Prognostic factors associated with mortality in patients with gastric fundal variceal bleeding

AIM To determine the prognostic factors associated with mortality in patients with gastric fundal variceal (GFV) bleeding.METHODS In total, 42 patients were endoscopically diagnosed with GFV bleeding from January 2000 to March 2014. We retrospectively reviewed the patients' medical records and assessed their history, etiology of liver cirrhosis, disease conditions, treatment options for GFV bleeding, medications administered before and after onset of GFV bleeding, blood test results(hemoglobin, albumin, and bilirubin concentrations), and imaging results(including computed tomography and abdominal ultrasonography). We also assessed the prognostic factors associated with short-term mortality(up to 90 d) and long-term mortality in all patients.RESULTS Multivariate analysis showed that prophylactic administration of antibiotics was an independent prognostic factor associated with decreases in short-term mortality (OR = 0.08, 95%CI: 0.01-0.52) and longterm mortality (OR = 0.27, 95%CI: 0.08-0.91) in patients with GFV bleeding. In contrast, concurrent hepatocellular carcinoma (HCC) and regular use of proton pump inhibitors (PPI) were independent prognostic factors associated with increases in shortterm mortality(HCC: OR = 15.4, 95%CI: 2.08-114.75; PPI: OR = 12.76, 95%CI: 2.13-76.52) and long-term mortality (HCC: OR = 7.89, 95%CI: 1.98-31.58; PPI: OR = 10.91, 95%CI: 2.86-41.65) in patients with GFV bleeding. The long-term overall survival rate was significantly lower in patients who regularly used PPI than in those who did not use PPI(P = 0.0074).CONCLUSION Administration of antibiotics is associated with decreased short- and long-term mortality, while concurrent HCC and regular PPI administration are associated with increased short- and long-term mortality.

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2:A project of the Kyushu University Liver Disease Study Group

AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16

Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma

AIM: To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma (HCC).

Hepatocellular carcinoma or interferon-based therapy history attenuates sofosbuvir/ribavirin for Japanese genotype 2 hepatitis C virus

AIM To investigate the real-world efficacy and safety of sofosbuvir/ribavirin(SOF/RBV) therapy for Japanese patients with genotype 2 hepatitis C virus(GT2-HCV).METHODS A total of 182 patients with GT2-HCV infection who received SOF/RBV therapy for 12 wk at our hospital were enrolled. The patients comprised 122 men and 60 women(age range: 17-84 years; mean age ± SD: 60.1 ± 12.1 years). Relationships between virological response and clinical data were examined by logistic regression analyses. RESULTS The proportions of patients with liver cirrhosis and history of hepatocellular carcinoma(HCC) were 29.0% and 17.3%, respectively. The proportion of patients with prior interferon(IFN)-based therapy was 25.6%. SOF/RBV therapy rapidly decreased HCV RNA levels. Several patients required RBV dose reduction because of anemia or fatigue. Four patients discontinued the therapy. The rates of sustained virological response at 12 wk after the end of treatment were 87.9%(intention to treat: 160/182) and 94.1%(per protocol: 159/169). Multivariate analyses showed that history of HCC or IFN-based therapy independently reduced the efficacy of SOF/RBV therapy. CONCLUSION SOF/RBV therapy for GT2-HCV is safe, highly tolerated, and effective. History of HCC or IFN-based therapy independently reduces the efficacy of this treatment.

Relationship between body surface area and ALT normalization after long-term lamivudine treatment

AIM： To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS： We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year （n = 249）, two years （n = 147）, and three years （n = 72） were evaluated from the levels of serum ALT and HBVoDNA, as biological and virological effects （undetectable levels by PCR）, respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBVoDNA, and HBeAg were analyzed. RESULTS： For 1-year treatment, multivariate analysis revealed that BSA （P = 0.0002） was the only factor for the biological effect, and that ALT （P = 0.0017）, HBV- DNA （P = 0.0004）, and HBeAg （P = 0.0021） were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA （P = 0.0147） was the only factor for the biological effect, and that ALT （P = 0.0192） and HBeAg （P = 0.0428） were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA （P = 0.0730） as a factor for the normalization of ALT levels. CONCLUSION： BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.

Long-term lamivudine treatment for chronic,hepatitis B in Japanese patients:A project of Kyushu University Liver Disease Study

AIM： To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS： In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 （median 21） mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS： Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL （P〈 0.0001）, HBeAg negativity （P〈 0.0001）, a platelet count of 100×10^9/L or more （P= 0.0162） at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment （P= 0.0003） to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥15 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION： Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

Multicentric recurrence of intraductal papillary neoplasm of bile duct after spontaneous detachment of primary tumor:A case report

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)rarely recurs in a multicentric manner.We encountered a patient with multiple recurrences of the gastric subtype of IPNB one year after spontaneous detachment of the primary tumor during peroral cholangioscopy(POCS).CASE SUMMARY A 68-year-old woman on maintenance hemodialysis because of lupus nephritis had several cardiovascular diseases and a pancreatic intraductal papillary mucinous neoplasm(IPMN).She was referred to our department for dilation of the common bile duct(CBD)and a tumor in the lumen,detected using ultrasonography.She had no complaints,and blood tests of hepatobiliary enzymes were normal.Magnetic resonance cholangiopancreatography(MRCP)showed a papillary tumor in the CBD with a filling defect detected using endoscopic retrograde cholangiography(ERC).Intraductal ultrasonography revealed a papillary tumor and stalk at the CBD.During POCS,the tumor spontaneously detached with its stalk into the CBD.Pathology showed low-intermediate nuclear atypia of the gastric subtype of IPNB.After 1 year,follow-up MRCP showed multiple tumors distributed from the left hepatic duct to the CBD.ERC and POCS showed multicentric tumors.She was alive without hepatobiliary symptoms at least two years after initial diagnosis of IPNB.CONCLUSION The patient experienced gastric subtype of IPNB without curative resection.Observation may be reasonable for patients with this subtype.

Immediate virological response predicts the success of shortterm peg-interferon monotherapy for chronic hepatitis C

AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological response.METHODS:Defining an"immediate virological response(IVR)"as the loss of serum hepatitis C virus(HCV) RNA 7 d after the first administration of PEG-IFNα,we conducted a 12-wk course of PEG-IFNα2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited IVR.The patients included 21 men and 17 women,whose ages ranged from 22 to 77 years(mean±SD:52.0±17.8 years).There were 4 patients with HCV genotype 1b,23 patients with genotype 2a and 4 patients with genotype 2b.HCV genotype was not determined for the remaining 7 patients.Patients were categorized into a sustained virological response(SVR)group,if serum HCV RNA remained negative for 24 wk after the end of treatment,or into a relapse group.RESULTS:Based on the intention-to-treat analysis,35 patients(92.1%)achieved SVR.One patient(2.6%)relapsed with serum HCV RNA 12 wk after the end of treatment.Two patients(5.3%)withdrew from the study during the 24-wk follow-up period.With regard to the HCV RNA genotype,the SVR rates were 100%(4/4) for genotype 1b,95.7%(22/23)for genotype 2a and 100%(4/4)for genotype 2b.The SVR rate in 7 patients,whose HCV RNA genotypes were not determined,was 71.4%(5/7).CONCLUSION:Short-term PEG-IFNα2a monotherapy is highly effective for chronic hepatitis C patients who have low pretreatment HCV RNA load and exhibit IVR.

Efficacy of tolvaptan for the patients with advanced hepatocellular carcinoma

To investigate the factors influenced the efficacy of tolvaptan (TLV) in liver cirrhosis. METHODSWe retrospectively enrolled 61 consecutive patients with refractory hepatic ascites. All of them had been treated with furosemide and spironolactone before admission, and treated with TLV for 7 d in our hospital. The effect of TLV was defined by the rate of body weight loss, and the factors that influenced TLV efficacy were analyzed using multiple regression. RESULTSCoexistent hepatocellular carcinoma (HCC) was the only significant predictive variable that attenuated the efficacy of TLV. In stratified analysis, high doses of furosemide decreased the efficacy of TLV in patients with HCC, and increased efficacy in those without HCC. In the latter, a high Child-Pugh-Turcotte score had a positive influence and a high concentration of lactate dehydrogenase had a negative influence on the effectiveness of TLV. CONCLUSIONDevelopment of ascites may differ between patients with liver failure and those with HCC progression. A sufficient preceding dose of furosemide decreases diuretic effect of TLV.