Jerzy Kaczynski

Metastases in Cases with Hepatocellular Carcinoma in Relation to Clinicopathologic Features of the Tumour An autopsy study from a low endemic area

In order to study clinicopathologic features of hepatocellular carcinoma (HCC) and their relation to metastatic growth, all autopsied cases with confirmed HCC (n = 490) from a period with a high autopsy frequency in a well-defined population were analyzed. Cirrhosis, usually of micronodular type, was found in 72%. The gross appearance of the tumour was predominantly massive (46%) or multinodular (42%). The tumour involved both liver lobes in 72% or the right lobe alone in 20%. Histologically, trabecular growth (79%) and grade II of differentiation (52%) prevailed. Vascular invasion was noted in 56%, whereas involvement of the biliary tract was unusual (4%). Metastases especially involved lymph nodes (42%), lungs (18%) and skeleton (17%). Increased weight of the liver, multinodular appearance, involvement of both liver lobes, low grade of differentiation and vascular invasion were significantly associated with presence of metastases.

Incidence, etiologic aspects and clinicopathologic features in intrahepatic cholangiocellular carcinoma--a study of 51 cases from a low-endemicity area.

A total of 51 cases (19 males and 32 females) of intrahepatic cholangiocellular carcinoma (CCC) from a low-endemicity area of primary liver cancer was analyzed during the periods from 1958 to 1979 and from 1984 to 1991. The mean annual age-adjusted incidence rate was 0.44 for males and 0.56 for females per 100,000 inhabitants. CCC was diagnosed before death in only 31%. There was a female predominance in patients over 70 years of age (p < 0.05). At presentation, malaise (85%), weight loss (73%) abdominal pain (50%) and hepatomegaly (80%) were common. The median survival time from diagnosis was 2 months. The mean age at the time of death was 72 years (range 41-92). At autopsy, cholelithiasis was found in 61% (81% in patients older than 70 years) and cirrhosis in 30% of patients. Cholelithiasis was more common in CCC (p < 0.01) than in hepatocellular carcinoma cases with the same mean age. Not one case of inflammatory bowel disease was found. The gross appearance of the tumor was predominantly massive (49%) or multinodular (35%). The most common histological features were tubular pattern of growth (82%) and abundant fibrous stroma. Metastases were particularly associated with the lymph nodes (41%), skeleton (26%) and lungs (16%).

Incidence of primary liver cancer and aetiological aspects: a study of a defined population from a low-endemicity area.

The prevalence of primary liver cancer (PLC) varies throughout the world. It has been attributed to variations in incidence of the predominant histological type, hepatocellular carcinoma (HCC). The incidence of PLC types other than HCC such as cholangiocellular carcinoma (CCC) is far less known, especially in low-incidence areas. The aetiology of HCC and other PLC types is obscure, with the exception of the association between HCC and cirrhosis as well as chronic viral hepatitis. The present retrospective incidence and aetiology study concerns a well-defined population from a period with a high autopsy frequency. Preserved biopsy specimens were re-evaluated histopathologically and patient records were studied. Among 590 histologically verified cases of PLC, HCC constituted 90%, CCC 8% and a mixed form of these types 1%. At the end of the study period the annual age-standardised incidence rate of HCC was 3.6 cases per 100,000 inhabitants. Other PLC types were hepatoblastoma (n = 3), fibrolamellar carcinoma (n = 2), angiosarcoma (n = 1) and infantile haemangioendothelioma (n = 1), each constituting less than 1% of the PLC cases. Comparing HCC with CCC we found that cirrhosis (70%) and alcoholism (21%) was significantly more frequent in HCC, and cholelithiasis was significantly more common (60%) in patients with CCC. In the majority of the PLC cases with liver cirrhosis this disorder was unknown before diagnosis of the tumour.

Hepatocellular Carcinoma in Sweden: its Association with Viral Hepatitis, Especially with Hepatitis C Viral Genotypes

Viral markers of chronic hepatitis were tested for in 95 frozen serum samples from 299 patients from Malmö, Sweden, with hepatocellular carcinoma (HCC), diagnosed between 1977 and 1994. Hepatitis B analysis included anti-HBc, HBsAg and, if anti-HBc positive, HBV DNA. Hepatitis C infection analysis included anti-HCV screening, RIBA, HCV RNA and HCV genotyping. HCV genotyping was also carried out in 9 HCV-viraemic HCC-patients from Gothenburg. HCV genotype distribution in HCC cases was compared with Swedish HCV-infected blood donors. Among the 95 patients from Malmö, 28 (29%) had anti-HBc, but only 5 (5%) were chronic HBV carriers, compared with 16 (17%) with chronic hepatitis C (p=0.021). HCV-related HCC was more common among immigrants (8/16 vs. 8/79; p<0.001). Genotyping of 25 HCV-infected cases showed genotype 1a in 6 (24%), genotype 1b in 13 (52%), genotype 2b in 4 (16%), and genotype 3a in 2 (8.0%) patients. Genotype 1b was more common among HCC patients than among blood donors (p<0.001), but 8 of 13 genotype 1b-infected patients were from countries where genotype 1b is predominant. Among native Swedes there was no difference between the HCV genotypes infecting blood donors and those found in HCC patients.Viral markers of chronic hepatitis were tested for in 95 frozen serum samples from 299 patients from Malmö, Sweden, with hepatocellular carcinoma (HCC), diagnosed between 1977 and 1994. Hepatitis B analysis included anti-HBc, HBsAg and, if anti-HBc positive, HBV DNA. Hepatitis C infection analysis included anti-HCV screening, RIBA, HCV RNA and HCV genotyping. HCV genotyping was also carried out in 9 HCV-viraemic HCC-patients from Gothenburg. HCV genotype distribution in HCC cases was compared with Swedish HCV-infected blood donors. Among the 95 patients from Malmö, 28 (29%) had anti-HBc, but only 5 (5%) were chronic HBV carriers, compared with 16 (17%) with chronic hepatitis C (p = 0.021). HCV-related HCC was more common among immigrants (8/16 vs. 8/79; p < 0.001). Genotyping of 25 HCV-infected cases showed genotype 1a in 6 (24%), genotype 1b in 13 (52%), genotype 2b in 4 (16%), and genotype 3a in 2 (8.0%) patients. Genotype 1b was more common among HCC patients than among blood donors (p < 0.001), but 8 of 13 genotype 1b-infected patients were from countries where genotype 1b is predominant. Among native Swedes there was no difference between the HCV genotypes infecting blood donors and those found in HCC patients.

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.

Lack of Correlation Between Hepatitis B Virus Infection and the Increasing Incidence of Primary Liver Cancer in Sweden

The incidence of primary carcinoma of the liver in Sweden has been reported to increase. In order to study the role of chronic hepatitis B virus (HBV) infection for liver cancer development 40 cases with hepatocellular carcinoma (HCC) were examined for the presence of HBV surface antigen and HBV core antigen in the cancer and in the surrounding non-neoplastic liver tissue. It was not possible to demonstrate a single case with tissue HBV antigen, indicating that HBV plays a minor role in the etiology of HCC in Sweden and thus does not seem to be responsible for the increasing incidence of this cancer.

Overweight and hypertriglyceridemia are risk factors for liver cirrhosis in middle-aged Swedish men

Abstract Objective. Hyperlipidemia, overweight, insulin resistance and hypertension are associated with non-alcoholic fatty liver disease. The knowledge about these conditions as etiologic factors in liver cirrhosis is, however, limited. In this study, we examined the relation between overweight and hypertriglyceridemia, and development of liver cirrhosis in a general population. Material and methods. An epidemiological, longitudinal study was conducted involving men at the age of 50 with 40 years of follow-up. Baseline data were collected in 1963 and 1967. Cases of liver cirrhosis were identified by searching the Swedish Hospital Discharge Register and death certificates of the Central Bureau of Statistics. The independent effect of BMI, triglyceride levels and alcohol habits for cirrhosis of the liver was calculated by using multiple logistic regression analysis. Results. Elevated BMI and triglycerides were significant independent risk factors for the development of liver cirrhosis (OR 1.27 and 1.99, respectively, p < 0.01). Conclusions. Overweight and hypertriglyceridemia are independent risk factors for liver cirrhosis in Swedish men.

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.

Increased Porphyrins in Primary Liver Cancer Mainly Reflect a Parallel Liver Disease

Hepatic porphyries have been associated with an increased risk of primary liver cancer (PLC), which on the other hand may cause an increased porphyrin production. To evaluate the role of an underlying liver disorder we analyzed porphyrins in patients with hepatocellular carcinoma (HCC) (n = 65), cholangiocellular carcinoma (n = 3), or suspected PLC, which turned out to be metastases (n = 18) or a benign disorder (n = 11). None of the patients had a family history of porphyry or clinical signs of porphyry. Increased aminolevulinic acid or porphyrin values were common not only in patients with PLC (43%) but also in metastatic (50%) and benign (64%) liver disorders. The corresponding proportion for HCC patients with liver cirrhosis (55%) was higher (P < .05) than in those without cirrhosis (17%). We conclude that symptomatic porphyries are unusual in PLC, whereas elevated urinary and/or faecal porphyrins are common, primarily reflecting a parallel liver disease and not the PLC.

Waist-to-hip ratio but not body mass index predicts liver cirrhosis in women

Abstract Background: Being overweight can lead to fatty liver and end-stage liver disease. In men, higher body mass index is associated with higher risk of developing liver cirrhosis. The extent of association between overweight and liver cirrhosis in women is not fully elucidated. Aims: This study aimed to investigate the association between overweight and liver cirrhosis in women, taking into account different measures of adipose tissue distribution. Methods: A cohort of 1462 middle-aged women was followed over 40 years. Cases of liver cirrhosis were identified by linkage to Hospital Discharge and Death Certificate registries. The hazard ratios for different anthropometric measures and liver cirrhosis were obtained by Cox proportional hazard regression, using propensity score methods to adjust for important confounders. Results: During 48,062 person-years of follow-up, 11 cases of liver cirrhosis were identified. The incidence rate in women with waist-to-hip ratio ≥ 0.8 was 131.8 (48.1–287.0), compared to 12.0 (3.9–28.1) in women with a lower ratio. A waist-to-hip ratio ≥ 0.8 was associated with an increased risk of liver cirrhosis, the hazard ratio being 5.8 (95% confidence interval 1.6–21.4). No association between body mass index and liver cirrhosis was found and the hazard ratio for body mass index >25 was 1.8 (0.5–5.8). Conclusion: In women, an unfavorable adipose tissue distribution is more important for development of liver cirrhosis than total body fat per se. When assessing the risk for development of liver cirrhosis in women, waist-to-hip ratio is a better predictor than body mass index.