The risk of #hepatocellular carcinoma in cirrhotic patients with hepatitis #C and sustained viral response: role of the treatment regimen
http://www.journal-of-hepatology.eu/article/S0168-8278(17)32429-7/fulltext

857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free receipt was associated with a significantly increased risk of HCC (HR: 2.48; P=0.021). However after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, P=0.744).

CONCLUSION

These findings suggest that the higher incidence of HCC following SVR with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se

Survival of children after liver #transplantation for #hepatocellular carcinoma
http://onlinelibrary.wiley.com/doi/10.1002/lt.24994/full

Hepatocellular carcinoma (HCC) in childhood differs from adult HCC as it is often associated with inherited liver disease. Survival analyses demonstrated a superior long-term survival of children with inherited liver disease when compared to children with HCC without inherited liver disease (HR:0.29; 95%CI:0.10-0.90; p=0.03) and adults with HCC with inherited liver disease (HR:0.27; 95%CI:0.06-1.25;p=0.09). There was no survival difference between adults with and without inherited disease (HR:1.05; 95%CI:0.66-1.66; p=0.84).

Conclusion: The potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings

Risk of posttransplant #hepatocellular carcinoma recurrence is greater in recipients with higher #platelet counts in living donor liver transplantation
http://onlinelibrary.wiley.com/doi/10.1002/lt.24961/abstract

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75 × 109/L were matched with 97 of 119 patients who had preoperative PLT >75 × 109/L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 109/L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow-up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio HR = 3.09; 95% confidence interval CI, 1.86-5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23-3.60; P =  0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR = 2.33; 95% CI, 1.36-4.01; P =  0.002) and multivariate analyses (HR = 1.90; 95% CI, 1.02-3.54; P =  0.04). Preoperative PLT had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation-based scores including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the inflammation-based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation

Liver #resection of #hepatocellular carcinoma in patients with portal #hypertension and multiple tumors
http://onlinelibrary.wiley.com/doi/10.1111/hepr.13047/abstract

Liver resection for hepatocellular carcinoma (HCC) has been recommended only for patients with a single tumor without portal hypertension. We aimed to validate this treatment strategy that is based on by the Barcelona Clinic Liver Cancer staging system The median overall and recurrence-free survival periods of patients in Group 1 (N= 695) were 8.5 years (95% confidence interval CI 6.6−9.0) and 2.4 years (2.2−2.7), respectively, and were significantly longer compared with those of patients in Group 2 (N = 197) (5.6 years 95% CI, 4.8−6.7, P = 0.001, and 1.9 years 1.6−2.1, P < 0.001). On multivariate analysis, the independent factors for overall survival were hepatitis C virus infection (HR 1.29 95% CI, 1.02−1.65, P = 0.032), multiple tumors (1.42 1.01−1.98, P = 0.040), and vascular invasion (1.66 1.31−2.10, P < 0.001). On the other hand, frequency of morbidities (23 3.3% patients vs 11 5.5% patients, P = 0.143) and mortalities (3 0.4% patients vs 2 1.0% patients, P = 0.305) was not significantly different between the two groups.

Conclusions
Patients with HCC with portal hypertension and/or multiple tumors could be the candidates for liver resection due to the safety of the procedure

Incidence and Risk Factors Associated with #Hepatocellular Carcinoma Surveillance #Failure


http://onlinelibrary.wiley.com/doi/10.1111/jgh.14108/abstract


At diagnosis, 50 (26.6%) HCC tumors were beyond the Milan criteria. In univariate analysis, Child-Pugh B at entry (p=0.03), development of complications of portal hypertension before tumor diagnosis (p=0.03) and failure to complete the prior screening round (p=0.02), Child-Pugh B/C (p=0.001) and AFP≥100 ng/ml (p=0.03) at diagnosis, were associated with failure. In multivariate analysis, only Child-Pugh B/C (HR, 3.18; 95% CI, 1.66–6.10, p<0.001) and AFP≥100 ng/ml, both at diagnosis (HR, 2.80; 95% CI, 1.37–5.71, p=0.005), were independently associated with failure. Survival was higher among patients with tumors within the Milan criteria than those with program failure (33.9 vs. 7.6 months, p<0.001).


Conclusions

Approximately 25% of HCC cases diagnosed among patients included in a surveillance program were beyond the Milan criteria. Child-Pugh B/C and AFP≥100 ng/ml at diagnosis were associated with program failure. However, Child-Pugh B at entry and development of liver-related complications during follow-up can be early predictors of failure

Direct-acting #Antivirals Do Not Increase the Risk of #Hepatocellular Carcinoma Recurrence after Local-Regional Therapy or Liver Transplant Waitlist Dropout

http://onlinelibrary.wiley.com/doi/10.1002/hep.29855/abstract

Whether direct-acting antivirals (DAA) increase the risk of hepatocellular carcinoma (HCC) recurrence after tumor-directed therapy is controversial. We sought to determine the impact of DAA therapy on HCC recurrence after local-regional therapy (LRT) and waitlist dropout among liver transplant (LT) candidates with HCC. We performed a retrospective cohort study of 149 LT candidates with HCV and HCC at a single center from 2014-2016. Cumulative incidence of HCC recurrence post-LRT and waitlist dropout was estimated by DAA group. Factors associated with each outcome were evaluated using competing risks regression. A propensity score stabilized inverse probability weighting approach was used to account for differences in baseline characteristics between groups. The no DAA group (n=87) had more severe cirrhosis and lower rates of complete radiologic tumor response after LRT than those treated with DAA (n=62), but had similar alpha-fetoprotein and tumor burden at listing. Cumulative incidence of HCC recurrence within 1-year of complete response after LRT was 47.0% in the DAA group and 49.8% in the no DAA group (p=0.93). In adjusted competing risk analysis using weighted propensity score modeling, risk of HCC recurrence was similar in the DAA group compared to those without DAA (HR 0.91, 95% CI 0.58-1.42, p=0.67). Patients treated with DAA had lower risk of waitlist dropout due to tumor progression or death compared to the no DAA group in adjusted weighted analysis (HR 0.30, 95% CI 0.13-0.69, p=0.005).

Conclusions: In LT candidates with HCV and HCC with initial complete response to LRT, DAA use is not associated with increased risk of HCC recurrence, but rather is associated with reduced risk of waitlist dropout due to tumor progression or death

Long Term Outcomes and Predictive Scores for #Hepatocellular Carcinoma and #HBsAg Seroclearance after #HBeAg Seroclearance

http://onlinelibrary.wiley.com/doi/10.1002/hep.29874/abstract

The significance of hepatitis B e-antigen seroclearance (ESC) in the long term is not well defined. The current study aimed to determine the clinical outcomes, the factors and predictive scores for hepatocellular carcinoma (HCC) and hepatitis B surface antigen (HBsAg) seroclearance of a large cohort of patients undergoing ESC. Patients with documented ESC were followed up 3-6 monthly. Baseline characteristics and longitudinal laboratory results were recorded. Predictive scores for HCC (HCC-ESC) and HBsAg seroclearance (HBsAg-ESC) were derived from multivariate Cox regression models. A total of 723 patients underwent ESC with a median ESC age and follow-up of 36.0 and 18.3 years respectively. Only 3.5% and 3.0% had persistently normal ALT and HBV DNA <2logs IU/mL respectively after ESC. For patients with 100%, 100-90%, 90-50%, 50-10%, 10-0%, and 0% normal ALT after HBeAg seroclearance, the rate of HCC was 4.3%, 2.2%, 3.6%, 3.9%, 17.3%, and 37.2% at 20 years after ESC respectively (p<0.001). At 20 years after ESC, the cumulative incidence of HCC and HBsAg seroclearance was 7.9% and 13.5% respectively, with an overall survival of 91.5%. ESC age, male sex, cirrhosis, hypoalbuminemia, viral load, and ALT were significant factors for HCC, whereas ESC age, male sex, viral load, and antiviral therapy were significant factors for HBsAg seroclearance. The AUROC for HCC-ESC and HBsAg-ESC scores to predict HCC and HBsAg seroclearance at 20 years after ESC was 0.92 and 0.74 respectively.

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High risk of #hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis #B

http://gut.bmj.com/content/67/5/945

The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT ≥80 IU/mL) treated with nucleos(t)ide analogues.

Results The IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses.

Conclusions Untreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients

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Association Between #Aspirin Use and Risk of #Hepatocellular Carcinoma

https://jamanetwork.com/journals/jamaoncology/fullarticle/2704212

Compared with nonregular use, regular aspirin use (≥2 standard-dose [325-mg] tablets per week) was associated with reduced HCC risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI, 0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96) for more than 5 tablets per week (P for trend = .006). Significantly lower HCC risk was observed with increasing duration (P for trend = .03); this decrease was apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin nonsteroidal anti-inflammatory drugs was not significantly associated with HCC risk (adjusted HR, 1.09; 95% CI, 0.78-1.51).

Conclusions and Relevance This study suggests that regular, long-term aspirin use is associated with a dose-dependent reduction in HCC risk, which is apparent after 5 or more years of use. Similar associations were not found with nonaspirin NSAIDs. Further research appears to be needed to clarify whether aspirin use represents a feasible strategy for primary prevention against HCC.

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#Direct-Acting Antiviral Therapy not Associated with Recurrence of #Hepatocellular Carcinoma in a Multicenter North American Cohort Study

https://www.gastrojournal.org/article/S0016-5085(19)30057-5/pdf

There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort.

In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P=.23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but neither achieved statistical significance.

Conclusion
In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

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Association of Intake of Whole #Grains and Dietary Fiber With Risk of #Hepatocellular Carcinoma in US Adults

https://jamanetwork.com/journals/jamaoncology/article-abstract/2725404

Increased whole grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: HR, 0.63; 95% CI, 0.41-0.96; P = .04 for trend). A nonsignificant inverse HCC association was observed for total bran (HR, 0.70; 95% CI, 0.46-1.07; P = .11 for trend), but not for germ. Increased intake of cereal fiber (HR, 0.68; 95% CI, 0.45-1.03; P = .07 for trend), but not fruit or vegetable fiber, was associated with a nonsignificant reduced risk of HCC.

Conclusions and Relevance Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among adults in the United States. Future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings, to examine these associations in other racial/ethnic or high-risk populations, and to elucidate the underlying mechanisms.

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Dietary #Tomato Powder Inhibits High-Fat Diet–Promoted #Hepatocellular Carcinoma with Alteration of Gut Microbiota in Mice Lacking Carotenoid Cleavage Enzymes

http://cancerpreventionresearch.aacrjournals.org/content/11/12/797

At 6 weeks of age, the mice were randomly assigned to an HFD (60% of energy as fat) with or without tomato powder (TP) feeding for 24 weeks. Results showed that TP feeding significantly decreased HCC development (67%, 83%, and 95% reduction in incidence, multiplicity, and tumor volume, respectively, P < 0.05). Protective effects of TP feeding were associated with (1) decreased hepatic inflammatory foci development and mRNA expression of proinflammatory biomarkers (IL1β, IL6, IL12α, monocyte chemoattractant protein-1, and inducible NO synthase); (2) increased mRNA expression of deacetylase sirtuin 1 and nicotinamide phosphoribosyltransferase involving NAD+ production; and (3) increased hepatic circadian clock genes (circadian locomotor output cycles kaput, period 2, and cryptochrome-2, Wee1).

Furthermore, TP feeding increased gut microbial richness and diversity, and significantly decreased the relative abundance of the genus Clostridium and Mucispirillum, respectively. The present study demonstrates that dietary tomato feeding independent of carotenoid cleavage enzymes prevents HFD-induced inflammation with potential modulating gut microbiota and inhibits HFD-promoted HCC development.

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Risks and clinical predictors of #cirrhosis and #hepatocellular #carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1321-x

Non-alcoholic fatty liver disease (NAFLD) is a common condition that progresses in some patients to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)..

Coded NAFLD/NASH patients were more likely to have diabetes, hypertension and obesity than matched controls. HR for cirrhosis in patients compared to controls was 4.73 (95% CI 2.43–9.19) and for HCC, 3.51 (95% CI 1.72–7.16). HR for either outcome was higher in patients with NASH and those with high-risk Fib-4 scores. The strongest independent predictor of a diagnosis of HCC or cirrhosis was baseline diagnosis of diabetes.

Conclusions
Real-world population data show that recorded diagnosis of NAFLD/NASH increases risk of life-threatening liver outcomes. Diabetes is an independent predictor of advanced liver disease diagnosis, emphasising the need to identify specific groups of patients at highest risk.

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Lipophilic #Statins and Risk for #Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population

https://annals.org/aim/article-abstract/2748619/lipophilic-statins-risk-hepatocellular-carcinoma-death-patients-chronic-viral-hepatitis

..Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], −4.8 percentage points [95% CI, −6.2 to −3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, −1.2 percentage points [CI, −2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08)..

In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC.

Plant‐based and animal‐based low‐carbohydrate #diets and risk of #hepatocellular carcinoma among US men and women
https://2medical.news/2020/04/06/plant%E2%80%90based-and-animal%E2%80%90based-low%E2%80%90carbohydrate-diets-and-risk-of-hepatocellular-carcinoma-among-us-men-and-women/

Little is known about the role of low‐carbohydrate diets (LCDs) in the development of hepatocellular carcinoma (HCC).. ..During 3,664,769 person years of follow‐up, there were 156 incident HCC cases. Although there were no associations between overall or animal‐based LCD score and risk of HCC, plant‐based LCD score was inversely associated with HCC risk (HR: 0.83; 95% CI: 0.70‐0.98; Ptrend=0.03). Carbohydrate intake, especially from refined grains …

High incidence of #hepatocellular carcinoma and #cirrhotic complications in patients with psychiatric illness: a territory-wide cohort study
https://2medical.news/2020/05/06/high-incidence-of-hepatocellular-carcinoma-and-cirrhotic-complications-in-patients-with-psychiatric-illness-a-territory-wide-cohort-study/

Because of high-risk behaviours, sedentary lifestyle and side effects of medications, psychiatric patients are at risk of viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. We aimed to study the incidence of hepatocellular carcinoma (HCC) and cirrhotic complications in psychiatric patients.. ..We included 105,763 psychiatric patients without prior liver-related events in the final analysis. During a median (interquartile range) follow-up of 12.4 (11.0–13.7) …

Safety and Efficacy of amplitude-modulated radiofrequency electromagnetic fields in advanced #hepatocellular carcinoma

https://2medical.news/2021/07/31/safety-and-efficacy-of-amplitude-modulated-radiofrequency-electromagnetic-fields-in-advanced-hepatocellular-carcinoma/