Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients ...with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive. Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive. 7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti-HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. Our results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis.
The role of hepatitis B virus (HBV) in the course of patients with primary liver cancer who are negative for hepatitis B surface antigen has been debated. We used the polymerase chain reaction to ...evaluate 28 such patients for the presence of DNA and RNA sequences of the virus; 22 of these patients had associated cirrhosis. The patients were from areas with different prevalences of HBV infection (South Africa, Italy, France, and Japan).
Antibodies to the surface and core antigens of HBV were detected in 10 of the 23 patients tested. HBV DNA sequences were detected in 17 of the 28 patients, including 8 of the 10 with HBV antibodies and 6 of 13 without HBV serologic markers. HBV RNA molecules were found in four of five tumors tested.
Our investigation indicates that transcriptionally active HBV genomes are present in various geographic areas among patients with liver cancer who are negative for hepatitis B surface antigen. This observation is consistent with an etiologic role for the virus in the development of these tumors.
In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, ...under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+0.2 (SD 1.4) g vs. -1.7 (2.4); P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.
The aim of this study was to evaluate the actual role of physical examination of the liver in normal subjects and in cirrhotic patients.
One hundred healthy subjects and 100 patients with liver ...cirrhosis underwent a physical and an ultrasonographic evaluation of the liver by independent operators. Physical examination was performed by means of percussion and palpation to determine total liver span, liver span below the costal margin, and liver consistency. Total liver span, liver span below the costal margin, and liver volume were also determined by means of ultrasonography.
The agreement between physical and ultrasonographic assessment of the liver span below the costal margin was poor in controls (chance corrected agreement index = 0.13) and excellent in patients (chance corrected agreement index = 0.93). Physical and ultrasonographic total liver span were correlated in patients with cirrhosis (r = 0.592) but not in controls (r = 0.205). Echo-measured liver span significantly correlated with the actual volume of the organ in both groups, whereas physical liver span significantly correlated with liver volume in cirrhosis but not in controls. The difference between actual liver volume and the value predicted by liver span was large. The cirrhotic liver was slightly reduced in size in comparison with that of healthy subjects and differed by an increase in consistency and a thickened edge.
The bedside examination of the liver does not provide any accurate information regarding the actual volume of the organ. Its major role remains to define the characteristics of lower edge, mainly consistency, which may help in clinical diagnosis. Liver volume proved to predict prognosis in patients with cirrhosis, but its measurement needs quantitative, reproducible methods, which can be obtained only by imaging techniques.
BACKGROUND
Contrasting data have so far been reported on the utility and efficacy of screening patients with cirrhosis for early detection of hepatocellular carcinoma (HCC). The goal of this study ...was to evaluate the efficacy of a regular ultrasonographic and laboratory follow‐up for the early detection of small HCC, and to identify parameters correlated with a higher risk of developing HCC.
METHODS
One hundred and sixty‐four consecutive patients with liver cirrhosis living in Emilia Romagna, Italy, were enrolled in the period 1989–1991. All patients underwent clinical, biochemical, and ultrasonographic evaluations at entry and at 3‐ and 6‐month intervals during follow‐up.
RESULTS
By April 1995, 34 patients had developed HCC. In 76% of the patients, ultrasonography identified HCC when it was still single and small (<4 cm). At discriminant, logistic regression and univariate analyses, sex and the entry concentration of alkaline phosphatase, α‐fetoprotein, gamma‐glutamyl transpeptidase, and albumin were associated with a higher risk of developing HCC, whereas at multivariate analysis (Cox's model), only sex and the entry concentration of alkaline phosphatase, albumin, and α‐fetoprotein were independently and significantly related to the appearance of HCC.
CONCLUSIONS
A regular ultrasonogrpahic follow‐up, timed at 3‐ to 6‐month intervals according to the risk of HCC development in patients with cirrhosis, allows the detection of liver carcinoma at an early stage in a high proportion of patients, possibly improving the prognosis of the disease. Cancer 1996;78:977‐85.
Alterations in carbohydrate metabolism are frequently observed in cirrhosis, and approximately 15% to 30% of patients have overt diabetes. In a retrospective and prospective study in cirrhosis, we ...analyzed the prognostic significance of diabetes, which was defined as the presence of hyperglycemia and overt glycosuria that in most cases required dietary restrictions or active treatment. The clinical records of all patients with cirrhosis admitted to our department for the period 1980 to 1985 were reviewed in 1985 and 1986, and surviving patients were prospectively followed up until December 1991. Final status could be obtained in 354 (98 with diabetes) of 382 eligible patients; 110 were alive at the end of follow‐up. Prognostic factors were identified by Kaplan‐Meier analysis, followed by Cox's stepwise regression. The model identified, in sequence, albumin, ascites, age, encephalopathy, bilirubin, diabetes, and platelets as prognostic factors. The larger mortality rate in patients with diabetes was not due to complications of diabetes but to an increased risk of hepatocellular failure. Diabetes was no longer a risk factor as a covariate in a subgroup of 271 patients when varices were added but was again significant when patients who died of gastrointestinal bleeding were excluded. The presence of diabetes, clinically detectable and often requiring adequate treatment, is a risk factor for long‐term survival in cirrhosis. (Hepatology 1994;20:119–125.)
Aims: The aim of this study was to assess the incidence of fatal, life-threatening side effects and the
de novo appearance of non-hepatic morbidity during interferon alfa therapy for chronic viral ...hepatitis. The relationship of these adverse events to actual total dose and duration of interferon was also evaluated.
Methods: We conducted a retrospective study at 73 Italian centers of 11 241 consecutive patients with chronic vital hepatitis who underwent interferon alfa treatment.
Results: Five patients died during interferon therapy due to liver failure (
n=4) or complications arising from sepsis. Life-threatening side effects were observed in eight patients: two cases where depression developed and led to a suicide attempt and six patients with bone marrow suppression (granulocytes <500/mm
3 or platelets <25 000/m
3). These symptoms and signs completely disappeared after interferon withdrawal. During interferon treatment, 131 patients developed the following
de novo non-hepatic disorders: symptomatic thyroid disease (
n=71), impotence (
n=5), systemic autoimmune disease (
n=5), immune-mediated dermatologic disease (
n=14), diabetes mellitus (
n=10), cardiovascular disease (
n=7), psychosis
n=10), seizures (
n=4), peripheral neuropathy (
n=3) and hemolytic anemia (
n=2). Most of these complications are reversible or can be ameliorated. Fatal or life-threatening side effects were not related to actual total dose or duration of interferon alfa, while the majority of patients with
de novo non-hepatic morbidity received medium/high doses ( > 200 million units) of interferon alfa or were treated for periods longer than 16 weeks (68% and 80%, respectively).
Conclusions: Treatment with interferon alfa may have fatal or life-threatening side effects, their incidence in this study being low (0.04% and 0.07%, respectively) and perhaps no different than in untreated patients with chronic viral hepatitis. Moreover
de novo non-hepatic morbidity occurred in 1.2% of patients, and the dose and duration of interferon therapy seem important in determining the frequency of this complication. The development of clinically-overt thyroid disease was most common.
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