The Association Between Breastfeeding and Nonalcoholic Fatty Liver Disease in Parous Women: A Nation-wide Cohort Study.

BACKGROUND AND AIMS: Breastfeeding has multiple effects on maternal health outcomes. However, the effect of breastfeeding on NAFLD in parous women remains unclear. APPROACH AND RESULTS: A total of 6,893 Korean parous women aged 30-50 years who participated in the Korean National Health and Nutrition Examination Survey were assessed for the association between breastfeeding and NAFLD. Duration of lactation was calculated by dividing the total lactation period by the number of breastfed children. NAFLD was defined by the hepatic steatosis index. Of 6,893 women, 1,049 (15.2%) had NAFLD. Prevalence of NAFLD was 18.3%, 14.3%, 12.3%, 14.4%, and 15.8% in women with a breastfeeding period of <1, ≥1-<3, ≥3-<6, ≥6-<12, and ≥12 months, respectively. In a fully adjusted model, breastfeeding (≥1 month) was associated with reduced NAFLD prevalence (OR, 0.67; 95% CI, 0.51-0.89) after adjusting for metabolic, socioeconomic, and maternal risk factors. Fully adjusted ORs (95% CI) decreased with an increase of breastfeeding duration: 0.74 (0.49-1.11), 0.70 (0.47-1.05), 0.67 (0.48-0.94), and 0.64 (0.46-0.89) for women with ≥1-<3, ≥3-<6, ≥6-<12, and ≥12 months of breastfeeding duration, respectively, compared to women with <1 month of breastfeeding duration. Such an association was also observed in all predefined subgroups without interaction. CONCLUSIONS: Breastfeeding showed a protective effect against NAFLD in later life of parous women, suggesting a maternal benefit of breastfeeding on NAFLD.

Incidence and risk factors for development of hepatocellular carcinoma at young age in patients with chronic hepatitis B.

BACKGROUND: Some young adults with chronic hepatitis B virus (HBV) infection might be at high risk for hepatocellular carcinoma (HCC), enough to justify regular HCC surveillance despite the young age of the patients. However, ways to identify at-risk individuals who may benefit from HCC surveillance need further evaluations. METHODS: A hospital-based retrospective cohort of 2757 chronic HBV mono-infected young adults (median age: 34 years, males 66%) were analyzed. The primary outcome was young-onset HCC, defined as a diagnosis made under 40 years of age. We calculated the HCC incidence/1000 person-years in the overall cohort and pre-defined subgroups of patients assessed the independent risk factors that can be used to identify surveillance targets. RESULTS: The HCC incidence was low (2.55/1000 person-years) in the overall cohort. However, the HCC incidence varied widely according to baseline characteristics: lowest among young adults with FIB-4 ≤ 0.70 (0.17/1000 person-years) and highest in young adults with radiological cirrhosis (30.7/1000 person-years). In multivariable analysis, radiological cirrhosis, the FIB-4 index, and serum HBV DNA level were independent factors associated with HCC development at a young age. Performance for prediction of young-onset HCC in radiological cirrhotic patients showed the highest specificity but sensitivity was <70%. Combination with FIB-4 index and HBV DNA levels increased sensitivity to 90%. CONCLUSION: Risk stratification using FIB-4 index, HBV DNA levels, and either combining radiological cirrhosis or gender and AFP levels would be helpful to stratify young patients who would and would not benefit from regular HCC surveillance.

Imaging features of hepatobiliary MRI and the risk of hepatocellular carcinoma development.

OBJECTIVE: This study aimed to determine whether hepatocellular carcinoma (HCC) risk and time to HCC development differ according to hepatobiliary magnetic resonance imaging (MRI) findings among people at risk for developing HCC. MATERIALS AND METHODS: A total of 199 patients aged 40 years or older with liver cirrhosis or chronic liver disease who underwent gadoxetic acid-enhanced hepatobiliary MRI between 2011 and 2015 were analyzed. An independent radiologist retrospectively reviewed MRI findings, blinded to clinical information, and categorized them into low-risk features, high-risk features and high-risk nodules. High-risk features were defined as liver cirrhosis diagnosed by imaging. High-risk nodules were defined as LR-3 or LR-4 nodules based on LI-RADS version 2018. The primary outcome was development of HCC within 5-year of MRI evaluation. RESULTS: HCC was diagnosed in 28 patients (14.1%). HCC development was null for those with low-risk features (n = 84). The cumulative incidence rates of HCC were 0%, 2.3%, 13.4% and 22.1% at 1-, 2-, 3- and 5-year for those with high-risk features (n= 64), and were 19.1%, 31.8%, 37.3% and 46.7% at 1-, 2-, 3- and 5-year for those with high-risk nodules (n= 51). Among 28 patients developed HCC, the median time from baseline MRI to HCC diagnosis was 33.1 months (interquartile range: 25.9-46.7 months) for high-risk feature group, and 17.3 months (interquartile range: 6.2-26.5 months) for high-risk nodule group. CONCLUSIONS: HCC risk and time to HCC development differ according to baseline hepatobiliary MRI findings, indicating that hepatobiliary MRI findings can be used as biomarkers to differentiate HCC risk.

Clinical Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients with Undetectable Serum HBV DNA Levels.

BACKGROUND AND AIMS: Some hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients show undetectable serum HBV DNA levels at HCC diagnosis. The risk of HBV reactivation and its impact on clinical outcomes are not well-unknown. METHODS: This retrospective cohort study included a total of 985 HBV-related HCC patients with undetectable serum HBV DNA levels (< 12 IU/mL) at HCC diagnosis (112 were antiviral treatment (AVT)-naïve; 873 were receiving AVT). Incidence and risk factors for HBV reactivation (re-detection of HBV DNA in serum) during follow-up, as well as its association to overall survival, were assessed. RESULTS: During a median of 33.4 months of follow-up (range: 0.2-124.2 months), HBV reactivation was observed in 279 patients. HBV reactivation rate was significantly lower for patients receiving AVT than AVT-naïve patients (three-year cumulative incidence rate: 27.3% versus 56.0%; P < 0.001). In multivariable-adjusted analysis, the risk of HBV reactivation was lower for those receiving AVT compared to AVT-naïve patients (adjusted hazard ratio: 0.39, 95% confidence interval: 0.29-0.54). Overall survival was significantly lower for those experiencing HBV reactivation than those who did not (71.5% and 85.7% at five-year) and was associated with higher risk of overall mortality (adjusted hazard ratio: 5.15, 95% confidence interval: 3.60-7.38). CONCLUSION: More than half of AVT-naïve patients experienced HBV reactivation within three years, which was associated with increased risk of overall mortality. The risk of HBV reactivation was lower for those receiving AVT, suggesting that prompt AVT needs to be considered for AVT naïve HBV-related HCC patients with undetectable HBV DNA levels.

Efficacy of entecavir versus tenofovir in preventing hepatocellular carcinoma in patients with chronic hepatitis B with maintained virologic response.

BACKGROUND & AIMS: Several studies suggested that efficacy of tenofovir in reducing the risk of the development of hepatocellular carcinoma (HCC) might be better than that of entecavir. It remains unknown whether a change in therapy can further reduce the risk of HCC in patients receiving entecavir therapy and achieved goal of antiviral therapy, a maintained undetectable hepatitis B virus (HBV) DNA level in the serum. METHODS: A total of 1336 treatment-naïve chronic HBV mono-infected adult patients, who started entecavir or tenofovir treatment and achieved a maintained virologic response during follow-up were analysed. RESULTS: During a median 4.4 years of follow-up (range, 1.0-7.4 years) after achieving virologic response, 99 patients developed HCC. The 5-year cumulative HCC incidence rate was 7.3% and 6.3% for the entecavir and tenofovir groups, respectively, with similar risk of HCC between the two groups (adjusted HR, 0.82; 95% CI, 0.52-1.29; p = 0.3). The risk of HCC was similar in the propensity score-matched cohort (HR, 1.02; 95% CI, 0.68-1.52; p = 0.94) and inverse probability treatment weighting analysis (HR, 1.11; 95% CI, 0.74-1.66; p = 0.62). In the subgroup analysis, HCC risk was similar between the two drugs in both patients with and without cirrhosis. DISCUSSION: In patients showing maintained virologic response, no difference in the risk of HCC between entecavir and tenofovir was observed. This indicates entecavir might be as effective as tenofovir in the prevention of HCC among those patients and suggest that a change in therapy in anticipation of further reducing the risk of HCC might not be necessary for patients receiving entecavir and showing virologic response.

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

BACKGROUND AND AIMS: Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. APPROACH AND RESULTS: A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow-up period were defined as statin users (n = 713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time-dependent covariates. During a median follow-up of 7.2 years (min-max: 0.5-9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio = 0.36, 95% confidence interval: 0.19-0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose-dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31-1.29]; 0.51 [0.21-1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28-365, 366-730, 731-1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. CONCLUSION: Statin use was associated with a reduced risk of HCC development in chronic HBV-infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation.

Prognosis of hepatocellular carcinoma patients diagnosed under regular surveillance: potential implications for surveillance goal.

AIMS: The goal of hepatocellular carcinoma (HCC) surveillance is to diagnose cancer at an early stage when treatment is likely to provide the best outcome and thereby, reduce mortality. However, no specific criteria define the 'early stage' for tumors diagnosed under HCC surveillance. We aimed to analyze factors that determined the outcome of HCC patients diagnosed under regular surveillance, to find out how early it is necessary to detect tumors during surveillance. METHODS: A retrospective cohort of 874 HCC patients with preserved liver function (Child-Pugh A) who were diagnosed under regular HCC surveillance at Samsung Medical Center from 2014 to 2016 and did not receive liver transplantation as an initial treatment were analyzed. The primary outcome was overall survival (OS). RESULTS: Tumor size, presence of vascular invasion, albumin-bilirubin grade, and initial treatment modality were independent factors for OS in multivariable analysis. When categorized according to the tumor size, the risk of mortality increased for tumors of > 3 cm, while tumors of 2-3 cm showed similar mortality risks as tumors of ≤2 cm. When categorized according to the tumor factors, curative-intent treatment (resection or ablation) can be applied to 84.5% with excellent outcomes (5-year OS rate, 93.4%), for tumors of ≤3 cm without vascular invasion. CONCLUSIONS: When tumors of ≤3 cm were detected and had no vascular invasion, curative-intent treatment was applied for most patients and showed excellent OS. This finding suggests that to detect tumors of <3 cm without vascular invasion may be considered as the goal of HCC surveillance.

Different Performance of Liver Stiffness Measurement According to Etiology and Outcome for the Prediction of Liver-Related Events.

BACKGROUND/AIMS: Liver stiffness measurement (LSM) by transient elastography (TE) has shown promising results for prediction of hepatocellular carcinoma (HCC) and hepatic decompensation in patients with chronic liver disease (CLD). However, whether prognostic performance of TE differs according to etiology or type of outcome remains further clarification. METHODS: Performance of LSM for the prediction of HCC and hepatic decompensation was analyzed in a cohort of 4026 patients with asymptomatic CLD. RESULTS: During median 4.5 years of follow-up (range 3.0-6.2 years), liver-related events (LRE) were observed in 196 patients (166 with HCC, 45 with hepatic decompensation, and 15 with both). In the multivariate analysis, LSM was independent factor associated with LRE and showed high AUROC (0.78). When stratified by type of outcome and etiology of liver disease, LSM showed high AUROC for the prediction of HCC for patients with non-viral hepatitis (0.89), while it showed relatively low AUROC for the prediction of HCC for patients with viral hepatitis (0.75). For the prediction of hepatic decompensation, LSM showed high AUROC for patients with both viral- and non-viral hepatitis (0.90, 0.90, respectively). CONCLUSIONS: LSM showed powerful prognostic role for the prediction of LRE in patients with CLD. Notably, HCC risk was not negligible in patients with viral hepatitis who showed LSM value < 10 kPa, indicating watchful attention for HCC is still needed for viral hepatitis patients with low LSM.

Long-term hepatitis B surface antigen (HBsAg) kinetics during entecavir treatment in Korean patients-Functional cure unlikely.

The aim of this study was to investigate the on-treatment kinetics of quantitative HBsAg during entecavir therapy to predict the treatment period needed to achieve functional cure. From a cohort of 1009 CHB treatment-naïve patients who were started on entecavir, the kinetics of quantitative HBsAg decline was assessed in 410 patients by a linear mixed model. The difference in the kinetics of quantitative HBsAg was determined based on the HBeAg positivity, HBeAg seroclearance and presence of baseline liver cirrhosis. Among the 410 patients, 213 patients (52.0%) were HBeAg-positive and 217 patients (66.1%) were male with a median age of 48 years. During a median follow-up of 53.5 months, the quantitative HBsAg level showed a slow but consistent decrease. The expected log qHBsAg levels as a function of time during entecavir treatment in HBeAg(+) and HBeAg(-) patients were 3.4773-0.0039 × Months and 3.1853-0.0036 × Months, respectively. The estimated time to clearance of quantitative HBsAg in our study was greater than 74.1 years in HBeAg-positive patients and 73.5 years in HBeAg-negative patients. The calculated time to achieve functional cure is lifelong without regard to HBeAg seroclearance or presence of liver cirrhosis. The mathematical modelling from a long-term follow-up of chronic hepatitis B patients on entecavir shows that HBsAg clearance requires decades of treatment. Thus, lifelong therapy is inevitable in entecavir-treated patients to achieve functional cure.

Hepatitis B reactivation after kidney transplantation in hepatitis B surface antigen-negative, core antibody-positive recipients.

Nowadays, intensive immunosuppressive therapy including rituximab is commonly used prior to kidney transplantation (KT), raising concerns over hepatitis B virus (HBV) reactivation among hepatitis B surface antigen (HBsAg)-negative and anti-hepatitis B core (HBc)-positive KT recipients. Recent practice guidelines suggested watchful monitoring or antiviral prophylaxis for the first 6-12 months, the period of maximal immunosuppression. However, the actual risk for HBV reactivation, and whether short-term antiviral therapy in the early period is necessary, remains unclear. A total of 449 HBsAg-negative and anti-HBc-positive KT recipients were analysed for HBV reactivation. During a median follow-up of 6.7 (interquartile range: 4.2-9.4) years, HBV reactivation was observed in 9 patients (2.0%). The median time of HBV reactivation from KT was 2.8 years (range: 1.4-11.5 years), with cumulative incidence rates of 0%, 1% and 2% for 1, 3 and 5 years, respectively. There were no severe adverse outcomes, including liver transplantation or mortality related to HBV reactivation. The risk of HBV reactivation was not high, even in anti-HBs-negative patients (n = 60, 4% at 5 years), ABO mismatch (n = 92, 4% at 5 years), use of rituximab (n = 66, 3% at 5 years) or plasmapheresis (n = 17, 7% at 5 years), and acute rejection (n = 169, 3% at 5 years). In conclusion, the HBV reactivation risk was not high and the time of detection was not clustered in the early post-KT period. Our findings favour continued watchful monitoring over antiviral prophylaxis in the early period.

Hepatitis B virus DNA levels and overall survival in hepatitis B-related hepatocellular carcinoma patients with low-level viremia.

BACKGROUND AND AIM: Clinical course of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients presenting with low-level viremia (LLV) is unclear. METHODS: A total of 565 HBV-related HCC patients with LLV (detectable but HBV DNA ≤ 2000 IU/mL) at the time of HCC diagnosis were analyzed. Based on patterns of HBV DNA levels during follow-up, patients were categorized into three groups: maintained virologic remission (MVR), LLV, and flare. Overall survival was compared between those three groups. RESULTS: During a median 4.5 years of follow-up, 33% showed MVR, 39% showed LLV, and 28% experienced flare. The overall survival differed between MVR, LLV, and flare groups (5-year overall survival: 74.3%, 67.3%, and 61.7%, respectively, 0.015). The patterns of HBV DNA levels were independent factors associated with overall survival, along with age, antiviral treatment, Barcelona clinic liver cancer stage, and initial treatment modality. Flare group showed increased risk of mortality (adjusted hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.15-2.55) compared with MVR group, while the risk was statistically marginal for the LLV group (adjusted HR 1.39, 95% CI 0.95-2.04). During follow-up, 183 patients (32.4%) newly started antiviral therapy (AVT) at LLV. Flare risk was significantly lower among patients who started AVT at LLV compared with those who did not (adjusted HR 0.26, 95% CI 0.17-0.38). CONCLUSIONS: Among HBV-related HCC patients with LLV, flare was frequent during follow-up and was associated with poorer overall survival compared with MVR group. Prospective studies that address whether inducing MVR by early AVT improves patient outcome are warranted.

Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment.

The long-term clinical impact of low-level viremia (LLV; <2,000 IU/mL) is not well understood. As a result, it is unclear whether the development of LLV during entecavir monotherapy requires a change in therapy. A retrospective cohort of 875 treatment-naive chronic hepatitis B virus (HBV) monoinfected patients (mean age 47.7 years, male = 564 [65.5%], cirrhosis = 443 [50.6%]) who received entecavir monotherapy were analyzed for the development of hepatocellular carcinoma (HCC). The HCC risk was compared between patients who maintained virological response (MVR), defined by persistently undetectable HBV DNA (<12 IU/mL), and patients who experienced LLV, defined by either persistent or intermittent episodes of <2,000 IU/mL detectable HBV DNA. During a median 4.5 years of follow-up (range 1.0-8.7 years), HCC was diagnosed in 85 patients (9.7%). HCC developed more frequently in patients who experienced LLV than MVR (14.3% versus 7.5% at 5 years, P = 0.015). The hazard ratio comparing those with LLV to MVR was 1.98 (95% confidence interval = 1.28-3.06, P = 0.002, adjusted for age, sex, hepatitis B e antigen, baseline HBV DNA levels, and cirrhosis). Among patients with cirrhosis, those with LLV exhibited a significantly higher HCC risk than those with MVR (HCC incidence rate at 5 years 23.4% versus 10.3%, adjusted hazard ratio = 2.20, 95% confidence interval 1.34-3.60; P = 0.002). However, for patients without cirrhosis, there was no significant difference in the HCC risk between LLV and MVR. CONCLUSION: LLV observed during entecavir monotherapy was associated with a higher risk of HCC, especially for those with cirrhosis, indicating that LLV during potent antiviral therapy is consequential. (Hepatology 2017;66:335-343).

Validation of the Baveno VI and the expanded Baveno VI criteria to identify patients who could avoid screening endoscopy.

BACKGROUND & AIMS: The Baveno VI and the expanded Baveno VI criteria were proposed to help identify patients who could safely avoid screening endoscopies for clinically significant varices among patients with compensated advanced chronic liver disease. However, these criteria require cross-validation, especially in Asian populations where the aetiologies of liver disease are different. METHODS: A total of 1035 patients, including 282 patients with compensated advanced chronic liver disease of different aetiology, were analysed. The compensated advanced chronic liver disease was defined by liver stiffness measurement ≥10 kPa, Child-Pugh class A and absence of prior liver decompensation. High-risk varix was defined as a grade ≥2 oesophageal varix, any varix with a red colour sign or gastric varices. RESULTS: High-risk varixs were present in 19.5% (55/282 patients) with compensated advanced chronic liver disease. Among compensated advanced chronic liver disease patients, the expanded criteria could spare more endoscopies (51.7%) than the original criteria (27.6%). However, the expanded criteria missed a greater number of high-risk varixs (6.8%) than the original criteria (3.8%). When stratified according to liver disease aetiology, the negative predictive values for the original Baveno VI criteria were 0.92, 1.00, 1.00 and 1.00, and the negative predictive values for the expanded criteria were 0.92, 0.96, 0.92 and 0.93 for hepatitis B, hepatitis C, alcohol and non-alcoholic fatty liver disease, respectively. High-risk varixs were rarely detected in patients without compensated advanced chronic liver disease (1.1%, 8/753 patients). CONCLUSIONS: In this Asian cohort study, the Baveno VI criteria were able to identify who could safely avoid screening endoscopy. The expanded Baveno VI criteria could spare more endoscopies but also could increase the odds of missing a high-risk varix.

Treatment for occult hepatocellular carcinoma: does it offer survival advantages over symptom-driven treatment?

OBJECTIVE: In order to claim a benefit of screen-based diagnosis for asymptomatic individuals, treatment of occult disease needs to offer survival advantages compared to the treatment of symptomatic disease, yet information on this issue is scarce with regard to hepatocellular carcinoma (HCC) screening. METHODS: A total of 3353 treatment-naïve, consecutive, newly diagnosed HCC patients [age: 57.9 ± 10.3, male: 2,689 (80.2%), hepatitis B virus: 2555 (76.2%)], diagnosed between 2010 and 2013 were analyzed. Data on the mode of detection was prospectively collected at the time of HCC diagnosis and was used to group patients into occult or symptomatic cases. RESULTS: Overall, 643 (19.2%) patients were symptomatic cases. The proportion of patients undergoing resection, radiofrequency ablation or transplantation were lower in symptomatic cases than occult cases (20.8 vs. 56.2%, p < .001). Survival was better in occult cases than symptomatic cases (71.2 vs. 30.4% at three-years, p < .001), with a multivariable-adjusted hazard ratio of 1.40 (95% confidence interval (CI), 1.24-1.58). When stratified by tumor stage, a survival benefit was not observed for patients diagnosed at modified International Union Against Cancer (mUICC) stage I, but presenting symptoms were diverse and nonspecific. In a statistical model adjusting for potential lead-time bias, the association between overall survival and the mode of detection was markedly attenuated and was no longer significant when the treatment modality was included in the model (hazard ratio, 0.94; 95% CI, 0.82-1.07). CONCLUSION: Treatment of occult disease offered a survival benefit to patients over symptomatic cases. These data support screening practices for asymptomatic individuals to diagnose occult HCC.

Novel Albumin-Bilirubin Grade-Based Risk Prediction Model for Patients with Hepatocellular Carcinoma Undergoing Chemoembolization.

BACKGROUND: Recently, albumin-bilirubin (ALBI) grade has been suggested as a better surrogate for hepatic functional reserve for patients with hepatocellular carcinoma (HCC). AIMS: We developed and validated a novel prediction model to predict outcome for HCC patients who underwent transcatheter arterial chemoembolization (TACE) as a first-line therapy. METHODS: From a multivariate Cox regression model for overall survival, five objective variables (ALBI grade), the Barcelona clinic liver cancer (BCLC) stage, response after the first TACE session, Alpha-fetoprotein level, and sex were chosen and the ABRAS score was developed from the derivation cohort (n = 476) and scored to generate an 8-point risk prediction model. The model's prognostic performance was assessed in the randomly assigned internal validation set (n = 475) and external validation set (n = 243). RESULTS: The ALBI grade was able to stratify patient survival within the same Child-Pugh class. The time-dependent area under receiver operating characteristics curves (AUROCs) for overall survival at 1 and 3 years were 0.78 and 0.73 in the training set, 0.78 and 0.71 in the internal validation set, and 0.70 and 0.65 in the external validation set, respectively. When stratified by BCLC stage, ABRAS score at a cutoff point of more than 3, 4, and 5 for BCLC stage 0/A, B, and C could identify subset of patients with dismal prognosis. CONCLUSION: ABRAS score was useful in estimating prognosis for patients who underwent TACE as a first-line therapy. This score can be useful in planning and guiding treatment strategies with TACE, which warrants prospective validation.

Proton pump inhibitors do not increase the risk for recurrent spontaneous bacterial peritonitis in patients with cirrhosis.

BACKGROUND AND AIM: The present study aimed to assess the real impact of proton pump inhibitor (PPI) use on incidence of recurrent spontaneous bacterial peritonitis (SBP) in a homogenous population composed of cirrhotic patients with a previous SBP where differences related with SBP incidence between PPI users and non-users are less likely to exist. METHODS: This retrospective cohort study enrolled 307 cirrhotic patients taking diuretics for ascites control and had a previous SBP. Patients who took any PPI for at least 1 week prior to a second SBP were included in the PPI group. The incidence of a second SBP was a primary outcome and was compared between PPI group and non-PPI group before and after propensity score matching. Risk factors for a second SBP were investigated by multivariate analysis. RESULTS: Second SBP occurred in 17 patients (29.3%) during mean 52.1 ± 5.2 months of PPI group and in 60 patients (24.1%) during mean 61.9 ± 4.8 months of non-PPI group, which did not differ (P = .185). In the matched cohort, second SBP similarly occurred in both groups [29.3% of PPI group vs 26.8% of non-PPI group (P = .271)]. According to the multivariate analysis, Child-Pugh score was the only significant risk factor for a second SBP (hazard ratio 1.68, 95% confidence interval, 1.13-2.50, P = .001). Isolated bacteria and clinical outcomes such as of mortality, presence of sepsis, and hospital stay did not differ between the two groups in the matched cohort. CONCLUSION: Proton pump inhibitor use is not a risk factor for recurrent SBP in cirrhotic patients.

Insulin resistance and the risk of hepatocellular carcinoma in chronic hepatitis B patients.

BACKGROUND AND AIM: We analyzed whether insulin resistance (IR) assessed by homeostasis model assessment (HOMA2-IR) index can stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B virus (HBV) infection. METHODS: A retrospective cohort of 1696 chronic HBV-infected patients (age: 50.0 ± 7.8 years, men = 964 [56.8%]) who underwent detailed health checkup program including C-peptide and fasting blood glucose measurement and followed up for more than a year were analyzed. RESULTS: During a median follow-up of 5.0 years (range, 1.0-10.5 years), 24 patients (1.4%) developed HCC. The HCC incidence rate was higher for patients with higher HOMA2-IR value than those with lower HOMA2-IR value (1.7% vs 0.5% for HOMA2-IR >1.200 vs ≤1.200, P = 0.009). HOMA2-IR was a significant factor associated with HCC development in multivariable-adjusted model (HR [95% CI]: 3.25 [1.13-9.31], adjusted for age, sex, cirrhosis, and HBV DNA levels). The association between HOMA2-IR and HCC was markedly attenuated and became no longer statistically significant (HR [95% CI]: 1.93 [0.57-6.51]) when further adjusted for obesity, hypertension, and diabetes. In subgroup analysis, HOMA2-IR value was an independent factor associated with HCC in patients without overt metabolic abnormalities (hypertension, diabetes, and metabolic syndrome) but not for those with overt metabolic abnormalities. CONCLUSION: Insulin resistance assessed by HOMA2 was associated with the risk of HCC, indicating that HOMA2-IR can be a useful tool for stratifying the risk of HCC in chronic HBV-infected patients, particularly in patients without overt metabolic abnormalities.

Liver Function Assessment Using Albumin-Bilirubin Grade for Patients with Very Early-Stage Hepatocellular Carcinoma Treated with Radiofrequency Ablation.

BACKGROUND/AIM: Assessment of liver function is essential for management of hepatocellular carcinoma (HCC). Recently, albumin-bilirubin (ALBI) grade has been reported as a useful tool for assessing hepatic reserve in patients with HCC. The objective of this study was to determine whether ALBI grade could be used to predict the overall survival of very early-stage HCC patients treated with radiofrequency ablation (RF ablation). METHODS: A cohort of 368 patients with very early-stage HCC treated with RF ablation was retrospectively analyzed. The overall survival and recurrence-free survival were calculated in groups classified by ALBI grade and Child-Pugh score. RESULTS: Overall survival of patients with ALBI grade 1 was better than that of patients with ALBI grade 2 (5-year survival rate 88.5 vs. 73.8%, P < 0.001). In multivariable-adjusted model, ALBI grade was found to be an independent factor associated with overall survival (hazard ratio 2.44; 95% confidence interval 1.43-4.15). ALBI grade was able to stratify patients with distinct overall survival among patients within the same Child-Pugh score (5-year survival rate for Child-Pugh score 5: 88.5 vs. 76.6%, P = 0.002; for Child-Pugh score 6: 88.9 vs. 70.1%, P = 0.064). In contrast, Child-Pugh score was unable to stratify patients with distinct overall survival within the same ALBI grade. CONCLUSIONS: Among patients with very early-stage HCC treated with RF ablation, ALBI grade was a good stratifying biomarker. ALBI grade was better tool for assessing liver function than Child-Pugh score for very early-stage HCC treated with RF ablation.

Short-Term Outcomes of Totally Laparoscopic Central Hepatectomy and Right Anterior Sectionectomy for Centrally Located Tumors: A Case-Matched Study with Propensity Score Matching.

BACKGROUND: Recent advances in technology and accumulation of surgical experience have expanded the indications for laparoscopic liver resection (LLR). However, compared to open liver resection (OLR), the feasibility of laparoscopic anatomical liver resection for centrally located tumor (CLT) has not been clearly established. The aim of our study was to assess the feasibility and safety of laparoscopic anatomical major liver resection for CLT. METHODS: From April 2011 to March 2016, 20 cases of anatomical LLR and 86 cases of OLR for CLTs such as central hepatectomy (CH) and right anterior sectionectomy (RAS) were performed at a single institution. We performed one-to-one propensity score matching and analyzed short-term outcomes between the LLR (n = 20) and OLR (n = 20) groups. RESULTS: Among 20 cases in the LLR group, two cases underwent open conversion due to common bile duct injury and anatomical distortion, respectively. There were no statistically significant difference between the LLR and OLR groups regarding clamping time of the Pringle maneuver (p = 0.502), blood loss (p = 0.746), surgical margin (p = 0.198), or length of hospital stay (p = 0.110). However, surgical time was significantly longer in the LLR group than in the OLR group (388 vs 268 min; p < 0.001). There were no significant differences between the two groups with regard to morbidity rate or mean comprehensive complication index (p = 0.716 and p = 0.819, respectively). CONCLUSION: Total anatomical LLR can be performed safely in selected CLT patients by experienced surgeons. Laparoscopic CH or RAS appears feasible with non-inferior perioperative outcomes compared to OLR.

Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated cirrhosis patients with low viral load.

UNLABELLED: Controversy exists about whether antiviral therapy (AVT) should be recommended for compensated cirrhosis patients with chronic hepatitis B virus (HBV) infection and detectable, but low, serum HBV-DNA levels. A retrospective cohort of 385 treatment-naïve, HBV-related compensated cirrhosis patients (mean age: 51.1 ± 9.7 years; 66% male) with low HBV-DNA levels (<2,000 IU/mL) was assessed for the development of hepatocellular carcinoma (HCC). During a median of 5.6 years of follow-up, HCC had developed in 37 (9.6%) patients. The 5-year cumulative HCC incidence rate was 2.2%, 8.0%, and 14.0% for patients with undetectable HBV DNA (<12 IU/mL), low HBV-DNA levels plus normal alanine aminotransferase (ALT) levels, and low HBV-DNA levels plus elevated ALT levels at baseline (P = 0.011). During follow-up, 71 patients maintained undetectable HBV-DNA levels, and 126 experienced HBV-DNA elevation over 2,000 IU/mL. AVT was initiated in 77 patients. In patients without AVT, the 5-year cumulative HCC incidence rates were 13.3%, 8.8%, and 1.4% for those who experienced HBV-DNA elevation, those who maintained detectable, but low, HBV-DNA levels, and those who maintained undetectable HBV-DNA levels, respectively. The 5-year cumulative HCC incidence rate was 5.9% for patients who started AVT; longer AVT duration and longer complete virological response (<12 IU/mL) duration was associated with lower HCC risk. CONCLUSION: Compensated cirrhosis patients with detectable, but low, viral load were not at low risk for HCC, and AVT was associated with lower HCC risk, suggesting that prompt AVT should be considered for these patients.