A Model to Predict 1-Month Risk of Transplant or Death in Hepatitis A-Related Acute Liver Failure.

Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease. Here, we developed a model to predict outcome in patients with ALF caused by hepatitis A. The derivation set consisted of 294 patients diagnosed with hepatitis A-related ALF (ALFA) from Korea, and a validation set of 56 patients from Japan, India, and United Kingdom. Using a multivariate proportional hazard model, a risk-prediction model (ALFA score) consisting of age, international normalized ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day of ALF diagnosis was developed. The ALFA score showed the highest discrimination in the prediction of liver transplant or death at 1 month (c-statistic, 0.87; 95% confidence interval [CI], 0.84-0.92) versus King's College criteria (KCC; c-statistic, 0.56; 95% CI, 0.53-0.59), U.S. Acute Liver Failure Study Group index specific for hepatitis A virus (HAV-ALFSG; c-statistic, 0.70; 95% CI, 0.65-0.76), the new ALFSG index (c-statistic, 0.79; 95% CI, 0.74-0.84), Model for End-Stage Liver Disease (MELD; c-statistic, 0.79; 95% CI, 0.74-0.84), and MELD including sodium (MELD-Na; c-statistic, 0.78; 95% CI, 0.73-0.84) in the derivation set (all P < 0.01). In the validation set, the performance of the ALFA score (c-statistic, 0.84; 95% CI, 0.74-0.94) was significantly better than that of KCC (c-statistic, 0.65; 95% CI, 0.52-0.79), MELD (c-statistic, 0.74; 95% CI, 0.61-0.87), and MELD-Na (c-statistic, 0.72; 95% CI, 0.58-0.85) (all P < 0.05), and better, but not statistically significant, than that of the HAV-ALFSG (c-statistic, 0.76; 95% CI, 0.61-0.90; P = 0.28) and new ALFSG indices (c-statistic, 0.79; 95% CI, 0.65-0.93; P = 0.41). The model was well-calibrated in both sets. Conclusion: Our disease-specific score provides refined prediction of outcome in patients with ALF caused by hepatitis A.

Changes in Characteristics of Patients with Liver Cirrhosis Visiting a Tertiary Hospital over 15 Years: a Retrospective Multi-Center Study in Korea.

BACKGROUND: Liver cirrhosis has become a heavy burden not only for patients, but also for our society. However, little is known about the recent changes in clinical outcomes and characteristics of patients with cirrhosis-related complications in Korea. Therefore, we aimed to evaluate changes in characteristics of patients with liver cirrhosis in Daegu-Gyeongbuk province in Korea over the past 15 years. METHODS: We retrospectively reviewed the medical records of 15,716 liver cirrhotic patients from 5 university hospitals in Daegu-Gyeongbuk province from 2000 to 2014. The Korean Standard Classification of Diseases-6 code associated with cirrhosis was investigated through medical records and classified according to the year of first visit. RESULTS: A total of 15,716 patients was diagnosed with cirrhosis. A number of patients newly diagnosed with cirrhosis has decreased each year. In 2000, patients were most likely to be diagnosed with hepatitis B virus (HBV) cirrhosis, followed by alcoholic cirrhosis. There was a significant decrease in HBV (P < 0.001), but alcohol, hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD) showed a significant increase during the study period (alcohol, P = 0.036; HCV, P = 0.001; NAFLD, P = 0.001). At the time of initial diagnosis, the ratio of Child-Turcotte-Pugh (CTP) class A gradually increased from 23.1% to 32.9% (P < 0.001). The most common cause of liver-related hospitalization in 2000 was hepatocellular carcinoma (HCC) (25.5%); in 2014, gastrointestinal bleeding with esophageal and gastric varices (21.4%) was the most common cause. Cases of hospitalization with liver-related complication represented 76.4% of all cases in 2000 but 70.9% in 2014. Incidence rate of HCC has recently increased. In addition, HCC-free survival was significantly lower in CTP class A than in classes B and C. Finally, there was significant difference in HCC occurrence according to causes (P < 0.001). HBV and HCV cirrhosis had lower HCC-free survival than alcoholic and NAFLD cirrhosis. CONCLUSION: In recent years, the overall number of cirrhosis patients has decreased. This study confirmed the recent trend in decrease of cirrhosis, especially of cirrhosis due to HBV, and the increase of HCV, alcoholic and NAFLD cirrhosis. Targeted screening for at-risk patients will facilitate early detection of liver diseases allowing effective intervention and may have decreased the development of cirrhosis and its complications.

Association of low skeletal muscle mass with advanced liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Although low skeletal muscle mass (LSMM) is known to increase the risk of non-alcoholic fatty liver disease (NAFLD), limited reports have described the relationship between LSMM and advanced fibrosis. Here, we investigated the association between LSMM and advanced liver fibrosis in NAFLD patients. METHODS: Fatty liver was diagnosed using ultrasound, and appendicular skeletal muscle mass (ASM) was measured using bioelectrical impedance analysis. LSMM was defined in two ways: ASM/body weight percentage (LSMM-BW) and ASM/body mass index. Liver fibrosis stage was assessed by two models, the NAFLD fibrosis score and the Fibrosis-4 index, which determined low and high cutoff values (COVs). RESULTS: Of 10 711 NAFLD patients, 615 were diagnosed with LSMM-BW. LSMM patients were older (47.6 vs 52.5 years, P = 0.001) and had higher body mass index values (23.6 vs 29.1 kg/m2 , P < 0.001) and waist circumferences (80.1 vs 93.3 cm, P < 0.001) than non-LSMM patients. LSMM was an independent risk factor for advanced fibrosis assessed by a low COV for the Fibrosis-4 index regardless of its classification (adjusted for metabolic and lipid profiles and sex, odds ratio [OR], 1.27-2.01; all P < 0.05). LSMM was an independent risk factor for advanced fibrosis assessed by both COVs of NAFLD fibrosis score (adjusted for obesity, hypertension, lipid profile, and sex; OR, 1.64-2.01, P < 0.01 in the low COV group; OR, 2.68-3.12, P = 0.002 in the high COV group). CONCLUSIONS: Low skeletal muscle mass is associated with advanced fibrosis in NAFLD patients independent of metabolic risk factors.

Cholestatic Jaundice as a Paraneoplastic Manifestation of Prostate Cancer Aggravated by Steroid Therapy.

OBJECTIVE: To report a rare case of paraneoplastic jaundice as a manifestation of prostate cancer. CLINICAL PRESENTATION AND INTERVENTION: We report on a case of paraneoplastic syndrome in a 72-year-old man with prostate cancer that manifested with idiopathic jaundice. Although steroids can be used as treatment in patients with prostate cancer, they could exacerbate paraneoplastic jaundice. The jaundice that flared up after treatment with 40 mg prednisone was improved with antiandrogen treatment. CONCLUSION: Physicians should be aware of the possibility of paraneoplastic jaundice in patients with prostate cancer. Appropriate antiandrogen therapy should be considered for paraneoplastic jaundice in these patients.

A 96-week randomized trial of switching to entecavir in patients who achieved virological suppression on lamivudine therapy.

BACKGROUND AND AIM: There are limited data assessing whether patients who achieved virological suppression on lamivudine but remain hepatitis B "e" antigen-positive should be switched to a more potent antiviral with a high genetic barrier to resistance or continue with lamivudine. We compared the safety and efficacy of switching with entecavir versus continuing lamivudine. METHODS: This was a Phase IV, randomized, open-label, prospective study in a tertiary care setting. Seventy-three chronic hepatitis B patients who achieved virological suppression on lamivudine (serum hepatitis B virus DNA < 60 International Unit (IU)/mL) were enrolled. Entecavir or lamivudine were administered orally for up to 96 weeks. Virologic and serologic responses were measured throughout the study. RESULTS: A significantly higher proportion of patients in the entecavir group achieved hepatitis B virus DNA < 60 IU/mL at Weeks 48 (100% [38/38] vs 62.8% [22/35]; P < 0.001) and 96 (97.4% [37/38] vs 57.1% [20/35]; P<0.001). A greater number of patients had virologic breakthrough (Week 96 cumulative incidence 42.9% vs 2.6%; P<0.001) and genotypic lamivudine resistance (28.6% [10/35] vs 0% [0/38]; P<0.001) in the lamivudine group. No serious adverse events or laboratory abnormalities were reported. CONCLUSIONS: Even after achieving virological suppression on lamivudine therapy, the risk of emergent lamivudine resistance increases over time. Switching to entecavir resulted in a maintained virologic response and superior serologic responses versus continued lamivudine therapy. This study supports a rationale for switching to entecavir in chronic hepatitis B patients with virological suppression on lamivudine.

A comparative first-principles study of the lithiation, sodiation, and magnesiation of black phosphorus for Li-, Na-, and Mg-ion batteries.

Using first-principles calculations, we describe and compare atomistic lithiation, sodiation, and magnesiation processes in black phosphorous with a layered structure similar to graphite for Li-, Na-, and Mg-ion batteries because graphite is not considered to be an electrode material for Na- and Mg-ion batteries. The three processes are similar in that an intercalation mechanism occurs at low Li/Na/Mg concentrations, and then further insertion of Li/Na/Mg leads to a change from the intercalation mechanism to an alloying process. Li and Mg show a columnar intercalation mechanism and prefer to locate in different phosphorene layers, while Na shows a planar intercalation mechanism and preferentially localizes in the same layer. In addition, we compare the mechanical properties of black phosphorous during lithiation, sodiation, and magnesiation. Interestingly, lithiation and sodiation at high concentrations (Li2P and Na2P) lead to the softening of black phosphorous, whereas magnesiation shows a hardening phenomenon. In addition, the diffusion of Li/Na/Mg in black phosphorus during the intercalation process is an easy process along one-dimensional channels in black phosphorus with marginal energy barriers. The diffusion of Li has a lower energy barrier in black phosphorus than in graphite.

Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: a randomised, non-inferiority, open trial.

BACKGROUND & AIMS: Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition. METHODS: In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey's discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone. RESULTS: The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, -4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 5 9): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups. CONCLUSIONS: The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.

Individual prediction model for lamivudine treatment response in hepatitis B virus e antigen-positive chronic hepatitis B patients.

BACKGROUND AND AIMS: Although prolonged lamivudine (LAM) therapy is associated with the emergence of LAM-resistant mutations, it is still a commonly used therapy in many Asian countries because of its established long-term safety and low cost. The aim of our study was to assess the predictors of long-term LAM treatment response and to establish an individual prediction model (IPM) for hepatitis B virus e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B (CHB) patients. METHODS: This was a multicenter analysis of 838 patients treated with LAM between January 1999 and August 2004. Of these, 748 patients were followed up for at least 24 months. RESULTS: The median age was 43.0 years (range, 19-79 years) and the mean duration of LAM monotherapy was 34.2 ± 0.7 months. In the multivariate analysis, age (odds ratio [OR] = 0.974, P < 0.001), baseline alanine aminotransferase level (OR = 1.001, P = 0.014), and baseline hepatitis B virus DNA level (OR = 0.749, P < 0.001) were independent factors for HBeAg seroconversion. Based on the predictors, an IPM was established. Patients were classified into high (> 50%), intermediate (30-50%), or low (≤ 30%) response groups based on their probability of HBeAg seroconversion according to the IPM. The cumulative HBeAg seroconversion rate at 6 years for the high, intermediate, and low response groups was 66.0%, 48.5%, and 21.8%, respectively (P < 0.001). CONCLUSIONS: An IPM was developed based on predictors of HBeAg seroconversion in HBeAg-positive CHB patients on LAM monotherapy. This model will allow screening of LAM responders prior to the commencement of antiviral treatment.

Clinical characteristics and outcomes of acute hepatitis a in Korea: a nationwide multicenter study.

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.

Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.

This study aimed to develop synthetic Claudin18.2 (CLDN18.2) chimeric antigen receptor (CAR)-T (CAR-T) cells as a treatment for advanced gastric cancer using lentiviral vector genetic engineering technology that targets the CLDN18.2 antigen and simultaneously overcomes the immunosuppressive environment caused by programmed cell death protein 1 (PD-1). Synthetic CAR T cells are a promising approach in cancer immunotherapy but face many challenges in solid tumors. One of the major problems is immunosuppression caused by PD-1. CLDN18.2, a gastric-specific membrane protein, is considered a potential therapeutic target for gastric and other cancers. In our study, CLDN18.2 CAR was a second-generation CAR with inducible T-cell costimulatory (CD278), and CLDN18.2-PD1/CD28 CAR was a third-generation CAR, wherein the synthetic PD1/CD28 chimeric-switch receptor (CSR) was added to the second-generation CAR. In vitro, we detected the secretion levels of different cytokines and the killing ability of CAR-T cells. We found that the secretion of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) secreted by three types of CAR-T cells was increased, and the killing ability against CLDN18.2-positive GC cells was enhanced. In vivo, we established a xenograft GC model and observed the antitumor effects and off-target toxicity of CAR-T cells. These results support that synthetic anti-CLDN18.2 CAR-T cells have antitumor effect and anti-CLDN18.2-PD1/CD28 CAR could provide a promising design strategy to improve the efficacy of CAR-T cells in advanced gastric cancer.

A nationwide seroepidemiology of hepatitis C virus infection in South Korea.

BACKGROUND & AIMS: The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large-scale survey. METHODS: From January to December 2009, a total of 291 314 adults underwent health check-up in 29 centres nationwide. The data concerning anti-HCV antibody and biochemical tests were obtained from all participants. Among subjects with positive anti-HCV, such data as HCV RNA, genotypes and treatment detail were additionally analysed. RESULTS: Using an estimated 2009 population of Korea, the age, sex and area-adjusted anti-HCV positive rate was 0.78%. Anti-HCV prevalence in female patients (0.83%) was higher than that in male patients (0.75%). Gradual increase in anti-HCV positivity was observed, from 0.34% in those aged 20-29 years to 2.31% in those >70 years. The age- and sex-adjusted anti-HCV prevalence varied in different areas, being higher in Busan and Jeonnam (1.53-2.07%), mid-level in Seoul and surrounding districts (0.50-0.61%) and lower in Jeju (0.23%). The comparative analysis of laboratory variables between anti-HCV (+) and anti-HCV (-) group revealed significantly higher levels of alanine aminotransferase and lower levels of serum lipids in anti-HCV (+) group. Among 1 718 anti-HCV positive subjects, serum HCV RNA was measured only in 478 people, of whom 268 (56.1%) patients had detectable HCV RNA in serum. Among 50 patients for whom assessment of response to antiviral therapy was feasible, overall sustained virological response was achieved in 84% of patients. CONCLUSION: The prevalence of HCV infection is low in South Korea. Studies to analyse risk factors are warranted to reduce HCV infection.

Study on effect of plasma surface treatments for diamond deposition by DC arc plasmatron.

To improve the thermal conductivity and wear resistance of ceramic materials in the field of renewable energy technologies, diamond coating by plasma processing has been carried out in recent years. This study's goal is to improve diamond deposition on Al2O3 ceramic substrates by plasma surface treatments. Before diamond deposition was carried out in a vacuum, plasma surface treatments using Ar gas were conducted to improve conditions for deposition. We also conducted plasma processing for diamond deposition on Al2O3 ceramic substrates using a DC arc Plasmatron. The Al2O3 ceramic substrates with diamond film (5 x 15 mm2), were investigated by SEM (Scanning Electron Microscopy), AFM (Atomic Force Microscopy) and XRD (X-ray Diffractometer). Then, the C-H stretching of synthetic diamond films by FTIR (Fourier Transform Infrared Spectroscopy) was studied. We identified nanocrystalline diamond films on the Al2O3 ceramic substrates. The results showed us that the deposition rate of diamond films was 2.3 microm/h after plasma surface treatments. Comparing the above result with untreated ceramic substrates, the deposition rate improved with the surface roughness of the deposited diamond films.

A prospective nationwide study of drug-induced liver injury in Korea.

OBJECTIVES: To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea. METHODS: From May 2005 to May 2007, cases of DILI (alanine transferase > 3 × upper normal limit or total bilirubin > 2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used. RESULTS: A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included "herbal medications" (102, 27.5%), "prescription or non-prescription medications" (101, 27.3%), "health foods or dietary supplements" (51, 13.7%), "medicinal herbs or plants" (35, 9.4%), "folk remedies" (32, 8.6%), "combined" (30, 8.2%), "herbal preparations" (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM. CONCLUSIONS: DILI appears to be a highly relevant health problem in Korea. "Herbal medications" are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.

Effect of switching from nucleos(t)ide maintenance therapy to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomized trial.

AIMS: Induction of a durable viral response is difficult to achieve in patients with chronic hepatitis B (CHB), even from long-term use of a nucleos(t)ide analogue (NA). This study investigated whether switching to peginterferon (PegIFN) alfa-2a after long-term NA therapy induced a durable viral response. METHODS: Patients with hepatitis B e antigen (HBeAg)-positive CHB who received any NA for at least 72 weeks and had a low level of HBV DNA (≤100 IU/mL) were randomized (1:1) to receive PegIFN alfa-2a (180 µg/week) or NA for 48 weeks. The primary endpoint was change in the hepatitis B surface antigen (HBsAg) titer during antiviral therapy. RESULTS: We randomized 149 CHB patients to the two groups. Compared to baseline, the HBsAg levels in both groups were not lower at week 12, but were lower after 24, 36, and 48 weeks (all p<0.001). The maximal HBsAg decline in the PegIFN alfa-2a group was at week 36 (0.50±0.88 log10 IU/mL), and this decline was smaller in the NA group (0.08±0.46 log10 IU/mL). The percentage of patients with HBeAg seroconversion at week 48 was also greater in the PegIFN alfa-2a group (15/75 [20.0%] vs. 5/74 [6.8%], p = 0.018). Multivariable analysis indicated the PegIFN alfa-2a group had a greater change in HBeAg seroconversion at week 48 (p = 0.027). Patients had relatively good tolerance to PegIFN alfa-2a therapy. CONCLUSIONS: CHB patients who switched to PegIFN alfa-2a for 48 weeks had a significantly lower HBsAg titer and increased HBeAg seroconversion relative to those who remained on NA therapy. TRIAL REGISTRATION: (ClinicalTrials.gov; NCT01769833).

Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-positive chronic hepatitis B.

UNLABELLED: The reported durability of virologic response after successful lamivudine monotherapy is variable, and the question remains as to whether virologic responses can be maintained over an extended follow-up period. The aim of this study was to investigate posttreatment durability, the optimal duration of additional treatment after HBeAg clearance or seroconversion, and determinants for sustained virologic response (SVR) following lamivudine monotherapy in patients with HBeAg-positive chronic hepatitis B (CHB). From January 1999 to August 2004, 178 Korean patients with HBeAg-positive CHB were treated with lamivudine and achieved complete responses, defined as a loss of serum HBeAg and hepatitis B virus DNA, and alanine aminotransferase normalization. The mean duration of lamivudine monotherapy was 26 months (range, 12-77). SVR was maintained in 138 patients (77.5%). Host and viral factors were compared between 138 patients with SVR and 40 patients whose response was not sustained. The cumulative relapse rates increased from 15.9% at 1 year to 30.2% at 5 years, with a mean time to relapse after cessation of lamivudine of 12 months (range, 7-42). Most relapses occurred within 2 years after discontinuation of lamivudine (33/40, 82.5%). On multivariate analysis, age

Association between acid suppressive therapy and spontaneous bacterial peritonitis in cirrhotic patients with ascites.

OBJECTIVE: Proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) therapy may cause intestinal bacterial overgrowth and translocation. Therefore, acid suppressive therapy may increase the risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. MATERIAL AND METHODS: A total of 176 cirrhotic patients with ascites who underwent diagnostic paracentesis between September 2004 and April 2009 were included in the analysis. Patients with gastrointestinal hemorrhage and/or antibiotic therapy within 2 weeks prior to hospital admission were excluded. SBP was defined as ≥250/mm(3) polymorphonuclear white blood cells with or without a positive culture from the ascitic fluid. Eighty-three patients (mean age 56.1 years, 63 males) had SBP and 93 (mean age 54.7 years, 75 males) did not. RESULTS: On the multivariate analysis, a Child-Pugh class C (OR = 2.890, 95% CI 1.443-5.786; p = 0.003), high MELD scores (≥ 20, OR = 3.540, 95% CI 1.155-10.849; p = 0.027), and PPI use (OR = 3.443, 95% CI 1.164-10.188; p = 0.025) were risk factors for SBP. H2RA was not associated with SBP. CONCLUSIONS: PPI use, as well as Child-Pugh class C and high MELD scores, was an independent risk factor for the development of SBP in cirrhotic patients with ascites. Further prospective studies are warranted to clarify this issue.

Diagnostic usefulness of the spot urine sodium/potassium ratio in cirrhotic patients with ascites.

BACKGROUND AND AIMS: The low-salt diet is considered important for control of ascites in cirrhotic patients. To validate whether the spot urine sodium (Na)/potassium (K) ratio could replace 24-h urine Na (uNa) excretion in assessing low-salt diet compliance. METHODS: We prospectively studied 175 patients. 24-h urine collection and spot urine collection were performed. Subsequently, 24-h uNa, urine creatinine (uCr), and spot urine Na and K were assessed. A complete urine collection was confirmed based on 24-h uCr excretion levels of 15mg/kg/day for men and 10mg/kg/day for women. The area under the receiver operating characteristic (AUROC) curve analysis was performed to evaluate the feasibility of spot urine Na/K ratio in predicting 24-h uNa greater than 78mmol/day. RESULTS: Out of 175 patients, 24-h urine samples were completely collected in 57 patients only. Moreover, urine samples were not completely collected in 118 patients because their 24-h uCr excretion level was less than the established criteria. In complete urine collection group, AUROC curve for spot urine Na/K ratio in predicting 24-h uNa greater than 78mmol/day was 0.874±0.051 (P<0.001). In the incomplete urine collection group, the AUROC was 0.832±0.039 (P<0.001). In complete urine collection group, the classical cutoff value greater than 1.0 of spot urine Na/K ratio showed 90.9% sensitivity and 56.0% specificity. CONCLUSIONS: The spot urine Na/K ratio reflects 24-h uNa, but the AUROC value obtained in this study is lower than that of a previous study. Considered the large number of patients with incomplete urine collection, validating 24-h complete urine collection criteria is necessary.

Risk assessment for the development of hepatocellular carcinoma: according to on-treatment viral response during long-term lamivudine therapy in hepatitis B virus-related liver disease.

BACKGROUND & AIMS: To assess the risk for the development of hepatocellular carcinoma (HCC) according to the underlying liver status and on-treatment viral response during long-term lamivudine therapy in patients with hepatitis B virus-related liver disease. PATIENTS AND METHODS: Between March 1997 and February 2005, a total of 872 patients were treated with lamivudine for more than one year. Between 1983 and 1998, a total of 699 patients were enrolled as historical controls. RESULTS: For patients with compensated cirrhosis, HCC occurred in 4.9% (5/103) of cases with sustained viral suppression (persistently <141,500 copies/ml), 11.8% (20/170) in cases with viral breakthrough, and 19.4% (7/36) in cases with a suboptimal response (persistently 141,500 copies/ml): the mean follow-up was 5.1+/-2.7, 5.4+/-2.3, and 3.7+/-1.8 years, respectively. For the control group, HCC developed in 25.0% (37/148) of the cases during a mean follow-up of 6.1+/-4.3 years. Thus, the annual incidence of HCC was 0.95%, 2.18%, 5.26%, and 4.10% in patients with sustained viral suppression, viral breakthrough, suboptimal response, and the control group, respectively. The cumulative incidence of HCC in patients with sustained viral suppression was significantly lower than in patients with a suboptimal response and the controls (p=0.002 and p=0.005, respectively). In patients without cirrhosis and with decompensated cirrhosis, the preventive effects of lamivudine on the development of HCC were not observed (p=0.446 and p=0.123, respectively). CONCLUSION: Lamivudine therapy reduced the incidence of HCC in patients with compensated cirrhosis when the viral suppression was sustained.

Early viral kinetics of telbivudine and entecavir: results of a 12-week randomized exploratory study with patients with HBeAg-positive chronic hepatitis B.

We characterized the early viral kinetic profiles of telbivudine and entecavir and the effects of these potent nucleoside analogs on hepatitis B virus (HBV) DNA and alanine aminotransferase levels in adults with hepatitis B e antigen-positive compensated chronic hepatitis B. Forty-four patients were enrolled in this open-label, parallel-group, multicenter study and randomized to receive telbivudine or entecavir for 12 weeks. Reductions in hepatitis B virus DNA and alanine aminotransferase levels from baseline to weeks 2, 4, 8, and 12 were assessed. Viral kinetic parameters, including viral clearance per day, loss of infected cells per day, and efficiency of inhibition of viral production, were estimated by using a biphasic mathematical model. Statistical analyses were limited to descriptive analyses. The 2 treatment groups achieved similar reductions in HBV DNA and alanine aminotransferase levels. Mean reductions in levels of hepatitis B virus DNA at week 12 were 6.6 +/- 1.6 and 6.5 +/- 1.5 log(10) copies/ml for the telbivudine- and entecavir-treated patients, respectively. There were no significant differences between groups in values for mean viral clearance per day, mean loss of infected cells per day, or efficiency of blocking viral production. The safety profiles for both medications were favorable. During the first 12 weeks of treatment, telbivudine and entecavir demonstrated similar antiviral potencies, resulting in a rapid and profound suppression of serum hepatitis B virus DNA and reduction of alanine aminotransferase levels. No differences in the effects of these 2 agents on early viral kinetics were observed. Both medications were well tolerated.

[Clinical features and prognosis of primary biliary cirrhosis in Korea].

BACKGROUND/AIMS: This study investigated the clinical features and prognosis of primary biliary cirrhosis (PBC) in Korea. METHODS: Clinical data of patients diagnosed as PBC between 1997 and 2008 at eight referral hospitals were analyzed retrospectively. PBC was diagnosed based on liver function tests, presence of serum antimitochondrial antibody (AMA), and histopathological findings. RESULTS: In total, 251 patients (218 females, 33 males; mean age 54 years) were enrolled, and the mean follow-up duration was 33.5 months. At the diagnosis, 61% of the patients were asymptomatic, 12% had decompensated liver cirrhosis, and 98% were positive for AMA. The serum alkaline phosphate (ALP) level was 2.6 times the upper limit of normal, aspartate aminotransferase was 105 U/L, and bilirubin was 2.0 mg/dL. The mean Mayo risk score was 5.5, and the Child-Pugh class was A, B, and C in 79%, 19%, and 2% of the patients, respectively. Ursodeoxycholic acid (UDCA) was used for treatment in 88% of the patients, among which 70% exhibited biochemical responses defined as normalization or a > 40% decrease in ALP at 6 months. Eight deaths occurred during the follow-up; the causes were variceal bleeding, hepatic failure, and sepsis. The overall 5-year survival rate was 95%. The poor prognostic factors were being older than 60 years, high bilirubin, low albumin, ascites, high Mayo risk score, Child-Pugh class C, and initial presence of hepatic decompensation. CONCLUSIONS: Most patients diagnosed as PBC were asymptomatic, and these patients had a favorable short-term prognosis. The prognosis of PBC was dependent on the initial severity of liver disease.