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Background: Locoregional therapy with curative intent (CLRT) followed by salvage liver transplantation (SLT) in case of hepatocellular carcinoma (HCC) recurrence is an alternative to primary liver transplantation (LT) in selected patients with HCC., Methods: We performed a systematic review and meta-analysis of studies comparing the survival of patients treated with CLRT versus LT, stratified by the stage of liver disease, extent of cancer, and whether SLT was offered or not., Results: We included 48 studies involving 9835 patients (5736 patients with CLRT and 4119 patients with primary LT). Five-year overall survival (OS) and disease-free survival (DFS) was worse for all categories of CLRT combined, than for primary LT (odds ratio [OR] for OS, 0.59; 95% confidence interval [CI], 0.48-0.71; P < 0.01). However, 5-year OS for CLRT and primary LT was not significantly different among patients with (i) Child-A cirrhosis and (ii) single HCC lesion, although DFS was worse. When SLT was offered after CLRT, intention-to-treat analysis showed no significant difference in 5-year OS (OR, 1.0; 95% CI, 0.6-1.7) between CLRT-SLT and primary LT, though noninferiority could not be shown. Only 32.5% patients with HCC recurrence after CLRT actually received SLT, as the rest were not medically eligible. Thus, the DFS was worse with CLRT-SLT (OR, 0.31; 95% CI, 0.2-0.6) compared with LT., Conclusions: CLRT-SLT may be offered as first-line therapy to patients with HCC and well-compensated cirrhosis instead of primary LT because it may lead to better utilization of donor liver. However, a large proportion of patients with HCC recurrence after CLRT may not be candidates for SLT.

Background: Graft-versus-host-disease (GVHD) after liver transplantation (LT) is a deadly complication with very limited data on risk factors, diagnosis and management. We report a case series and a comprehensive review of the literature., Methods: Data were systematically extracted from reports of GVHD after LT, and from the United Network for Organ Sharing database. Group comparisons were performed., Results: One hundred fifty-six adult patients with GVHD after LT have been reported. Median time to GVHD onset was 28 days. Clinical features were skin rash (92%), pancytopenia (78%), and diarrhea (65%). Six-month mortality with GVHD after LT was 73%. Sepsis was the most common cause of death (60%). Enterobacter bacteremia, invasive aspergillosis, and disseminated Candida infections were frequently reported. Recipient age over 50 years is a risk factor for GVHD after LT. Hepatocellular carcinoma was overrepresented, whereas chronic hepatitis C was underrepresented, in reported United States GVHD cases relative to all United Network for Organ Sharing database LT cases. Mortality rate with treatment of GVHD after LT was 84% with high-dose steroids alone, 75% to 100% with regimens using dose increases of calcineurin inhibitors, and 55% with IL-2 antagonists. Mortality was 25% in small case series using the CD2-blocker alefacept or TNF-α antagonists., Conclusions: Age older than 50 years and hepatocellular carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High-dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD after LT. CD2-blockers and TNF-α antagonists appear promising. We propose a diagnostic algorithm to assist clinicians in managing adults with GVHD after LT., Competing Interests: No conflicts of interest.

Background: Patients with hepatocellular carcinoma (HCC) outside Milan criteria (MC) may be candidates for liver transplantation (LT) after successful downstaging. Factors that predict successful downstaging are unclear. We aimed to identify the predictors of successful downstaging of HCC in patients outside MC., Methods: We performed a retrospective cohort study on consecutive patients with HCC outside MC who received downstaging with locoregional therapy. Clinical and laboratory variables, tumor characteristics including total tumor volume (TTV) and up-to-7 criteria were recorded. We performed univariate and multivariate logistic regression analyses to identify variables associated with successful downstaging., Results: Of 675 patients with HCC, 90 patients outside MC received downstaging. Fifty-three (59%) patients were successfully downstaged, 37 (41%) failed downstaging. University of California at San Francisco criteria, α-fetoprotein, up-to-7 criteria, TTV, and platelet count were predictors of successful downstaging on univariate analysis. Total tumor volume was an independent predictor of successful downstaging on multivariate logistic regression (P = 0.04, area under receiver operating characteristic curve 0.89 (95% confidence interval, 0.82-0.96). Fifty-two (76%) of 68 patients with TTV less than 200 cm were successfully downstaged, whereas only 1 (4.5%) of 22 patients with TTV greater than 200 cm were successfully downstaged. Forty-five (50%) patients underwent LT. Kaplan-Meier survival rates at 1 and 5 years post-LT were 95.3% and 79.4%, respectively. Patients who were successfully downstaged had better survival than patients who failed downstaging (P < 0.01)., Conclusions: Total tumor volume is a good predictor of successful downstaging of HCC. Patients with TTV less than 200 cm may be considered good candidates for downstaging. Further studies with larger cohort of patients are needed to validate this approach in patients with HCC outside Milan.

Hepatocellular carcinoma (HCC) is an important cause of death in patients with liver disease, and its incidence appears to be rising in the United States. Because early diagnosis improves the chances of survival, it is important to identify patients who would benefit from surveillance. Once HCC is suspected on surveillance, noninvasive diagnostic tests are available to make an accurate diagnosis. Treatment should be individualized, based on the characteristics of the tumor and the degree of liver dysfunction.