Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome

Objective

Liver transplantation has become an effective treatment for cirrhotic patients with early-stage hepatocellular carcinoma. We hypothesized that the quality of surveillance for hepatocellular carcinoma influences prognosis by affecting access to liver transplantation.

Methods

A total of 269 patients with cirrhosis and hepatocellular carcinoma were retrospectively categorized into 3 groups according to quality of surveillance: standard-of-care (n = 172) (group 1); substandard surveillance (n = 48) (group 2); and absence of surveillance in patients not recognized to be cirrhotic (n = 59) (group 3).

Results

Three-year survival in the 60 patients who underwent liver transplantation was 81% versus 12% for patients who did not undergo transplantation (P <.001). The percentages of patients who underwent transplantation according to tumor stage at diagnosis (T1, T2, T3, and T4) were 58%, 35%, 10%, and 1%, respectively. Hepatocellular carcinoma was diagnosed at stages 1 and 2 in 70% of patients in group 1, 37% of patients in group 2, and only 18% of patients in group 3 (P <.001). Liver transplantation was performed in 32% of patients in group 1, 13% of patients in group 2, and 7% of patients in group 3 (P <.001). Three-year survival from cancer diagnosis in patients in group 3 (12%) was significantly worse than in patients in group 1 (39%) or group 2 (27%) (each P <.05). Eighty percent of patients in group 3 had subtle abnormalities of cirrhosis on routine laboratory tests.

Conclusion

The quality of surveillance has a direct impact on hepatocellular carcinoma stage at diagnosis, access to liver transplantation, and survival.     

Liver resection of transplantation for hepatocellular carcinoma?: Restrospective analysis of 215 patients with cirrhosis

Background/Aims: Currently, surgical treatment of hepatocellular carcinoma in patients with cirrhosis is not clearly defined. The objective of this study was, in patients with cirrhosis with hepatocellular carcinoma, to compare liver resection to transplantation assessed by patient survival and to determine whether the tumor recurrence might be influenced by prognostic factors.Methods: We have gathered all the available data from six French Medical Universities, for 215 patients with cirrhosis with hepatocellular carcinoma surgically treated either by liver resection (102) or by transplantation (113).Results: The overall 5-year survival rate was similar in the transplantation group and in the resection group (32% vs. 31%, p0.7). However, the 5-year survival rate without recurrence was higher in the transplantation group than in the resection group (60% vs. 14%, p<0.001). Three independent prognostic factors influenced significantly the survival without recurrence: the surgical treatment by transplantation (p<0.001), the number of tumors (p<0.01) and the tumor size (p<0.001). With these factors we defined a prognostic index (Ip) which allowed assessment of the probability of survival without recurrence: Ip(Xie.x1.41)+(Nbr T.x0.19)+(Size TV.x0.16); Xiesurgical treatment (XieO if transplantation, Xie1 if resection), Nbr.T. and Size TV.number of tumors and size of the most voluminous tumor, respectively, according to the histologic study.Conclusions: These results and this prognostic index are encouraging for liver transplantation as treatment of hepatocellular carcinoma in selected patients with cirrhosis.     

Limits and benefits of exclusive transthoracic hepatectomy approach for patients with hepatocellular carcinoma

BACKGROUND/AIMS: The purpose of this study was to evaluate the results of liver resection in cirrhotic patients for liver hepatocellular carcinoma located near the diaphragm through an exclusive transthoracic approach. METHODOLOGY: Between 1995 and 1999, 19 cirrhotic patients with hepatocellular carcinoma underwent a liver resection through an exclusive transthoracic approach. This approach was indicated in 11 cases for previous upper abdominal surgery, including hepatobiliary surgery in 3 and before liver transplantation in 8. Results of the transthoracic approach were compared to 84 cirrhotic patients who underwent transabdominal limited resection of hepatocellular carcinoma matched for age, sex and localization of the tumor. RESULTS: Resection was feasible by an exclusive transthoracic approach in 18 (95%) cases with a mean operating time of 201 +/- 53 min. In 8 (44%) patients a Pringle maneuver was performed. No postoperative deaths were observed after the transthoracic approach. Pulmonary complications rate was significantly higher (P < 0.001) after transthoracic resection compared to transabdominal resection (67% vs. 25%, P < 0.001). In contrast, ascites were observed in only one (5%) of the transthoracic group compared to 35 (42%) in the transabdominal group (P < 0.01). The resection margin was positive in 3 (17%) after transthoracic approch and in 1 (2%) patient after the transabdominal resection (P < 0.02). In patients who underwent liver transplantation after the transthoracic approach, total hepatectomy was performed without increasing difficulties. CONCLUSIONS: The transthoracic approach is a safe procedure for resection of hepatocellular carcinoma located under the right diaphragm in cirrhotic patients. However, this approach allows only limited resection with a high risk of positive margin, resulting in a restriction of indications either for patients with previous major abdominal surgery than before liver transplantation.     

The risk of hepatocellular carcinoma in cirrhotic patients with small liver nodules on MRI

BACKGROUND AND AIM: The presence of hepatocellular carcinoma (HCC) has important implications for patients with cirrhosis. Studies have not compared the risk of cancer in cirrhotic patients with small liver nodules to cirrhotic patients without nodules. Our aim was to determine the risk of HCC in cirrhotic patients with small liver nodules on MRI compared to those without nodules. METHODS: We conducted a prospective study to determine the rate of HCC in cirrhotic patients with and without liver nodules. Cases were patients with liver nodule(s) less than 2 cm on MRI and controls were cirrhotic patients without nodules. Kaplan-Meier estimates and multivariate analysis were performed to estimate the risk of HCC in the two groups. RESULTS: A total of 310 liver transplant candidates with a mean follow-up of 663 days were included in the study and 133 underwent liver transplant during follow-up. The 1-yr incidence of HCC in the liver nodule group and control group was 11% and 0.5%, respectively, p < 0.001. The adjusted risk for HCC in the liver nodule group was 25 times higher compared to the control group, HR = 25.1 [95% CI 8.0, 78.9]. In 133 candidates who underwent transplant with and without liver nodules the rate of HCC was 11 (50%) and 4 (3.6%), respectively, p < 0.001. CONCLUSION: The incidence of HCC in patients with small liver nodules is significantly higher compared to patients with cirrhosis without liver nodules. The presence of small liver nodules warrants increased imaging surveillance for HCC.     

Clinical Course and Survival after Liver Transplantation for Hepatitis B Virus Infection Complicated by Hepatocellular Carcinoma

Objectives and Methods : The outcome after liver transplantation for HBsAg-positive liver disease complicated by hepatocellular carcinoma is not clearly defined, and in the present study we analyzed the clinical course in 39 patients transplanted for hepatitis B virus (HBV)-re-lated liver disease (group 1) compared with 16 patients with chronic HBV and hepatocellular carcinoma (group 2) and 52 patients with primary hepatocellular carcinoma seronegative for HBsAg (group 3). Results : Despite similar pretransplant viral serology, HBV recurred more often in patients with tumor (group 2) than in nontumor cases (group 1), with 1-yr actuarial cumulative reinfection rates of 85.4% versus 65.0%, respectively ( p < 0.05). In group 2 cases, we observed a more aggressive pattern of HBV-related graft injury with a higher frequency of graft loss (56.3% vs . 12.8%, p < 0.001). Long-term outcome was worse in the group 2 cases, with 5-yr actuarial survival rates of 16.7% compared with 73.2% and 28.2% for groups 1 and 3, respectively. In group 2, recurrence of HBV in the graft, rather than tumor recurrence, was the principal cause of the high mortality observed (56.2% vs. 12.5%), which, in some cases, may have been potentiated by adjuvant chemotherapy. Conclusion : The poor outcome of patients transplanted for HBsAg-positive cirrhosis and hepatocellular carcinoma is due to HBV reinfection of the graft, rather than tumor recurrence. Antiviral agents in association with hepatitis B immunoglobulin would be the most promising approach to improving survival in this patient population.     

Prognostic factors and survival in patients with hereditary hemochromatosis and cirrhosis.

OBJECTIVES: The survival of treated, noncirrhotic patients with hereditary hemochromatosis is similar to that of the general population. Less is known about the outcome of cirrhotic hereditary hemochromatosis patients. The present study evaluated the survival of patients with hereditary hemochromatosis and cirrhosis. METHODS: From an established hereditary hemochromatosis database, all cirrhotic patients diagnosed from January 1972 to August 2004 were identified. Factors associated with survival were determined using univariate and multivariate regression. Survival differences were assessed using the Kaplan-Meier life table method. RESULTS: Ninety-five patients were identified. Sixty patients had genetic testing, 52 patients (87%) were C282Y homozygotes. Median follow-up was 9.2 years (range 0 to 30 years). Nineteen patients (20%) developed hepatocellular carcinoma, one of whom was still living following transplantation. Cumulative survival for all patients was 88% at one year, 69% at five years and 56% at 20 years. Factors associated with death on multivariate analysis included advanced Child-Pugh score and hepatocellular carcinoma. Patients with hepatocellular carcinoma were older at the time of diagnosis of cirrhosis (mean age 61 and 54.6 years, respectively; P=0.03). The mean age at the time of diagnosis of hepatocellular carcinoma was 70 years (range 48 to 79 years). No other differences were found between the groups. CONCLUSIONS: Patients with hereditary hemochromatosis and cirrhosis are at significant risk of developing hepatocellular carcinoma. These patients are older when diagnosed with carcinoma and may have poorer survival following transplantation than patients with other causes of liver disease. Early diagnosis and treatment of hereditary hemochromatosis by preventing the development of cirrhosis may reduce the incidence of hepatocellular carcinoma in the future.     

Hepatocellular carcinoma: impact of waiting list and pre-operative treatment strategies on survival of cadaveric liver transplantation in pre-MELD era in one center in Brazil

BACKGROUND: Liver transplantation is the main treatment option for hepatocellular carcinoma in patients with cirrhosis. AIM: Three months and 3 years survival were analysed in patients with cirrhosis and hepatocellular carcinoma and in patients with only cirrhosis. METHODS: Charts of patients subjected to cadaveric liver transplantation at the Clinical Hospital of the Federal University of Paraná, Curitiba, PR, Brazil, between January 5th of 2001 and February 17th of 2006 were reviewed. Patients were divided into two groups for 3 months and 1 year survival analysis: cirrhosis and hepatocellular carcinoma and cirrhosis only. The two groups were also compared in relation to donor and recipient sex and age, etiology of cirrhosis, Child-Pugh and MELD scores at the time of the transplantation, warm isquemia time, cold isquemia time, units of red blood cells transfused during the transplantation, intensive care unit stay and total hospital stay. RESULTS: One hundred and forty six liver transplantation patients were analysed: 75 were excluded because of incomplete data and 71 were included. General 3 months and 1 year survivals were 77,4% and 74,6% respectively. Patients with hepatocellular carcinoma (n = 12) presented 3 months and 1 year survivals of 100%. These rates were significantly higher than those of patients without hepatocellular carcinoma (n = 59; 72,8% and 69,4%). Mean MELD score, mean Child-Pugh score and mean number of red blood cells transfused were significantly higher in patients without hepatocellular carcinoma. In this group it was also observed more Child-Pugh B and C patients and the diagnosis of cirrhosis because other causes. The rate of Child-Pugh A and hepatitis C was higher in patients with hepatocellular carcinoma. The two groups were identical in all other parameters analysed. CONCLUSION: Patients with cirrhosis and hepatocellular carcinoma presented better 3 months and 1 year survival rates than patients with only cirrhosis. This is possibly due to an early stage of cirrhosis at transplantation of patients with hepatocellular carcinoma.     

Surveillance for early diagnosis of hepatocellular carcinoma: is it effective in intermediate/advanced cirrhosis?

OBJECTIVES: Surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on ultrasonography and alpha-fetoprotein (AFP) measurement, is widely used. Its effectiveness depends on liver function, which affects the feasibility of treatments and cirrhosis-related mortality. We assessed whether patients with intermediate/advanced cirrhosis benefit from surveillance. METHODS: We selected 468 Child-Pugh class B and 140 class C patients from the ITA.LI.CA database, including 1,834 HCC patients diagnosed from January 1987 to December 2004. HCC was detected in 252 patients during surveillance (semiannual 172, annual 80 patients; group 1) and in 356 patients outside surveillance (group 2). Survival of surveyed patients was corrected for the estimated lead time. RESULTS: Child-Pugh class B: cancer stage (P < 0.001) and treatment distribution (P < 0.001) were better in group 1 than in group 2. The median (95% CI) survivals were 17.1 (13.5-20.6) versus 12.0 (9.4-14.6) months and the survival rates at 1, 3, and 5 yr were 60.4%versus 49.2%, 26.1%versus 16.1%, and 10.7%versus 4.3%, respectively (P= 0.022). AFP, gross pathology, and treatment of HCC were independent prognostic factors. Child-Pugh class C: cancer stage (P= 0.001) and treatment distribution (P= 0.021) were better in group 1 than in group 2. Nonetheless, median survival did not differ: 7.1 (2.1-12.1) versus 6.0 (4.1-7.9) months (P= 0.740). CONCLUSIONS: These results suggest surveillance be offered to class B patients and maintained for class A patients who migrate to the subsequent class. Surveillance becomes pointless in class C patients probably because the poor liver function adversely affects the overall mortality and HCC treatments.     

Liver transplantation for hepatocellular carcinoma

Liver transplantation has become the best option in patients with decompensated cirrhosis and a small hepatocellular carcinoma. Indeed, because of the severity of cirrhosis, resection is usually impossible and in addition, transplantation provides survival rates close to those obtained in cirrhotic patients without malignancy (70 to 80% 3-year survival rate). In patients with a small hepatocellular carcinoma and compensated cirrhosis, both resection and transplantation can be performed. Because of the scarcity of donors, there have been reservations concerning transplantation in patients who otherwise could have undergone resection. However, there is increasing evidence that long-term results of transplantation are significantly superior to those of resection. Therefore, patients with a small hepatocellular carcinoma and compensated cirrhosis are increasingly considered as suitable candidates for transplantation. In contrast to cirrhotic patients with a small hepatocellular carcinoma, patients with large and/or multifocal tumors should no longer be transplanted because of a high rate of early recurrence and the accelerated course of tumor progression due to immunosuppression, both factors being the source of poor results. On rare occasions, hepatocellular carcinoma develops in patients without underlying liver disease. In such cases the tumor is usually recognized when it is large and symptomatic. The absence of underlying liver lesions offers the possibility of extended resection. However, in case of nonresectable (bilobar) tumors or limited recurrence after resection, transplantation may be considered due to the slow progression this subtype of hepatocellular carcinoma. Whatever the underlying liver parenchymal status, efforts should be made to reduce the risk of recurrence.     

Better post-resectional survival in female cirrhotic patients with hepatocellular carcinoma

BACKGROUND/AIMS: Hepatocellular carcinoma is notably more prevalent in male. The purpose of this study was to assess the surgical results in male and female cirrhotic patients. METHODOLOGY: The surgical outcomes of 129 hepatocellular carcinoma patients with cirrhosis, including 109 males and 20 females, who had undergone hepatic resection were studied. The clinical, histologic features, DNA ploidy and proliferative phase fraction of tumor and cirrhotic liver were compared between male and female patients. RESULTS: Female patients had significantly lower incidences of history of smoking (5.6% vs. 52.9%, P < 0.001), alcohol intake (5.6% vs. 42.3%, P = 0.003) and hepatitis B surface antigen positivity (47.1% vs. 73.5%, P = 0.028) than male. Cell-cycle analysis of tumor part revealed female had a significant lower G2M phase fraction (3.4%) than male (5.7%) (P = 0.027). The 1-, 3-, and 5-year disease-free survival rates in male and female patients were 65.5% and 88.2%, 36% and 64.4%, and 29.7% and 64.4%, respectively. Female patients had a significantly better disease-free survival than male (P = 0.034, log-rank test). CONCLUSIONS: Female hepatocellular carcinoma with cirrhosis had lower incidences of hepatitis B surface antigenemia, alcohol abuse and lower DNA postsynthetic phase fraction in tumor tissue than male. Consequently, female hepatocellular carcinoma with cirrhosis had better survival than male.     

Hepatic resection for hepatocellular carcinoma existing with liver cirrhosis

BACKGROUND/AIMS: Hepatocellular carcinoma is usually complicated with liver cirrhosis, which makes its treatment difficult. Also a high rate of recurrence exists after surgical resection. However, how the prognosis after surgical treatment is affected by the severity of coexisting cirrhosis has not been clarified. METHODOLOGY: We compared the postoperative longterm courses of hepatocellular carcinoma patients with cirrhosis according to the liver function. All 112 hepatocellular carcinoma patients in this study underwent curative hepatic resection, and were classified into three groups according to the severity of liver dysfunction. The ICG R15' (indocyanine green retention test) normal: < 10%) was used in this study. Patients whose ICG R15' was less than 20% were classified as group I of 62, patients equal to 20% or between 20% and 30% as group II of 24, and patients equal to and more than 30% as group III of 26. RESULTS: In this series, 76 of 112 patients had recurrence (68%). A second hepatic resection was performed in six cases of group I and one case in group II. Fifty-eight of 76 recurrent cases (76%) were treated with transcatheter arterial chemoembolization. A total of eleven cases had no transcatheter arterial chemoembolization in the three groups: 3 cases in group I, 5 cases in group II, and 3 cases in group III; The three cases of group III had no treatment because of extremely poor liver dysfunction, whilst the 8 patients without transcatheter arterial chemoembolization in groups I and II had hepatocellular carcinoma itself and other diseases. The 1-, 3-, and 5-year survival rates after recurrence were 92%, 48%, and 14%, respectively, in group I; 83%, 37%, 12%, respectively, in group II; and 66%, 30%, 0%, respectively, in group III. The prognosis was significantly worse according to the degree of liver dysfunction (p = 0.0206). CONCLUSIONS: The prognosis of hepatocellular carcinoma with liver cirrhosis is affected not only by hepatocellular carcinoma itself, but also by the severity of the coexisting cirrhosis. Moreover, the cirrhotic liver can decline due to surgery. Surgical resection of this disease should be performed after careful patient selection and using a less invasive technique.     

Results of liver transplantation in patients with hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies worldwide. Liver transplantation has emerged as a good option for early-stage hepatocellular carcinoma yielding survival rates as good as for recipients without this type of tumor. OBJECTIVE: To assess the outcome of cirrhotic patients with hepatocellular carcinoma undergoing liver transplantation at the Liver Transplantation Service of the "Hospital de Clinicas", Federal University of Paraná, Curitiba, PR, Brazil. METHODS: Retrospective study of cirrhotic patients with hepatocellular carcinoma undergoing orthotopic liver transplantation at the mentioned Institution between September 1991 and September 2000. The diagnosis of hepatocellular carcinoma was established during the pretransplant workup in five patients and the tumor was an incidental finding in the native liver in three. The indication for liver transplantation was restricted to solitary tumor equal to or less than 5 cm or up to 3 nodules, with each nodule measuring less than 3 cm, and no evidence of vascular invasion or extrahepatic spread. Patient survival and evidence of tumoral recurrence posttransplant were evaluated. RESULTS: The most common cause for pretransplantation liver disease was hepatitis C virus (50%). On examination of the explanted liver, the majority of patients (6/8, 75%) had a single lesion; one patient had two nodules and one had a multifocal hepatocellular carcinoma found incidentally in the native liver. Tumor size ranged from 0.2 to 5.0 cm. All cases had neither vascular invasion nor linfonodal envolvement. All patients remained alive and free of tumor recurrence at the time of the study with a mean follow-up of 18.5 months (range, 5-29 months). CONCLUSION: Liver transplantation is a good therapeutic option for early stage hepatocellular carcinoma arising in cirrhotic patients. With proper selection, liver transplantation can offer excellent survival rates free of tumor recurrence.     

Results of liver transplantation in patients with preoperative diagnosis of hepatocellular carcinoma

BACKGROUND: [corrected] Hepatocellular carcinoma is the most frequent malignant hepatic tumor in humans, and its association with cirrhosis makes the therapeutic approach still a challenge. Liver transplantation is the treatment of choice for cirrhotic patients with unresectable early hepatocellular carcinoma AIM: To evaluate the post-transplant outcome of a cohort of 15 cirrhotic patients with preoperative diagnosis of unresectable early hepatocellular carcinoma according the Milan criteria who underwent liver transplantation between September 1991 and December 2003 METHODS: We retrospectively reviewed the clinical data from 15 liver transplant recipients and the explanted livers were assessed for the efficacy of preoperative therapy. Patient survival and tumor recurrence were evaluated as primary outcome measures RESULTS: The mean age of the patients was 49.2 +/- 14.3 years and hepatitis C was the etiology of the underlying liver disease in 60%. Preoperative therapy, either chemoembolization or percutaneous ethanol injection, was performed in 12 (86%) patients. Complete necrosis of all tumoral lesions were observed in 5 of 12 patients (44,66%); all others had variable amounts of viable tumor in the explanted liver. Only 4 of the 15 (26.6%) explanted livers had microscopic vascular invasion. The median post-transplant follow-up was 33 months (range: 8-71 months) and no tumor recurrence was detected during this period. The only death was an early event not related to the tumor. The recurrence-free survival rates at 1 and 3 years were 93% CONCLUSION: Liver transplantation has emerged as a good alternative for cirrhotic patients with early hepatocellular carcinoma not amenable to curative resection, offering excellent recurrence-free survival rates.     

Influence of prognostic factors on the outcome of liver transplantation for hepatocellular carcinoma on cirrhosis: a univariate and multivariate analysis

BACKGROUND/AIMS: Hepatocellular carcinoma is related to liver cirrhosis in 70-85% cases. During the '80s, the best treatment was represented by liver resection. Recently, liver transplantation has been introduced as an optimal therapeutic alternative. The purpose of this study is to select the best candidates for liver transplantation considering several prognostic factors that are related to tumor characteristics. METHODOLOGY: Among 573 liver transplantations, we have retrospectively analyzed 87 patients undergoing liver transplantation for hepatocellular carcinoma on cirrhosis; in 30 (34.5%) patients, hepatocellular carcinoma was an incidental finding in the surgical specimen. RESULTS: Operative mortality was 2.2% (2/87). Twenty-five patients died during the follow-up. The main cause of death was represented by tumor recurrence in 10.3% of cases. The 3-year and 5-year overall survival was 71.6% and 66.2% respectively. On a univariate analysis, the only variable significantly related with overall-survival was alpha-fetoprotein levels (p=0.01). Furthermore, alpha-fetoprotein, the diameter of tumor greater than 3 cm, the presence of satellite nodules, Edmonson's grade III-IV, micro-macro vascular thrombosis, and TNM stadium III-IV were significantly related with the development of tumor recurrence. On a multivariate analysis, only alpha-fetoprotein (p=0.01, Risk ratio = 2.7) resulted as a risk independent factor of patient overall-survival; vascular invasion (p=0.02, Risk ratio = 2.1) was predictive of tumor recurrence. CONCLUSIONS: Liver transplantation is a good therapeutic option in a selected group of patients, with a small nodule (<3 cm), low alpha-fetoprotein levels (<20 ng/mL), with absence of micro-macro vascular thrombosis in which conventional liver resection is unfeasible.     

Liver resection in advanced hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to assess the results of major liver resection in patients with advanced hepatocellular carcinoma in terms of safety and survival. METHODOLOGY: The subjects of this study are 19 patients that underwent 24 resections for advanced (stage IV) hepatocellular carcinoma. Eighteen of these resections were performed for primary tumor and 6 were repeat resections. Nine patients presented without cirrhosis, 5 with cirrhosis, and 5 patients had the fibrolamellar variant of hepatocellular carcinoma. RESULTS: Hospital mortality was recorded in 1 case (5%). Morbidity was noted in 7(37%) cases. All patients with fibrolamellar variant of hepatocellular carcinoma are alive at 78, 41, 24, 12 and 9 months (P = 0.008), compared with a median survival of 18 and 9 months for the noncirrhotic hepatocellular carcinoma and cirrhotic hepatocellular carcinoma groups, respectively (P = 0.24). CONCLUSIONS: We conclude that an aggressive policy of major liver resection with vascular reconstruction was justifiable in patients with advanced fibrolamellar variant of hepatocellular carcinoma and in selected patients with noncirrhotic hepatocellular carcinoma, and of doubtful value in patients with cirrhosis.     

Incidence of hepatocellular carcinoma in outpatients with cirrhosis in Brazil: A 10-year retrospective cohort study

AIM To determine the incidence of hepatocellular carcinoma(HCC) and the impact of HCC surveillance on early diagnosis and survival of cirrhotic outpatients. METHODS In this retrospective cohort study, cirrhotic outpatients undergoing HCC surveillance between March 2005 and March 2014 were analyzed. Exclusion criteria were HIV coinfection; previous organ transplantation; diagnosis of HCC at first consultation; missing data in the medical chart; and less than 1 year of follow-up. Surveillance was carried out every six months using ultrasound and serum alpha-fetoprotein determination. Ten-year cumulative incidence and survival were estimated through Kaplan-Meier analysis. RESULTS Four hundred and fifty-three patients were enrolled, of which 57.6% were male. Mean age was 55 years. Hepatitis C virus and heavy use of alcohol were the main etiologic agents of cirrhosis. HCC was diagnosed in 75 patients(16.6%), with an estimated cumulative incidence of 2.6% in the 1st year, 15.4% in the 5th year, and 28.8% in the 10 th year. Median survival was estimated at 17.6 mo in HCC patients compared to 234 mo in non-HCC patients(P 0.001). Early-stage HCC was more often detected in patients who underwent surveillance every 6 mo or less(P = 0.05). However, survival was not different between patients with early stage vs non-early stage tumors [HR = 0.54(0.15-1.89), P = 0.33].CONCLUSION HCC is a frequent complication in patients with cirrhosis and adherence to surveillance programs favors early diagnosis.     

Serum levels of estrogens and testosterone in cirrhotic men with and without hepatocellular carcinoma

Serum levels of estrogens and testosterone were measured in 25 male patients with hepatocellular carcinoma and associated cirrhosis of the liver and in another 25 male patients with cirrhosis only. The two groups were statistically comparable in terms of age distribution, duration of liver disease, incidence of alcohol abuse, incidence of hepatitis B surface antigenemia, and grade of hepatic dysfunction. Estrone was significantly elevated in both groups of patients. Estradiol concentrations were above normal in 10 patients with hepatocellular carcinoma and in 11 with cirrhosis only. All patients had normal concentrations of estriol. There were no statistical differences between the two groups in either individual or total estrogen levels (estrone 0.05 less than p less than 0.1). Eight of the patients with hepatocellular carcinoma and 5 of the cirrhotics had lower testosterone levels than normal, but this difference was not significant. However, the estrone to testosterone ratios were significantly higher in the hepatocellular carcinoma group than in the cirrhosis group (p less than 0.05). The present study seems to indicate that hyperestrogenemia commonly seen in male patients with liver cirrhosis may play some role in hepatic carcinogenesis of cirrhotic livers. Further studies are needed to determine if the estrone to testosterone ratio is implicated in hepatocarcinogenesis in cirrhotic men.     

Risk of HBV reinfection after liver transplantation in HBsAg-positive cirrhosis: Primary hepatocellular carcinoma is not a predictor for HBV recurrence

Abstract: Two hundred and twenty-eight patients who underwent orthotopic liver transplantation for hepatitis B-related cirrhosis in 11 European Liver Transplant Centers were collected. The male/female ratio was 184/44, with a median age of 41 years (13–66). In 55 patients (24%) hepatocellular carcinoma was associated with liver disease. All cases were stratified for pre-orthotopic liver transplantation viral characteristics: HBV-DNA neg/HBeAg neg: 106 patients (47%), HBV-DNA neg/Delta pos: 80 (35.5%), HBV-DNA pos/HBeAg pos: 28 (12.5%), other 14 (5%). In 49 patients (21.4%) post-orthotopic liver transplantation passive prophylaxis with anti-HBs immunoglobulins was not followed, while in 179 patients the anti-HBs serum titer was kept above 100–200 mU/ml. Overall 5-year actuarial survival of the series was 54%. One hundred and eighty-five patients were evaluable for HBsAg reappearance in the serum at various intervals after orthotopic liver transplantation. Overall 3-year HBV-free survival of these patients was 55%. There was a significant difference in 3-year HBV-free survival between HBV-DNA neg (52%), HBV-DNA pos (13%) and Delta pos (73%) patients (p: 0.03). Sixty-three percent of patients in the prophylaxis group were HBV-free, compared to only 25% of untreated patients (p>0.001). Three-year HBV-free survival in patients with or without HCC was 44% and 59%, respectively. Cox-multivariate analysis revealed that only post-transplantation prophylaxis (p: 0.003) and pre-transplantation viral activity (p: 0.004) can be considered as independent factors affecting HBV recurrence. Candidates with hepatocellular carcinoma in HBV-cirrhosis should not be excluded from orthotopic liver transplantation, supporting the idea of a higher risk of post-transplantation viral reactivation.     

Monoclonal anti-AFP immunoscintigraphy of human hepatocellular carcinoma. Influence of biological, anatomical and vascular factors

The actual interest of immunoscintigraphy for the detection of alphafetoprotein-producing liver tumors was investigated by both visual examination and quantitative analysis in 61 patients with either hepatocellular carcinoma (39 patients, group I), secondary liver cancer (11 patients, group II), or non tumoral liver (9 cirrhosis, 2 healthy liver, group III): All patients received injections of 123I-anti-alphafoetoprotein monoclonal antibodies and planar scans were performed after 28 hours. Only 18 out of 39 hepatocellular carcinoma-bearing patients had a positive scan (46 p. 100). Such a moderate sensibility was due to a striking inhibitory influence of cirrhosis: the positivity rate was 6/24 and 12/15 respectively when hepatocellular carcinoma was and was not associated with cirrhosis (p less than 0.01). Specificity was also moderate (55 p. 100) for detection of hepatocellular carcinoma in tumor-bearing patients (group I and II). In the absence of cirrhosis, the intensity of the tumoral uptake was highly correlated with high serum alphafoetoprotein level (p less than 0.001) and tumor arterial hypervascularization (p less than 0.01). Anti-alphafoetoprotein monoclonal antibody uptake by the extratumoral liver was found to be very specific of hepatocellular carcinoma since it was high in 23 out of 39 patients of group I but in only 1 out of 22 in groups II and III (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholangiocarcinoma in liver cirrhosis

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is usually associated with chronic liver diseases and liver cirrhosis, while conversely, cholangiocarcinoma (CC) usually occurs in a non-cirrhotic liver. The purpose of the present study was to evaluate CC in liver cirrhosis. METHODS: Between January 1998 and December 1999, 26 patients with CC were retrospectively reviewed. The occurrence of CC in chronic hepatitis B infection-related liver cirrhosis, portal vein thrombosis (PVT) and survival were analyzed. RESULTS: Twenty-six patients with CC (19 with a non-cirrhotic liver and seven with chronic hepatitis B infection-related liver cirrhosis) were included in the present study. All cases of CC in the cirrhotic group were incidentally discovered during routine screening for HCC. The mean age (+/- SD) was 58.8 +/- 14 years in the cirrhotic group and 73.2 +/- 15.9 years (P = 0.001) in the non-cirrhotic group. When compared to the cirrhotic group, the non-cirrhotic group had a higher median level of albumin (42 compared to 30 g/L, P = 0.005), bilirubin (117.5 compared to 18 micro mol/L, P = 0.01), alkaline phosphatase (291.5 compared to 100 U/L, P = 0.001) and gamma glutamyl transpeptidases (215.5 compared to 31 U/L, P = 0.001). In contrast, the cirrhotic group had a higher median prothrombin time (PT) compared to the non-cirrhotic group (18.2 compared to 12 s, P = 0.05). In the non-cirrhotic group, only one patient (5.3%) showed evidence of PVT on a computerized tomography and Doppler ultrasound, while in the cirrhotic group six patients (85.7%) had PVT (P < 0.001). The median survival period in the cirrhotic group was six months (range 2-24 months) compared to 16 months (range 6-41 months) in the non-cirrhotic group (P = 0.036). CONCLUSION: CC in cirrhotic liver presented at a younger age and patients who developed CC were prone to PVT. The survival period was also shorter in comparison to that of non-cirrhotic liver patients.