Hepatocellular carcinoma in cirrhotic liver in Trieste

One hundred consecutive cases of hepatocellular carcinoma (HCC) in cirrhosis observed at autopsy were studied and their pathological aspects were compared with those reported in the literature. The results, which are representative of HCC epidemiology in a geographical area where cirrhosis is mostly due to alcohol abuse, show that similarities in the architectural pattern of HCC and weight of the liver exist between our material and samples with different aetiology and epidemiology. A relationship between the histological grade of HCC and its propensity to metastasize was demonstrated. The reported better prognosis of clear cells per se could not be confirmed, although clear cell HCC occurred exclusively in grade 2. It was also demonstrated that the relationship between grading and staging was strongly influenced by the association of HCC with cirrhosis, which is a fact that is usually overlooked by the common staging (and grading) methods.     

Hepatocellular carcinoma in a cirrhotic liver becoming detectable within a month

A case of hepatocellular carcinoma (HCC) in a cirrhotic liver which became detectable within a month is reported here. The patient was admitted for treatment of oesophageal varices due to Child's C grade liver cirrhosis. A hepatic angiogram was performed before the treatment and showed no neovasculature. After undergoing variceal treatment by injection sclerotherapy, the patient underwent another angiogram 28 days later in order to measure the efficacy of the treatment. The second angiogram revealed the emergence of small multiple neovasculatures throughout the entire liver. From the angiographic findings, those tumours were considered to be HCC. The present report suggests that small HCC latent in a cirrhotic liver can thus acquire neovasculature within a short period of time.     

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma(HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC.     

Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) worldwide due to the high prevalence of HCV infection and the high rate of HCC occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence has been observed during the past decades in most industrialized countries, partly related to the growing number of patients infected by HCV. HCC is currently the main cause of death in patients with HCV-related cirrhosis, a fact that justifies screening as far as curative treatments apply only in patients with small tumors. As a whole, treatment options are similar in patients with cirrhosis whatever the cause. Chemoprevention could be also helpful in the near future. It is strongly suggested that antiviral treatment of HCV infection could prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained virological response is obtained.     

Resecting hepatocellular carcinoma in cirrhotic liver

Abstract   Resecting hepatocellular carcinoma (HCC) in a cirrhotic patient is potentially dangerous and recurrence of HCC after operation is high. Our current strategy consists of careful preoperative assessment of liver functions by indocyanine green clearance test, intraoperative techniques to reduce blood loss, and postoperative surveillance and prompt treatment of recurrences. The 5-year overall survival rate of HCC patients after resection is 34.3%, which is comparable with that in patients with normal liver (37.3%) or chronic hepatitis (45.3%).     

Hepatocellular carcinoma associated with Wilson's disease

A 23-year-old man was admitted to our department due to hemorrhage from gastric varices. He had been diagnosed as having Wilson's disease at the age of 17. Abdominal ultrasonography and computed tomography (CT) showed portal thrombosis and a large mass occupying most of the right lobe in the liver. The tumor was diagnosed as hepatocellular carcinoma (HCC) by image views and tumor markers. He died 3 months after the diagnosis, and an autopsy was performed. Histologic examination of the tumor showed moderately to poorly differentiated HCC. The nontumorous lesion of the liver revealed cirrhosis. HBX-DNA sequence was not detected in the liver. Hepatic cirrhosis is a well-recognized complication of Wilson's disease, but HCC is extremely rare. We describe the clinical findings of this patient and discuss the relationship of the development of HCC with a review of the relevant literature.     

Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease

AIM: To determine characteristics and prognosticpredictors of patients with hepatocellular carcinoma(HCC) in association with non-alcoholic fatty liver disease(NAFLD).METHODS: We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index(BMI), and the presence of diabetes, hypertension, or dyslipidaemia.RESULTS: Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent(8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of 25 kg/m2, 25-29 kg/m2 and ≥ 30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤ 1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics(P = 0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC.CONCLUSION: HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis.     

Hepatocellular carcinoma complicating liver cirrhosis in type IIIa glycogen storage disease

Type III glycogen storage disease (GSD III) is an autosomal recessive disorder characterized by the accumulation of abnormal glycogen in the liver and, in most patients, in the muscle. Although liver fibrosis is a well-known consequence of GSD III, until now only eight cases of liver cirrhosis and two cases of hepatocellular carcinoma have been described in patients affected by this disease. In this case report, the authors describe the clinical history of a patient affected by GSD III who developed severe liver disease during her adult life, progressing from fibrosis to cirrhosis and finally to hepatocellular carcinoma. Until now, the hepatic involvement in GSD III has been considered by most authors as mild and almost always self-limiting. This report, together with the previously published cases, clearly indicates that severe and progressive liver disease may complicate this metabolic disorder. These observations advise a careful hepatologic follow-up of patients affected by GSD III.     

Hepatocellular carcinoma in nonalcoholic fatty liver disease: A growing challenge

Nonalcoholic fatty liver disease(NAFLD) is the most common cause of liver disease worldwide, and its prevalence increases continuously. As it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis, it is not surprising that the incidence of NAFLD-related hepatocellular carcinoma would also rise. Some of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver, and they help explain why liver cancer develops even in patients without cirrhosis. Genetic and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this population. Currently, it is consensual that patients with NAFLD-related cirrhosis should be surveilled with ultrasonography every 6 mo (with or without alpha-fetoprotein), but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver disease. Moreover, the performance of the methods of surveillance are lower in NAFLD than they are in other liver diseases. Furthermore, it is not clear which subgroups of patients without cirrhosis should undergo surveillance. Understanding the mechanisms of hepatocarcinogenesis in NAFLD could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these individuals. By improving surveillance, tumors could be detected in earlier stages, amenable to curative treatments.     

Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace

Hepatocellular carcinoma (HCC) is a common cancer worldwide that primarily develops in cirrhosis resulting from chronic infection by hepatitis B virus and hepatitis C virus, alcoholic injury, and to a lesser extent from genetically determined disorders such as hemochromatosis. HCC has recently been linked to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity and related metabolic disorders such as diabetes. This association is alarming due to the globally high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. There is also evidence that NAFLD acts synergistically with other risk factors of HCC such as chronic hepatitis C and alcoholic liver injury. Moreover, HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk. Major systemic and liver-specific molecular mechanisms involved include insulin resistance and hyperinsulinemia, increased TNF signaling pathways, and alterations in cellular lipid metabolism. These provide new targets for prevention, early recognition, and effective treatment of HCC associated with NAFLD. Indeed, both metformin and PPAR gamma agonists have been associated with lower risk and improved prognosis of HCC. This review summarizes current evidence as it pertains to the epidemiology, pathogenesis, and prevention of NAFLD-associated HCC.     

Hepatocellular carcinoma in patients with chronic kidney disease

AIM: To investigate outcomes of hepatocellular carcinomas (HCCs) in patients with chronic kidney disease (CKD). METHODS: Four hundred and forty patients referred between 2000 and 2002 for management of HCCs were categorized according to their CKD stage, i.e. , estimated glomerular filtration rate (eGFR) > 90 (stage 1), 60-90 (stage 2), 30-60 (stage 3), 15-30 (stage 4), and < 15 (stage 5) mL/min per 1.73 m 2 , respectively. Demographic, clinical and laboratory data were collected and mortality rates and cause of mortality were analyzed. The mortality data were examined with Kaplan-meier method and the significance was tested using a log-rank test. An initial univariate Cox regression analysis was performed to compare the frequency of possible risk factors associated with mortality. To control for possible confounding factors, a multivariate Cox regression analysis (stepwise backward approach) was performed to analyze those factors that were significant in univariate models (P < 0.05) and met the assumptions of a proportional hazard model. RESULTS: Most HCC patients with CKD were elderly, with mean age of diagnosis of 60.6 ± 11.9 years, and mostly male (74.8%). Hepatitis B, C and B and C coinfection virus were positive in 61.6%, 45.7% and 14.1% of the patients, respectively. It was found that patients with stages 4 and 5 CKD were not only older (P = 0.001), but also had higher hepatitis C virus carrier rate (P = 0.001), lower serum albumin level (P = 0.001), lower platelet count (P = 0.037), longer prothrombin time (P = 0.001) as well as higher proportions of advanced cirrhosis (P = 0.002) and HCCs (P = 0.001) than patients with stages 1 and 2 CKD. At the end of analysis, 162 (36.9%) patients had died. Kaplan-Meier analysis revealed that patients with stages 4 and 5 CKD suffered lower cumulative survival than stages 1 and 2 CKD (log-rank test, χ 2 = 11.764, P = 0.003). In a multivariate Cox-regression model, it was confirmed that CKD stage [odds ratio (OR) = 1.988, 95%CI: 1.012-3.906, P = 0.046)], liver     

非酒精性脂肪性肝病与肝细胞癌发生

肝细胞癌的发病率在全球逐年升高。绝大多数肝细胞癌与肝炎病毒感染有关,然而非酒精性脂肪性肝病也是引起肝细胞癌的重要原因之一。近年来,随着饮食习惯及生活方式的改变,非酒精性脂肪性肝病发病率持续升高,其与肝细胞癌发生的关系也得到了更多的关注。本文主要从非酒精性脂肪性肝病相关肝细胞癌的发病进程、危险因素及发病机制等方面做一介绍。     

Hepatocellular carcinoma in cirrhotic patients: role of hepatitis B virus

Four hundred and fifty seven Italian patients with liver cirrhosis--140 with hepatocellular carcinoma (HCC) and 317 without HCC (CP)--were studied in order to assess the risk factors of HCC in cirrhotic patients in Italy and, particularly, the role of HBV infection, that seems to be important in high and not in low incidence areas of HBV infection. All HCC were histologically confirmed and all cirrhotic patients were followed-up for one year or more without evidence of HCC. The statistical analysis was carried out by means of Stepwise Logistic Regression. Increasing age, male sex and HBV infection were found to be significant risk factors of HCC in CP, in a medium-incidence area of HCC and HBV as in Italy. There is, therefore, a striking correlation between HBV and the geographical incidence of HCC. In general, the higher the incidence of HBV, the greater its importance as a risk factor of HCC.     

Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma

AIM: The aim of this study is to assess the poly ADP-ribosylation activity in human hepatocellular carcinoma (HCC) and in liver cirrhosis (LC) as compared to the activity in normal livers (NL). METHODS: Hepatocellular carcinoma and LC tissues were sampled from 19 patients with HCC. Normal liver tissue was obtained from 19 patients with metastatic liver cancer. Poly ADP-ribosylation activity of these tissues was measured by using [32P]-adenylate nicotinamide adenine dinucleotide (NAD)-incorporation into the 116-kDa protein. Nicotinamide adenine dinucleotide glycohydrolase activity of these tissues was determined with thin layer chromatography. The immunohistochemical expression of Ki-67 was also assessed as a parameter of cell proliferative activity. RESULTS: The poly ADP-ribosylation of the 116 kDa protein was significantly increased in patients with HCC and LC as compared with NL (P<0.0001, P<0.05, respectively) and was inhibited by poly (ADP-ribose) polymerase inhibitors in a dose-dependent manner. There was no significant difference in NAD glycohydrolase activity among the three groups. A significant correlation was found between the Ki-67 positive cell rate and the relative radioactivity of poly ADP-ribosylation in HCC patients (r=0.794, P<0.0001). The poly ADP-ribosylation of the 116 kDa protein of LC was significantly higher in patients who had recurrences of HCC after hepatic resection than in patients without recurrence (P<0.05). CONCLUSION: Poly ADP-ribosylation of the 116 kDa protein in HCC patients might be enhanced with its proliferative activity, and poly ADP-ribosylation of the same protein in LC patients might be a useful parameter of carcinogenic potential for predicting HCC recurrence after hepatectomy in patients who have had HCC.