Raffaele Orlando

Early and late complications after radiofrequency ablation of malignant liver tumors in 608 patients

Background:Radiofrequency ablation (RFA) has become a common treatment of patients with unresectable primary and secondary hepatic malignancies. We performed this prospective analysis to determine early (within 30 days) and late (more than 30 days after) complication rates associated with hepatic tumor RFA. Methods:All patients treated between January 1, 1996 and June 30, 2002 with RFA for hepatic malignancies were entered into a prospective database. Patients were evaluated during RFA treatment, throughout the immediate post RFA course, and then every 3 months after RFA to assess for the development of treatment-related complications. Results:A total of 608 patients, 345 men (56.7%) and 263 women (43.3%), with a median age of 58 years (range 18–85 years) underwent RFA of 1225 malignant liver tumors. Open intraoperative RFA was performed in 382 patients (62.8%), while percutaneous RFA was performed in 226 (37.2%). The treatment-related mortality rate was 0.5%. Early complications developed in 43 patients (7.1%). Early complications were more likely to occur in patients treated with open RFA (33 [8.6%] of 382 patients) compared with percutaneous RFA (10 [4.4%] 226 patients, P < 0.01), and in patients with cirrhosis (25 [12.9%] complications in 194 patients) compared with noncirrhotic patients (31 [7.5%] complications in 414 patients, P < 0.05). Late complications arose in 15 patients (2.4%) with no difference in incidence between open and percutaneous RFA treatment. The combined overall early and late complication rate was 9.5%. Conclusions:Hepatic tumor RFA can be performed with low mortality and morbidity rates. Though relatively rare, late complications can develop and physicians performing hepatic RFA must be cognizant of these delayed treatment-related problems.

Safety and immunogenicity of hepatitis A vaccine in infants: a candidate for inclusion in the childhood vaccination programme

Forty-eight infants received a single dose (720 ELISA units = 0.5 ml) of inactivated hepatitis A vaccine at the fifth month of age with booster at the 11th month of age, together with the second and third doses of the vaccines compulsory under Italian law (diphtheria, tetanus, oral polio and hepatitis B). Overall, the seroconversion rate was 100%. The anti-HAV geometric mean titre (GMT) reached 3,021 mIU/ml in infants born to anti-HAV-negative mothers, but only 399 mIU/ml in infants born to anti-HAV-positive mothers. Hepatitis A vaccine was immunogenic, safe and well tolerated without significant side-effects. There seems to be no reason for not including it in childhood vaccination programmes particularly in low endemic HAV areas.

Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis

Background:  The arginine‐degrading enzyme, arginine deiminase conjugated to polyethylene glycol (ADI‐SS PEG 20 000 mw), reduces extracellular arginine, has minimal toxicity, decreases tumor burden and improves liver function in patients with chronic hepatitis C virus infection (HCV) and inoperable hepatocellular carcinoma (HCC). Reduced extracellular arginine inhibits viral replication through unknown mechanisms. It is hypothesized that ADI‐SS PEG 20 000 mw reduces HCV viral titers through nitric oxide (NO)‐dependent effects.

A case of pegylated interferon alpha-related diabetic ketoacidosis: can this complication be avoided?

We report the case of a 42-year-old woman with chronic hepatitis C (genotype 1), who in June 2004 started therapy with pegylated interferon alpha (PEG-IFNα) plus ribavirin. Two months later, she discontinued treatment because of polydipsia, polyuria and vomiting leading to a marked dehydration. Biochemical data showed type 1 diabetes mellitus with ketoacidosis, and insulin therapy was started. The patient, who before starting PEG-IFN α plus ribavirin therapy tested negative for glutamic acid decarboxylase antibodies (GADAb) and islet cell (ICAb) antibodies, became strongly positive for both autoimmune markers. This case confirms that patients with chronic hepatitis C who do not have baseline markers of pancreatic autoimmunity may develop severe ketoacidosis during treatment with PEG-IFNα, as well as with standard IFNα. In order to avoid this complication, as no guidelines are available and the pancreatic autoimmunity markers are not routinely analysed, we suggest frequent monitoring (e.g., every one to two weeks) of glycaemic values: e.g., every one to two weeks during the first 3 months (when this complication occurs most frequently) and monthly thereafter so as to identify diabetes at an early stage and before the onset of the appearance of severe ketoacidosis, which is life-threatening.

Vertical hepatitis C virus transmission: Main questions and answers.

Hepatitis C virus (HCV) affects about 3% of the worlds population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.

Prevalence of hepatitis C virus genotypes in southern Italy

HCV is ubiquitous. In 50% of all cases it causes chronic hepatitis that often evolves into liver cirrhosis and hepatocellular carcinoma. Recently HCV has been classified in 5 genotypes by Okamoto. The purpose of this study is to evaluate the prevalence of 5 genotypes in Campania, a region of Southern Italy, where the prevalence of anti-HCV antibodies ranges from 0.87 to 4%, and to evaluate the correlation between the HCV genotypes and the severity of histological damage. One hundred and thirty-five anti-HCV positive patients were enrolled and tested by PCR to identify HCV-RNA. One hundred and twenty-four patients resulted HCV-RNA positive. Genotyping was performed as described by Okamoto et al. with minor modifications of the specific primer to type III proposed by Silini et al. Eight patients were negative for all genotypes. Eight patients were positive for type I(1a), 61 for type II(1b), 39 for type III(2a), 11 for type IV(2b) and 1 for type V(3a). In 4 cases two different genotypes were present in the same sample [II(1b)-IV(2b), III(2a)-II(1b) twice, III(2a)-IV(2b)]. Histological evaluation of liver damage showed: CPH (22 cases), minimal CAH (56), severe CAH (31) and liver cirrhosis (15). There was no statistically significant correlation between the 5 genotypes and the severity of histological damage. Data on the prevalence of genotype II(1b) in Italy are similar to those reported for other European countries. The prevalence of genotypes in Southern Italy is similar to that reported in the population of Northern Italy.

Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8900 high-risk patients

OBJECTIVES Historically, only 10% of patients with hepatocellular carcinoma (HCC) are diagnosed with early-stage, potentially curable disease. In this study, chronic hepatitis virus-infected patients were prospectively screened to determine: (i) the proportion of patients diagnosed with potentially curable HCC, and (ii) survival following curative therapy. METHODS The study included 8900 chronic hepatitis virus-infected patients enrolled in a prospective screening programme, of whom 1335 (15.0%) were infected with hepatitis B virus (HBV), 7120 (80.0%) with hepatitis C virus (HCV), and 445 (5.0%) with both HBV and HCV. Screening was conducted every 6 months and included serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, radiofrequency ablation and/or ethanol injection. RESULTS Hepatocellular carcinoma was diagnosed in 765 (8.6%) patients. Of 1602 patients with cirrhosis, 758 (47.3%) developed HCC. Curative treatment was possible in 523 (68.4%) of the 765 HCC patients. Two- and 5-year rates of overall survival in the curative treatment group were 65% and 28%, respectively, compared with 10% and 0% in the advanced disease group (P < 0.001). CONCLUSIONS Prospective screening of patients at high risk for the development of HCC increases the proportion of patients diagnosed with potentially curable disease. This may result in an increase in the number of longterm survivors. Screening strategies should focus on patients with chronic HBV or HCV infection who have progressed to cirrhosis because more than 40% of these patients will develop HCC.

Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women?

Hepatitis C virus (HCV) affects about 3% of the worlds population, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution (highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.

Efficacy of ultra-short single agent regimen antibiotic chemo-prophylaxis in reducing the risk of meningitis in patients undergoing endoscopic endonasal transsphenoidal surgery.

OBJECTIVES The study aims to evaluate the incidence of infectious complications (namely meningitis) within 30 days after endoscopic endonasal transspheinodal neurosurgery (EETS) in patients receiving an ultra-short peri-operative chemo-prophylaxis regimen with 2 doses of 1st generation cephalosporin or macrolide. PATIENTS AND METHODS We retrospectively analyzed the clinical records of 145 patients who received an ultra-short chemoprophylaxis with two doses of an antibiotic, given 30 min before and 8h after EETS, over a 30-month time-frame. Ninety-seven patients (66.89%) received endovenous cefazolin, a 1st generation cephalosporin, administered at a dosage of 1000 mg, and 48 patients (33.10%) with an history of allergy to various agents, received endovenous clarithromycin at a dosage of 500 mg. RESULTS No case of peri- and post-operative meningitis occurred in patients receiving the 2 doses of antibiotic. Only one patient (0.68%) developed cerebral fluid leakage on the 7th postoperative day, which required the switching to a broad-spectrum antibiotic prophylaxis for one week; this patient received the ultrashort prophylaxis with a macrolide. In addition, 7 patients (4.82%) developed minor infectious complications such as low-grade fever (3 cases, all of them receiving cefazolin), enlarged submandibular and cervical lymphnodes (3 cases, all of them receiving cefazolin), and upper and lower respiratory tract infection (1 case receiving clarithromycin). The cost of this prophylaxis regimen ranged from 7.76 Euro (cefazolin) to 39.54 Euro (clarithromycin). CONCLUSIONS This study suggested that an ultra-short single-antibiotic prophylaxis is a safe, cheap and effective regimen to prevent post-operative meningitis in patients undergoing EETS and who do not require lumbar drainage after surgery. In these patients also the rate of minor infective complications was acceptable when compared with the previous more expensive regimen based on 3rd generation cephalosporin plus aminoglycoside or alone, that could be suitable only for at-risk patients (e.g. smokers, cerebrospinal leak or Cushings diseases).

Diabetes Mellitus Type 1, Latent Autoimmune Diabetes of Adults and Hepatitis C Virus: What we Know and what we Need to Know

Hepatitis C virus infection and diabetes mellitus are two major public health problems worldwide and the burden of these diseases is expected to increase in the near future. Hepatitis C virus is associated to autoimmune disorders of several organs (e.g. thyroid and kidney) and has recently been reported to be associated also to metabolic disorders including type 2 diabetes mellitus. Biologically, the homologies between the hepatitis C virus polyprotein and the pancreas antigens could underlie a mechanism of molecular mimicry that could lead to autoimmune diabetes (type 1 diabetes mellitus and latent autoimmune diabetes of adults). Here we review the data on the potential relationship between HCV-related chronic liver disease and autoimmune mediated diabetes mellitus.