Long-term posttransplant survival outcome following bridging locoregional therapy in hepatocellular carcinoma patients: A systematic review and meta-analysis.

Aim: Liver transplantation (LT) is essential due to its curative efficacy, but liver-graft shortages have limited its widespread application. Bridging locoregional therapy (LRT) before LT has been performed to prevent tumor progression, and a recent literature review revealed that it is associated with a nonsignificant trend toward better survival outcomes. However, much more information on bridging therapy has become available since then. This meta-analysis aimed to compare the posttransplant survival and HCC recurrence between patients with and without pretransplant bridging LRT. Methods: Studies were identified in MEDLINE, SCOPUS, and the Cochrane Library. Two independent researchers screened titles and full articles, extracted relevant data, and conducted a parametric survival analysis. Results: Out of 4794 studies, 18 cohort studies were eligible. The 1-, 3-, and 5-year overall survival (OS) rates were 93.1%, 85.0%, and 79.1% for those in the bridging LRT group, while they were 91.8%, 81.1%, and 75.5% for those who did not receive LRT, respectively. There were no differences in overall survival between these groups (HR 0.90; 0.78-1.05, P = 0.17). Interestingly, we discovered that bridging therapy helped prolong survival significantly in a high-risk population with a long waiting time (HR 0.76; 0.60-0.96, P = 0.02). Unfortunately, bridging LRT did not improve disease-free survival (HR 0.98; 0.86-1.11, P = 0.70). Conclusions: The results indicate that bridging LRT does not generally change post-LT outcomes. However, bridging LRT can significantly improve survival in patients with a long waiting time for LT.

Outcomes of direct-acting antivirals in patients with HCV decompensated cirrhosis: a systematic review and meta-analysis.

Background: Direct-acting antivirals (DAA) are effective for chronic hepatitis C virus (HCV) treatment. However, their impact on overall survival (OS), hepatocellular carcinoma (HCC) occurrence, HCC-free survival, and liver function in patients with HCV decompensated cirrhosis remains uncertain. This study aimed to evaluate the effects of DAA treatment on this population. Methods: Studies were identified by searching the MEDLINE, SCOPUS, and CENTRAL databases. OS and HCC-free survival probabilities and time data were extracted from Kaplan-Meier curves. A one-stage meta-analysis using parametric Weibull regression was conducted to estimate the relative treatment effects of DAA vs. no DAA. The primary outcome was the OS rate. The secondary outcomes were HCC-free survival, HCC occurrence rate, and improvement in the Model for End-stage Liver Disease (MELD) score. Results: Eight cohorts comprising 3,430 participants (2,603 in the DAA group and 1,999 in the no-DAA group) were included. The OS probabilities at 12 and 24 months were 95 and 90% for the DAA group, respectively, compared with 89 and 80% in the no-DAA group, respectively. Hazard ratio (HR) was 0.48 (95% confidence interval (CI): 0.39, 0.60; p < 0.001). The HCC-free survival probabilities at 12 and 24 months were 96 and 90%, respectively, in the former, and 94 and 85%, respectively, in the latter. The HR of HCC occurrence was 0.72 (95% CI: 0.52, 1.00; p = 0.05), which suggests that DAA treatment in decompensated cirrhosis may lead to a 28% lower risk of HCC occurrence. The mean MELD score difference was -7.75 (95% CI: -14.52, -0.98; p = 0.02). Conclusion: Improvement in OS and MELD score is a long-term benefit of DAA treatment in patients with HCV decompensated cirrhosis, with a marginal effect of the treatment on HCC development.

The detection of hepatocellular carcinoma (HCC) from patients' breath using canine scent detection: a proof-of-concept study.

Patients with hepatocellular carcinoma (HCC) have poor outcomes as a result of late detection of the disease. We investigated the possibility of using smell detection by dogs for detecting HCC from the breath of patients. Patients whose diagnosis of HCC was confirmed histologically or radiologically according to the American Association for the Study of Liver Diseases criteria had breaths collected using face masks and transported to the study test site. The numbering of the HCC samples was sent in a sealed envelope to blind the dog trainer during testing but allow for correct rewarding of the dog afterwards. One golden retriever was trained to detect HCC with positive feedback using known samples of HCC and healthy controls in a step-wise manner. The controls were selected from hospital staff and relatives of patients who were not involved in the study. They were questioned about the risks of their disease before selection. When the trainer was confident that the dog could recognize the HCC scent, blind testing was performed using 1 HCC : 3 healthy controls per test run. Once the dog signaled on a specimen, it was given a reward. The correct-detection rate was compared to the theoretical detection rate expected based on chance of 25% using the statistical one-sample test of proportions. Thirty-seven HCC patients were tested. The patients had a mean age of 58 years and 21/37 were male. Seventeen patients had hepatitis B and 14 patients had hepatitis C. Twenty-six patients had one HCC lesion; four patients had two lesions in the liver, whilst seven had many lesions. The number of patients in the very early, early, intermediate, advanced, and terminal stages of the Barcelona Clinic Liver Cancer classification was 5, 9, 21, 1, and 1, respectively. The dog detected correctly in 29 runs. The sensitivity for canine detection was 78% (95% CI: 62%-90%). Compared to the 25% correct indication expected based on chance, this was statistically significant (p < 0.001). CONCLUSION: This is the first study to look at the possibility of detecting HCC from breath using canine olfaction. Our results show that this is possible with an accuracy of 78% (p < 0.001 when compared to chance alone), and are thus a proof of concept. Further refinement of the process of detection will be needed before clinical application.

Advances in Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival.

Donor outcomes after living donor liver transplantation (LDLT).

Liver transplantation is an accepted management for end stage liver disease, early-stage hepatocellular carcinoma, and acute liver failure. The number of patients with end stage liver disease is growing rapidly. Living Donor Liver Transplantation (LDLT) has become an important alternative to cadaveric organ transplant for patients with end stage liver disease. On average, about one in three potential donors eventually donate part of their liver The overall reported donor mortality was 0.2% and median morbidity of l6%. Understanding donor outcomes is important as it enables the transplant team to fully inform the potential donor In addition, this information will help the transplant team improve their post operative management and plan for long-term follow-up after liver donation.

Evaluation of donors for living donor liver transplantation (LDLT).

Liver transplantation has been the last resort of definite treatment for decompensate cirrhosis, early-stage of hepatocellular carcinoma, and acute liver failure. Organ shortage is the major obstacle of deceased-donor liver transplantation. Since the first case of living-donor liver transplantation (LDLT), many centers around the world started the LDLT program. Living donors should be informed about the possible risk of morbidity and mortality, and later give consent for liver donation without coercion. Donor selection and evaluation have become one of the important steps prior to LDLT, aiming to exclude donors who may have high risks from LDLT and to assure that LDLT recipients will receive perfect liver grafts. In Thailand, living donors must have been blood relatives or be legally married with recipients for at least three years. Donor evaluation can be divided into three step-by-step phases. Psychological evaluation of living donors is also included in pre-transplant assessment.

Predictors of relapse to significant alcohol drinking after liver transplantation.

BACKGROUND: End-stage alcoholic liver disease is common, with many of these patients referred for liver transplantation (LT). Alcohol relapse after LT can have detrimental outcomes such as graft loss and can contribute to a negative public perception of LT. OBJECTIVE: To identify factors that predict the recurrence of harmful alcohol consumption after LT. METHODS: A total of 80 patients who underwent LT for alcoholic cirrhosis or had significant alcohol consumption in association with another primary liver disease, from July 1992 to June 2006 in British Columbia, were retrospectively evaluated by chart review. Several demographic-, psychosocial- and addiction-related variables were studied. Univariate and multivariate logistic regression analyses were used to test possible associations among the variables studied and a return to harmful drinking after LT. RESULTS: The relapse rate of harmful alcohol consumption post-liver transplant was 10%, with two patient deaths occurring directly as a result of alcohol relapse. Univariate analysis revealed relapse was significantly associated with pretransplant abstinence of less than six months (P=0.003), presence of psychiatric comorbidities (P=0.016), female sex (P=0.019) and increased personal stressors (P=0.044), while age at transplant of younger than 50 years approached significance (P=0.054). Multivariate logistic regression analysis revealed the following independent factors for relapse: pretransplant abstinence of less than six months (OR 77.07; standard error 1.743; P=0.013) and female sex (OR 18.80; standard error 1.451; P=0.043). CONCLUSION: The findings of the present study strongly support a required minimum of six months of abstinence before LT because duration of abstinence was found to be the strongest predictor of recidivism. Female sex, younger age at transplant and psychiatric comorbidities were also associated with relapse to harmful drinking.

Expression of integrin-linked kinase is not a useful prognostic marker in resected hepatocellular cancer.

BACKGROUND: Hepatocellular cancer (HCC) is one of the most common malignancies worldwide, and is known to be associated with a poor prognosis. Unfortunately there are no available reliable markers of prognosis. The aim of this study was to determine whether integrin-linked kinase (ILK) expression correlates with post-resection survival from HCC. PATIENTS AND METHODS: A tissue microarray was constructed using HCC samples, and immunohistochemical analysis for ILK was then carried out and scored by three independent observers. Clinical chart review was performed to determine survival parameters. RESULTS: Of the 52 cases of HCC, 22 cases were associated with hepatitis B (HBV), 18 with hepatitis C (HCV), 2 with HBV and HCV co-infection; 81% of all patients were male and 19% female. Western immunoblotting showed a highly significant correlation between levels of expression of ILK and ser473-PKBphosphorylation, both in control and tumor sections (Spearman rank correlation, r=0.8155, p=0.0004), however, there was no direct correlation between the levels of expression of ILK with patient survival (log-rank test, p= 0.864). CONCLUSION: ILK expression does not appear to have a role in predicting outcome in patients with resected HCC.

Utilization of a liver allograft from a hepatitis B surface antigen positive donor.

With today's donor organ shortage, enhanced efforts must be made to utilize organs that previously would have been declined. We report a 26-year-old man with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection who received a liver transplant from an HBsAg-positive donor. HBV viremia (6,281,185 copies/ml) was seen early posttransplant despite lamivudine prophylaxis, but became negative with addition of adefovir. Virologic analysis revealed predominantly donor HBV strain immediately posttransplant. At 5 months there was an elevation of liver enzymes accompanied by histologic evidence of hepatitis. At this time, HCV-RNA was positive but HBV DNA was undetectable. Treatment with pegylated interferon and ribavirin resulted in sustained clearance of HCV RNA. Two years posttransplant, the patient has normal liver biochemistry and HCV and HBV viral load are undetectable with persistence of HBsAg. Our experience suggests that with effective antiviral therapy, the use of HBsAg seropositive donors is feasible in selected circumstances.