Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.

Years of life that could be saved from prevention of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥ 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome.

BACKGROUND: Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. AIM: To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. METHODS: A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. RESULTS: Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. CONCLUSIONS: Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.

Nodular regenerative hyperplasia of the liver: coral atoll-like lesions on ultrasound are characteristic in predisposed patients.

Nodular regenerative hyperplasia (NRH) is an uncommon liver disease characterised histologically by numerous small hyperplastic nodules that are not separated by fibrotic tissue. It is thought to be the result of obliterative vasculopathy, and it has been associated with chronic use of medications, toxic substances and a wide variety of systemic diseases. Imaging diagnosis of early-stage NRH remains problematic. The nodules are rarely discerned and their appearance and behaviour before and after contrast medium administration are heterogeneous and not specific. A review of the literature shows that ultrasound has succeeded on occasion in revealing small focal liver lesions in patients with NRH. To our knowledge, there has been no published data on the performance in this setting of last-generation ultrasound scanners and techniques such as contrast-enhanced ultrasound (CEUS). The question is an important one because abdominal ultrasound is widely used as a first-line imaging technique for the evaluation of liver disease, and this makes it particularly suitable as a potential tool for the early diagnosis of NRH. Owing to the prolonged subclinical period and the limited help provided by imaging, the diagnosis in vivo of NRH is currently frequently missed, and it is still made exclusively on the basis of liver biopsy. In conclusion, this report describes 4 cases of biopsy-proven NRH that have been diagnosed over the past 2 years by our group. All were characterised by known comorbidities that confer a predisposition to NRH and by a peculiar parenchymal ultrasound pattern that we refer to as the "atoll sign".

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

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.

Survival of patients with early hepatocellular carcinoma treated by percutaneous alcohol injection.

BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma, are detected in cirrhotics, the European Association for the Study of the Liver guidelines recommend to delay histological confirmation and treatment until they increase in size. AIM: To validate this policy by evaluating survival of 450 cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular carcinoma treated by percutaneous alcohol injection. METHODS: Patients were sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to < or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P = 0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months (P = 0.51), respectively. When patients were sorted by Child status, mean survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001). CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated patients with single, early hepatocellular carcinoma sorted by nodular size supports the European Association for the Study of the Liver 'wait-and-see' policy for patients with lesions <10 mm, and suggests that allowing the nodules to grow prior to taking further diagnostic or therapeutic actions would not harm these patients.

Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis.

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.

Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study.

BACKGROUND: Because hepatic cirrhosis is a major risk factor for hepatocellular carcinoma, recent guidelines by the European Association for the Study of the Liver (EASL) on clinical management of hepatocellular carcinoma recommend periodic ultrasound surveillance of cirrhotic patients with immediate workup for nodules >1 cm; an increase in the frequency of screening is considered sufficient for smaller lesions. AIMS: To determine the actual risk of hepatocellular carcinoma associated with the latter lesions and to assess the role of ultrasound guided-fine needle biopsy in their diagnosis. PATIENTS AND METHODS: Data were analysed for 294 new nodular lesions <20 mm, including 48 that were <10 mm, detected during a prospective multicentre study involving ultrasound surveillance of 4375 patients with hepatic cirrhosis. In the absence of alpha fetoprotein (AFP) levels diagnostic of hepatocellular carcinoma, ultrasound guided-fine needle biopsy was performed (n = 274). AFP and fine needle biopsy diagnoses of malignancies (hepatocellular carcinoma and lymphoma) were considered definitive. Non-malignant fine needle biopsy diagnoses (dysplastic or regenerative nodule) were verified by a second imaging study. Diagnoses of hepatocellular carcinoma based on this study were considered definitive; non-malignant imaging diagnoses were considered definitive after at least one year of clinical and ultrasound follow up. RESULTS: Overall, 258/294 (87.6%) nodules proved to be hepatocellular carcinoma, including 33/48 (68.7%) of those < or =10 mm. Overall typing accuracy of ultrasound guided-fine needle biopsy was 89.4%, and 88.6% for lesions < or =10 mm. CONCLUSIONS: In a screening population, well over half of very small nodules arising in cirrhotic livers may prove to be hepatocellular carcinoma, and approximately 90% of these malignancies can be reliably identified with ultrasound guided-fine needle biopsy.

Hemangioma-like lesions in chronic liver disease: diagnostic evaluation in patients.

PURPOSE: To quantify the risk of misdiagnosis of focal hepatic lesions manifesting at ultrasonography (US) as typical hemangiomas in a population at high risk for hepatocellular carcinoma (HCC) and to identify the most effective approach to their diagnostic evaluation. MATERIALS AND METHODS: A total of 1,982 patients with newly diagnosed cirrhosis underwent US and serum alpha-fetoprotein determinations for early detection of HCC. Focal lesions with typical features of hemangioma were evaluated with confirmatory findings of contrast material-enhanced dynamic or spiral computed tomography (CT) and/or single photon emission CT with technetium 99m-labeled red blood cells and, in the absence of confirmatory imaging findings, US-guided fine-needle biopsy. Patients whose initial US scan depicted no lesions or hemangiomas were enrolled in a US follow-up program. All hemangioma-like lesions detected during follow-up were evaluated, or biopsy was performed. RESULTS: US depicted hemangioma-like lesions in 44 of 1,982 patients: 22 hemangiomas and 22 HCCs. Hemangioma-like lesions detected during follow-up in 1,648 patients were HCCs (n = 22) or dysplastic nodules (n = 4). Only 85 (22%) of 383 patients with HCC had alpha-fetoprotein levels suggestive of the diagnosis. The probability of a diagnosis of HCC (or preneoplastic lesion) is 100% for hemangioma-like lesions depicted on subsequent US scans. CONCLUSION: If initial US examination of a cirrhotic liver depicts a hemangioma, confirmatory findings of imaging studies are necessary since 50% of hemangiomas in this study were hyperechogenic HCCs. US-guided biopsy can be safely performed, and its findings can be used to confirm the diagnosis.

Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy.

BACKGROUND: The objective of this study was to identify clinical, biochemical, ultrasound, and/or pathologic parameters capable of predicting survival in a cohort of patients with well compensated cirrhosis and small hepatocellular carcinoma (HCC) who were treated with percutaneous ethanol injection (PEI). METHODS: The study group included 111 patients with Child--Pugh Class A cirrhosis and with one (93 patients) or two (18 patients) HCC nodules measuring < 5 cm in greatest dimension. All patients underwent multisession PEI. The prognostic values of pretreatment and post-treatment variables were analyzed using the Kaplan-Meier method. RESULTS: The overall 3-year and 5-year survival rates of 62% and 41%, respectively, were not influenced by age, gender, duration of chronic hepatitis, serum albumin, prothrombin time ratio, total bilirubin, gamma-glutamyl transferase, hepatitis B surface antigen, antihepatitis C virus, HCC size, HCC ultrasound pattern, HCC histologic or cytologic grading, greatest spleen dimension, esophageal varices, or ascites. Levels of alpha-fetoprotein (AFP) > 14 ng/mL (P < 0.006), alanine aminotransferase > 75 IU/L (P < 0.04), and aspartate aminotransferase > 80 IU/L (P < 0.009) and platelet count < 92 x 10(9)/L (P < 0.02) before treatment were independent predictors of decreased survival. Among post-treatment parameters, AFP levels 6 months after PEI > 13.3 ng/mL (P < 0.003) and HCC recurrence in another segment of the liver (P < 0.04) were linked to decreased survival in univariate analysis. CONCLUSIONS: Among patients with Child--Pugh Class A cirrhosis with small uninodular or binodular HCC who are treated with multisession PEI, those with elevated serum AFP and transaminase levels and low platelet count before treatment are characterized by decreased survival. During follow-up, intrahepatic recurrence of the tumor is the main factor affecting survival.

Ultrasound-guided fine needle biopsy of the spleen: high clinical efficacy and low risk in a multicenter Italian study.

The aim of this study was to evaluate the clinical efficacy and safety of the ultrasound-guided fine needle biopsy (UG-FNB) of the spleen in a large population of patients. We collected retrospectively the findings concerning the application of UG-FNB of the spleen from eight Italian clinical centers that utilized this technique for at least ten years. A data schedule was sent to all centers to collect information about techniques, results, and complications of UG-FNB of the spleen. We analyzed 398 biopsy procedures both on focal lesions (257 cases) and on splenic parenchyma (141 cases). The overall accuracy was 90.9% for the series as a whole, 84.9% for cytological sampling, 88.3% for microhistological sampling, and 90.3% for both cytological and histological sampling (double biopsy). Tissue core biopsy yielded better overall accuracy in patients with suspected splenic involvement by lymphoma (90.9% vs. 68.5% for cytology). The complication rate was low (no death cases, less than 1% for major complications, and 5.2% for all complications). No predictive factors were able to detect high-risk situations. The operator's skill (higher number of performed procedures) was significantly related to better overall accuracy. Conversely, the complication rate was not affected. UG-FNB of the spleen is a very effective diagnostic procedure with low risk for the patient. Aspiration cytology and core needle biopsy showed similar diagnostic yields, except for the diagnosis of splenic lymphoma, in which core needle biopsy obtained better results.

Interstitial laser photocoagulation under ultrasound guidance of liver tumors: results in 104 treated patients.

OBJECTIVE: To evaluate the efficacy and complications of interstitial laser photocoagulation (ILP) under ultrasound (US) guidance as a technique for focal ablation of liver tumors in patients with normal and impaired hepatic function. PATIENTS AND METHODS: A total of 104 patients, 77 with 85 nodules of hepatocellular carcinoma on cirrhosis (29 in Child-Pugh A class, 43 in B e 5 in C class) and 27 patients with hepatic metastases (25 from colon, two from lung carcinoma) underwent ILP under US guidance. Depending on tumor size up to four needles were inserted in the tumor and multiple laser illuminations were performed in one or multiple sessions. Necrosis of the nodules was evaluated with triphasic contrast-enhanced CT. RESULTS: Ninety-four patients underwent a single ILP session and nine patients two sessions. CT showed complete necrosis in 70 out of 85 HCC nodules in 65 treated patients and in 24 out of 31 patients with metastases. Three Child C class patients dropped out the control of efficacy by CT because of severe liver failure associated in one case with transient paralytic ileum. One of these patients died 2 months after treatment. Two patients with metastasis dropped the completion of the treatment because of complication occurred after the ILP session (one paralytic ileum, one gastric haemorrage). CONCLUSIONS: ILP under US guidance is effective in inducing complete necrosis in small and large liver tumors. Nevertheless, ILP can cause severe derangement of liver function in patients with advanced cirrhosis.

Utility of alpha-fetoprotein (AFP) in the screening of patients with virus-related chronic liver disease: does different viral etiology influence AFP levels in HCC? A study in 350 western patients.

BACKGROUND/AIMS: Dosage of serum AFP (alpha-fetoprotein) is widely used for HCC screening in patients with chronic liver disease. Virus-related chronic liver disease is the main cause of cirrhosis and HCC in Western and Far Eastern countries, but the relationship between viral etiology and AFP levels in HCC is still unclear. The aim of this study was to verify, in Western patients with post-viral chronic liver disease, the usefulness of AFP dosage for the detection of HCC, and the influence of viral etiology on AFP levels in HCC. METHODOLOGY: The study population included 350 patients with post viral chronic liver disease that underwent liver biopsy, serum AFP determination and ultrasound liver evaluation. Seven patients had normal liver histology, 197 had chronic hepatitis, 72 had cirrhosis, and 74 had cirrhosis and HCC. ROC (receiver operating characteristic) analysis was used to assess the best diagnostic AFP threshold value for HCC detection. Logistic regression analysis was performed to individuate independent predictors of HCC diagnosis. RESULTS: No difference was observed in AFP levels between HCV- and HBV-positive patients, neither in the whole population nor in the HCC patients only. ROC area under curve for AFP was 0.801 (95% CI: 0.721-0.867). The analysis individuated a best accurate AFP threshold value for HCC diagnosis of 50 ng/mL. HCC was detected with specificity > or = 95% only for AFP > 100 ng/mL. The sensitivity however was poor (25%). Male sex, age > 60, and AFP were independent predictors of HCC diagnosis. CONCLUSIONS: Serum AFP levels in HCC patients are not influenced by virus B or C hepatitis pattern. AFP dosage should not be used for HCC diagnosis in non-cirrhotic patients. Male patients with cirrhosis should be regarded with a more "aggressive" screening program compared to females.