Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS: We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ±â€¯dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION: Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY: There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

FACT-Hep increases the accuracy of survival prediction in HCC patients when added to ECOG Performance Status.

BACKGROUND AND AIM: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) is a strong predictor of survival for patients with hepatocellular carcinoma (HCC), and is used with liver function and tumour burden in the Barcelona Clinic Liver Cancer (BCLC) staging system. This work assesses whether the health-related quality of life (HRQL), measured by the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire, discriminates HCC patients in terms of survival and adds prognostic information to ECOG PS. METHODS: A total of 242 patients participating in the prospective Bern HCC Cohort at the University Hospital Bern were analysed. The relationship between FACT-Hep and sociodemographic and clinical factors, including survival, were assessed. An analysis on treatment subgroups was performed using Kaplan-Meier curves and Long-Rank test. Additionally, the ability to predict overall survival was compared between the ECOG PS and FACT-Hep total and subscales using Nagelkerke pseudo-R2 . RESULTS: FACT-Hep subscales were significantly worse in females and in patients with limited liver function. FACT-Hep total and all subscales, except the social/family well-being subscale showed significant differences between ECOG PS groups and were significant predictors of survival. ECOG PS groups, followed by the functional well-being subscale, were the best at predicting survival. In the resection subgroup, significant differences in OS regarding to HRQL were found. When adding the functional well-being subscale to ECOG PS, the accuracy of the survival prediction was significantly increased. CONCLUSION: HRQL assessed by the FACT-Hep questionnaire is a reliable prognostic predictor of survival for patients with HCC and it adds prognostic information to the ECOG PS.

Effect of smoking on survival of patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. METHODS: Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. RESULTS: Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, P<.001) and remained independently predictive when adjusted for confounding variables. CONCLUSIONS: This study shows that smoking is an independent predictor of survival in hepatitis B virus/hepatitis C virus-infected patients with hepatocellular carcinoma.

A new method for estimating patient body weight using CT dose modulation data.

BACKGROUND: Body weight (BW) is a relevant metric in emergency care. However, visual/physical methods to estimate BW are unreliable. We have developed a method for estimating BW based on effective mAs (mAseff) from computed tomography (CT) dose modulation. METHODS: The mAseff of CT examinations was correlated with the BW of 329 decedents. Linear regression analysis was used to calculate an equation for BW estimation based on the results of decedents with a postmortem interval (PMI) < 4 days (n = 240). The equation was applied to a validation group of 125 decedents. Pearson correlation and t-test statistics were used. RESULTS: We found an overall strong correlation between mAseff and BW (r = 0.931); r values ranged from 0.854 for decedents with PMI ≥ 4 days to 0.966 for those with PMI < 4 days; among the latter group, r was 0.974 for females and 0.960 for males and 0.969 in the presence and 0.966 in the absence of metallic implants (all correlations with p values < 0.001). The estimated BW was equal to 3.732 + (0.422 × mAseff) - (3.108 × sex index), where the sex index is 0 for males and 1 for females. The validation group showed a strong correlation (r = 0.969) between measured BW and the predicted BW, without significant differences overall (p = 0.119) as well as in female (p = 0.394) and in male decedents (p = 0.196). No outliers were observed. CONCLUSIONS: CT dose modulation is a rapid and reliable method for BW estimation with potential use in clinical practice, in particular in emergency settings.

Surveillance for Hepatocellular Carcinoma in Patients with NASH.

European and American guidelines recommend surveillance for hepatocellular carcinoma (HCC) by performing ultrasonography on a six-month basis on an at risk population, defined by presence of cirrhosis. HCC, due to non-alcoholic steatohepatitis (NASH), is rising. Patients with NASH have a high risk of developing HCC and, therefore, have to be enrolled in a screening program. One of the challenges with NASH-induced HCC is that half of the cases arise in non-cirrhotic patients. There is a need to identify those patients in order to screen them for HCC. The obesity of these patients is another challenge, it makes ultrasound screening more difficult. Other radiological methods, such as computer tomography (CT) scans or magnetic resonance imaging (MRI), are available, but the surveillance program would no longer be cost-effective. There is a need to prospectively acquire information on cohorts of patients with NASH in order to improve the tools we have to diagnose early tumors in these patients.

Assessment of the Hong Kong Liver Cancer Staging System in Europe.

BACKGROUND & AIMS: European and American guidelines have endorsed the Barcelona Clinic Liver Cancer (BCLC) staging system. The aim of this study was to assess the performance of the recently developed Hong Kong Liver Cancer (HKLC) classification as a staging system for hepatocellular carcinoma (HCC) in Europe. METHODS: We used a pooled set of 1693 HCC patients combining three prospective European cohorts. Discrimination ability between the nine substages and five stages of the HKLC classification system was assessed. To evaluate the predictive power of the HKLC and BCLC staging systems on overall survival, Nagelkerke pseudo R2, Bayesian Information Criterion and Harrell's concordance index were calculated. The number of patients who would benefit from a curative therapy was assessed for both staging systems. RESULTS: The HKLC classification in nine substages shows suboptimal discrimination between the staging groups. The classification in five stages shows better discrimination between groups. However, the BCLC classification performs better than the HKLC classification in the ability to predict overall survival (OS). The HKLC treatment algorithm tags significantly more patients to curative therapy than the BCLC. CONCLUSIONS: The BCLC staging system performs better for European patients than the HKLC staging system in predicting OS. Twice more patients are eligible for a curative therapy with the HKLC algorithm; whether this translates in survival benefit remains to be investigated.

Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm.

BACKGROUND AND AIMS: The Barcelona Clinic Liver Cancer (BCLC) staging system is the algorithm most widely used to manage patients with hepatocellular carcinoma (HCC). We aimed to investigate the extent to which the BCLC recommendations effectively guide clinical practice and assess the reasons for any deviation from the recommendations. MATERIAL AND METHODS: The first-line treatments assigned to patients included in the prospective Bern HCC cohort were analyzed. RESULTS: Among 223 patients included in the cohort, 116 were not treated according to the BCLC algorithm. Eighty percent of the patients in BCLC stage 0 (very early HCC) and 60% of the patients in BCLC stage A (early HCC) received recommended curative treatment. Only 29% of the BCLC stage B patients (intermediate HCC) and 33% of the BCLC stage C patients (advanced HCC) were treated according to the algorithm. Eighty-nine percent of the BCLC stage D patients (terminal HCC) were treated with best supportive care, as recommended. In 98 patients (44%) the performance status was disregarded in the stage assignment. CONCLUSION: The management of HCC in clinical practice frequently deviates from the BCLC recommendations. Most of the curative therapy options, which have well-defined selection criteria, were allocated according to the recommendations, while the majority of the palliative therapy options were assigned to patients with tumor stages not aligned with the recommendations. The only parameter which is subjective in the algorithm, the performance status, is also the least respected.

Hepatocellular carcinoma and lifestyles.

The majority of hepatocellular carcinoma occurs over pre-existing chronic liver diseases that share cirrhosis as an endpoint. In the last decade, a strong association between lifestyle and hepatocellular carcinoma has become evident. Abundance of energy-rich food and sedentary lifestyles have caused metabolic conditions such as obesity and diabetes mellitus to become global epidemics. Obesity and diabetes mellitus are both tightly linked to non-alcoholic fatty liver disease and also increase hepatocellular carcinoma risk independent of cirrhosis. Emerging data suggest that physical activity not only counteracts obesity, diabetes mellitus and non-alcoholic fatty liver disease, but also reduces cancer risk. Physical activity exerts significant anticancer effects in the absence of metabolic disorders. Here, we present a systematic review on lifestyles and hepatocellular carcinoma.

Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: A Problem of Growing Magnitude.

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.