Lein-Ray Mo

Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis

BACKGROUND & AIMSnTaiwan has a high prevalence of hepatitis B viral (HBV) infection and hepatocellular carcinoma (HCC) with increasing consumption of alcohol. We investigated the impact of heavy alcohol consumption and HBV infection on HCC in cirrhotic patients.nnnMETHODSn966 cirrhotic patients (132 with HBV infection and alcoholism, 632 with HBV infection, and 202 patients with alcoholism) were enrolled between 2000 and 2009 and followed until 2011. The primary end point was newly developed HCC.nnnRESULTSnWithin the three patient groups (cirrhotic patients with HBV infection and alcoholism, HBV infection alone, and alcoholism alone) 38 (28.8%), 100 (15.8%), and 21 (10.4%) showed newly developed HCC, respectively. The 10-year cumulative (52.8% vs. 39.8% vs. 25.6%, p <0.001) and annual incidences (9.9%, 4.1%, and 2.1%) of HCC were significantly higher in cirrhotic patients with HBV infection and alcoholism than those in patients with HBV infection or alcoholism alone. For patients with HBV infection and alcoholism, baseline serum HBV DNA (OR=16.8, p=0.025), antiviral nucleos(t)ides analogues (NUCs) therapy (OR=0.01, p=0.035), and serum α-fetoprotein (OR=1.18, p=0.045) were risk predictors of HCC by multivariate logistic regression models. The cumulative incidence of HCC was higher in patients with higher baseline serum HBV DNA. Antiviral NUCs therapy reduced the incidence of HCC.nnnCONCLUSIONSnHeavy alcohol consumption significantly increased the risk of HCC in HBV-related cirrhotic patients. Elevated baseline serum HBV DNA was a strong risk predictor of HCC and antiviral NUCs therapy reduced the incidence of HCC in cirrhotic patients with HBV infection and alcoholism.

Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), des- carboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

Effectiveness of Intragastric Balloon Treatment for Obese Patients: One-Year Follow-up After Balloon Removal

BackgroundThe Bioenterics Intragastric Balloon (BIB) is effective for weight loss. However, comparisons of its effectiveness between groups with different body mass index (BMI) are rare. This study compared the effectiveness of BIB treatment in patients with BMI <32xa0kg/m2 and those with BMI ≧32xa0kg/m2 at the time of BIB removal and at 1xa0year later.MethodsBetween April 2009 and June 2011, 28 obese patients who completed a full course of BIB treatment were enrolled. There are 16 patients with BMI <32 and 12 with BMI ≧32. Patients who lost more than 20xa0% of excess weight (% EWL) were categorized as responders.ResultsThe BMI significantly fell from 32.4u2009±u20093.7 to 28.5u2009±u20093.7xa0kg/m2 (Pu2009<u20090.01) at the time of BIB removal. All biochemical measurements except for cholesterol level were significantly improved. The median value of %EWL of all patients at BIB removal was 40.1, and 20 patients (71.4xa0%) were responders. Adherence to dietitian counseling was significantly better in responders than in non-responders (85 vs. 25xa0%, respectively; Pu2009<u20090.01). The percentage of responders at 1xa0year after BIB removal was significantly higher among patients with BMI <32 than those with ≧32 (62.5 vs. 16.7xa0%, respectively; Pu2009=u20090.02).ConclusionsBIB placement can achieve significant weight loss and improvement of co-morbidities in obese patients. Better adherence to dietitian counseling is associated with better response. Patients with BMI <32 maintain better weight loss at 1xa0year after BIB removal.

Entecavir versus lamivudine in the treatment of chronic hepatitis B patients with hepatic decompensation.

BACKGROUNDnLamivudine has been widely used in chronic hepatitis B patients with hepatic decompensation, but its use is limited by drug resistance. This outcome research aimed to investigate the comparative efficacy and safety of entecavir versus lamivudine in decompensated patients.nnnMETHODSnBetween November 2004 and February 2010, 126 consecutive treatment-naive patients received either entecavir (n=53) or lamivudine (n=73) for decompensated chronic hepatitis B. All patients presented with both hyperbilirubinaemia and coagulopathy. Primary outcome was mortality within 1 year; secondary outcomes included liver-related mortality, biochemical and virological response, and improvement of hepatic dysfunction.nnnRESULTSnBoth treatment groups were comparable in baseline characteristics. A total of 19 (35.8%) entecavir and 33 (45.2%) lamivudine receivers expired within 1 year, respectively (P=0.29, log rank test). Age (hazard ratio [HR] 1.04 per year, 95% CI 1.01, 1.06), cirrhosis (HR 2.07, 95% CI 1.02, 4.23), and international normalized ratio for prothrombin time (HR 1.44, 95% CI 1.20, 1.74) were independent baseline predictors for all-cause mortality. Antiviral therapy was also unrelated to liver-specific death. However, more patients taking entecavir tended to attain aminotransferase normalization (76.5% versus 52.5%; P=0.05) and viral DNA undetectability (100% versus 58.3%; P=0.06). Moreover, entecavir was associated with significantly greater reduction of the model for end-stage liver disease scores (median 10.0 versus 4.3; P=0.02). Overall, 3 (7.5%) lamivudine but no entecavir users acquired drug resistance in 1 year (P=0.25).nnnCONCLUSIONSnEntecavir as compared with lamivudine is similar in the effect on short-term mortality but is associated with greater clinical improvement among chronic hepatitis survivors who recovered from hepatic decompensation.

Determinants of hepatocellular carcinoma in cirrhotic patients treated with nucleos(t)ide analogues for chronic hepatitis B

OBJECTIVESnWe aimed to identify determinants of hepatocellular carcinoma (HCC) in cirrhotic patients who received nucleos(t)ide analogues for chronic hepatitis B (CHB).nnnPATIENTS AND METHODSnThis retrospective-prospective study screened all patients (nu200a=u200a1630) who received antiviral therapy for CHB between 1 September 2007 and 31 March 2013 at the E-Da Hospital and enrolled 210 consecutive cirrhotic patients with pretreatment viral DNA >2000 IU/mL. Those who developed HCC within 3 months of treatment were excluded. All participants were observed until occurrence of HCC, death or 1 January 2014. The incidence and determinants of HCC were estimated using competing risk analyses adjusted for mortality.nnnRESULTSnThirty-five (16.7%) patients developed HCC during a median follow-up of 25.2 months (IQR, 16.3-37.3 months), with a cumulative incidence of 24.1% (95% CI, 16.3%-32.0%) at 5 years. Multivariate-adjusted analyses identified age >55 years [adjusted hazard ratio (HR), 2.19; 95% CI, 1.03-4.66], male gender (adjusted HR, 3.07; 95% CI, 1.05-9.02), model for end-stage liver disease (MELD) score >12 points (adjusted HR, 2.16; 95% CI, 1.10-4.23) and diabetes mellitus (DM; adjusted HR, 3.49; 95% CI, 1.54-7.91) as independent risk factors after adjusting for multiple covariates, including antidiabetes medication. A scoring formula that used information on age, gender, MELD score, DM and antidiabetes regimen significantly discriminated patients at high or low risk of HCC, with sensitivity and specificity of 82.9% and 62.3%, respectively.nnnCONCLUSIONSnAge, gender, hepatic dysfunction, DM and medication for DM are baseline factors that stratify the risk of HCC in cirrhotic patients who receive nucleos(t)ide analogues for CHB.

Association Between Serum Level of Hepatitis B Surface Antigen at End of Entecavir Therapy and Risk of Relapse in E Antigen-Negative Patients.

BACKGROUND & AIMSnThis study investigated whether serum level of hepatitis B surface antigen (HBsAg) at the end of entecavir treatment was associated with risk of relapse.nnnMETHODSnWe performed a prospective multicenter study of 161 consecutive patients with chronic hepatitis B in whom the hepatitis B virus was no longer detected after 3 years or more of entecavir therapy. Treatment ended between July 1, 2011 and July 1, 2015. Patients were monitored for clinical relapse (hepatitis B virus DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) and virologic relapse (hepatitis B virus DNA >2000 IU/mL). Outcomes were calculated using the Kaplan-Meier method and risk factors were identified by Cox proportional hazards modeling.nnnRESULTSnTwo years after therapy ended, 49.2% of patients in the entire cohort had a clinical relapse (95% confidence interval [CI], 40.9%-58.1%) and 81.7% had a virologic relapse (95% CI, 74.3%-88.0%). Among patients who were hepatitis B e antigen-negative at the end of therapy, 39.2% had a clinical relapse (95% CI, 30.3%-49.6%) and 77.4% had a virologic relapse (95% CI, 68.6%-85.2%). Serum level of HBsAg was associated with relapse in the hepatitis B e antigen-negative patients (Ptrendxa0= .006 for clinical relapse; Ptrendxa0= .0001 for virologic relapse). In multivariate Cox regression analysis, the hazard ratio (per log IU/mL increment) forxa0clinical relapse was 2.47 (95% CI, 1.45-4.23) and for virologic relapse was 1.80 (95% CI, 1.33-2.45). The 11 (9%) patients with levels of HBsAg <10 IU/mL did not relapse.nnnCONCLUSIONSnSerum level of HBsAg is associated with risk of relapse in patients who are hepatitis B e antigen-negative after treatment with entecavir. A low titer of HBsAg might be used to identify patients at low risk for relapse after treatment.

Circumferential balloon-based radiofrequency ablation for ultralong and extensive flat esophageal squamous neoplasia

Esophageal cancer is highly lethal and causes more than 400,000 deaths per year worldwide. In the Asia-Pacific region, esophageal squamous cell carcinoma is the major form of the disease, and its incidence is increasing. Recent advances in image-enhanced endoscopy have led to earlier diagnosis of esophageal squamous mucosal cancer or precancerous lesions. Endoscopic submucosal dissection (ESD) enables large en bloc resection of these superficial esophageal cancers, but the technique is complicated and requires considerable expertise. In particular, when there are large lesions or lesions that occupy more than threefourths of the circumference of the esophagus, patients will have esophageal stenosis. Stenosis can decrease quality of life, and treatment requires multiple sessions of endoscopic balloon dilation. Therefore, it is important to have an alternative and more convenient method to treat these large and extensive esophageal squamous neoplasias. Radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality, and recent studies have shown its efficacy and safety for eradicating high-grade dysplasia in cases of Barrett’s esophagus. RFA also has theoretical potential for treating squamous epithelial neoplasias. However, only a few studies have demonstrated the potential efficacy for squamous neoplasia, and no studies have

Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia

AbstractRadiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities.We retrospectively enrolled the patients with flat-type “large” (length ≥3u200acm extending ≥1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events.Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8u200amin; Pu200a<u200a0.001). The complete resection rate of ESD and complete response rate after primary RFA were 89.3% and 77.8%, respectively. Based on the histological evaluation of the post-ESD specimens showed 14 of 47 (29.8%) had histological upstaging compared with the pre-ESD biopsies, and 4 of them had lymphovascular invasion requiring chemoradiation or surgery. After additional therapy for residual lesions, 46 (97.9%) patients in the ESD group and 17 (94.4%) patients in the RFA group achieved a complete response at 12 months. Four patients (8.5%) developed major procedure-related adverse events in the ESD group, but none in the RFA group. In patients with lesions occupying more than 3/4 of the circumference, a significantly higher risk of esophageal stenosis was noted in the ESD group compared with RFA group (83% vs 27%, Pu200a=u200a0.01), which required more sessions of dilatation to resolve the symptoms (median, 13 vs 3, Pu200a=u200a0.04). There were no procedure-related mortality or neoplastic progression in either group; however, 1 patient who received ESD and 1 who received RFA developed local recurrence during a median follow-up period of 32.4 (range, 13–68) and 18.0 (range, 13–41) months, respectively.RFA and ESD are equally effective in the short-term treatment of early flat large ESCNs; however, more adverse events occur with ESD, especially in lesions extending more than 3/4 of the circumference. RFA does not allow for pathology to evaluate the curability after ablation, and thus currently the use for invasive ESCNs should be conservative until longer follow-up studies are available.

The impact of human papillomavirus infection on the survival and treatment response of patients with esophageal cancers

This study aimed to investigate the impact of human papillomavirus (HPV) infection on the prognosis and treatment response of esophageal squamous cell carcinoma (ESCC).

Pretreatment viral DNA stratifies mortality risk in patients receiving antiviral therapy for severe acute exacerbation of chronic hepatitis B.

BACKGROUNDnPrognostic factors have not been elucidated for severe acute exacerbation of chronic hepatitis B treated with antiviral therapy. This study aimed to explore the role of baseline viral load in predicting mortality.nnnMETHODSnThis retrospective cohort study screened consecutive chronic hepatitis B patients (n=84) receiving antiviral therapy for severe acute exacerbation, defined as abrupt elevation of serum alanine aminotransferase >10× the upper limit of normal along with hyperbilirubinaemia. Survival pattern was evaluated by the Kaplan-Meier method and predictors for mortality determined by the Cox regression analysis.nnnRESULTSnA total of 66 patients were eligible and followed-up for a median of 23 months (range 0.1-75.0). Overall, 20 (30.3%) patients died during the study period, with the vast majority (n=17) succumbing rapidly within 3 months of severe acute exacerbation. The multivariate Cox model revealed that mortality was associated with baseline viral DNA level (HR 1.49 per log copies/ml, 95% CI 1.13, 1.96), international normalized ratio for prothrombin time (HR 2.68 per unit, 95% CI 1.81, 3.98), platelet count (HR 0.87 per 10(4) cells/μl, 95% CI 0.78, 0.98) and age (HR 1.10 per year, 95% CI 1.05, 1.15). A significant interaction existed between viral DNA and prolonged prothrombin time (P=0.005). Stratified analyses further demonstrated that pronounced coagulopathy heralded death irrespective of viral load, whereas serum level of viral DNA stratified mortality risk among those without marked coagulopathy.nnnCONCLUSIONSnPretreatment viral DNA level stratifies risk of death in patients with severe acute exacerbation of chronic hepatitis B before the manifestation of overt liver failure.