Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program.

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/µL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.

Focal splenic lesions: US findings.

Ultrasound (US) imaging of the spleen was considered of little use in the past and was performed only to distinguish between cystic and solid lesions. However, in the last decade due to experience acquired and the introduction of second-generation contrast agents, this technique has been re-evaluated as contrast-enhanced US (CEUS) allows detection and characterization of most focal lesions of the spleen with a high sensitivity and a good specificity. Gray-scale US presents a low specificity in splenic infarctions with a high rate of false negative cases, whereas specificity reaches 100 %, if the examination is performed using US contrast agents. Gray-scale US can provide a correct diagnosis in simple cysts, whereas CEUS is useful when cystic lymphangioma is suspected. In the study of splenic lesions, the most important problem is to differentiate between angioma, hamartoma, lymphoma, and metastasis. CEUS reaches a good specificity in the differentiation of benign from malignant splenic lesions, as hypo-enhancement in the parenchymal phase is predictive of malignancy in 87 % of cases. In conclusion, Gray-scale US and particularly CEUS are at present widely indicated in the study of focal splenic lesions.

Sonographic management of mediastinal syndrome.

INTRODUCTION: Mediastinal syndrome is suspected on the basis of clinical symptoms and is generally confirmed by chest radiography or computed tomography (CT). However, also grey scale ultrasound (US) and contrast enhanced US (CEUS) are useful in this hematologic emergency as they provide the possibility to perform US-guided biopsy and histological diagnosis. MATERIALS AND METHODS: 15 Patients affected by mediastinal syndrome were prospectively studied using B-mode US and CEUS; 13 of these patients, who had no other lesions, were proposed for US-guided biopsy of the mediastinal mass, but only in 12 patients biopsy was technically possible. RESULTS: In this study, B-mode US reached an excellent sensitivity (100%) in evidencing the lesions but a low specificity which did not exceed 30-40%. CEUS reached an elevated specificity identifying neoplastic pathologies if both the early and the late phases are considered (90-86.6%). US-guided biopsy was possible in 92.3% of lesions showing a diagnostic adequacy of 91.66%. CONCLUSIONS: B-mode US associated with CEUS and US-guided biopsy reached an elevated accuracy in the diagnosis of mediastinal masses. If these results are confirmed by further studies, this diagnostic procedure could be included in the routine management of mediastinal syndrome.

Pseudoaneurysm of the hepatic artery, a rare complication of an amebic liver abscess.

Hepatic artery pseudoaneurysm is a rare complication of amebic or pyogenic liver abscesses, and it is generally diagnosed because of hemobilia due to rupture of the aneurysm into the biliary tract. The authors describe a case of vascular complication in a patient affected by amebic liver abscess. Pseudoaneurysm was diagnosed and resolved without hemobilia.

Contrast enhanced ultrasonography (CEUS) in peripheral lung lesions: A study of 60 cases.

INTRODUCTION: The authors report their experience in 60 patients with infectious and neoplastic peripheral pulmonary lesions studied by conventional radiology, B-Mode ultrasound (US) and computed tomography (CT). In view of the particular pulmonary vascularization (consisting of both pulmonary and bronchial arteries) the patients underwent also contrast enhanced ultrasound (CEUS) using a II-generation contrast agent, SonoVue (sulphur hexafluoride microbubbles surrounded by a phospholipid shell). METHODS AND RESULTS: In this study, the sensitivity of CEUS reached 95% in the characterization of peripheral pulmonary lesions, which is similar to the sensitivity of CT (97%). The method used in this case-study was free of significant side effects. DISCUSSION: This preliminary clinical experience seems to confirm the possibility of using SonoVue enhanced US to make a differential diagnosis between infectious and neoplastic lesions based on a qualitative and quantitative assessment, by evaluating the enhancement pattern (homogeneous or inhomogeneous), arrival time of the contrast agent in the lesion, the possibility to identify the pulmonary arteries and time of contrast agent elimination.

Clinical management of patients with recurrent viral hepatitis after liver transplantation.

Liver transplantation is indicated in end-stage chronic viral liver disease, but unless adequate prophylaxis is administered, the patient will in most cases develop recurrent hepatitis B (HBV) and C (HCV) virus infection. Today, patients receiving prophylaxis using nucleoside analogue drugs with or without specific immune globulin drugs in connection with orthotopic liver transplantation for HBV related cirrhosis, present low risk of relapse and high 5-10 year survival rates. Lamivudine was the first drug used in the prophylactic treatment, but this drug has increasingly been combined with or replaced by adefovir due to the low genetic barrier, which causes viral resistance. Most patients develop viral recurrence after orthotopic liver transplantation for HCV related cirrhosis, and in an elevated number of cases, cirrhosis and hepatic insufficiency set in after a few years. Prophylaxis before transplantation and pre-emptive treatment using interferon and ribavirin present numerous side effects resulting in reduction of doses and suspension of therapy, with consequently low sustained virological remission rates and risk of rejection.The treatment is better tolerated by patients with histologically confirmed chronic disease, but also in these patients virological remission rates are low. This pathology requires new therapeutic protocols and/or new drugs in order to obtain better compliance and better responses.

Sonographic management of complicated cystic echinococcosis.

INTRODUCTION: In this survey we evaluated the usefulness of ultrasonography (US) in the diagnosis, and in the treatment of complicated hydatid cysts. MATERIALS AND METHODS: From June 1985 to June 2004, 221 patients with 294 hydatid cysts were examined. Twenty patients (9.0%) presented 22 complicated cysts (7.4%): 9 with infection, 5 ruptured into the bile ducts, 2 bilomas, 2 cysto-pleural fistulas, 2 allergic reactions, 1 rupture into the peritoneum and 1 intrasplenic hematoma. In all cases, US yielded a specific or suspected diagnosis, also in complications affecting non-hepatic sites, confirmed by computed tomography (CT), endoscopic papillotomy or percutaneous US-guided sampling. All patients with complicated cystic echinococcosis were treated with Albendazole 800 mg/day for at least 3 months. In addition to this therapy, 12 underwent US-guided drainage (9 infected cysts, 2 bilomas, 2 cysto-pleural fistulas, 1 intrasplenic hematoma); of these patients 3 subsequently underwent surgery because US-guided treatment was ineffective. Five patients were treated with perendoscopic sphincterotomy for obstruction of the bile passages, while 3 patients received only medical therapy. RESULTS: Medical, echoguided and surgical treatments led to resolution of the complications and complete remission of the parasitic pathology in 19/20 patients (95%) and in 21/22 cysts (95.4%). There was partial remission in 1 case only. The therapy did not cause major complications and the results were confirmed during follow-up lasting from 5 months to 15 years (mean time 3 years). DISCUSSION AND CONCLUSION: This study shows that the incidence of complications of hydatid cysts is low and that correct echographic management allows a rapid diagnosis and optimization of treatment in most cases.

Thrombocytopenia in patients with HCV-positive chronic hepatitis: efficacy of leucocyte interferon-alpha treatment.

Treating patients with HCV-associated thrombocytopenia is a problem, because the pathogenesis of thrombocytopenia is still unclear. We evaluated the clinical and haematological response to leucocyte interferon-alpha in 20 naive patients with chronic hepatitis C and thrombocytopenia (platelet count <140 x 10(9)/l for at least six months) without portal hypertension and/or hypersplenism. They were treated with leucocyte interferon-alpha (3 MU three times per week) for 12 months and followed up for 12 months. Biochemical (ALT) and virological (HCV-RNA) responses were determined. Two patients discontinued treatment because of hyperthyroidism. Of the 18 patients who completed treatment, 12 (66%) showed a biochemical response, 10 of whom (55.5%) also showed a virological response. At the end of follow-up, four patients (22%) showed a complete (biochemical and virological) response. During treatment, platelet counts decreased to less than 10-20% of pretreatment values in most patients. Three of the four patients with a complete response showed a platelet increase during treatment and throughout the follow-up period. In HCV-associated thrombocytopenia leucocyte interferon-alpha is well tolerated and in cases of sustained virological inhibition is able to ameliorate the disease by increasing the platelet count.

Ultrasound-guided fine needle biopsy of the spleen: high clinical efficacy and low risk in a multicenter Italian study.

The aim of this study was to evaluate the clinical efficacy and safety of the ultrasound-guided fine needle biopsy (UG-FNB) of the spleen in a large population of patients. We collected retrospectively the findings concerning the application of UG-FNB of the spleen from eight Italian clinical centers that utilized this technique for at least ten years. A data schedule was sent to all centers to collect information about techniques, results, and complications of UG-FNB of the spleen. We analyzed 398 biopsy procedures both on focal lesions (257 cases) and on splenic parenchyma (141 cases). The overall accuracy was 90.9% for the series as a whole, 84.9% for cytological sampling, 88.3% for microhistological sampling, and 90.3% for both cytological and histological sampling (double biopsy). Tissue core biopsy yielded better overall accuracy in patients with suspected splenic involvement by lymphoma (90.9% vs. 68.5% for cytology). The complication rate was low (no death cases, less than 1% for major complications, and 5.2% for all complications). No predictive factors were able to detect high-risk situations. The operator's skill (higher number of performed procedures) was significantly related to better overall accuracy. Conversely, the complication rate was not affected. UG-FNB of the spleen is a very effective diagnostic procedure with low risk for the patient. Aspiration cytology and core needle biopsy showed similar diagnostic yields, except for the diagnosis of splenic lymphoma, in which core needle biopsy obtained better results.

Ultrasound guided percutaneous drainage of abdominal abscesses in the hands of the clinician: a multicenter Italian study.

OBJECTIVE: Image guided percutaneous drainage is a well established therapeutic technique. The results of these procedures, when performed directly by the clinician and under sonographic guidance,in respect to other imaging techniques are not yet clarified. METHODS: The 886 cases of ultrasound guided drainage were collected from eight italian clinical institutions and the results were analyzed according to location of the abscess, drainage technique, underlying diseases, microbiological findings, immunological patient status and previous surgical intervention. RESULTS: We observed an overall cure rate of 90.4%. The best results were obtained in hepatic abscesses, both amoebic and pyogenic (cure rate 98.7 and 94.3%). Slightly lower cure rates were obtained in abdominal and splenic abscesses, postoperative collections and severely immunocompromised patients. The frequency of complications was low (6.6%) and mostly related to catheter drainage. No drainage-related deaths occurred. CONCLUSIONS: The study confirms the high clinical efficiency and safety of ultrasound guided percutaneous drainage, even when performed directly by the clinician. The sonographic guidance showed similar efficacy, more manageability and lower costs than other imaging techniques and it should be preferred whenever possible. For hepatic abscesses, ultrasound guided needle aspiration showed good results and less complications than catheter drainage.

Low-dose leukocyte interferon-alpha therapy in dialysed patients with chronic hepatitis C.

Kidney failure is a contraindication to interferon therapy, and active chronic hepatitis is incompatible with kidney transplantation. Our study was aimed at investigating the activity and tolerability of leukocyte interferon-alpha in patients undergoing pre-transplant dialysis and suffering from chronic active hepatitis due to Hepatitis C virus infection. Ten patients, with persistently high ALT levels, were treated with leukocyte interferon-alpha, at a dose of 1 MU three times weekly for one year. Viraemia, ALT levels and other blood and urine tests, hepatitis stage and drug tolerance were all monitored throughout the study and the six-month follow-up period. After six months of treatment, two patients had continuing normalisation of ALT, negative HCV-RNA tests and normalisation of histological features ('long-term responders'). Four patients relapsed; three did not respond to treatment; and one patient discontinued it because of intolerance. The four relapsing patients received a second cycle with the same interferon, at a dose of 3 MU three times weekly, with attainment, in one patient, of complete remittance after six months of follow-up. Leukocyte interferon-alpha yielded an overall 30% therapeutic response in dialysed patients with chronic hepatitis C. Its use is helpful in enabling dialysed patients to undergo transplantation.

Clinical efficacy of ultrasound guided percutaneous drainage of abscesses in patients with leukaemia and lymphoma.

Ultrasound guided percutaneous drainage (US-PD), a minimally invasive technique, has been reported as highly effective for the treatment of deeply located abscesses, particularly in immunocompromised patients. Therefore, we retrospectively studied its therapeutic efficacy and safety in a series of 14 patients with leukaemia and lymphoma. We collected the clinical and sonographic data of 14 patients with various types of leukaemia and lymphoma. These patients were consecutively observed in four clinical centres with long-term experience with ultrasound guided therapeutic techniques. The cases were analysed according to underlying disease, clinical features, location of the abscess, drainage technique, microbiological data and both short- and long-term outcome. In our series, 11 patients were treated with repeated ultrasound guided needle aspirations (US-NA) and 3 underwent catheter drainage (US-PCD). In 12/14 cases the procedure was successful (86%): the mortality rate was 14%. 5 patients died during the follow-up period because of the underlying disease, without abscess recurrence. No complications were reported. Our data suggest that ultrasound guided percutaneous drainage should be considered the first choice, minimally invasive procedure for the treatment of deeply located abscesses in patients with leukaemia and lymphoma.

Percutaneous ethanol injection in the treatment of hepatocellular carcinoma. A multicenter survey of evaluation practices and complication rates.

BACKGROUND: Percutaneous ethanol injection (PEI) has become a widely used procedure in the treatment of hepatocellular carcinoma (HCC). However, the criteria for selecting patients are not standardized, and little information is available about the complications of the procedure. METHODS: A questionnaire was sent to 11 experienced Italian centers. It investigated: the size and the number of HCC nodules suitable for treatment and the Child-Pugh risk class of the associated cirrhosis; the performance of the procedure; the number and characteristics of the patients treated; and, finally, any complications. RESULTS: Most of the centers performed PEI in single HCC nodules less than 5 cm in diameter or in multiple nodules if fewer than three, the larger being less than 3 cm. Patients in Child-Pugh's classes A, B, and C with single nodules were generally considered for PEI. A prothrombin time of less than 40% and a platelet count of less than 40,000/mm3 contraindicated PEI in most of the centers. PEI was generally performed on outpatients, using Chiba or spinal needles. One thousand and sixty-six patients (8118 sessions) were enrolled; 74% had a single HCC nodule and 26% multiple nodules. All except four had cirrhosis; 53% were in Child class A, 38% in class B, and 9% in class C. The mean number of sessions needed to destroy an HCC nodule was 6.7 (range, 2-14), with a mean alcohol injection volume of 5.0 ml per session (range, 2-20 ml). One death (0.09%) and 34 complications (3.2%) were reported. Among the complications we call attention to the hemorrhagic ones (eight cases) and tumoral seeding (seven cases). Severe pain experienced during the maneuver led to discontinuation of the procedure in 3.7% of the patients; 13.5% of the patients required analgesics and 24% had fever after PEI. CONCLUSIONS: Some procedural aspects of PEI treatment differ among the various centers a standardization is advisable. In the present survey PEI is a low-risk technique.

Ultrasound imaging in cystic echinococcosis. Proposal of a new sonographic classification.

The ultrasonography permits the study of the natural history of cystic echinococcosis (CE) and evaluation of stages of the parasitic pathology. The evolution of abdominal CE was studied in 54 patients suffering from 97 abdominal cysts treated with albendazole, in 20 patients suffering from 20 hepatic cysts treated with echoguided percutaneous ethanol injection and in 39 patients suffering from 42 abdominal cysts, but left untreated. A new sonographic classification is suggested. Type I: Simple CE; (a) overall echofree; (b) with fine echos. Type II: Multiple CE; (a) multiple contiguous; (b) multiseptated with rosette, honeycomb and wheel-like pattern. Type III: With detachment of endocyst CE; (a) with double layer image; (b) with water-lily sign. Type IV: Mixed type CE; with fluid and solid aspect. Type V: Heterogeneous CE; (a) with ball of wool pattern; (b) with hypoechogenic image. Type VI: Hyperechoic CE; (a) with snow-storm pattern; (b) with dyshomogeneous aspect. Type VII: Calcified CE; (a) with advanced calcification of the layer only; (b) with calcification of overall cyst. This classification appears more appropriate to the natural history of CE and permits a better differential diagnosis and more suitable treatment.

Pregnancy in a patient with essential thrombocytosis.

An insurgent case of pregnancy in a patient in whom essential thrombocytosis was diagnosed five years earlier is described. Pregnancy was confirmed and therapy with platelet aggregation inhibitor was introduced. The pregnancy reached full term notwithstanding a positive result of the "Triple Test" during the 15th week of gestation. A histology exam of the placenta revealed an ischemic lesion. We retain that platelet aggregation inhibitor therapy remains an important aid in eliminating the risk of thrombosis determined by the presence of two conditions that are predisposed to these risks, such as pregnancy and essential thrombocytosis.

Abdominal cystic hydatid disease (CHD): classification of sonographic appearance and response to treatment.

The natural history of cystic hydatid disease (CHD) can be divided into two stages. The first is characterized by the proliferation of the parasite; the second is marked by involution, ie, when the hydatid undergoes spontaneous distress or is subjected to pharmacological treatment. Echography makes it possible to study this evolution and to evaluate the stages of this parasitic pathology. This study of the evolution of abdominal CHD in 81 patients suffering from 127 cysts, with or without Albendazole treatment suggests a new sonographic classification: type I: simple CHD; type II: multiple CHD, type III: with detachment of membrane CHD; type IV: mixed CHD, type V: heterogeneous CHD; type VI: hyperechogenic CHD; type VII calcified CHD. Forty-seven patients suffering from 90 cysts of types I, II, III, IV, and V were treated with Albendazole; 31, suffering from 34 CHD of types VI and VII, were not treated, as they were considered involutional; 3 patients with 3 cysts refused therapy. Albendazole treatment resulted in the disappearance of 9 and in the solidification of 62 cysts. Of the remaining cases of CHD, 10 cysts showed sonographic alterations and 5 showed no modifications. Surgery was necessary for 2 patients (4 cysts). This new classification seems to be an aid in the recognition of the natural and therapy-induced involution of CHD and seems to improve the evaluation of the efficaciousness of the therapy.

Spontaneous appearance of human and porcine factor VIII inhibitors: which therapeutic approach?

An 82-year-old woman presented with severe bleeding due to antibodies inactivating both human and porcine factor VIII. Treatment with porcine factor VIII was successful in correcting the hemorrhagic manifestations, despite the fact that subsequent studies showed that the baseline porcine inhibitor titer was greater than the human inhibitor titer. Anamnestic response to porcine factor VIII did not allow us to use it longer; immunosuppressive therapy, however, was successful in long-term control of the anti-factor VIII antibody titer and in preventing further bleeding.

[Treatment of pylethrombosis with alteplase. Description of a clinical case]. / Trattamento di una piletrombosi con alteplase. Descrizione di un caso clinico.

The authors report a case of venous pylethrombosis of the proximal splanchnic circuit treated with rt-PA (alteplase) for the first two days and later associated with high doses of heparin. rt-PA demonstrated a good level of efficacy with the partial resolution of the thrombus already after the first administration and in spite of the late commencement of therapy.

Inflammatory pseudotumour of the liver: diagnosis by fine needle biopsy in two cases and a review of the literature.

Inflammatory pseudotumours of the liver are rare: over 40 cases had been reported up to 1992, the majority of which are surgical or laparoscopic findings. In this paper we describe two additional cases in which diagnosis was acquired by fine needle biopsy under ultrasonographic guidance. This approach allowed sufficient sampling of tissue for diagnostic purposes.

Echographic epidemiology of cystic hydatid disease in Italy.

This study was carried out in order to establish the actual prevalence of cystic hydatid disease in Italy using ultrasound. In fact, there is a great difference between the official reports of the disease and epidemiological investigations. From 1988 to 1990, 424 cases of cystic hydatid disease were diagnosed in 333,144 examinations performed in nineteen Italian Echographic Departments, giving a mean incidence of 0.16%. Most of the examined persons arriving at the 19 Echographic Departments had symptoms independent from hydatidosis, were affected with other pathologies, or they were patients attending follow-up for neoplasms. The authors note that human hydatidosis has a high incidence in the south and in the isles; hepatic lesions were 85.61% of all cases of abdominal hydatidosis, asymptomatic cystic hydatid disease was present in 60% of the total number; the average age of the sample examined was 45.38 years without significant differences between men and women. Finally the Authors suggest the importance of echography in planning therapeutic programs.