Diabetes: One of Few Remarkable Differences in Clinicopathologic Features Between Cirrhotic and Noncirrhotic Swedes With Hepatocellular Carcinoma

The prognosis of hepatocellular carcinoma (HCC) is usually very poor, so increased knowledge of clinicopathologic characteristics and etiologic factors may improve the clinical handling. Because HCC in many patients is unrecognized before death, it is of particular interest to study cases from a period with a high autopsy frequency. The records and liver biopsies from all patients with a diagnosis of primary liver cancer in Göteborg, Sweden, during a 22-year period were scrutinized. Only patients with evaluable non-neoplastic liver tissue were included in the final analysis. The majority (95%) of 478 HCC cases were autopsied and cirrhosis of the liver could be established in 71%. At presentation, general paramalignant symptoms such as malaise, weight loss, anorexia, and hepatomegaly (84%) were common irrespective of cirrhosis. Alcoholism and diabetes mellitus were each significantly more common among cirrhotics (29% and 20%, respectively; P < .001), than among noncirrhotics, in which cholelithiasis was more common (54%; P < .001). The correlation between diabetes and cirrhosis was independent of reported alcoholism. In an unselected population in a low HCC incidence area, there are few differences in clinicopathologic features between cirrhotic and noncirrhotic patients. Diabetes mellitus seems to play an etiologic role in HCC in cirrhotics, and cholelithiasis in noncirrhotics.     

Risk and outcome of hepatocellular carcinoma in liver cirrhosis in Southern Sweden: a population-based study

Background and aims: Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC). While the HCC risk is thought to be highest in hepatitis B and hepatitis C, the risk in other cirrhosis etiologies is not fully established. Therefore, we aimed to study the risk and outcome of HCC in alcoholic cirrhosis compared to cirrhosis of other etiologies, in Sweden.

Material and methods: We used population-based medical registries to identify patients diagnosed with cirrhosis in the Scania region in southern Sweden between 2001 and 2010. Medical records were reviewed to identify all HCC cases and to register clinical parameters. All patients were followed until death, emigration or December 2017.

Results: The cohort comprised 1317 patients with cirrhosis. A total of 200 patient developed HCC, including 75 with prevalent HCC. The annual incidence of HCC after six months was 1.5% in alcoholic cirrhosis and 4.7% in hepatitis C cirrhosis. In alcoholic cirrhosis, 40 patients were diagnosed with HCC during follow-up, of which 15 patients fulfilled the Milan criteria and 10 received treatment, curative or palliative. The overall median survival after HCC diagnosis was 7.7 months, with 4.5, 11 and 9.3 months, in cirrhosis due to alcohol, hepatitis C or remaining causes, respectively.

Conclusion: We find an annual incidence of HCC in alcoholic cirrhosis of 1.5% indicating need for surveillance in these patients. Survival after HCC diagnosis was worst in alcoholic cirrhosis due to more advanced stage at diagnosis with few patients eligible for treatment.     

Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992-2008

Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology, and End Results-13 registries, HCC stage, histological confirmation, and first-course surgery were examined. Among 21,390 HCC cases diagnosed with follow-up of vital status during 1998-2008, there were 4,727 (22%) with reported first-course invasive liver surgery, local tumor destruction, or both. The proportion with reported liver surgery or ablation was 39% among localized stage cases and only 4% among distant/unstaged cases. Though 70% of cases had histologically confirmed diagnoses, the proportion with confirmed diagnoses was higher among cases with reported invasive surgery (99%), compared to cases receiving ablation (81%) or no reported therapy (65%). Incidence rates of histologically unconfirmed HCC increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per year). Two encouraging findings were that incidence rates of localized-stage HCC increased faster than rates of regional- and distant-stage HCC combined (8% versus 4% per year), and that incidence rates of reported first-course surgery or tumor destruction increased faster than incidence rates of HCC without such therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific HCC survival increased from just 3% to 18%. Survival was 84% among transplant recipients, 53% among cases receiving radiofrequency ablation at early stage, 47% among cases undergoing resection, and 35% among cases receiving local tumor destruction. Asian or Pacific Islander cases had significantly better 5-year survival (23%) than white (18%), Hispanic (15%), or black cases (12%). CONCLUSION: HCC survival is improving, because more cases are diagnosed and treated at early stages. Additional progress may be possible with continued use of clinical surveillance to follow individuals at risk for HCC, enabling early intervention.     

Pheochromocytoma in Sweden 1958–1981

ABSTRACT An epidemiological study of 439 cases (184 males, 255 females) of pheochromocytoma (paraganglioma) diagnosed in Sweden from 1958-81 is presented. From the mid 1960's an average of 22 cases have been diagnosed each year. In 255 cases, the pheochromocytoma was diagnosed by clinical examination and/or surgery. In 184 cases (40%), the diagnosis was achieved by autopsy and out of which 60 (14% of all cases) were reported as incidental findings. Ninety-five pheochromocytomas (22%) were located outside the adrenals. The average (±SD) age at diagnosis for the total study population was 55.8 ± 17.7 years. Clinically diagnosed tumour cases were significantly younger (48.5±16.3 years) compared to cases diagnosed at autopsy (65.8±14.0). Pheochromocytomas were more common among women than among men. The age specific incidence rate increased continuously for both sexes from the youngest to the oldest age groups. The average incidence of pheochromocytoma in the 24 counties of Sweden was 2.1 cases per million inhabitants per year, range 0.9–5.3. A North to South gradient was noted with a higher incidence in the Southern parts of the country. Whether this is due to a real geographical variation of incidence, to a larger number of unreported cases in the Northern parts, or to presence of families with Sipple's syndrome in the South is unclear.     

Minor Role of Hepatitis B and C Virus Infection in the Etiology of Hepatocellular Carcinoma in a Low-Endemic Area

Background: The etiologic role of hepatitis B (HBV) and C virus (HCV) for hepatocellular carcinoma (HCC) in a low-endemicity area is obscure. Methods: Patients suspected of having primary liver cancer (PLC) in Göteborg, Sweden (n = 113), were tested serologically for HBV surface antigen and antibodies to HBV surface and core antigens. The presence of HBV surface and core antigens in cancer and non-neoplastic liver tissue in HCC cases was investigated immunohistochemically. Antibodies to HCV were tested by third-generation tests. The prevalence of HBV and HCV infection was compared in 73 patients with HCC and 32 patients with a final diagnosis other than PLC. Results: No patient had signs of chronic HBV infection. Seven of 64 (11%) HCC patients were anti-HCV-positive, compared with 1 of 31 (3%) without PLC. All seven patients with HCC and HCV infection had liver cirrhosis, and two were alcoholics. Alcoholism was judged the commonest (42%) cause of cirrhosis. Conclusion: Contrary to areas with a high incidence of HCC, chronic viral hepatitis, particularly HBV, seems to play a minor etiologic role for HCC in Sweden compared with alcohol-related cirrhosis.     

Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low-endemic area

AIMS/BACKGROUND: This study was undertaken in order to assess the main features of hepatocellular carcinoma in Germany, a country with low incidences of this tumor. METHODS: Two hundred and eighty consecutive patients with hepatocellular carcinomas admitted to the Medical School Hannover between 1993-1997 were retrospectively studied. RESULTS: Reliable data for the assessment of the etiology and the tumor stage of HCC were available for 268 patients. The female/male ratio was 1/4. In 51.9% of the patients, HCC was associated with hepatitis virus B or C (HBV, HCV) infection: 35.1% with HBV, 26.9%) with HCV and 10% coinfection with HBV/HCV This result emphasizes the major impact of HBV and HCV infection in liver cancer in Germany. Of all patients with HCC 74.6%) had liver cirrhosis. The predominant majority of the HCC (87%) were restricted to the liver: in only 5.9% could regional lymph node metastases as well as 8.5%) metastases in other organs be clinically diagnosed by chest X-ray, computed tomography scan or sonography. Data to asses the Okuda tumor stage were available for 166 patients: 47% were classified as stage I, 47% as stage II and only 6% as stage III. Serum AFP were determined in 195 patients. In 66% of the patients, the AFP value was elevated, but only in 30% did the AFP level reach the value of 500 microg/l, which is considered to be significant for HCC diagnosis in patients with liver cirrhosis. The proportion of liver cirrhosis was higher in HCV (97.8%) versus HBV (80.6%) associated HCC, which was the only significant (p<0.05) difference in the characteristics of HCC according to the etiology. CONCLUSION: Our study shows that liver cirrhosis is the prime risk factor for hepatocarcinogenesis in Germany. However, the very high proportion of hepatitis virus related HCC, in particular the high proportion of HBV infections, contradicts the common view that alcohol is by far the most important etiological factor for hepatocarcinogenesis in low hepatitis virus endemic areas such as Germany.     

Relative incidence of primary liver cancer in cirrhosis in Austria. Etiological considerations

ABSTRACT— The incidence of primary liver cancer (PLC) was assessed in 652 patients (429 male, 223 female) with liver cirrhosis. By the end of the study 416 (64%) of all patients had died. The autopsy rate was 65%. PLC developed in 73 patients. Histologically, 67 cases were classified as hepatocellular (HCC), one as mixed hepatocellular-cholangiocellular and five as cholangiocellular carcinoma. In 30 cases, HCC was confirmed within a year of diagnosis of cirrhosis, and in the remaining 37 cases HCC developed 2–13 years later. At autopsy, the frequency of HCC was almost twice as high in males (27%) as in females (15%) (p<0.025). This difference occurred in alcoholic and posthepatitic cirrhosis but not in cryptogenetic cirrhosis. HBsAg was detected in 19.0% of male and 9.2% of female patients (p<0.01). Comparison of patients with and without HCC revealed no significant differences in the prevalence of HBsAg. These data indicate that HCC is common in Austrian patients with cirrhosis, representing 60% of all malignant tumors in this group. In view of the high HBsAg carrier rate and the prevalence of chronic alcoholism in patients with cirrhosis, it is suggested that the two factors together lead to an increased risk of cirrhosis followed by an increased incidence of HCC.     

Utilization of screening for hepatocellular carcinoma in the United States

BACKGROUND: Screening for hepatocellular carcinoma (HCC) has been recommended for patients at high-risk of developing HCC. Yet, the utilization and determinants of screening remain unclear. METHODS: All patients diagnosed with HCC at 3 medical centers during 1998 to 2003 were identified. Information regarding receipt of HCC screening, demographics, risk factors, liver disease severity, number of HCC lesions, therapy, and date of death was abstracted from medical records. Multivariable logistic regression models were conducted to evaluate determinants of HCC screening and therapy. Cox proportional hazards models were developed to assess the effect of screening on risk of mortality. RESULTS: We identified 157 patients diagnosed with HCC. The majority of patients were <65 years (62%), white (59%), had a single mass (42%), and a Child-Pugh-Turcotte score B (41%). Approximately, 28% (n=44) received at least one possible screening test (36% alpha-fetoprotein only, 23% abdominal ultrasound only, 7% computed tomography only; 34% had more than one test). Screened patients were younger [odds ratio (OR)=2.70; 95% confidence interval (CI): 1.22-5.99) and were more likely to have underlying HCV (OR=2.91; 95% CI: 1.36-6.23), or alcoholic liver disease (OR=4.20; 95% CI: 1.89-9.35). The only predictors of receipt of therapy were presentation at tumor board conference (OR=2.85; 95% CI: 1.42-5.72) and documented referral to oncology (OR=2.33; 95% CI: 1.10-4.94). CONCLUSIONS: Less than one-third of patients who were diagnosed with HCC received screening before their diagnosis, and of those a large proportion received an alpha-fetoprotein test only. In this study, the use of screening was too suboptimal to be expected to affect outcomes.     

Natural history of hepatocellular carcinoma in Spain. Five year's experience in 249 cases

In this study we attempted to define the clinical pattern and prognosis of hepatocellular carcinoma (HCC) patients in Spain. Two hundred and forty-nine patients were included in the study. One hundred and eighty-seven were male and 62 female, with their mean age being 62.5 +/- 0.6 years. The majority of patients (92.8%) had an underlying cirrhosis. In most of the patients, the disease appeared as decompensated liver disease. Only 18.5% of the HCC cases were asymptomatic. Only 8.2% of the cases were HBsAg positive. alpha-Fetoprotein reached diagnostic values in only 37.2% of the patients. Surgical treatment was successfully performed in 14 patients: one underwent orthotopic liver transplantation and the 13 others complete tumor resection. Chemotherapy was administered to 38 subjects, while percutaneous ethanol injection was applied in seven cases. Patients receiving only symptomatic treatment, comprised 76.7%. Survival was related to tumor size and liver function. While the median survival of the whole series was 3.3 +/- 0.4 months, it was 14.5 +/- 2.2 months in patients with preserved liver function and small tumors. These results reflect that in Spain HCC patients are diagnosed at a moderately advanced phase. Since early diagnosis is the only way to increase the proportion of patients suitable for curative treatment, early detection plans are mandatory in the population at risk.     

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.     

Evaluation of accuracy of clinical diagnosis of TB by annual autopsy report

PURPOSE: To investigate the accuracy of clinical diagnosis of TB in Japan in recent years and to compare them with previous studies. METHOD: Data (sex, age, clinical diagnosis, pathological diagnosis as cause of death) on deceased cases clinically or pathologically diagnosed ante mortem as having tuberculosis was collected from annual reports of the pathological autopsy cases in 1984, 1989, 1994, and 1999-2004. Information on TB death from population statistics in those 9 years also was collected and compared with data of autopsied cases. RESULT: Autopsy rate in these years was stably around 10 %. Comparison of gender ratio and mean age between the two surveys showed similar numbers. During 1999-2004, 1725 death cases were diagnosed as TB clinically or pathologically. Number of pathologically proven pulmonary TB cases was 429 and that of miliary TB was 283. 55.7% of pulmonary tuberculosis and only 21.9% of miliary tuberculosis were correctly diagnosed before death. Out of 156 cases clinically diagnosed as non-TB diseases but proven as TB pathologically, 30.8% of clinical diagnosis was pneumonia and/or bronchitis, followed by diagnoses of interstitial pneumonia, respiratory failure, pneumoconiosis and lung cancer. However, the main clinical diagnoses of 175 miss-diagnosed miliary TB cases were diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis. CONCLUSION: In order to reduce undiagnosed pulmonary TB cases and to prevent nosocomial TB infection, differential diagnosis among pneumonia and/or bronchitis cases should be done. In case of miliary TB, not only pneumonia but also diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis should be included in the list differential diagnosis.     

Hepatocellular carcinoma in an Australian tertiary referral hospital 1975-2002: change in epidemiology and clinical presentation

AIM: We compared the epidemiology and clinical features of hepatocellular carcinoma (HCC) cases diagnosed between 1975 and 2002. METHODS: Retrospective and prospective analysis was performed of HCC cases diagnosed at The Alfred during the time periods 1975-1983 and 1995-2002. Demographic, epidemiological, clinical and laboratory data were recorded and compared between the two periods. RESULTS: Comparing the 1995-2002 cohort to the 1975-1983 cohort, patients were older (64 years vs 60 years; P = 0.02), and were more likely to be non-Caucasian (25%vs 9%; P = 0.003) and born overseas (57%vs 40%; P = 0.03) particularly from Asia. In addition, hepatitis C virus (HCV) (35%), hepatitis B virus (HBV) (22%), and alcoholic liver disease (29%) were the major etiological factors for HCC with alcohol less likely the cause of underlying liver disease (33%vs 55%; P < 0.01). Among the 1995-2002 cohort, overseas-born patients were more likely to be infected with HBV (P < 0.001) and HCV (P = 0.01), while alcohol was more likely to be the etiological factor in Australian-born cases (P = 0.02), particularly among males. Detection of HCC by screening was the initial presentation in 38% of patients, and diagnosis of HCC was often by non-invasive means. CONCLUSIONS: The epidemiology of HCC has changed in Australia over the past 20 years with hepatitis C and hepatitis B now major etiological factors, and an increase in cases born overseas particularly from areas where HCV and HBV are endemic. This suggests the recent increase in incidence and death rates due to HCC in Australia relate to HCV and HBV infection.     

A high risk group of hepatocellular carcinoma in man, with special reference to its clinical significance for the screening of early liver cancer. Gifu Study Group for Early Liver Cancer

A high risk group of hepatocellular carcinoma (HCC) was statistically established using multiple regression analysis of 331 cases with liver cirrhosis (LC), in which 78 cases later developed HCC. Highly contributing factors to hepatocarcinogenesis were found to be positive HBsAg, age, drinking history, sex (male), history of blood transfusion, history of acute hepatitis (or jaundice) and elevated plasma levels of alpha-fetoprotein. A prospective study was initiated in April, 1985 employing another 122 LC patients to clinically evaluate the significance of the high risk group of HCC. 28 cases with small HCC (less than 3 cm in diameter) were newly found: 4 with chronic hepatitis and 24 with LC, among whom 22 developed from the high risk group (sensitivity 92%, specificity 44%). Three year survival rate of 28 cases thus found was 56%, and causes of death of 9 fatal patients were 4 cancer death, 4 hepatic failure and 1 gastrointestinal bleeding. In conclusion, the high risk group is valuable for the screening of early liver cancers, and treatments of hepatic failure as well as of HCC itself are important to improve the prognosis of HCC patients thus diagnosed.     

Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year follow-up in northern Sweden

Abstract. Innala E, Andersson C (Umeå University, Umeå, Sweden). Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15‐year follow‐up in northern Sweden. J Intern Med 2011; 269 : 538–545. Objectives. To evaluate the benefit of screening for hepatocellular carcinoma (HCC) in gene carriers of acute intermittent porphyria (AIP) and estimate the annual incidence of HCC in this group. Subjects. All AIP gene carriers aged ≥55 years from the northernmost county in Sweden, Norrbotten, were invited for screening in this prospective study every 1–1.5 years during the period 1994–2009. We registered all HCC cases amongst AIP gene carriers in the northern region of Sweden (four counties). We compared gene carriers with repeated screening intervals of <2 years (Group A) with controls (Group B; i.e. gene carriers who had never been screened, those screened for the first time or screened at intervals of >2 years, or dropouts). The screening included radiological examination of the liver and relevant laboratory tests. Results. A total of 62 AIP subjects participated in the study, comprising 33% of the total AIP population aged >55 years in the northern region of Sweden. HCC was diagnosed in 22 AIP subjects (12 men and 10 women), mean age 69 (59–82) years. Amongst these subjects, 73% had experienced prior AIP attacks. The incidence rate ratio for HCC was 64 (52 in men and 93 in women). There were no cases of hepatitis B/C or alcohol abuse. Liver cirrhosis was rare. Liver resection could be performed in most subjects in Group A. Fourteen patients died of HCC, one in Group A and 13 in Group B. Compared with those who were not screened regularly, screening was associated with improved 3‐year and 5‐year survival (P = 0.005 and 0.038). Conclusions. Screening for HCC in carriers of AIP enables early diagnosis and a choice of potentially curative treatments with improved prognosis. We recommend annual screening using liver imaging for AIP gene carriers >50 years of age.     

外周血白蛋白mRNA分析在肝癌诊断和转移监测中的价值

目的     

Hepatocellular carcinoma risk in patients with porphyria cutanea tarda

AIM: It has been suggested that patients with porphyria cutanea tarda (PCT) are at high risk of developing hepatocellular carcinoma (HCC); however, this has not been confirmed by other workers. The aim of our study was to evaluate the incidence of HCC in patients with PCT, and to assess the possible co-factors associated with cancer development. METHODS: Thirty-nine consecutive patients with a diagnosis of PCT were included. Hepatitis B virus and hepatitis C virus (HCV) infection was investigated, and a percutaneous liver biopsy was performed. Patients were treated with phlebotomies, which resulted in a clinical remission in all. These patients were included in a surveillance programme for the detection of HCC, with ultrasonography and serum alpha-fetoprotein every 6 months. RESULTS: Thirty-nine patients (92% male; mean age, 55 +/- 16 years) with PCT were included. Alcohol abuse was reported in 87% of the cases. The mean follow-up time since the initial diagnosis of PCT was 9.7 years (378 patient-years of follow-up). Serological markers of past infection with hepatitis B virus were found in 20% of the patients, while HCV infection was diagnosed in 56%. The stage of fibrosis in patients having liver biopsy was: 0 (32%), 1 (32%), 2 (9%), 3 (18%), and 4 (9%). HCC was diagnosed in 1/39 patients with PCT (cumulative incidence, 2.6%), giving a yearly incidence of 0.26% per patient-year. This patient was a 69-year-old male, alcohol abuser, with HCV infection, with a 12-year period between diagnosis of PCT and HCC, and with liver biopsy (3 years before) showing fibrosis stage 3. CONCLUSION: The risk of developing HCC in patients with PCT in our area is relatively low (a yearly incidence of less than 1% per patient-year of follow-up), and perhaps attributable, at least in part, to concomitant HCV infection. Patients presenting with PCT should undergo both HCV infection determination and liver biopsy, and those with concomitant HCV infection or advanced fibrosis/cirrhosis should probably be included in a standard surveillance programme in order to achieve early diagnosis of HCC.     

A prospective study of the incidence of deep-vein thrombosis within a defined urban population.

In a prospective study all positive phlebographies within the well-defined population of the city of MalmÖ, Sweden, during 1987 were studied in order to determine the incidence of deep venous thrombosis (DVT). Epidemiological data were analysed for the detection of patient groups at increased risk of DVT. The incidence was found to be equal for both sexes, i.e. 1.6 per 1000 inhabitants and year. Risk factors were found to be in accordance with earlier studies. The median age for men was 66 years, compared to 72 years for women. At diagnosis of DVT, 19% of subjects had a known malignancy and within 1 year 5% (19 cases) developed a new malignancy. Of the men, 29% had postoperative or post-traumatic (fracture) DVT, compared to 46% of the women. Fewer patients with DVT than expected (39%) belonged to blood group 0 (31%) (P < 0.005). Pulmonary embolism (PE) was clinically suspected in only 5% of cases, and diagnosis was verified scintigraphically in 2% of cases. None of these died of PE, but of 6 patients who were found to have PE at autopsy, four died about 4 weeks after the DVT was diagnosed.     

Fatty liver disease,an emerging etiology of hepatocellular carcinoma in Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.     

Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low‐endemic area

Abstract: Aims/Background: This study was undertaken in order to assess the main features of hepatocellular carcinoma in Germany, a country with low incidences of this tumor. Methods: Two hundred and eighty consecutive patients with hepatocellular carcinomas admitted to the Medical School Hannover between 1993–1997 were retrospectively studied. Results: Reliable data for the assessment of the etiology and the tumor stage of HCC were available for 268 patients. The female/male ratio was 1/4. In 51.9% of the patients, HCC was associated with hepatitis virus B or C (HBV, HCV) infection: 35.1% with HBV, 26.9% with HCV and 10% coinfection with HBV/HCV. This result emphasizes the major impact of HBV and HCV infection in liver cancer in Germany. Of all patients with HCC 74.6% had liver cirrhosis. The predominant majority of the HCC (87%) were restricted to the liver: in only 5.9% could regional lymph node metastases as well as 8.5% metastases in other organs be clinically diagnosed by chest X‐ray, computed tomography scan or sonography. Data to asses the Okuda tumor stage were available for 166 patients: 47% were classified as stage I, 47% as stage II and only 6% as stage III. Serum AFP were determined in 195 patients. In 66% of the patients, the AFP value was elevated, but only in 30% did the AFP level reach the value of 500 μg/l, which is considered to be significant for HCC diagnosis in patients with liver cirrhosis. The proportion of liver cirrhosis was higher in HCV (97.8%) versus HBV (80.6%) associated HCC, which was the only significant (p<0.05) difference in the characteristics of HCC according to the etiology. Conclusion: Our study shows that liver cirrhosis is the prime risk factor for hepatocarcinogenesis in Germany. However, the very high proportion of hepatitis virus related HCC, in particular the high proportion of HBV infections, contradicts the common view that alcohol is by far the most important etiological factor for hepatocarcinogenesis in low hepatitis virus endemic areas such as Germany.     

A 6-month versus a 12-month surveillance for hepatocellular carcinoma in 559 hemophiliacs infected with the hepatitis C virus

Hepatocellular carcinoma (HCC) is an increasingly frequent cause of mortality in hemophiliacs with chronic viral hepatitis. Early diagnosis of the tumor at an initial stage is known to improve the outcome of HCC treatment. Because all HCC cases detected in a previous study based upon annual ultrasound (US) surveillance of hemophiliacs with elevated alanine aminotransferase levels were multinodular, this study was designed to evaluate if a more intense surveillance with US and alphafetoprotein (AFP) serum levels of all the patients infected with the hepatitis C virus (HCV) improved the identification of single nodule tumors. A multicenter cohort of 559 HCV-infected hemophiliacs was divided into 2 arms, one followed up at 6-month intervals and one at 12-month intervals depending on the choice and available facilities of each treatment center. During a 6-year surveillance period, HCC was diagnosed in 5 (2.4%) of 210 patients in the 6-month group and in 3 (0.9%) of 349 patients in the 12-month group. The overall incidence rate of HCC was 239 per 100 000 per year (397 per 100 000 per year in the 6-month group and 143 per 100 000 per year in the 12-month group; differences not statistically significant). By multivariate analysis, HCC risk was increased 12.9-fold with alcohol intake more than 80 g/d and 15.2-fold with AFP levels higher than 11 ng/mL. Liver-related death occurred in 8 cases (1.4%), including 3 with HCC. Still alive and tumor free after 24 to 34 months from diagnosis are 3 patients with multinodular tumors treated with repeat chemoembolization followed by orthotopic liver transplantation. In conclusion, 6-month surveillance with US did not increase the chances of detection of single nodule tumors, but it is reasonable to assume that successful treatment of multinodular tumors based upon debulking with chemoembolization and liver transplantation was facilitated by this approach.