Esterita Accogli

Serum α-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease : influence of HBsAg and anti-HCV status

BACKGROUND It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.

Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis

BACKGROUND/AIMS The aims of alpha-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease. Hepatocellular carcinoma is a complication of viral cirrhosis; but it is not yet known whether treatment of viral cirrhosis with alpha-interferon prevents this complication. METHODS The incidence and the risk (Cox regression analysis) of developing hepatocellular carcinoma were calculated in 347 patients with hepatic cirrhosis; 227 (34 hepatitis B virus and 193 hepatitis C virus related) were treated with alpha-interferon and 120 (28 hepatitis B virus and 92 hepatitis C virus) did not receive this treatment, in order to evaluate the efficacy of alpha-interferon in the prevention of hepatocellular carcinoma. In all patients, the cirrhosis was well compensated (Child A). RESULTS Over mean follow-up periods of 49 months for hepatitis B virus and 32 months for hepatitis C virus, 20/347 patients (6/62 hepatitis B virus and 14/285 hepatitis C virus) developed hepatocellular carcinoma. The risk of developing this tumor was significantly greater in males (p < 0.007) and in patients not treated with alpha-interferon (p < 0.01). The Relative Risk of developing hepatocellular carcinoma increased significantly (p < 0.0002) with each passing year. In patients with hepatic cirrhosis secondary to hepatitis B virus infections, the risk did not seem to be modified by alpha-interferon treatment, even though a greater, but not significant risk (Relative Risk = 4.9; p = 0.3) was calculated for untreated patients; in contrast, in hepatitis C virus-related cirrhosis, this risk was reduced by a factor of 4.0 (p = 0.04). The tumor developed only in non-responder patients regardless of virus type. After adjustment for confounding factors (sex, age, alcohol consumption, cigarette smoking), a statistically significant (p < 0.025) effect of interferon treatment in preventing hepatocellular carcinoma was still demonstrated when responders were matched with controls, but not when responders were compared with non-responders. CONCLUSIONS These results show that, in addition to its ability to halt the progression of viral-induced liver disease, alpha-interferon is also of benefit in patients with hepatitis C virus cirrhosis who respond to this treatment by lowering their risk of developing hepatocellular carcinoma.

Bedside Ultrasonography (US), Echoscopy and US Point of Care as a new kind of stethoscope for Internal Medicine Departments: the training program of the Italian Internal Medicine Society (SIMI)

In recent years, thanks to the development of miniaturized ultrasound devices, comparable to personal computers, tablets and even to smart phones, we have seen an increasing use of bedside ultrasound in internal medicine departments as a novel kind of ultrasound stethoscope. The clinical ultrasound-assisted approach has proved to be particularly useful in assessing patients with nodules of the neck, dyspnoea, abdominal pain, and with limb edema. In several cases, it has allowed a simple, rapid and precise diagnosis. Since 2005, the Italian Society of Internal Medicine and its Ultrasound Study Group has been holding a Summer School and training courses in ultrasound for residents in internal medicine. A national network of schools in bedside ultrasound was then organized for internal medicine specialists who want to learn this technique. Because bedside ultrasound is a user-dependent diagnostic method, it is important to define the limits and advantages of different new ultrasound devices, to classify them (i.e. Echoscopy and Point of Care Ultrasound), to establish appropriate different levels of competence and to ensure their specific training. In this review, we describe the point of view of the Italian Internal Medicine Society on these topics.

Efficacy of ursodeoxycholic acid in association with α-interferon for chronic hepatitis C in α-interferon non-responder patients

BACKGROUND The aim of the present study was to evaluate the effect of combined treatment with alpha-interferon (alpha-IFN) and ursodeoxycholic acid (UDCA) on liver function tests and serum HCV-RNA in patients with chronic hepatitis C who had not responded to alpha-IFN alone. METHOD One hundred and three patients (60 men, 43 women, mean age 49 +/- 1.3 years) who had not responded (both HCV-RNA positive and increased serum ALT levels) to 4 consecutive months of treatment with alpha-IFN (3 MU three times weekly) were randomly assigned to receive UDCA (IFN-UDCA, 53 patients, 600 mg/day) in addition to the same alpha-IFN dose, or to continue alpha-IFN alone (IFN-controls, 50 patients). After stopping alpha-IFN, patients who had received UDCA continued to receive UDCA for an additional 6-month period. The two groups were comparable for sex, basal ALT, basal yGT, genotype distribution and liver histology, while mean age was lower in controls (53 +/- 1.8 vs 46 +/- 1.8 years; P< 0.01). RESULTS Twenty (38%) out of 53 IFN-UDCA patients had normal ALT, compared with only six (12%) out of 50 IFN-control patients (P < 0.01). HCV-RNA became undetectable in four IFN-UDCA patients. Three months after withdrawal of alpha IFN, 15 IFN-UDCA responders, but none of the IFN-controls, had normal ALT values (P< 0.01); 6 months after withdrawal, nine IFN-UDCA responders still had normal ALT (P= NS) and HCV-RNA was still undetectable in four of them. Portal and periportal inflammation showed a statistically significant improvement (Fishers exact test P< 0.01) in IFN-UDCA patients as compared with IFN-controls, while no effect was observed on portal fibrosis. CONCLUSIONS These data demonstrate that UDCA improves the response rate to alpha-IFN. Furthermore, in 8% of IFN-UDCA patients the response rate was sustained and associated with HCV-RNA clearance.

Ultrasonography (US) and non-invasive diagnostic methods for non-alcoholic fatty liver disease (NAFLD) and early vascular damage. Possible application in a population study on the metabolic syndrome (MS)

Abdominal ultrasonography (US) represents the first-line imaging examination in chronic liver diseases; in most cases, US, laboratory findings and the clinical context are generally sufficient to guide the diagnosis. Thanks to the considerable diffusion of US, we have seen an increased diagnosis of NAFLD in recent years, although this condition is generally silent from a clinical point of view. We have to identify the metabolic syndrome in the general population and to promptly recognize NAFLD to prevent its development into non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. Among the non-invasive diagnostic techniques for NAFLD and for early vascular damage, ultrasonography represents the method of choice. In fact, besides the traditional semiotics of fundamental US of the liver, new US techniques have recently been proposed (contrast enhancement US, acoustic structure characterization), with respect to serum biomarkers and Fibroscan, for the study of liver fibrosis. Similarly, also as concerns the US measurement of carotid intima-media thickness, new automated methods with sophisticated software and radio-frequency signal have recently been introduced. Finally, we report the preliminary results of a personal experience on liver and carotid US in the epidemiology of the metabolic syndrome.

A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

Incidence of hepatocellular carcinoma in hepatitis C virus‐related cirrhosis is 4% per year. Although cost‐effective, current screening could be improved.

Update on ultrasound in bowel obstruction.

Bowel obstructions (BO) can be due to mechanical causes (block of the intestinal lumen), or a paralytic ileus (failure of intestinal motility due to an electrolyte disturbance or neuropathy). Mechanical bowel obstruction (MBO) is defined by (complete) obstruction of the intestinal passage resulting in extreme filling and dilatation of the prestenotic segments and in emptying (collapsed bowel) of the poststenotic ones. About 60–85 % of cases of obstruction occur in the small bowel, 10–15 % in the colon [1]. The etiology of MBO includes both intrinsic and extrinsic causes (Table 1). The most common cause of small bowel obstruction (SBO) is adhesions (75 % of cases), while the most common cause of colonic bowel obstruction (CBO) is carcinoma, either primary or metastatic (Table 1).

The severity of HCV-related chronic hepatitis correlates with AgNOR protein expression while response to alpha interferon treatment is associated with its decrease

L0003 THE SEVERITY OF HCV-RELATED CHRONIC HEPATITIS CORRELATES WITH AgNOR PROTEIN EXPRESSION WHILE RESPONSE TO ALPHA INTERFERON TREATMENT IS ASSOCIATED WITH ITS DECREASE. E, Accoeli. D. Trer~ °, G. Mazzella, A Colecchia, S. Sottili, S. Casanova, S. Marchetto, C. Fabbri, F. Jaboli, D. Festi#, E. Roda, M. Derenzini°.Dpt. of Internal Medicine and Gastroenterology, °Dpt. of Experimental Pathology, University of Bologna,#1st. of Medical Physiopathology University of Chieti Italy.

Pharmacological Treatment of Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is a rare hepatic disorder, but its incidence is increasing. It is chronic and progressive, eventually leading to the development of cirrhosis. During the course of the disease, symptoms such as pruritus and asthenia may appear. At present, the only successful treatment for PBC is liver transplantation. While no pharmaceutical treatment is truly effective, some newer drugs, or new combinations of these drugs, have given some promising results. In this chapter, the efficacy of the more important pharmacological agents in use, as well as some currently under study, are examined in terms of laboratory parameters, symptoms, end points, histological presentation and natural history of the disease.