M.A. Manini

The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients†

Large databases of consecutive patients followed for sufficiently long periods are needed to establish the rates, chronology, and hierarchy of complications of cirrhosis as well as the importance of other potential causes of liver disease. In accordance with this goal, a cohort of patients with compensated cirrhosis due to hepatitis C virus (HCV) was followed for 17 years. Two hundred and fourteen HCV RNA–seropositive patients with Child‐Pugh class A cirrhosis who had no previous clinical decompensation were prospectively recruited and followed up with periodic clinical and abdominal ultrasound examinations. During 114 months (range 1–199), hepatocellular carcinoma (HCC) developed in 68 (32%), ascites in 50 (23%), jaundice in 36 (17%), upper gastrointestinal bleeding in 13 (6%), and encephalopathy in 2 (1%), with annual incidence rates of 3.9%, 2.9%, 2.0%, 0.7%, and 0.1%, respectively. Clinical status remained unchanged in 154 (72%) and progressed to Child‐Pugh class B in 45 (21%) and class C in 15 (7%). HCC was the main cause of death (44%) and the first complication to develop in 58 (27%) patients, followed by ascites in 29 (14%), jaundice in 20 (9%), and upper gastrointestinal bleeding in 3 (1%). The annual mortality rate was 4.0% per year and was higher in patients with other potential causes of liver disease than in those without them (5.7% vs. 3.6%; P = .04). In conclusion, hepatitis C–related cirrhosis is a slowly progressive disease that may be accelerated by other potential causes of liver disease. HCC was the first complication to develop and the dominant cause for increased mortality. (HEPATOLOGY 2006;43:1303–1310.)

The impact of infection by multidrug‐resistant agents in patients with cirrhosis. A multicenter prospective study

Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation.

Transarterial chemoembolization with drug‐eluting beads is effective for the maintenance of the Milan‐in status in patients with a small hepatocellular carcinoma

Transarterial chemoembolization (TACE) is the standard of care for the treatment of patients with an intermediate (Barcelona Clinic Liver Cancer [BCLC] B) hepatocellular carcinoma and to bridge patients with an early cancer to liver transplantation (LT). We explored the efficacy of TACE with drug‐eluting beads (DEB) in BCLC A patients. Included are all BCLC A patients unsuitable for resection or locoregional ablation who underwent a DEB TACE between 2006 and 2012. Treatment was carried out “a la demande” until complete tumor devascularization or progression beyond Milan criteria. In patients with a complete response (CR), a contrast computed tomography (CT) scan was repeated at 3‐month intervals during the first 2 years and then every 6 months alternating with abdominal ultrasound in the subsequent 3 years. Fifty‐five patients had 79 tumor nodules ranging 7 to 50 mm; 32 (58%) achieved a CR that was maintained up to 4 and 7 months in 21 (38%) and 17 (31%) patients, respectively. The 24‐ and 36‐month tumor‐free survivals were 21% and 9%, respectively. The overall cumulative progression beyond Milan criteria at 3, 6, 12, and 24 months was 2%, 5%, 30%, and 54%. LT eligibility was maintained for a median of 19 months (range, 2‐63 months). CR to first TACE was the strongest independent predictor of Milan‐in maintenance. In conclusion, DEB TACE may effectively bridge patients with an early cancer to LT, and a CR to the first procedure may guide patient prioritization during the waiting list. Liver Transpl 21:1259‐1269, 2015.

Contrast-enhanced computed tomography and ultrasound-guided liver biopsy to diagnose dysplastic liver nodules in cirrhosis.

BACKGROUND Dysplastic nodules in cirrhosis herald a very high risk of transition to hepatocellular carcinoma. A better understanding of the relationships between dysplastic nodules and hepatocellular carcinoma development may help refining strategies of enhanced follow-up. METHODS All consecutive cirrhotics with a histologically proven de novo dysplastic nodule, were retrospectively identified and underwent alternating abdominal ultrasound and contrast-computed tomography every 3 months. An ultrasound-guided liver biopsy was the diagnostic gold standard, whereas surveillance and recall policies were according to current guidelines. RESULTS Among 36 patients with dysplastic nodule (21 low-grade, 15 high-grade, 17.4 ± 2.6mm), 17 (47%) showed arterial wash-in, 15 (42%) portal/venous hypodensity whereas 4 (11%) had neither pattern. During 6-128 (median 36) months, 21 patients developed a hepatocellular carcinoma at a rate of 13.8% per year, intranodular=8.7% vs extranodular=7.1% per year. Hepatocellular carcinoma occurred more frequently in high-grade than low-grade dysplastic nodules (32.2% vs 9.3% per year, p=0.0039); the maximum time to hepatocellular carcinoma transformation was 27 months for intranodular vs 67 months for extranodular tumours (p=0.025). No contrast-computed tomography pattern predicted neoplastic transformation of dysplastic nodules. CONCLUSION The histological examination of liver nodules in cirrhosis lacking the imaging hallmark of hepatocellular carcinoma improves both prognostication and outcome of surveillance, since it dictates the intensity of the radiological follow-up.

Risk of hepatocellular carcinoma in relation to ABO blood type.

BACKGROUND Mortality and incidence rates of hepatocellular carcinoma (HCC) parallel the geographical distribution of hepatitis B and C viruses among the general population, however genetic factors modulate individual cancer risk. AIMS ABO blood type, as a genetic marker, has previously been associated with the risk of several malignancies; we aimed to evaluate whether an association exists with HCC. METHODS This is a retrospective case-control study based on ABO distribution in 194 patients with HCC, compared with 215 decompensated cirrhotics without HCC listed for liver transplantation, and 90,322 healthy blood donors. RESULTS In patients with HCC, prevalence of blood type O was 35%, vs. 44% in cirrhotics (OR: 0.67, 95% CI 0.45-0.99; p=0.046) and 45% in blood donors (OR: 0.65, 95% CI 0.48-0.88; p=0.004). CONCLUSIONS ABO blood type non-O is associated with higher risk of hepatocellular carcinoma, compared to cirrhotics without HCC and healthy subjects.

Transarterial embolization with microspheres in the treatment of monofocal HCC

BACKGROUND Transarterial embolization using one permanent embolic agent alone enhances tumour ischaemia and spares patients with hepatocellular carcinoma form toxic chemotherapeutic drugs. PURPOSE We assessed feasibility, tolerability and efficacy of transarterial embolization with microspheres in patients with a single node hepatocellular carcinoma. MATERIALS AND METHODS Eighteen consecutive patients with compensated cirrhosis, hypervascularized single hepatocellular carcinoma, in whom liver transplantation was indicated (no.=3), or excluded from radical therapies (no.=15), received selective transarterial embolization with microspheres. Treatment was repeated every other month until complete devascularitazion was demonstrated by computed tomography, for a maximum of 3 cycles. RESULTS Fifty transarterial embolization courses (mean: 2.8 courses, range 1-6) were administered, corresponding to a 100% applicability rates. Initial complete response was achieved in 16 (89%) patients and confirmed by histology in 2 transplanted patients. During 21-month follow-up (range 8-36), hepatocellular carcinoma recurred in 10 (62%) patients who achieved initial complete response, and de novo tumour nodes developed in 10 (56%). No patient required analgesics and none had liver function deteriorated following transarterial embolization. CONCLUSIONS Transarterial embolization is a well-tolerated treatment for patients with early or intermediate hepatocellular carcinoma who are not suitable for radical treatment or await liver transplantation, but it allows to achieve a sustained complete response in a minority of patients.

Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules

Background & Aims. The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned for the risk of false positive diagnosis in case of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS LI-RADS) classifying lesions at risk for HCC investigated by CEUS. Aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. Methods. A total of 1006 nodules in 848 patients with chronic liver disease at risk for HCC collected in 5 Italian centers were retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥ 1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 seconds after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (=506) or histology (n=500). Results. Median size was 2 cm. Of 1006 nodules, HCC were 820 (81%), cholangiocarcinoma 40 (4%), regenerative nodules (±dysplastic) 116 (11%). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96=47%) and the LR-4 202 (HCC 173=87%). Conclusions. The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non invasive diagnosis.BACKGROUND & AIMS The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned because of the risk of a false positive diagnosis in cases of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS Liver Imaging Reporting and Data System [LI-RADS®]) to classify lesions at risk of HCC investigated by CEUS. The aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. METHODS A total of 1,006 nodules from 848 patients with chronic liver disease at risk of HCC were collected in five Italian centers and retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 s after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (n = 506) or histology (n = 500). RESULTS The median nodule size was 2 cm. Of 1,006 nodules, 820 (81%) were HCC, 40 (4%) were cholangiocarcinoma, 116 (11%) regenerative nodules (±dysplastic). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96 [47%]) and the LR-4 202 (HCC 173 [87%]). CONCLUSIONS The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non-invasive diagnosis. LAY SUMMARY This is a retrospective study of approximately 1,000 focal lesions at risk for hepatocellular carcinoma (HCC). Herein, we demonstrate that the refined definition of the typical contrast enhanced ultrasound pattern of HCC introduced by the Liver Imaging Reporting and Data System (LI-RADS®) practically abolishes the risk of misdiagnosis of other malignant entities (e.g. cholangiocarcinoma) for HCC with negligible reduction in sensitivity. These data support the use of contrast enhanced ultrasound to diagnose HCC in cirrhosis.

108 A NOVEL MODEL OF PRIORITY ASSESSMENT FOR PATIENTS WITH AND WITHOUT HEPATOCELLULAR CARCINOMA ON A COMMON LIVER TRANSPLANT WAITING LIST: A MULTICENTRE, COHORT STUDY

108 A NOVEL MODEL OF PRIORITY ASSESSMENT FOR PATIENTS WITH AND WITHOUT HEPATOCELLULAR CARCINOMA ON A COMMON LIVER TRANSPLANT WAITING LIST: A MULTICENTRE, COHORT STUDY A. Vitale, T.M. De Feo, P. Burra, A.C. Frigo, R. Ramirez Morales, L. De Carlis, M. Manini, S. Fagiuoli, A. Picciotto, P. Toniutto, E. Regalia, U. Cillo, on behalf of the Liver Transplantation NITp Working Group. University Hospital of Padova, Padova, North Italy Transplant Program, Fond. IRCCS Ca’ Granda OMP, Milan, Biostatistics Unit, University of Padova, Padova, Liver Transplantation, Ospedale Niguarda Ca’ Granda, Gastroenterology Unit, Maggiore Hospital Policlinico, Milan, Gastroenterology and Transplantation Hepatology, Ospedali Riuniti, Bergamo, IRCCS San Martino, IST, Genova, Medical Liver Transplant Unit, University of Udine, Udine, Liver Transplantation, IRCCS INT, Milan, Italy E-mail: alessandro.vitale@unipd.it

Diagnostic accuracy and standardization of fine needle biopsy in the characterization of liver nodules in cirrhosis.

e14576 Background: The diagnostic sensitivity of fine needle biopsy (FNB) for liver nodules in cirrhotic patients is both operator and disease characteristic dependant. The performance FNB needs to...

Natural history and multimodality treatment of early hepatocellular carcinoma prospectively detected in cirrhotic patients under surveillance.

e14574 Background: Surveillance with abdominal US of cirrhotic patients increases the identification of small hepatocellular carcinoma (HCC) to be treated with radical therapies. Aim: To define the...