid tumors (mRECIST): 1, enhancing tumor <25%; 2, 25%< or =enhancing tumor<50%; 3, 50%< or =enhancing tumor<75%; and 4, enhancing tumor> or =75%). A score of 1 was defined as a "good response" to TACE. The predictive factors for the response to TACE were evaluated during CEUS based on the maximum tumor diameter, initial arterial enhancing time, arterial enhancing duration, intensity of arterial enhancement, presence of a hypoenhanced pattern, and the feeding artery to the tumor. RESULTS: The median tumor size was 3.1 cm. The distribution of tumor response scores after TACE in all tumors was as follows: 1, n=11; 2, n=4; 3, n=2; and 4, n=1. Fifteen tumors showed feeding arteries. The presence of a feeding artery and the tumor size (< or =5 cm) were the predictive factors for a good response (P=0.043 and P=0.047, respectively). CONCLUSIONS: The presence of a feeding artery and a tumor size of less than 5 cm were the predictive factors for a good response of HCC to TACE on CEUS.
Adult ; Aged ; Aged, 80 and over ; Antibiotics, Antineoplastic/administration & dosage ; Carcinoma, Hepatocellular/pathology/therapy/*ultrasonography ; Chemoembolization, Therapeutic ; Contrast Media/*chemistry ; Doxorubicin/administration & dosage ; Female ; Humans ; Liver Neoplasms/pathology/therapy/*ultrasonography ; Male ; Microspheres ; Middle Aged ; Tomography, X-Ray Computed ; Treatment Outcome

BACKGROUND/AIMS: The relationship between portal hemodynamics and fundal varices has not been well documented. The purpose of this study was to understand the pathophysiology of fundal varices and to investigate bleeding risk factors related to the presence of spontaneous portosystemic shunts, and to examine the hepatic venous pressure gradient (HVPG) between fundal varices and other varices. METHODS: In total, 85 patients with cirrhosis who underwent HVPG and gastroscopic examination between July 2009 and March 2011 were included in this study. The interrelationship between HVPG and the types of varices or the presence of spontaneous portosystemic shunts was studied. RESULTS: There was no significant difference in the HVPG between fundal varices (n=12) and esophageal varices and gastroesophageal varices type 1 (GOV1) groups (n=73) (17.1+/-7.7 mm Hg vs 19.7+/-5.3 mm Hg). Additionally, there was no significant difference in the HVPG between varices with spontaneous portosystemic shunts (n=28) and varices without these shunts (n=57) (18.3+/-5.8 mm Hg vs 17.0+/-8.1 mm Hg). Spontaneous portosystemic shunts increased in fundal varices compared with esophageal varices and GOV1 (8/12 patients [66.7%] vs 20/73 patients [27.4%]; p=0.016). CONCLUSIONS: Fundal varices had a high prevalence of spontaneous portosystemic shunts compared with other varices. However, the portal pressure in fundal varices was not different from the pressure in esophageal varices and GOV1.
Adult ; Aged ; Endoscopy, Gastrointestinal ; Esophageal and Gastric Varices/etiology/*physiopathology ; Esophagus ; Female ; Gastric Fundus ; Gastrointestinal Hemorrhage/etiology/*physiopathology ; Humans ; Hypertension, Portal/complications/*physiopathology ; Liver Cirrhosis/complications/*physiopathology ; Male ; Middle Aged ; *Portal Pressure ; *Renal Veins ; Risk Factors ; *Splenic Vein ; Stomach/*blood supply ; Vascular Fistula/complications/*physiopathology