Hepatocellular carcinoma in patients without cirrhosis in Italy

BackgroundIn the Western world, hepatocellular carcinoma seldom develops in patients without cirrhosis, and reports describing the characteristics of non-cirrhotic patients with hepatocellular carcinoma are rather infrequent.MethodsWe evaluated the main clinical characteristics, treatment options, and survival of patients with hepatocellular carcinoma developed in non-cirrhotic liver among the 3027 consecutive cases of hepatocellular carcinoma accrued in the Italian Liver Cancer database during the last 20 years.ResultsWe identified 52 patients with hepatocellular carcinoma in non-cirrhotic livers (1.7% of all hepatocellular carcinomas), 42 with (80.8%) and 10 without (19.2%) chronic liver disease. In patients without chronic liver disease, median tumour diameter was greater compared to patients with chronic liver disease (7.8 versus 4.0 cm, P = 0.046). Curative treatment was feasible in 20 patients (38.5%). Median overall survival was 26 months and 5-year survival rate was 23.7%. Detection of hepatocellular carcinoma outside surveillance (P = 0.036), advanced hepatocellular carcinoma stage (P < 0.0001), and non-curative treatment (P = 0.007) were associated with worse prognosis, but tumour stage was the only independent predictor of survival.ConclusionsIn Italy, less than 2% of hepatocellular carcinomas develop in a non-cirrhotic liver, and almost never in a normal liver. These patients frequently present with advanced tumours, have low eligibility rates for curative treatment, and have a dismal prognosis despite their preserved liver function.     

Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis

Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.     

Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis

AIM:To investigate and characterise patients with chronic hepatitis C virus(HCV) infection presenting with hepatocellular carcinoma(HCC) in the absence of cirrhosis.METHODS:Patients with chronic hepatitis C infection without cirrhosis presenting with HCC over a 2-year period were identified.The clinical case notes,blood test results and histological specimens were reviewed to identify whether additional risk factors for the development of HCC were present.RESULTS:Six patients(five male,one female) with chro...     

Hepatocellular carcinoma in a patient with hereditary hemochromatosis without cirrhosis

Hepatocellular carcinoma in patients with hereditary hemochromatosis in the cirrhotic phase is one of the complications causing greatest mortality and may present in spite of removal of excess iron by bloodletting. Hepatocellular carcinoma is usually considered to occur in cirrhotic livers and consequently measures for the early diagnosis of this complication are only recommended in this type of patient. We present the case of a 69-year-old female patient with non-cirrhotic hemochromatosis who, 6 years after undergoing successful treatment, developed hepatocellular carcinoma. This observation should be added to the 12 cases published in the literature. Criteria should be established for the early diagnosis of hepatocellular carcinoma in patients with hereditary hemochromatosis, irrespective of whether they have cirrhosis.     

Hepatocellular carcinoma without cirrhosis in a patient with nonalcoholic steatohepatitis

All cases of hepatocellular carcinoma reported thus for in patients with nonalcoholic steatohepatitis have occurred on preexisting cirrhosis. We report the case of a 68-Year-old male patient with nonalcoholic steatohepatitis who developed hepatocellular carcinoma in the absence of cirrhosis. This observation suggests a possible relationship between nonalcoholic steatohepatitis and/or excess body weight, and hepatocellular carcinoma independent of cirrhosis. Further epidemiological studies are needed to evaluate the incidence of this association.     

Hepatocellular carcinoma in young, mentally retarded HBsAg carriers without cirrhosis

In a Californian institution for the mentally retarded, surveillance by autopsy of all deaths (n = 138) identified three cases of hepatocellular carcinoma. Hepatocellular carcinoma cases occurred in young (mean age = 26 years) male carriers of HBsAg and were not associated with cirrhosis. They were of the nonfibrolamellar oncocytic type and were rapidly fatal. Hepatocellular carcinoma incidence in HBsAg carriers was estimated to be 246 times greater than United States males.     

Hepatocellular carcinoma development in cirrhosis

The development of hepatocellular carcinoma (HCC), the mechanisms of hepatocarcinogenesis, the prevention of HCC, and screening for HCC will be discussed. Cirrhosis has been considered as a pre-neoplastic condition for the development of HCC. The worldwide incidence of HCC differs according to different hepatitis viruses, and information is lacking. Hepatocarcinogenesis is a multistep process involving a number of different genetic alterations and is poorly understood. Interferon should help prevent the development of HCC in patients with chronic hepatitis C. Screening is the only practical approach for improving the management of HCC patients, as early detection increases the application of curative treatments. However, the cost-effectiveness of various screening strategies needs to be analysed.     

Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis

The incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) is not well known. The aims of this study are to determine HCC incidence and survival, and to identify risk factors associated with these outcomes in patients with PBC. We collected information on 396 patients with PBC at enrollment and followed-up from 6 to 271 months. They were all negative for hepatitis B and C virus markers. HCC was detected by scanning with ultrasonography, computed tomography, or both every 4 to 6 months. Life expectancy (LE) was approximated with the declining exponential approximation of LE. A total of 14 patients developed HCC. The cumulative appearance rate of HCC in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly higher than that for patients with early-stage (stage I or II) (12.3% and 7.7% by the tenth year, respectively. P =.021). Proportional hazards analysis showed 3 factors are independently associated with the development of HCC: age at the time of diagnosis, male gender, and history of blood transfusion. Age, male gender, and advanced-stage PBC were associated with survival, but HCC development was not. The disease-specific annual mortality rate was estimated to be 0.008 for women and 0.028 for men with advanced-stage PBC. In conclusion, HCC develops in old patients with advanced-stage PBC, but HCC does not affect the patients' survival.     

Hepatocellular carcinoma with and without cirrhosis. A comparison in southern African blacks

Hepatocellular carcinoma and cirrhosis frequently coexist. In populations with a low incidence of hepatocellular carcinoma, the tumor often arises as a complication of long-standing symptomatic cirrhosis, which may be micronodular or macronodular and which is usually alcoholic in origin, and cirrhosis per se is the major etiologic association of the tumor. The relation between these two pathologic conditions in populations with a high incidence of hepatocellular carcinoma has not hitherto been analyzed. In this study the association was examined in 463 southern African black men with hepatocellular carcinoma. Cirrhosis, almost always macronodular and rarely showing features of alcholic toxicity, was present in 63.1% of the patients. No differences were found in the age structure, clinical features, hepatic function, serum alpha-fetoprotein concentrations, or hepatitis B virus status between patients with hepatocellular carcinoma with and without cirrhosis. Patients with cirrhosis survived slightly longer, but the difference was not biologically significant. It is concluded that the relation between hepatocellular carcinoma and cirrhosis in southern African blacks differs substantially from that in low incidence regions of the tumor.     

Hepatocellular carcinoma with sarcomatous change arising in primary biliary cirrhosis

We report an autopsy case of hepatocellular carcinoma (HCC) with sarcomatous change arising in the context of primary biliary cirrhosis (PBC) in a 79-year-old man. Primary biliary cirrhosis was diagnosed (stage I according to Scheuer's classification) by findings on blood biochemical analysis, laparoscopy, and liver biopsy at age 69 years. Five years later, (at age 74 years), a mass lesion was detected in the S₆ region of the liver by abdominal ultrasonography, and target biopsy revealed well differentiated HCC. Blood biochemistry, ultrasonography, and computed tomography findings showed that the PBC had progressed to stage IV (cirrhotic stage). Percutaneous ethanol injection therapy (PEIT) was administered to the HCC several times over a 5-year period; however, the patient died of liver failure in February, 1994 (at age 79 years). Viral markers for hepatitis B and C were negative during the course, and hepatitis C virus RNA was not detected by polymerase chain reaction. Autopsy findings showed liver cirrhosis and diffuse involvement of spindle-shaped sarcomatoid cells in the liver, particularly in the S₆ region, associated with several nodules of trabecular HCC cells. A zone of transition between the sarcomatoid cells and the trabecular hepatocellular carcinoma cells was observed. The sarcomatoid cells were diffusely disseminated in the peritoneal cavity and had metastasized to multiple organs. Immunohistochemically, the cells were positive for fibrinogen, as were the coexisting trabecular hepatocellular carcinoma cells. The HCC had been treated several times with PEIT. Of interest, PEIT may be an important factor in this type of tumor progression.     

Hepatocellular carcinoma in a patient with precirrhotic primary biliary cirrhosis

Hepatocellular carcinoma is generally associated with long-standing chronic liver disease of diverse etiology, most commonly HBsAg-positive chronic active hepatitis, hemochromatosis, or alcoholic liver disease. Patients with primary biliary cirrhosis have only rarely developed a subsequent hepatocellular carcinoma. We report such a patient, a 77-year-old woman with an early, precirrhotic stage of primary biliary cirrhosis who developed a hepatoma.     

Hepatocellular carcinoma incidence post direct-acting antivirals in hepatitis C-related advanced fibrosis/cirrhosis patients in Australia

BackgroundDespite efficacy in HCV eradication, direct-acting antiviral (DAA) therapy has raised controversies around their impact on hepatocellular carcinoma (HCC) incidence. Herein we reported the first Australian data on HCC incidence in DAA-treated HCV patients with advanced fibrosis/cirrhosis.MethodsWe conducted a retrospective single center study of DAA-treated HCV patients with advanced fibrosis/cirrhosis from April 2015 to December 2017. Patients with prior HCC were included if they had complete response to HCC treatment.ResultsAmong 138 patients who completed DAA therapy, 133 (96.4%) achieved sustained virologic response (median follow-up 23.8 months). Ten had prior HCC and 5/10 (50.0%) developed recurrence, while de novo HCC developed in 7/128 (5.5%). Median time from DAA to HCC diagnosis was 34 weeks in recurrent HCC vs. de novo 52 weeks (P = 0.159). In patients with prior HCC, those with recurrence (vs. without) had shorter median time between last HCC treatment and DAA (12 vs. 164 weeks, P < 0.001). On bivariate analysis, failed sustained virologic response at 12 weeks (SVR12) (P = 0.011), platelets (P = 0.005), model for end-stage liver disease (MELD) score (P = 0.029), alpha fetoprotein (AFP) (P = 0.013), and prior HCC (P < 0.001) were associated with HCC post-DAA. On multivariate analysis, significant factors were prior HCC (OR = 4.80; 95% CI: 1.47–48.50; P = 0.010), failed SVR12 (OR = 2.83; 95% CI: 1.71–16.30; P = 0.016) and platelets (OR = 0.97; 95% CI: 0.95–0.99; P = 0.009).ConclusionsOur study demonstrates a high incidence of recurrent HCC in HCV patients with advanced fibrosis/cirrhosis treated with DAA. Factors associated with HCC development post-DAA were more advanced liver disease, failed SVR12 and prior HCC, with higher rates of recurrence in those who started DAA earlier.     

Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis.

Two patients with primary haemochromatosis are reported in whom hepatocellular carcinoma supervened despite removal of excess iron after venesection therapy. These are the first patients described in whom hepatocellular carcinoma has complicated primary haemochromatosis in the absence of concomitant cirrhosis.