Yu Rim Lee

Prospective validation of Baveno V definitions and criteria for failure to control bleeding in portal hypertension

New definitions and criteria were released at the Baveno V consensus meeting. The purposes of this study were to verify Baveno V definitions and criteria for failure to control bleeding and to determine the usefulness of the combined use of the Adjusted Blood Requirement Index [ABRI: (number of blood units)/(final hematocrit‐initial hematocrit)+0.01] with Baveno V criteria. In all, 246 consecutive liver cirrhosis patients with acute bleeding associated with portal hypertension were enrolled prospectively between January 2010 and October 2012. The treatment outcome on day 5 was assessed by endoscopy. For the ABRI calculation, two hematocrit levels were used as the initial hematocrit: the first level measured upon patient arrival (ABRI‐A) and the lowest level measured before transfusion (ABRI‐B). Treatment failures were identified in 53 patients, of whom 24 died. Based on repeated endoscopic findings, 29 patients were identified as treatment failures, while according to Baveno V criteria, 47 patients were regarded as treatment failures. The area under the receiver operating characteristic curve (AUROC) of Baveno V criteria was 0.906, and the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 83.0%, 98.4%, 93.6%, 95.5%, 53.41, and 0.17, respectively. The AUROC of Baveno V criteria was significantly greater than those of Baveno IV (P = 0.0001) and Baveno II/III (P < 0.0001) criteria. Adding ABRI‐A or ‐B to Baveno V criteria resulted in a significant reduction of the AUROC (P < 0.05). Conclusion: The Baveno V criteria are good predictors of treatment failure of early‐stage acute gastrointestinal bleeding in patients with portal hypertension, while the addition of ARBI does not improve the prediction accuracy of the outcome of bleeding. (Hepatology 2015;61:1033–1040)

Clinical significance of lncRNA-ATB expression in human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a worldwide health problem and it is important to understand the mechanistic roles of the biomolecules involved in its pathogenesis. Long non-coding RNAs (lncRNAs) are frequently and aberrantly expressed in various human cancers and are known to play a role in cancer pathogenesis. The aim of this study was to analyze the expression of lncRNA-ATB in HCC and investigate the implications for prognoses. In total, 100 samples of HCC tissues and their corresponding, adjacent, non-cancerous liver tissues were collected. Total RNAs were extracted and the expression levels of lncRNA-ATB were measured by qRT-PCR. The association of lncRNA expression with clinicopathological features and patient survival were then analyzed. LncRNA-ATB was significantly upregulated in HCC tissues compared with the levels in corresponding non-cancerous tissues. Expression of lncRNA-ATB was significantly associated with portal vein thrombosis, intrahepatic or extrahepatic metastases, mUICC stage, and the BCLC stage. Large tumors (> 5 cm, HR = 3.851, 95% CI = 1.431–10.364, p = 0.008) and higher lncRNA-ATB expression (HR = 4.158, 95% CI = 1.226–14.107, p = 0.022) were the significant prognostic factors for overall survival. With this novel evidence of the involvement of lncRNA-ATB in HCC pathogenesis and clinical features, lncRNA-ATB can be concluded to have potential as a biomarker for the prognosis of HCC and as a targeted therapy for afflicted patients.

Effects of branched-chain amino acids (BCAAs) on the progression of advanced liver disease: A Korean nationwide, multicenter, retrospective, observational, cohort study.

Abstract Evidence of the potential benefits of long-term oral branched-chain amino acid (BCAA) supplementation in reducing the severity of liver disease is limited. Patients who were diagnosed with liver cirrhosis with a Child–Pugh (CP) score of 8–10 were included. The BCAA group consumed BCAAs daily for at least 6 months, and the control group consumed a diet without BCAA. We analyzed the improvements based on the model for end-stage liver disease (MELD) score, CP score, incidence of cirrhosis-related complications, and event-free survival over 2 years. Among the 867 recruited patients, 307 (166 in the BCAA group and 141 in the control group) were analyzed. The BCAA group was divided into 3 subgroups, whose patients consumed 4.15 g, 8.3 g, or 12.45 g of BCAAs daily for the analysis. There were significant differences in the CP score, albumin, and hepatic encephalopathy between the 2 groups at baseline. After matching the propensity scores, we analyzed patients in the BCAA-12.45 g group (12.45 g of BCAAs daily, n = 41) and matched control group (n = 41). The MELD score significantly improved in the BCCA-12.45 g group compared to the matched control group (P = .004). The changes in the serum bilirubin level (P = .014) and CP score (P = .033) over time also differed significantly between the 2 groups. The incidence rates of cirrhosis-related complications (P = .973) and development of hepatocellular carcinoma (2 cases each) did not differ significantly between the 2 groups. Long-term oral BCAA supplementation has beneficial effects in patients with advanced liver cirrhosis. A further large-scale prospective study is needed to delineate these beneficial effects.

Clinical Outcomes of Argon Plasma Coagulation Therapy for Early Gastric Neoplasms

Background/Aims Argon plasma coagulation (APC) has some merits in the treatment of gastric neoplasms including a shorter operative time and fewer complications compared with endoscopic mucosal resection or endoscopic submucosal dissection. However, there are few reports on the outcomes of gastric neoplasms treated using APC. The aim of this study was to evaluate APC in the treatment of early gastric neoplasms in terms of clinical efficacy, safety, and local recurrence. Methods We enrolled 28 patients who received APC therapy at the Kyungpook National University Hospital between May 2007 and April 2013. Clinical outcomes were analyzed. Results The median follow-up period was 24.8 months (range, 2 to 78). Among the 28 lesions treated using the APC procedure, tumor recurrence was encountered in seven lesions (25.0%). Recurrence was found in 50% (5/10) of single APC cases and 11% (2/18) of rescue APC cases. The mean time to recurrence was 16.1 months (range, 2 to 78). There were no serious APC-related complications such as perforation, bleeding, or infection. Conclusions APC therapy can be a useful treatment with a favorable safety profile for patients with early gastric neoplasms. However, further studies are necessary to determine the long-term prognosis of patients undergoing this treatment.

Using transient elastography to predict hepatocellular carcinoma recurrence after radiofrequency ablation

Liver stiffness (LS) value determined using transient elastography (TE) can be used to assess the degree of liver fibrosis. The study investigated whether TE can predict the recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).

Survival estimates after stopping sorafenib in patients with hepatocellular carcinoma: NEXT score development and validation

Background/Aims Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model. Methods Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed. Results In the training cohort, four factors were independent negative predictors of survival (p<0.05). Based on the β regression coefficient of each factor, we established the NEXT score (Survival after Stopping Nexavar Treatment), allocating 1 point each for an Eastern Cooperative Oncology Group score ≥2, Child-Pugh class B or C, serum sodium ≤135 mEq/L, and α-fetoprotein >400 ng/mL. Area under the receiver operating characteristic curve values to predict 1-, 3-, and 6-month survival rates were 0.805, 0.809, and 0.774, respectively, in the training cohort and 0.783, 0.728, and 0.673, respectively, in the validation cohort (n=137). When the training and validation cohorts were stratified into three risk groups (NEXT score 0 [low-risk] vs 1 to 2 [intermediate-risk] vs 3 to 4 [high-risk]), survival differed significantly between the groups (p<0.05, log-rank test). Conclusions In patients with HCC, survival after stopping sorafenib is poor. However, risk estimates based on a new “NEXT score” may help predict survival and prognosis even in patients who discontinue sorafenib treatment.

Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years

AIM To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. MATERIALS AND METHODS The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. RESULTS The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/μl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). CONCLUSIONS RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.

P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma.

See Article on Page 257 Hepatocellular carcinoma (HCC) is the second leading cause of cancer related death with increasing incidence.1 The standard treatments of HCC consist of surgical resection, liver transplantation, radiofrequency ablation and transarterial chemoembolization. However, because a large proportion of HCC patients are diagnosed in advanced stage, long-term prognosis is disappointing with few available therapeutic modalities.2,3 Although Radiotherapy is not included in the Barcelona Clinic Liver Cancer (BCLC) algorithm, it has shown acceptable therapeutic efficacy as one of the therapeutic options for HCC patients.4 However, as HCC often acquires radioresistance which are correlated with treatment failure,5 only a small number of radionuclides, such as iodine-131, yttrium-90, rhenium-188 and holmium-166, have been used to the HCC treatment.6,7 The P53 protein is a transcription factor related to DNA damage repair, growth arrest and apoptosis leading to uncontrolled proliferation, associated with more than 50% of human cancers.8,9,10 P53 normally exists in low steady level, but the expression and activation of P53 increases after radiation. The P53 is thought to be one of the key elements involved in the response to radiotherapy.8 Many studies have been conducted for elucidating relationship between P53 and effectiveness of radiotherapy in cancer and revealed that mutation or inactivation of P53 causes genetic instability, resulting in development of tumors and ineffectiveness of radiotherapy.9,10,11 In this issue, Gomes et al. reported influence of P53 on the radiotherapeutic response of the HCC. In this study, investigation of the effect of iodine-131 radiotherapy in three human HCC cell lines with different degrees of P53 expression was conducted to assess the influence of P53 on the HCC cell survival after radiation therapy. As a result, Hep3B2.1-7 cell line, which has a homozygous deletion in the TP53 gene, did not express P53, HepG2 expresses its normal form, and HuH7, which has a mutated codon, overexpressed P53. For HepG2 and HuH7 cell lines, an increase in P53 expression was observed after both external and internal radiation with I-131, especially in HuH7. Level of phosphorylated P53 was higher after external irradiation than internal radiation with highest levels of phosphorylation in HepG2 cell line. The Hep3B2.1-7 cells were less radiosensitive than other two cell lines. More radiosensitive cell lines, which exhibit a great decrease in cell survival (HepG2, HbH7) showed a higher expression of P53. Thus, P53 protein, encoded by the TP 53 tumor suppressor gene, might be an important factor in radiotherapeutic response in HCC, which is consistent with previous studies.9,10 Although P53 triggered most apoptotic cell death, in this study, cells died by late apoptosis/necrosis and necrosis. We must consider the possibility of the aggressiveness of radiation to cells or observation of cell death in later stage. Moreover, HepG2 cell line is more sensitive to both external and internal radiation than HuH7 cell line. It might be related to the character of HepG2 cell line which expressed the normal and more functional form of P53. Further studies are warranted about more detail signaling pathways. It would be an important target for HCC treatment.

Long‑term follow‑up of complete remission of advanced hepatocellular carcinoma following sorafenib therapy: A case report

Sorafenib is a tyrosine kinase inhibitor that has been demonstrated to improve the overall survival time of patients with advanced hepatocellular carcinoma (HCC). Although there have been a number of reports of patients achieving complete remission (CR) following sorafenib therapy, the long-term clinical outcomes of these patients have yet to be ascertained. A 72-year-old male patient with chronic hepatitis C, diabetes, hypertension and an old cerebral infarction was referred for the evaluation of a liver mass identified on an abdominal ultrasound. Abdominal computed tomography (CT) demonstrated a 13-cm mass replacing the right lobe of the liver, with portal vein thrombosis. HCC was confirmed by a percutaneous needle biopsy and treated with sorafenib. At 4 months, a follow-up CT demonstrated no enhancing viable lesions in the tumor and recanalization of the portal vein. Sorafenib therapy was continued for 48 months until the patient experienced dyspnea due to congestive heart failure, with pleural effusion. Following the discontinuation of sorafenib, the patients symptoms improved. The patient followed up without recurrence for 52 months. Subsequent to achieving CR through treatment with sorafenib, long-term sorafenib therapy may be an option and efforts should be made to monitor cardiac toxicity during sorafenib therapy, particularly in high-risk patients.

Tenofovir, entecavir, and lamivudine in patients with severe acute exacerbation and hepatic decompensation of chronic hepatitis B

OBJECTIVE To compare the efficacy of and mortality after lamivudine (LAM), tenofovir (TDF), and entecavir (ETV) treatment in patients with severe acute chronic hepatitis B (CHB) exacerbation. METHODS We analyzed 91 patients with severe acute CHB exacerbation treated with LAM (n=28), TDF (n=26), or ETV (n=37) for 10 years. The primary endpoint was overall mortality or liver transplantation (LT) by 48 weeks. The determined predictors of mortality, virologic and biochemical responses, and drug resistance were also evaluated. RESULTS The overall mortality or LT rate was not significantly different among the LAM (14.3%), ETV (10.8%), and TDF (3.8%) groups (P=0.435). In the multivariate analysis, the occurrence of ascites (hazard ratio [HR] 10.467, 95% confidence interval [CI] 1.596-68.645, P=0.014) and model for end-stage liver disease (MELD) scores above 25 (HR 28.920, CI 4.719-177.251, P=0.000) increased the risk of mortality or LT. All groups showed similar biochemical responses (P=0.134), virologic responses (HBV DNA <116copies/mL, P=0.151), and HBeAg seroconversion (P=0.560). Antiviral resistance emerged in five patients treated with LAM by 48 weeks (17.9%, P=0.003). CONCLUSION LAM, ETV, and TDF selection is not related with mortality and LT in patients with severe acute CHB exacerbation and hepatic decompensation. To reduce mortality, patients with ascites and MELD scores above 25 should be considered for LT.