Trans-catheter arterial chemoembolisation for hepatocellular carcinoma in patients with viral cirrhosis: role of combined staging systems,Cancer Liver Italian Program (CLIP) and Model for End-stage Liver Disease (MELD), in predicting outcome after treatment

BACKGROUND: Trans-catheter arterial chemoembolisation (TACE) is the most common palliative treatment for hepatocellular carcinoma (HCC). The therapeutic options depend both on the characteristics of the tumour and on functional staging of the cirrhosis. AIM: To evaluate the effects of TACE on the survival of cirrhotic patients with HCC according to different staging systems [Okuda score, Cancer Liver Italian Program (CLIP) score, Model for End-stage Liver Disease (MELD) score] and in relation to the side-effects of TACE. METHODS: Fifty cirrhotic patients, 36 CTP class A and 14 class B, underwent 106 TACE treatments with mitoxantrone. Survival at 12, 24, and 36 months was evaluated. RESULTS: MELD at 12 months and CLIP at 24 months were identified as significant variables associated with survival. Combined cut-offs of CLIP and of MELD identified four subgroups of patients with different survivals, at 12, 24 and 36 months, respectively: CLIP >or= 2 and MELD >or= 10 (63%, 20% and 0%), CLIP < 2 and MELD >or= 10 (73%, 40% and 22%), CLIP >or= 2 and MELD < 10 (73%, 40% and 22%) and CLIP < 2 and MELD < 10 (100%, 63% and 50%). Post-TACE side-effects proved to have no influence on survival. CONCLUSION: In patients with poor probability of survival (CLIP >or= 2 and MELD >or= 10), TACE must be planned with a great deal of caution, while in patients with possibly good outcomes (CLIP < 2 and MELD < 10), more 'aggressive' therapy should be taken into consideration.     

Ki67 在HBV 相关肝细胞癌病理组织中的表达及其临床意义

目的探讨细胞核增殖抗原Ki67 在乙型肝炎病毒（HBV）相关肝细胞癌（HCC）病理组织中的表达及其与临床病理指标的关联性。方法134 例HBV 相关HCC 患者按Ki67 阳性细胞所占百分数（Ki67 指数）分为Ki67 指数＜10%（阴性）组30 例和≥10％（阳性）组104 例。采用免疫组化法检测Ki67 在正常及不同分化程度肝组织中的表达情况。分别计算2 组Ki67 指数与年龄、性别、磷脂酰肌醇蛋白3(GPC3)、组织学分级、BCLC 分期、门脉转移、甲胎蛋白（AFP）、肝功能Child-pugh 分级资料的相关性。依Ki67 指数区间设定评分以评估Ki67 评分与BCLC 分级的关系。结果（1）SP 染色结果显示,Ki67 在正常肝组织、高分化、中分化及低分化组织中的表达强度呈增加趋势。（2）阳性组Ki67 指数与BCLC 分期、门脉转移、组织学分级、GPC3、AFP 及Child-pugh 分级呈正相关（P＜0.05）;阴性组Ki67 指数与各临床指标均无相关性（P > 0.05）。（3）Ki67 评分随着BCLC 分级的进展呈增加趋势。结论阳性组Ki67 指数联合患者的GPC3、组织学分级、BCLC 分期、门脉转移、AFP、肝功能Child-pugh 分级可评估患者HCC 的严重程度,其表达水平有望成为HBV 相关HCC 早期诊断、晚期预后评估的重要指标。     

Pilot study: rapamycin in advanced hepatocellular carcinoma

Background The PI3K/Akt/mTOR signal pathway is involved in hepatocarcinogenesis. Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Aim To study the toxicity and tolerability of rapamycin therapy in patients with advanced hepatocellular carcinoma (HCC). Methods Between June 2005 and February 2007, patients with advanced HCC, not eligible for any established therapy, were included in the study. Results Eighteen patients (F/M: 5/13) with compensated liver cirrhosis (Child A n = 11, Child B n = 5, Child C n = 2) and histologically proven HCC were included in this study. According to the BCLC staging system, most of the patients enrolled had an advanced HCC: BCLC stage B: n = 2, Barcelona Clinic Liver‐Cancer (BCLC) stage C: n = 14, BCLC stage D: n = 2. Overall, therapy with rapamycin was well tolerated. Most common toxicities were thrombocytopaenia and anaemia. We did not observe any partial or complete tumour response. At 3 months, two patients had stable disease and at 6 months, all patients had progressed. The median overall survival was 5.27 months, median time to progression was 3 months. Conclusion Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective.     

Impact of evidence‐based medicine on the treatment of patients with unresectable hepatocellular carcinoma

Aliment Pharmacol Ther 31 , 493–501

Summary

Background A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well‐selected patients with unresectable hepatocellular carcinoma (HCC). Aim To access whether this information has modified the use of TACE in clinical practice. Methods From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4‐year periods (1999–2002, n = 161 and 2003–2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival. Results Patients undergoing TACE increased in the 2003–2006 period (from 62% to 73%, P = 0.035), with an increase in of Child‐Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999–2002 period, there was no significant difference in survival between TACE‐treated and untreated patients, while in the 2003–2006 period, TACE‐treated patients survived longer (P < 0.0001). Conclusions Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well‐compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage.     

Transcatheter arterial chemoembolization vs. chemoinfusion for unresectable hepatocellular carcinoma in patients with major portal vein thrombosis

Background  Transcatheter arterial chemoembolization (TACE) has been limited in palliative treatment of unresectable hepatocellular carcinoma (HCC) with major portal vein (PV) invasion due to the possibility of liver failure following embolization. Transcatheter arterial chemoinfusion (TACI) has been an option in such cases.
Aim  To compare clinical outcomes after TACE vs. TACI in HCC patients with major PV occlusion.
Methods  We compared clinical outcomes after TACE vs. TACI in HCC patients with major PV occlusion. From 2005 to 2007, 110 HCC patients with major PV thrombosis were treated with TACE ( n  = 49) or TACI ( n  = 61).
Results  The morbidity rate was similar for both TACE (6.1%) and TACI (6.5%) patients, and complications were adequately managed using medical treatment. The Kaplan–Meier survival analysis showed that the survival period was significantly longer for the TACE group (median: 14.9 months) than for the TACI (median: 4.4 months) group ( P  < 0.001). There was a higher probability of death in the TACI group than in the TACE group in both our multivariate Cox-proportional hazards (OR 3.09, P  < 0.001) and the propensity score-matched (27 pairs) cohort analyses (OR 2.27, P  = 0.024).
Conclusions  Transcatheter arterial chemoembolization can be safely performed in HCC patients with main PV occlusion. Compared with TACI, TACE may result in longer survival of HCC patients with major PV occlusion.     

肝细胞肝癌中Notch1蛋白和ADAM17蛋白的表达及其临床意义

目的探讨Notch1蛋白和ADAM 17蛋白在肝细胞肝癌(HCC)中的表达及临床病理学意义。方法采用免疫组织化学ENVISION法检测Notch1和ADAM 17蛋白在78例HCC组织和10例癌旁正常肝组织标本中的表达,并分析其与临床病理参数的相关性。结果 HCC组织Notch1的表达率为66.67%(52/78),明显高于癌旁组织的20.00(2/10)(P<0.05);HCC组ADAM17表达率为87.18%(68/78),明显高于癌旁组织的10.00(1/10)(P<0.01)。Notch1和ADAM17阳性表达与HCC大小、TNM分期、有无转移及生存时间相关。结论 Notch1和ADAM17蛋白可能协同参与了HCC的发生发展和转移,并可以作HCC预后判断的指标。     

Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib

Background Sorafenib is the new reference standard for patients with advanced hepatocellular carcinoma (HCC). Aim To identify prognostic factors in sorafenib‐treated HCC patients and to evaluate outcomes with respect to liver function. Methods In this retrospective study, 148 HCC patients received sorafenib 400 mg b.d. across 11 Austrian institutions. Seventy‐eight HCC patients who received best supportive care (BSC) in the pre‐sorafenib era served as a control. Results In sorafenib‐treated patients, low baseline α‐fetoprotein, low Child–Pugh (CP) score, compensated cirrhosis, and low baseline aspartate aminotransferase (AST) were associated with significantly longer overall survival (OS) on univariate analysis. CP score and baseline AST remained independent prognostic factors on multivariate analysis. In patients with Barcelona Clinic liver Cancer (BCLC) stage B or C HCC (sorafenib: n = 139; BSC: n = 39), CP‐A patients had a median OS of 11.3 (sorafenib [n = 76]) vs. 6.4 (BSC [n = 17]) months (P = 0.010), and CP‐B patients had a median OS of 5.5 (sorafenib [n = 55]) vs. 1.9 (BSC [n = 22]) months (P = 0.021). In the sorafenib group, median OS according to baseline AST was 11.8 (<100 U/L [n = 58]) vs. 3.9 (≥100 U/L [n = 15]) months for CP‐A patients (P = 0.127), and 6.5 (<100 U/L [n = 33]) vs. 2.1 (≥100 U/L [n = 21]) months for CP‐B patients (P = 0.011). There was no survival difference between sorafenib and BSC in patients with BCLC stage D HCC (1.5 vs. 1.4 months; P = 0.116). Conclusions Sorafenib was associated with improved survival in both CP‐A and CP‐B patients. In CP‐B patients, baseline AST may be helpful in determining which patients are most likely to benefit from sorafenib.     

不同方案经导管栓塞治疗对肝癌疗效影响的回顾性分析

目的评价经导管不同方案栓塞治疗对肝癌疗效的影响。方法收集我院2010年收治行经导管栓塞治疗的BCLC分期为A期或B期的肝癌患者44例,根据采用经动脉栓塞（TAE）、经动脉碘油化疗栓塞（TOCE）及联合采用TAE、TOCE及经动脉化疗栓塞（TACE）治疗将其分为TAE组、TOCE组及混合组。结果所有44例患者中入选TAE组21例,入选TOCE组15例,入选混合组8例,3组肝癌患者生存期的差异无统计学意义。结论经导管不同方案栓塞治疗对肝癌患者的生存期无明显影响。     

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma – a long-term follow-up study

Background  The long-term outcome of percutaneous acetic acid injection (PAI) and percutaneous ethanol injection (PEI) for treating small hepatocellular carcinoma (HCC) remains unclear.
Aim  To compare the long-term outcome of PAI vs. PEI for treating small HCC.
Methods  From July 1998 to July 2004, 125 patients with small HCC were enrolled. Seventy patients receiving PAI and 55 patients receiving PEI were enrolled. There were no significant differences in the clinical characteristics between the two groups. Tumour recurrence and survival rates were assessed.
Results  Mean follow-up time was 43 months. The local recurrence rate and new tumour recurrence rate were similar between the PAI and PEI groups. The PAI group had significantly better survival than the PEI group ( P  = 0.027). Multivariate analysis revealed that PAI was the significant factor associated with overall survival [PAI vs. PEI, RR: 0.639, 95% CI: (0.419–1.975), P  = 0.038]. The treatment sessions required to achieve complete tumour necrosis were significantly fewer in the PAI group than in the PEI group (2.4 ± 1.0 vs. 2.9 ± 1.3, P  = 0.018).
Conclusion  Percutaneous acetic acid injection required fewer treatment sessions than PEI and provided better survival after long-term follow-up.     

Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial

BACKGROUND: In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment. METHODS: The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death. RESULTS: 496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis. CONCLUSIONS: the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.     

Predicting survival in patients with hepatocellular carcinoma treated by transarterial chemoembolisation

Aliment Pharmacol Ther 2011; 34: 196–204

Summary

Background Transarterial chemoembolisation (TACE) is first‐line treatment in unresectable hepatocellular carcinoma (HCC) and rescue treatment after failure of radical treatments in early stage HCC. Prognostic tools for HCC using time‐fixed Cox models may be unreliable in patients treated with TACE because time‐varying predictors interact. Aim To explore time‐dependent variables as survival predictors in patients with HCC receiving TACE as first‐line or second‐line treatment. Methods Eighty four consecutive patients with HCC (mean age 68; male gender 62%; Child‐Pugh class: A n = 73, B n = 11; Barcelona Clinic Liver Cancer class: A n = 44, B n = 24, C n = 16) treated with TACE were enrolled. Clinical, laboratory and radiological follow‐up data were collected from the time of first treatment. Time‐fixed and time‐dependent Cox analyses were done. Results Overall survival rates were 89.6% (95% CI 82.5–97.2) at 12 months, 58.8% (95% CI 46.2–74.9) at 24, 35.4% (95% CI 22.3–56.1) at 36 and 17.2% (95% CI 7.0–41.7) at 48 months. Performance status (P < 0.001), number of nodules (P < 0.016) and prior therapy (P = 0.017) were the only variables strongly linked to survival by time‐fixed Cox model. Performance status (P < 0.001), prior therapy (P = 0.005), number of treatments (P = 0.013), complete response after TACE (P = 0.005) and bilirubin level (P < 0.001) were associated with survival using a time‐dependent Cox model. Conclusions Survival after TACE is influenced most by performance status, complete response and bilirubin. Compared with the time‐fixed models, a time‐dependent Cox model has the potential to estimate a more precise prognosis in HCC patients treated with TACE.     

Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease

Background  Small-intestinal bacterial overgrowth (SIBO) is known to be present in patients with cirrhosis, predisposing to various complications.
Aim  To determine the frequency of SIBO in cirrhotics and correlate with severity of cirrhosis.
Methods  Small-intestinal bacterial overgrowth was determined by glucose–hydrogen breath test (GHBT). A basal breath-hydrogen >20 ppm or a rise by ≥12 ppm above baseline following glucose administration was taken as positive test. Prevalence of SIBO in cirrhotics was compared with healthy controls and correlated with severity of cirrhosis.
Results  Of the 53 cirrhotics, 26 (49%) had SIBO, compared to one (8%) control ( P  = 0.010). The prevalence of SIBO increased with severity of cirrhosis (Child–Pugh A 20%, B 52% and C 73%; P  = 0.013). On multivariate analysis, SIBO was independently associated with serum bilirubin and ascites. The best cut-off of serum bilirubin was ≥2 mg/dL [AUROC 0.77 (95% CI 0.64–0.90)] predicting SIBO with sensitivity 65%, specificity 81%, positive predictive value 77%, negative predictive value 71% and accuracy 74%. Patients having combination of ascites and serum bilirubin ≥2 mg/dL had 82% chance, while patients having neither had only 10% chance of having SIBO.
Conclusions  Small-intestinal bacterial overgrowth was prevalent in about half of cirrhotics. Its frequency increased with increase in severity of cirrhosis. Ascites and raised serum bilirubin reliably predicted presence of SIBO.     

Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio

1 Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a central compound of the mitochondrial respiratory chain. The main adverse effect of statins is a toxic myopathy possibly related to mitochondrial dysfunction.
2 This study was designed to evaluate the effect of lipid-lowering drugs on ubiquinone (coenzyme Q10) serum level and on mitochondrial function assessed by blood lactate/pyruvate ratio.
3 Eighty hypercholesterolaemic patients (40 treated by statins, 20 treated by fibrates, and 20 untreated patients, all 80 having total cholesterol levels >6.0  mmol l⁻¹) and 20 healthy controls were included. Ubiquinone serum level and blood lactate/pyruvate ratio used as a test for mitochondrial dysfunction were evaluated in all subjects.
4 Lactate/pyruvate ratios were significantly higher in patients treated by statins than in untreated hypercholesterolaemic patients or in healthy controls ( P <0.05 and P <0.001). The difference was not significant between fibrate-treated patients and untreated patients.
5 Ubiquinone serum levels were lower in statin-treated patients (0.75  mg l⁻¹±0.04) than in untreated hypercholesterolaemic patients (0.95  mg l⁻¹±0.09; P <0.05).
6 We conclude that statin therapy can be associated with high blood lactate/pyruvate ratio suggestive of mitochondrial dysfunction. It is uncertain to what extent low serum levels of ubiquinone could explain the mitochondrial dysfunction.     

Natural course of treated and untreated chronic HCV infection: results of the nationwide Hepnet.Greece cohort study

Background  Interferon (IFN-α)-based regimens have been used with varying success in the treatment of chronic hepatitis C (CHC) for over two decades. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results.
Aim  To investigate the natural course of IFNα-based -treated and untreated patients with CHC by analysing data from the HEPNET.GREECE study.
Methods  We retrospectively analysed 1738 patients from 25 Greek Centres (median age 40.1; males 57.6%; cirrhosis 9.2%), 734 untreated and 993 treated with IFNα-based regimens [44.7% sustained viral response (SVR)], followed-up for median 25.2 and 46.8 months, respectively.
Results During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P  < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit.
Conclusions IFNα-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR.     

Sorafenib extends the survival time of patients with multiple recurrences of hepatocellular carcinoma after liver transplantation

Aim:

To determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver transplantation in a Chinese population.

Methods:

Twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization (TACE) or TACE combined with sorafenib.

Results:

The median survival times (MST) after multiple recurrences was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The difference was significant in MST between the two groups (P=0.005). The TACE + sorafenib group had more stable disease (SD) patients than the TACE group. The most frequent adverse events of sorafenib were hand–foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE+sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP.

Conclusion:

Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.     

Clip评分系统在肝癌经肝动脉化疗栓塞术后急性肝损伤的意义

目的探讨Clip评分系统在原发性肝癌(HCC)经肝动脉化疗栓塞术(TACE)后急性肝损伤的意义。方法对151例HCC自诊患者行TACE术后发生急性肝损伤的临床资料进行回顾性分析。结果Clip评分系统得分为2分的患者接受TACE术后发生急性肝损伤明显(P<0.05)。结论Clip评分系统由于兼顾了肿瘤及肝功能两方面因素,在预测TACE术后发生急性肝损伤方面显示其独特优势,是评价TACE术后发生急性肝损伤及肝功能衰竭的有效手段。     

肝细胞癌化疗栓塞后经皮瘤内注射无水乙醇的疗效

目的比较肝动脉化疗栓塞术(THAE)后经皮瘤内注射无水乙醇(PEI)与单纯THAE治疗单个肝细胞癌的疗效。方法53例肝细胞癌随机分成A(26例)、B(27例)两组。A组单纯THAE治疗;B组THAE治疗后,在CT引导下行PEI治疗。结果THAE组肿瘤治疗的部分缓解率为26.7%,1、2、3年生存率分别为56.0%、30.0%、0.0%。THAE+PEI组肿瘤治疗的部分缓解率为55.5%(P<0.05),1、2、3年生存率分别为91.0%、57.0%、22.0%(P<0.05)。结论THAE+PEI较单纯THAE对单个肝细胞癌的治疗更安全有效。     

Etiology, natural history and treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is linked to environmental, dietary and lifestyle factors. Patients with cirrhosis and chronic carriage of hepatitis B virus (HBV) are at risk for HCC at annual rates of 3%. HCC risk is particularly high in patients with evidence of cirrhosis and histological markers of increased liver cell proliferation. In addition, thrombocytopenia, prolonged prothrombin time and over 55 years of age also predict the development of HCC. Treatment options are defined according to the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic decompensation. Hepatic resection is the primary intervention for these few patients with tumor but surrounding normal liver tissue and well preserved hepatic function. Under such circumstances, the cumulative 5-year survival is approximately 45%. Liver transplantation (OLT) provides long term survivals (90% at 5 years) in patients with a HCC discovered by chance as a minute nodule and of 75% in patients with viral cirrhosis and a single <5 cm tumor or fewer than three <3 cm nodes. Since liver transplantation cannot be offered to most patients with HCC, hepatic resection remains the primary therapeutic option; 5-year survival of 50% is anticipated in patients with compensated cirrhosis and <5 cm of tumor and 75% for those with moderate portal hypertension and normal serum bilirubin values. Ultrasound-guided tumor injection with absolute ethanol or tumor thermoablation with radiofrequency provide similar survival rates but with fewer complications. Whether arterial chemoembolization benefits patients with HCC remains controversial.     

Comparison of transarterial chemoembolization and percutaneous acetic acid injection as the primary loco-regional therapy for unresectable hepatocellular carcinoma: a prospective survey

BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous acetic acid injection (PAI) are effective loco-regional therapies for hepatocellular carcinoma (HCC). AIM: To compare the therapeutic efficacy of TACE vs. PAI for unresectable HCC. METHODS: A total of 310 patients with unresectable HCCs (size 相似文献   

Evolution of prognostic factors in hepatocellular carcinoma in Japan

Aliment Pharmacol Ther 31 , 407–414

Summary

Background The surveillance of hepatocellular carcinoma (HCC) has become prevalent, and the modalities for its treatment have improved. Aim To understand the changes that occur in the characteristics and prognostic factors of HCC with time. Methods Newly diagnosed HCC patients were divided into two groups; patients treated before 31 December 2000 (n = 504), and after 1 January 2001 (n = 746), and their clinical backgrounds and prognostic factors were analysed. Results The number of patients negative for both Hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibody (HCVAb) increased with time (NBNC‐HCC). The size of HCC decreased in patients who were positive for HBsAg (B‐HCC) or HCVAb (C‐HCC), whereas no difference was observed in NBNC‐HCC. The patient survival of C‐HCC improved; however, no difference was detected for NBNC‐HCC. In multivariate analysis, low albumin, high aspartate aminotransferase (AST), ascites, large tumour size, multiple tumour number and high alpha‐fetoprotein were risk factors for survival before 2000, whereas the presence of HBsAg was additionally selected as a good prognostic factor and AST was excluded after 2001. Conclusions The prognostic factors as well as clinical background of HCC changed with time, and the presence of HBsAg was found to be an additional good prognostic factor after 2001.