Pierangelo Fasani

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.)

Segmental transcatheter arterial chemoembolization treatment in patients with cirrhosis and inoperable hepatocellular carcinomas

PURPOSE To establish whether segmental transcatheter arterial chemoembolization (TACE) treatment may improve the rates of survival in patients with compensated cirrhosis and inoperable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Fifty-six patients with compensated cirrhosis and inoperable HCC were treated with segmental TACE. One hundred forty treatments (mean, 2.5 per patient; 30-60 mg Epirubicin, 4-10 mL Lipiodol, and Gelfoam particles) were administered. RESULTS During the 69-month study, 25 patients (45%) died of tumor progression, 12 (21%) of liver failure, nine (16%) of gastrointestinal hemorrhage, and three (5%) of other causes; seven patients (13%) are still alive. The 3-year rate of survival was 32%. Intention-to-treat analysis determined that patients with Child-Pugh class A disease (n = 44; 79%) or a single <5-cm HCC (n = 21; 37%) had a higher rate of survival than those with Child-Pugh class B disease (n = 12; 21%; P <.002) or a larger HCC (n = 35; 63%; P <.02) and patients (n = 41) who were treated with more than one course of TACE had a higher rate of survival than those who were treated with a single TACE procedure (n = 15; P <.0003). Multivariate analysis was used to predict rates of survival by number of treatments (hazard ratio, 0.6; CI, 0.48-0.86; P <.004), Child-Pugh class (hazard ratio, 2.8; CI, 1.41-5.74; P <.003), and tumor size (hazard ratio, 3.8; CI, 1.81-8.01; P <.001). The 3-year rate of survival in patients with Child-Pugh class A disease and a < or =5-cm-HCC (n = 16) was 56%. This result was similar to the 50% 3-year rate of survival in untreated historic controls with similar characteristics. CONCLUSION The rate of survival in patients with compensated cirrhosis and inoperable HCC did not appear to improve with use of TACE therapy.

Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis

BACKGROUND Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity

Can the unenhanced phase be eliminated from dual-phase CT angiography for chest pain? Implications for diagnostic accuracy in acute aortic intramural hematoma.

OBJECTIVE The purposes of this study were to retrospectively assess the frequency of acute aortic intramural hematoma and evaluate whether the elimination of the unenhanced imaging acquisition series from the dual-phase MDCT angiography (CTA) protocol for chest pain might affect diagnostic accuracy in detecting intramural hematoma and justify the reduced radiation dose. MATERIALS AND METHODS From October 2006 to November 2012, 306 patients (mean age, 65.0 years) with acute chest pain underwent emergency CTA with a 64-MDCT scanner. Two experienced cardiovascular radiologists, blinded to the diagnosis, assessed the images in two different sessions in which enhanced (single-phase CTA) and combined unenhanced and contrast-enhanced (dual-phase CTA) findings were evaluated. Sensitivity, specificity, and accuracy along with 95% CIs were calculated. Surgical and pathologic diagnoses, including findings at clinical follow-up and any subsequent imaging modality, were used as reference standards. RESULTS Thirty-six patients were suspected of having intramural hematoma; 16 patients underwent both surgery and transesophageal echocardiography (TEE), and the remaining 20 underwent TEE. Single-phase CTA showed a higher number of false-negative and false-positive results than dual-phase CTA. With intramural hematoma frequency of 12% (95% CI, 8.38-15.91%), sensitivity, specificity, and accuracy were 94.4% (81.3-99.3%), 99.3% (97.4-99.9%), and 98.7% (96.7-99.6%) for combined dual-phase CTA and 68.4% (51.4-82.5%), 96.3% (93.2-98.2%), and 92.8% (89.3-95.4%) for single-phase CTA. Dual-phase was significantly better than single-phase CTA with respect to sensitivity (p=0.002), specificity (p=0.008), overall accuracy (p<0.001), and interrater agreement (p=0.001). CONCLUSION The frequency of acute aortic intramural hematoma is similar to that previously reported. The acquisition of unenhanced images during the chest pain dual-phase CTA protocol significantly improves diagnostic accuracy over single-phase CTA.

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.

Hepatitis C virus and hepatocellular carcinoma

Hepatitis C virus (HCV) is pathogenetically involved in many cases of hepatocellular carcinoma (HCC) worldwide. HCV-related HCC is on the rise in many developed countries as a consequence of past infections with HCV. The time lag between HCV infection and cancer development is several decades. HCV-related tumors arise in older patients, are almost invariably associated with cirrhosis, and often have a less aggressive course than HCC related to other etiologic factors. In most patients, HCC grows as a single hepatic node for years before generating satellite or distant tumor nodes. However, there are tumors that originate as multifocal disease. Tumor progression and hepatic failure are the leading causes of death in most patients. HCV has been almost invariably detected in tumor tissue of anti-HCV patients with HCV, but it is not clear whether the virus promotes cancer through chronic hepatocellular inflammation, which is per se an important risk factor for HCC, or has a direct role in liver carcinogenesis. No reverse transcriptase activity has been found in infected livers, but there are data suggesting that HCV has oncogenic properties, because its interacts with cellular genes regulating cell growth and differentiation.