Sebastiano Siringo

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis

BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. AIMS To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. PATIENTS A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. METHODS Surveillance was based on ultrasonography (US) and α fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. RESULTS Surveillance lasted a mean of 56 (31) months (range 6–100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US

What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy

753 226, the cost per treatable HCC was US

Prognostic indicators of risk for first variceal bleeding in cirrhosis: a multicenter study in 711 patients to validate and improve the North Italian Endoscopic Club (NIEC) index

17 934, and the cost for year of life saved was US

High Prevalence of Helicobacter pylori in Liver Cirrhosis (Relationship with Clinical and Endoscopic Features and the Risk of Peptic Ulcer)

112 993. CONCLUSION Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.

Serological and histological aspects of hepatitis C virus infection in alcoholic patients

BACKGROUND/AIMS/METHODS The diagnosis of cirrhosis is currently based on percutaneous liver biopsy, although this procedure may give rise to false negative results. This prospective study blindly investigates the accuracy of an ultrasonographic score, derived from liver, spleen and portal vein features, in predicting the final diagnosis in 212 patients with compensated chronic liver disease undergoing percutaneous liver biopsy. RESULTS Taking biopsy as the standard, the ultrasonographic score differed significantly between chronic hepatitis (39+/-33) and cirrhosis (100+/-35) (p<0.0001). Discriminant analysis with stepwise forward selection of the variables identified liver surface nodularity and portal flow velocity as independently associated with the diagnosis of cirrhosis (p<0.005), and a score based on these two variables correctly identified cirrhosis in 82.2% of cases. One or both of these abnormalities were also found in 27/32 patients who were diagnosed as having cirrhosis at ultrasound, but were not cirrhotic histologically. Eight of these 32 cases developed signs of decompensated liver disease and/or portal hypertension in the subsequent 6-month follow-up, thus supporting the diagnosis of cirrhosis. CONCLUSIONS Our data suggest that ultrasound is accurate in predicting the final diagnosis in patients with compensated chronic liver disease and may identify cirrhosis even in the absence of a typical histopathological pattern. However, neither percutaneous liver biopsy nor ultrasonography can be assumed to be the definitive criterion for the diagnosis of compensated cirrhosis.

Intra- and extrahepatic arterial resistances in chronic hepatitis and liver cirrhosis

OBJECTIVE:The best known indicator of risk for first bleeding in patients with cirrhosis without previous bleeding is the index devised by the North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices (NIEC index), which results from the combination of size of esophageal varices, severity of red wale marks, and Child-Pugh class. Its efficiency is far from optimal, and validation studies have reported sensitivities and specificities markedly lower than those reported in the original study. In the present study we analyzed the efficiency of NIEC index in a large series of cirrhotic patients with varices without previous bleeding. In addition, we tried to improve the effectiveness of the index by modifying it, and to validate the modifications in an independent group of patients.METHODS:A total of 627 patients were enrolled and followed until either a variceal bleeding or for a maximum of 2 yr. During this time, 117 experienced a first variceal bleeding.RESULTS:Using Coxs regression analysis, size of varices, severity of red wale marks, and Child-Pugh score were significant and independent predictors of first bleeding, as already noted in the original report of the NIEC group. However, coefficients and standard errors were markedly different, and the importance of size of esophageal varices in the regression was much larger, whereas that of Child-Pugh score was much lower. According to these data, a revised index was developed (Rev-NIEC). Using receiver operating characteristic (ROC) curve analysis, the revised index showed a larger efficiency, and the area under the curve was significantly larger (0.80 ± 0.02 vs 0.74 ± 0.02; p < 0.01). In particular, the curve showed that for a specificity of 75%, the new index had a sensitivity of 72% compared to that of 55% of the NIEC index. Validation in an independent sample of 84 patients showed good agreement between predicted and observed risk for bleeding. Validation with the bootstrap technique also showed adequate stability of the results.CONCLUSIONS:The revised index seems to be superior to the traditional index, and may turn out to be more useful in the selection of patients for different therapeutic procedures and in the stratification of patients in clinical trials.

The relationship of endoscopy, portal Doppler ultrasound flowmetry, and clinical and biochemical tests in cirrhosis.

In 153 consecutive patients with cirrhosis weassessed: (1) the prevalence of IgG to Helicobacterpylori and compared it with that found in 1010 blooddonors resident in the same area; and (2) therelationships of IgG to Helicobacter pylori with clinical andendoscopic features and with the risk of peptic ulcer.The IgG to Helicobacter pylori prevalence of cirrhoticswas significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was notassociated with sex, cirrhosis etiology, Child class,gammaglobulins and hypertensive gastropathy. In bothgroups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Amongpatients with cirrhosis a significantly higherprevalence of Helicobacter pylori was found in patientswith previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) andpatients with peptic ulcer (P = 0.0004). Multivariateanalysis identified increasing age and male sex as riskfactors for a positive Helicobacter pylori serology and no independent risk factors for pepticulcer. The high prevalence of Helicobacterpylori-positive serology found in the present series isrelated to age and sex and might also be explained byprevious hospital admissions and/or uppergastrointestinal endoscopy. Our results do not confirmthe role of Helicobacter pylori as risk factor forpeptic ulcer in patients with liver cirrhosis.

Superior mesenteric artery impedance in chronic liver diseases: relationship with disease severity and portal circulation

The recent cloning of the genome of hepatitis C virus (HCV) has allowed the detection of antibodies to HCV (anti-HCV) in human serum. The presence of serum antibodies to HCV often indicates active infection with HCV. We have assessed the serological and histological features in a group of alcoholic patients with chronic liver disease and have evaluated the possible etiologic role of HCV infection in the development of liver damage. Serum samples and liver biopsy specimens were obtained from 41 consecutive patients, all having a definite history of alcohol abuse and evidence of chronic hypertransaminasemia. Fifteen patients (37%) were positive for anti-HCV by ELISA, and 13 (86.6%) of them were also positive by RIBA. Eleven of these patients had histologic features of chronic active hepatitis (CAH), a lesion which is not known to be induced by excessive alcohol intake. No other possible causes of CAH were found, and CAH was not present in any of the anti-HCV negative patients. In patients with CAH, mean AST to ALT ratio was less than 1 (0.6), a finding which is characteristic of viral rather than alcoholic chronic liver disease. In conclusion, our study suggests that sporadic hepatitis C virus infection plays an etiologic role in the development of chronic active liver disease in a subgroup of alcoholic patients.

Relationship between splanchnic, peripheral and cardiac haemodynamics in liver cirrhosis of different degrees of severity

Thirty patients with chronic hepatitis (CH), 84 with liver cirrhosis (LC) and 42 controls, underwent noninvasive measurement of hepatic artery resistance index (RI) by means of Doppler ultrasound (US), at the porta hepatis and in the intrahepatic branches, in order to investigate possible changes related to: (a) the liver disease; (b) the site of measurement; and (c) ageing. The intrahepatic RI differed among LC, CH and controls (0.731, 0.690 and 0.643, p < 0.05), whereas the RI at the porta hepatis did not (0.754, 0.748 and 0.729, respectively). Intrahepatic RI correlated with age in LC (r = 0.51, p < 0.0001) and in controls (r = 0.49, p < 0.001). In LC, it correlated also with the presence and size of esophageal varices (r = 0.32, p < 0.05). In conclusion, an increase of hepatic artery RI in chronic liver diseases can be demonstrated when assessed in the intraparenchymal branches. The increase of hepatic artery RI with ageing should be considered in future studies.

Circadian occurrence of variceal bleeding in patients with liver cirrhosis

The relationship of the endoscopic aspect of esophageal varices, portal quantitative Doppler ultrasound parameters and clinical and biochemical findings was assessed in 149 patients with cirrhosis stratified according to the presence of esophageal varices (n = 115) and the absence of previous bleeding (n = 96). In this series of patients the presence of esophageal varices and red signs proved to be significantly correlated with the severity of cirrhosis. However, in the group of patients with varices, no correlation was found between variceal size and the degree of liver failure. Portal blood flow velocity was significantly different in the endoscopic subgroups, but not in the clinical and biochemical subgroups. Furthermore, portal blood flow velocity was found to correlate only with the presence and size of esophageal varices. The Congestion Index of the portal vein (derived from the ratio between the cross-sectional area of the portal vein and the mean velocity of portal flow) was significantly different in most clinical, biochemical and endoscopic subgroups and was correlated with liver function, presence and size of varices, and presence and degree of red signs. We conclude that the Congestion Index of the portal vein, the clinical status and the endoscopic aspect of varices are not independent features in patients with cirrhosis. As for liver function and endoscopic findings, portal Doppler ultrasound parameters, in particular the Congestion Index, may contribute to a better clinical assessment in patients with cirrhosis.