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Simple Summary: Emerging evidence suggests that altered gut microbiota composition has the potential to promote hepatocellular carcinoma development and progression. This review outlines the role of gut microbiota in causing hepatocellular carcinoma, investigates its value in improving the its outcome after early diagnosis, and summarizes the latest progress regarding its potential for hepatocellular carcinoma therapy. In recent decades, gut microbiota have received emerging attention regarding their integral role in chronic liver disease progression, given the anatomic connection and the gut–liver axis. Emerging evidence has indicated a complex link between gut microbiota and hepatocellular carcinoma. This review explores the pathophysiological crosstalk between gut dysbiosis and hepatocarcinogenesis. The metabolic and immunologic effects mediated by gut-microbiota-derived metabolites, such as bile acids, short-chain fatty acids, and alcohol, could impact the aberrant biological behavior of hepatocellular carcinoma. This review also investigates the value of gut microbiota as novel non-invasive diagnostic biomarkers for the early detection of hepatocellular carcinoma, and summarizes the changes in the gut microbiota spectrum in patients with liver cancer. The current literature and studies on the role of the gut microbiota as adjuvant agents in liver cancer immunotherapy are reviewed. [ABSTRACT FROM AUTHOR]

Background: The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. Objective: To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. Methods: A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model's performance. Results: The final CR model consisted of 5 independent predictors, including TPR-signature (p < 0.001), AFP (p = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification (p = 0.01), tumor location (p = 0.039), and arterial hyperenhancement (p = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60–3.69; p < 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. Conclusions: The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE. [ABSTRACT FROM AUTHOR]

Background: The Child-Turcotte-Pugh (CTP) score is a widely used and validated predictor of long-term survival in cirrhosis. However, the cutpoints for stratifying laboratory variables in CTP have never been validated.Objective: The objective of this study was to identify evidence-based cutpoints for the CTP laboratory subscores to improve its predictive capacity for transplant-free survival.Design: Retrospective observational study.Data Source: Using a cohort of 30,897 cirrhotic US Veteran patients with at least 5 years of follow-up, we performed Cox proportional hazard survival model iterations varying the upper and lower cutpoints for INR, total bilirubin and albumin CTP subscores. Cutpoints yielding the highest Harrell's C-statistics for concordance with transplant-free survival were incorporated into a modified CTP (mCTP) score. Validation of the mCTP was performed at multiple time frames within the follow-up period of the cohort and within subsets defined by disease etiology.Results: Modification of CTP cutpoints increased the Harrell's C-statistic for age- and gender-adjusted Cox proportional hazard models from 0.701 ± 0.002 to 0.709 ± 0.002 and the risk ratio per unit change from 1.49 (1.48-1.50) to 1.53 (1.52-1.54). The modified cutpoints showed superiority in predicting 5-year transplant-free survival in various disease etiology subgroups. A mCTP substituting serum creatinine for INR performed superiorly for predicting 5-year transplant-free survival.Conclusion: We propose an evidence-based recalibration of CTP score cutpoints that optimizes this model's capacity to predict transplant-free survival in patients with cirrhosis. The CTP score remains the best predictor of 5-year overall and transplant-free survival in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Background: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.Aim: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.Methods: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.Results: A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.Conclusions: As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a cancer with globally rising incidence. Growing evidence supports associations between metabolic syndrome and diabetes as well as obesity and HCC arising in patients with nonalcoholic fatty liver disease (NAFLD). This constitutes a problem of alarming magnitude given the rising epidemic of these conditions. The role of diabetes seems to be particularly important when associated with obesity or cirrhosis. Excess hepatic iron may be another potential risk factor for the development of NAFLD-associated HCC. In the context of NAFLD, HCC frequently develops in a not-yet cirrhotic liver. As there are no surveillance programs for these patients, diagnosis often occurs at a tumor stage beyond curative options. Clinical, tumor, and patient characteristics in NAFLD-associated HCC differ from other etiologies. Older age and cardiovascular comorbidities may limit treatment options further. The outcome in patients with NAFLD-associated early HCC is excellent and therefore aggressive treatment should be pursued in appropriate patients. Population-based prevention to reduce the culprit-NAFLD-early recognition through targeted surveillance programs in risk-stratified patients and effective treatment of HCC associated with NAFLD are urgently needed. In this review, the authors summarize the epidemiology, risk factors, features, and prevention of NAFLD-associated HCC. [ABSTRACT FROM AUTHOR]

Aims To determine the efficacy of motivational enhancement therapy (MET) on alcohol use in patients with the hepatitis C virus ( HCV) and an alcohol use disorder ( AUD). Design Randomized, single-blind, controlled trial comparing MET to a control education condition with 6-month follow-up. Setting Patients were recruited from hepatitis clinics at the Minneapolis, Minnesota and Portland, Oregon Veterans Affairs Health Care Systems, USA. Participants and Intervention Patients with HCV, an AUD and continued alcohol use ( n = 139) were randomized to receive either MET ( n = 70) or a control education condition ( n = 69) over 3 months. Measurements Data were self-reported percentage of days abstinent from alcohol and number of standard alcohol drinks per week 6 months after randomization. Findings At baseline, subjects in MET had 34.98% days abstinent, which increased to 73.15% at 6 months compared to 34.63 and 59.49% for the control condition. Multi-level models examined changes in alcohol consumption between MET and control groups. Results showed a significant increase in percentage of days abstinent overall ( F(1120.4) = 28.04, P < 0.001) and a significant group × time effect ( F(1119.9) = 5.23, P = 0.024) with the MET group showing a greater increase in percentage of days abstinent at 6 months compared with the education control condition. There were no significant differences between groups for drinks per week. The effect size of the MET intervention was moderate (0.45) for percentage of days abstinent. Conclusion Motivational enhancement therapy ( MET) appears to increase the percentage of days abstinent in patients with chronic hepatitis C, alcohol use disorders and ongoing alcohol use. [ABSTRACT FROM AUTHOR]

Background: Antiviral therapy for the hepatitis C virus (HCV) reduces all-cause and liver-related morbidity and mortality. Few studies are available from populations with multiple medical and psychiatric comorbidities where the impact of successful antiviral therapy might be limited. Aim: The purpose of this study was to determine the effect of sustained virologic response (SVR) on all-cause and liver-related mortality in a cohort of HCV patients treated in an integrated hepatitis/mental health clinic. Methods: This was a retrospective review of all patients who initiated antiviral treatment for chronic HCV between January 1, 1997 and December 31, 2009. Cox regression analysis was used to determine factors involved in all-cause mortality, liver-related events and hepatocellular carcinoma. Results: A total of 536 patients were included in the analysis. Median follow-up was 7.5 years. Liver and non-liver-related mortality occurred in 2.7 and 5.0 % of patients with SVR and in 17.8 and 6.4 % of patients without SVR. In a multivariate analysis, SVR was the only factor associated with reduced all-cause mortality (HR 0.47; 95 % CI 0.26-0.85; p = 0.012) and reduced liver-related events (HR 0.23; 95 % CI 0.08-0.66, p = 0.007). Having stage 4 liver fibrosis increased all-cause mortality (HR 2.50; 95 % CI 1.23-5.08; p = 0.011). Thrombocytopenia at baseline (HR 2.66; 95 % CI 1.22-5.79; p = 0.014) and stage 4 liver fibrosis (HR 4.87; 95 % CI 1.62-14.53; p = 0.005) increased liver-related events. Conclusions: Despite significant medical and psychiatric comorbidities, SVR markedly reduced liver-related outcomes without a significant change in non-liver-related mortality after a median follow-up of 7.5 years. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the United States population and 4% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation in the United States. Management of chronic HCV is aimed at halting disease progression, preventing cirrhosis decompensation, reducing the risk of HCC, and treating extrahepatic complications of the infection. As part of a comprehensive HCV management strategy, peginterferon alfa and ribavirin, along with the addition of a hepatitis C protease inhibitor therapy for many genotype 1-infected patients, are the current standard of care. Antiviral therapy should be provided to those individuals who are clinically stable, have moderate liver disease or compensated cirrhosis, and are motivated to pursue therapy. Many patients have comorbid medical and psychiatric conditions, which may affect their adherence to antiviral therapy or worsen while on antiviral therapy. To optimally manage hepatitis C and associated comorbidities, patients benefit from multidisciplinary teams that can provide HCV-specific care and treatment. Sustained virologic response is associated with 'cure' of chronic HCV, and results in improved liver disease outcomes and prolonged survival. [ABSTRACT FROM AUTHOR]

In 2005, a professional society issued a level I recommendation to use ultrasonography to screen the 3 million Americans with cirrhosis for hepatocellular carcinoma (HCC) every 6 months. This designation was based on a large randomized trial from China that reported a reduction in HCC deaths from screening in carriers of hepatitis B surface antigen. However, besides the difference in population, this trial did not report all deaths, excluded patients after randomization, and would almost certainly have found no significant difference if the cluster randomization had been accounted for in the analysis. Misplaced confidence in the Chinese trial has led many writers to accept the effectiveness of HCC screening as proven, making it more difficult to conduct the highquality randomized trials that are needed to ensure optimal patient care. [ABSTRACT FROM AUTHOR]

Intrahepatic portal-systemic venous shunt is defined as a communication between the portal and the systemic-venous circulation, measuring more than 1 mm in diameter and at least partially located inside the liver. This is a rare condition, and the etiopathogenesis is unclear. Of the various types, Type I, with patent paraumbilical veins, located in the liver, is commonly encountered in portal hypertension. Other types are much less common. Only 47 cases have been reported in the entire French and English literature. Shunts may be congenital or acquired. This report describes a case of portal-systemic encephalopathy due to a spontaneous large-caliber portal-hepatic venous shunt in the right lobe of the liver confirmed by percutaneous transhepatic portography and hepatic venous angiogram. The treatment with coil embolization was successful, and hepatic encephalopathy resolved postoperatively with normalization of ammonia level. The etiology of the shunt was unclear. Given the age of the patient, the shunt was thought to have developed spontaneously. [ABSTRACT FROM AUTHOR]

Intrahepatic portal–systemic venous shunt is defined as a communication between the portal and the systemic–venous circulation, measuring more than 1 mm in diameter and at least partially located inside the liver. This is a rare condition, and the etiopathogenesis is unclear. Of the various types, Type I, with patent paraumbilical veins, located in the liver, is commonly encountered in portal hypertension. Other types are much less common. Only 47 cases have been reported in the entire French and English literature. Shunts may be congenital or acquired. This report describes a case of portal–systemic encephalopathy due to a spontaneous large-caliber portal–hepatic venous shunt in the right lobe of the liver confirmed by percutaneous transhepatic portography and hepatic venous angiogram. The treatment with coil embolization was successful, and hepatic encephalopathy resolved postoperatively with normalization of ammonia level. The etiology of the shunt was unclear. Given the age of the patient, the shunt was thought to have developed spontaneously. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Screening for liver cancer: the rush to judgment," by Frank A. Lederle and Christine Pocha and a response by them to the same is presented.