Hepatocellular Carcinoma Recurrence Patterns Research Articles

Recurrence of Hepatocellular Carcinoma after Liver Transplantation: Clinical Patterns and Hierarchy of Salvage Treatments

Introduction: The multiparametric nature of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) still leads to uncertainty with its practical management. This study aims to characterize the main posttransplant recurrence patterns of HCC and to explore the therapeutic modalities targeting recurrence. Methods: Consecutive patients who underwent LT for HCC at a single tertiary center were analyzed. The time from first recurrence to death was investigated for each site of presentation. The impact of each recurrence-targeted treatment on survival was studied. Results: Of 660 patients with HCC, any recurrence occurred in 96 (15.4%) patients with a median time to recurrence of 20.0 months (95% CI: 15.6–23.8). Patients recurred across different patters including solitary distant locations (30.8%, n = 28), liver only (24.2%, n = 22), lung (18.7%, n = 17), multi-organ disease (17.6%, n = 16), and bone (8.8%, n = 8). Multi-organ and bone recurrences had the poorest survival, while solitary distant lesions and pulmonary recurrences had the best outcomes. Each treatment modality carried a distinctive survival. Conclusions: Patients recurred across 3 patterns with different prognostic implications. The benefit of each treatment option on distinct recurrence patterns appears to be influenced by the biological behavior inherent in the recurrence pattern itself.

Impact of HCV eradication on recurrence pattern and long-term outcomes in patients with HCV-related hepatocellular carcinoma undergoing radiofrequency ablation.

The benefits of HCV eradication on distinct recurrence patterns and long-term hepatic outcomes in patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) remain uncertain. This study aims to assess the impact of HCV eradication on HCC recurrence patterns and long-term hepatic outcomes after RFA and to identify predictors of recurrence in patients achieving sustained virological response (SVR). We retrospectively enrolled 274 patients receiving RFA for HCV-related HCC, including 73 and 88 patients treated with interferon-based (IFN) and direct-acting antivirals (DAA) therapy, respectively. We analysed factors associated with local tumour progression (LTP), distant recurrence, overall survival, and hepatic decompensation. SVR was achieved in 49.3% of patients undergoing IFN therapy and 93.2% of patients undergoing DAA therapy. HCV eradication was not associated with LTP but significantly correlated with reduced risk of distant recurrence (by DAA: hazard ratio (HR) = 0.449, p = 0.006), overall survival (by IFN: HR = 0.242, p < 0.001; by DAA: HR = 0.274, p < 0.001) and hepatic decompensation (by IFN: HR = 0.313, p = 0.004; by DAA: HR = 0.281, p < 0.001). The benefits of achieving SVR in terms of overall survival and hepatic decompensation remained significant in subgroups of patients with and without recurrence. Patients with SVR showed a significant decline in FIB-4 score and a higher proportion of ALBI grade improvement. Among SVR patients, the IMbrave050 criteria predicted LTP but not distant recurrence, whereas the FIB-4 score after SVR, rather than the baseline FIB-4, predicted distant recurrence. HCV eradication was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following RFA in patients with HCV-related HCC.

Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis.

Background: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. Aim: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). Methods: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. Results: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26–34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17–28%) to US studies (34%, CI, 30–38%), to Egyptian studies (37%, CI, 27–47%), and to Asian studies (33%, CI, 27–40%). Sixty-eight percent (CI, 45–91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51–0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49–0.94). Conclusions: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.

Clinical outcomes of direct-acting antiviral treatments for patients with hepatitis C after hepatocellular carcinoma are equivalent to interferon treatment.

It remains unclear how direct-acting antiviral (DAA) treatments influence hepatocellular carcinoma (HCC) recurrence and survival in comparison with interferon (IFN). In total, 338 patients with chronic hepatitis C virus (HCV) infection and previous HCC treatments who initiated IFN (N = 88, IFN group) or DAA treatment (N = 250, DAA group) from January 2005 to November 2017 at 23 hospitals and achieved sustained virologic response (SVR) were analyzed. Cumulative HCC recurrence and survival rates were compared between the two groups using propensity score (PS) matching. After PS matching, 63 patients were selected for each group. The cumulative HCC recurrence rates at 1 and 3years were 20.6% and 34.6% in the IFN group and 19.2% and 43.0% in the DAA group, respectively; the difference in cumulative HCC recurrence rates between the two groups was not significant (P = 0.332). No significant differences in HCC recurrence patterns were observed between the two groups. Overall survival rates at 1 and 3years were 100% and 96.6% in the IFN group and 100% and 96.4% in the DAA group, respectively; the difference in overall survival rates between the two groups was not significant (P = 0.132). No significant differences in HCC recurrence and overall survival rates were observed between the two groups in subgroup analyses of patients receiving curative treatment (liver resection or radiofrequency ablation) for the most recent HCC before HCV treatment. The recurrence rates and patterns of HCC and overall survival rates do not differ between SVR patients receiving IFN and DAA treatments.

Recurrence beyond the Milan criteria after curative-intent resection of hepatocellular carcinoma: A novel tumor-burden based prediction model.

Accurate prediction of recurrence patterns of hepatocellular carcinoma (HCC) may allow for prioritization of patients for resection or transplantation as well as guide post-resection surveillance strategies. Patients who underwent curative-intent R0 resection for HCC between 2000 and 2017 were identified using a multi-institutional database. A prognostic model that incorporated HCC tumor burden score (TBS) to predict recurrence beyond the Milan criteria (MC) was developed and validated. Among 718 patients who underwent R0 resection for HCC, 185 (25.8%) recurred within and 110 (15.3%) beyond the MC. On multivariable analysis, AFP more than 400 ng/mL (hazard ratio [HR] = 2.26; 95% confidence interval [CI]: 1.27-4.02), lymphovascular invasion (HR = 2.00; 95% CI: 1.14-3.50), and TBS (HR = 1.08; 95% CI: 1.03-1.12) were associated with recurrence beyond the MC. A weighted TBS-based score was constructed: [0.074*TBS + 0.692*lymphovascular invasion (yes: 1, no: 0) + 0.816*AFP > 400 (yes:1, no:0)]. Patients with a low, medium, and high TBS-based risk score had a 5-year incidence of recurring beyond the MC of 16.2%, 28.6%, and 47.2%, respectively (P < .001). The predictive accuracy of the model was very good in the training (C-index: 0.761) and validation (C-index: 0.706) datasets and outperformed the previously reported clinical risk score (CRS; C-index: 0.680). A TBS-based model accurately predicted recurrence beyond MC after curative-intent resection of HCC and outperformed the CRS. Incorporating TBS allows for better risk stratification and identifies patients in need of closer surveillance.

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study

There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (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. We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. 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 this did not achieve statistical significance. 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.

Pattern of hepatocellular carcinoma recurrence following living donor liver transplantation

Pattern of hepatocellular carcinoma recurrence following living donor liver transplantation

Pattern of hepatocellular carcinoma recurrence following living donor liver transplantation

Background: The aim of the present study was to identify the pattern of HCC recurrence after LDLT for early detection and management Methods: From April 2003 to October 2014, the record of 60 patients who underwent LDLT for HCC at the National Liver Institute, Menoufia University, Egypt, were retrospectively reviewed. Results: Seven patients (11.7 per cent) had HCC recurrence after LDLT. Pretransplant α-fetoprotein (AFP) > 1000 ng/mL, tumour grade and microvascular invasion were the incriminated risk factors for recurrence. Three patients (42.8 per cent) had intrahepatic and extrahepatic recurrence (lung and bone), two patients (28.6 per cent) had only extrahepatic recurrence in bones and two patients (28.6 per cent) had only intrahepatic recurrence. Management was as follows: two patients (28.6 per cent) had surgical excision of intrahepatic recurrence and extrahepatic metastasis, two patients (28.6 per cent) underwent radiotherapy for bone metastasis, one patient (14.2 per cent) underwent intraoperative radiofrequency ablation for liver recurrence and two patients (28.6 per cent) received sorafenib as medical treatment. The mean time of recurrence was 19.7 months, and mean survival was 29 months. Conclusion: The majority of HCC recurrences after LDLT are extrahepatic and occur mainly in the first 2 years; strict follow up is required during this period. A high level of pretransplant serum AFP and microvascular invasion are risk factors for tumour recurrence and should be taken into account when selecting candidates for LDLT.

Clinical Features and Surveillance of Very Late Hepatocellular Carcinoma Recurrence After Liver Transplantation.

BackgroundThis study aimed to assess patterns of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and to establish long-term surveillance protocols for late HCC recurrence.Material/MethodsThe 232 LT recipients experiencing subsequent HCC recurrence were categorized as Group 1, early recurrence (within 1 year of LT; n=117); Group 2, late recurrence (occurring in years 2–5; n=93); and Group 3, very late recurrence (after year 5; n=22).ResultsRecurrence was detected by only elevated tumor marker levels in 11.1%, 30.1%, and 45.5% of patients in Groups 1, 2, and 3, respectively (p<0.001). The proportion of intrahepatic and extrahepatic metastases was similar in all 3 groups. Common sites of extrahepatic metastasis were the lung and bone; these were also similar across the 3 groups. Overall post-recurrence patient survival rates were 60.2% at 1 year, 28.2% at 3 years, 20.5% at 5 years, and 7.0% at 10 years. Median post-recurrence survival periods were 10.2, 23.8, and 37.0 months in Groups 1, 2, and 3, respectively.ConclusionsWhile the pattern of HCC recurrence was similar regardless of time of recurrence, post-recurrence survival was significantly longer in patients with later recurrence. Long-term surveillance for HCC recurrence beyond 5 years after LT is recommended.

Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy.

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA), data are conflicting regarding HCC recurrence and aggressiveness in patients who have a history of HCC with complete response. Characterize HCC recurrence patterns after DAA therapy. Two reviewers searched MEDLINE and SCOPUS from January 2015 to December 2017 and identified studies evaluating HCC recurrence patterns following DAA therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random effects model. The study was conducted in accordance with PRISMA guidelines. Among 24 studies (n=1820 patients), the proportion of patients with HCC recurrence following DAA therapy ranged from 0% to 59% (pooled estimate 24.4%; 95% CI: 18.4%-30.4%). Among 11 full text manuscripts, pooled HCC recurrence was 21.9% (95% CI: 16.2%-28.3%). Factors associated with recurrence included history of prior HCC recurrence and a shorter interval between HCC complete response and DAA initiation. Nine studies comparing DAA-treated and interferon-treated or untreated patients found similar recurrence among DAA-treated patients. Most (77.8%) patients with HCC recurrence were detected at an early tumour stage, of whom 64.7% received curative treatment. Study limitations included heterogeneous cohorts, potential misclassification of HCC absence prior to DAA, ascertainment bias for recurrence, and short durations of follow-up. Current data suggest acceptable HCC recurrence rates after DAA therapy, particularly if DAA therapy is delayed at least 6months after HCC complete response. However, data characterising HCC recurrence after DAA therapy are of limited quality, highlighting the need for high quality prospective studies.

Pattern of hepatocellular carcinoma recurrence following living donor liver transplantation

Pattern of hepatocellular carcinoma recurrence following living donor liver transplantation

Effect of ischaemic preconditioning on recurrence of hepatocellular carcinoma in an experimental model of liver steatosis.

Livers with parenchymal abnormalities tolerate ischaemia-reperfusion (IR) injury poorly. IR injury is a risk factor for hepatocellular carcinoma (HCC) recurrence. This study assessed the link between liver parenchymal abnormalities and HCC recurrence, and evaluated the protective effect of ischaemic preconditioning. C57BL/6 mice were fed a choline-deficient diet for 6 and 12 weeks, or standard chow. Hepatic IR and ischaemic preconditioning were achieved by clamping liver blood inflow. Hepa 1-6 HCC cells were inoculated through the spleen. Thereafter, tumour burden, serum α-fetoprotein and cancer cell aggressiveness were compared among groups. Hepatocellular damage and expression of inflammatory genes (encoding interleukin 6, tumour necrosis factor α, hypoxia inducible factor 1α and E-selectin) were exacerbated after IR injury in mice with severe steatosis. Compared with control livers or those with minimal steatosis, livers exposed to a prolonged choline-deficient diet developed larger tumour nodules and had higher serum α-fetoprotein levels. Non-ischaemic liver lobes from mice with steatosis were not protected from accelerated tumour growth mediated by IR injury. This remote effect was linked to promotion of the aggressiveness of HCC cells. Ischaemic preconditioning before IR injury reduced the tumour burden to the level of that in non-ischaemic steatotic controls. This protective effect was associated with decreased cancer cell motility. Livers with steatosis tolerated IR poorly, contributing to more severe HCC recurrence patterns in mice with increasingly severe steatosis. IR injury also had a remote effect on cancer cell aggressiveness. Ischaemic preconditioning before IR injury reduced tumour load and serum α-fetoprotein levels. Liver ischaemia-reperfusion (IR) injury is associated with organ dysfunction and surgical morbidity. Livers with steatosis tolerate IR injury poorly in the setting of both liver resection and liver transplantation. Ischaemic preconditioning is a simple method to mitigate IR injury. This study shows that ischaemic preconditioning of mouse livers with steatosis reduces ischaemia-mediated tumour growth acceleration. Liver parenchymal abnormalities such as warm IR injury and liver steatosis should be taken into account to predict accurately the risk of liver cancer recurrence after surgical management. Ischaemic preconditioning strategies may hold therapeutic potential not only to mitigate surgical morbidity but also to reduce postoperative recurrence of liver cancer.

Pattern of hepatocellular carcinoma recurrence following living donor liver transplantation

AimLiving donor liver transplantation (LDLT) is a promising treatment option for patients with hepatocellular carcinoma (HCC), but tumour recurrence can affect long‐term survival. The aim of the present study was to identify the pattern of HCC recurrence after LDLT for early detection and management.Patients and MethodsFrom April 2003 to October 2014, the record of 60 patients who underwent LDLT for HCC at the National Liver Institute, Menoufia University, Egypt, were retrospectively reviewed. The clinicopathological data were analysed to determine factors associated with HCC recurrence and outcome.ResultsSeven patients (11.7 per cent) had HCC recurrence after LDLT. Pretransplant α‐fetoprotein (AFP) &gt; 1000 ng/mL, tumour grade and microvascular invasion were the incriminated risk factors for recurrence. Three patients (42.8 per cent) had intrahepatic and extrahepatic recurrence (lung and bone), two patients (28.6 per cent) had only extrahepatic recurrence in bones and two patients (28.6 per cent) had only intrahepatic recurrence. Management was as follows: two patients (28.6 per cent) had surgical excision of intrahepatic recurrence and extrahepatic metastasis, two patients (28.6 per cent) underwent radiotherapy for bone metastasis, one patient (14.2 per cent) underwent intraoperative radiofrequency ablation for liver recurrence and two patients (28.6 per cent) received sorafenib as medical treatment. The mean time of recurrence was 19.7 months, and mean survival was 29 months.ConclusionThe majority of HCC recurrences after LDLT are extrahepatic and occur mainly in the first 2 years; strict follow up is required during this period. A high level of pretransplant serum AFP and microvascular invasion are risk factors for tumour recurrence and should be taken into account when selecting candidates for LDLT.

Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation.

To evaluated patterns and outcomes of hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). From 2001 to 2014, 293 patients underwent LDLT for HCC at our transplant center. We retrospectively reviewed 54 (18.4%) patients with HCC recurrence after LDLT. We evaluated patterns and outcomes of HCC recurrence after LDLT, with particular attention to the Milan criteria at transplantation, treatments for HCC-recurrent patients, and factors related to survival after HCC recurrence. Furthermore, we evaluated the efficacy of combination treatment of sorafenib and an mTOR inhibitor. The 1-, 2-, and 3-year overall survival rates after HCC recurrence were 41.1%, 20.5%, and 15.4%, respectively. The median time interval between LDLT and HCC recurrence was 6.5 mo. Although recurrence rates according to the Milan criteria at LDLT were significantly different, HCC recurrence patterns and survival rates after HCC recurrence were not significantly different between the two groups. Time to recurrence < 12 mo (P = 0.048), multiple recurrences at HCC recurrence (P = 0.038), and palliative treatment for recurrent tumors (P = 0.003) were significant independent prognostic factors for poor survival after HCC recurrence in a multivariate analysis. The combination treatment of sorafenib and sirolimus showed survival benefits in the palliative treatment group (P = 0.005). Curative treatment for recurrent HCC after LDLT is the most important factor in survival rates after HCC recurrence and combination treatments of sorafenib and an mTOR inhibitor could have survival benefits in patients with HCC recurrence after LT in the palliative treatment group.

Genomic predictors for recurrence patterns of hepatocellular carcinoma: model derivation and validation.

Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications. Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus. Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. Please see later in the article for the Editors' Summary.

Highlights in this issue

Highlights in this issue

Issues of hepatocellular carcinoma recurrence after curative resection

Regarding the prevention and treatment of hepatocellular carcinoma (HCC) recurrence after curative resection,surgeons do not have a clear consensus to evaluate the risk factors of recurrence and effectiveness of surgical resection.Therefore,postoperative HCC recurrence patterns were reviewed in this article,including differentiating intrahepatic metastasis (IM) and multicentric occurrence (MO),which play a key role in manifesting recurrence and patient prognosis.Additionally,the definitions of small HCC and curative resection,and the prophylactic and therapeutic values of anatomic resection and repeated hepatectomy in patients with recurrent HCC were reviewed.Fully understanding these issues might allow for a more objective,precise,and consistent clinical assessment of HCC. Key words: Hepatocellular carcinoma; Curative resection; Recurrence

Milan Criteria, Multi-nodularity, and Microvascular Invasion Predict the Recurrence Patterns of Hepatocellular Carcinoma After Resection

AimsThis study aims to evaluate the risk factors for tumor recurrence beyond the Milan criteria (MC) for patients with hepatocellular carcinoma (HCC) after surgical resection (SR) in which salvage liver transplantation is relatively contraindicated. MethodsA total of 447 patients who underwent SR for HCC were enrolled consecutively. Among them, 248 and 199 patients were within the Milan criteria and beyond the Milan criteria (BMC group), respectively. Overall survival, recurrence, and disease-free survival were analyzed by multivariate analysis. ResultsAfter a median follow-up of 34.4 months, 130 patients died. Microvascular invasion, higher Edmondson stage of tumor cell differentiation, BMC group, and no anti-viral therapy were associated with poor overall survival. Multi-nodularity, higher Edmondson stage, BMC group, and no anti-viral therapy were independent risk factors for tumor recurrence, while BMC group and no anti-viral therapy were independent risk factors for disease-free survival. The Milan criteria, multi-nodularity, and microvascular invasion were used to stratify the patients into low-, medium-, and high-risk groups for tumor recurrence outside the MC and showed statistical significance (low vs. medium, p = 0.011; low vs. high, p < 0.001; medium vs. high, p = 0.009). ConclusionsThe combination of the MC, multi-nodularity, and microvascular invasion predict the post-operative recurrence of HCC and may provide a roadmap for further treatment.

Long-Term Immunosuppression for Prevention of Nonviral Disease Recurrence

The choice of immunosuppressive regime used after liver transplantation depends on many factors, which should include the effect of disease recurrence; recurrence of disease after liver transplantation may be affected by the degree and type of immunosuppression used and recurrent disease may affect patient and graft survival. For autoimmune diseases, recurrence of primary biliary cirrhosis develops sooner and more rapidly in those on tacrolimus compared with cyclosporine, but graft loss from recurrent disease is uncommon; recurrence rates of primary sclerosing cholangitis is unaffected by immunosuppressive regimes and recurrence of autoimmune hepatitis may be reduced by prescription of corticosteroids. Whether the immunosuppressive regime affects the pattern of hepatocellular carcinoma recurrence is uncertain. It is probable that the use of calcineurin inhibitor does not have a significant effect and inhibitors of TOR may have an anti-cancer effect, but this still has to be shown clinically. Most metabolic diseases are not affected by the choice of immunosuppression, although recurrence of sarcoidosis may be prevented by corticosteroids.

Hepatocellular carcinoma recurrence after percutaneous ablation therapy: helical CT patterns.

To categorize the helical computed tomographic (CT) intrahepatic recurrence patterns of hepatocellular carcinoma (HCC) after treatment with percutaneous ablation procedures. Double-phase helical CT studies of 67 patients with HCC recurrence were reviewed. The study population had undergone percutaneous ablation therapy procedures (multisession or single-session ethanol injection therapy, radiofrequency thermal ablation therapy, and interstitial laser photocoagulation therapy) for 120 HCC nodules. Four patterns were defined. (A) Enhancing tissue within the edge of the ablated nodule on arterial phase images (ingrowth): this pattern was seen in five treated lesions (4.2% of all treated nodules) in five patients (7.5% of all patients with recurrence) 3-7 months after treatment (mean = 4 months). (B) Enhancing tissue around the treated nodule but continuously to its border on arterial-phase images (outgrowth): this pattern was found in 12 (10%) treated lesions in 12 patients (18%) 3-6 months after ablation (mean = 4 months). (C) Enhancing tissue within the same segment of the treated nodule on arterial phase images (spread): this pattern was detected in 10 (8%) treated lesions in 10 patients (15%) 3-6 months after treatment (mean = 5 months). (D) Enhancing tissue within different segments from the treated nodule on arterial phase images (progression): this pattern was identified in 34 patients (51%) with 53 (44%) treated tumors 5-22 months after ablation (mean = 8 months). A mixed pattern was found in six subjects (9%) with seven (6%) treated nodules. Among the 61 patients with a nonmixed pattern, there were 85 treated nodules with persistent necrosis, 17 treated nodules with local recurrence (pattern A or B), and 107 new nodules due to nonlocal recurrence (pattern C or D). Portal phase enhanced images and especially unenhanced images showed a lower detection rate and a lower lesion-to-liver conspicuity score (for all patterns but mainly for pattern C). Four patterns of recurrence after percutaneous ablation procedures can be categorized on double-phase helical CT and are best depicted on arterial phase images. Knowledge of these patterns is relevant for early detection and may be helpful in understanding the recurrence mechanism.