Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study.

BACKGROUND: Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. AIM: To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. METHODS: We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the probability of HCC early recurrence from DAA starting by Kaplan-Meier method. RESULTS: Eighty-six per cent of patients were in Child-Pugh class A and 76% of patients were BCLC A. Almost all patients (96%) achieved sustained virological response. Twenty-four HCC recurrences were observed, with nodular or infiltrative pattern in 83% and 17% of patients, respectively. The 6-, 12- and 18-month HCC recurrence rates were 12%, 26.6% and 29.1%, respectively. Main tumour size and history of prior HCC recurrence were independent risk factors for HCC recurrence by Cox multivariate model. CONCLUSIONS: Probability of HCC early recurrence in patients who had HCC previously cured remains high, despite HCV eradication by DAAs. Risk was comparable but not higher to that reported in literature in DAA-untreated patients. Previous HCC recurrence and tumour size can be used to stratify the risk of HCC early recurrence. Further studies are needed to assess impact of DAAs on late recurrence and mortality.

Cirrhotic patients are still at risk of developing hepatocellular carcinoma despite Interferon-induced sustained virological response.

INTRODUCTION: Hepatitis C virus (HCV) infection is a common cause of chronic liver disease and hepatocellular carcinoma (HCC). The prevalence of HCC significantly declines among patients achieving a sustained virological response (SVR) after antiviral therapy with pegylated(PEG)-interferon (IFN) and ribavirin. However, up to 5% of patients with SVR may develop HCC. PATIENTS AND METHODS: We investigated the epidemiological, clinical, biochemical and virological characteristics of a small cohort of patients with chronic hepatitis C (CHC) who developed HCC after being successfully treated with PEG-IFN-α and ribavirin. RESULTS: Between September 2000 and January 2003, 598 patients with CHC underwent a complete course of treatment with PEG-IFN-α and ribavirin; 221 out of 598 (37%) patients obtained a SVR. Throughout the 10-year post-treatment follow up, 13 of 221 ( 5.8% ) SVR patients developed HCC. All 13 patients were male and were affected with Child A liver cirrhosis; in addition, at baseline they were significantly older (p < 0.05) and had higher alpha-fetoprotein levels (p < 0.05) in comparison with those who did not develop HCC. Nine patients (69.3%) developed HCC within the first 3 years after antiviral treatment completion, one patient (7.7%) between 3 and 5 years and 3 subjects (23%) between 5 and 10 years; 12 of 13 had a solitary lesion with a mean diameter of 2.5± 0.5 cm. Eleven cases (84.6%) underwent surgical resection, one (7.7%) received liver transplantation, one (7.7%) received palliative care. CONCLUSIONS: The risk of developing HCC after achieving SVR persists in patients with HCV-related cirrhosis. As a consequence, these patients should continue to undergo long-term surveillance for HCC, in order to early detect and treat it.

Trimethoprim-sulfamethoxazole-associated severe hypoglycaemia: a sulfonylurea-like effect.

AIM: To report hypoglycaemia, a life-threatening adverse event, associated with trimethoprim-sulfamethoxazole. A sulfonylurea-like effect, leading to insulin raise, was investigated. METHODS: Two cases of trimethoprim-sulfamethoxazole-associated hypoglycaemia in 2 patients with a diagnosis of new HIV-1-infection presenting with Pneumocystis jiroveci pneumonia are reported. The patients had no predisposing factors, such as renal or liver impairment, interfering with trimethoprim-sulfamethoxazole elimination, thus leading to hypoglycaemia. Insulin plasma levels were measured in both patients. RESULTS: Severe hypoglycaemia was associated with increased serum levels of insulin up to 84 microU/ml (normal values < 10 microU/ml). Continuous dextrose infusion was necessary, further suggesting the sulfonylurea-like effect of sulfamethoxazole. Interestingly, plasma levels of insulin progressively raised after trimethoprim-sulfamethoxazole administration. CONCLUSIONS: Only 18 cases of trimethoprim-sulfamethoxazole associated hypoglycaemia are reported in the literature. Hypoglycaemia is a life-threatening condition, likely underreported, to consider when trimethoprim-sulfamethoxazole administration is required, even in the absence of predisposing factors or other hypoglycaemic agents. Physician should bear in mind the potential trimethoprim-sulfamethoxazole-associated adverse event especially when prolonged treatments and elevated dosage are used.

Leukocyte interferon alpha early retreatment for Child A HCV genotype 1b-infected cirrhotics intolerant to pegylated interferons.

BACKGROUND AND AIM: The pegylated interferon (PEG-IFN)/ribavirin combination has been shown to be effective for hepatitis C virus (HCV)-related compensated cirrhosis, but it frequently causes adverse events, leading to premature termination. In this open study we evaluated the safety and efficacy of early retreatment with leukocyte IFN-alpha in Child A HCV genotype 1b-infected cirrhotics intolerant to PEG-IFNs. PATIENTS AND METHODS: 61 patients were treated with PEG-IFN (either alpha-2b 1.2-1.5 lg/kg weekly or alpha-2a 180 lg/weekly) plus ribavirin (1,000 mg/day) for 48 weeks. During the first 6 months, patients who discontinued treatment because of side effects were retreated with leukocyte IFN-alpha (6 MU/three times weekly) plus ribavirin (1,000 mg/day) for 48 weeks after a 1-month wash-out. The primary end points were safety and efficacy in terms of sustained virological response (SVR). RESULTS: At intention-to-treat analysis of the 61 patients receiving PEG-IFNs plus ribavirin revealed that 18 (29.5%) obtained a SVR. 16 patients (26.2%) prematurely discontinued treatment and were retreated with leukocyte IFN-alpha plus ribavirin. The switch was well tolerated, and all but one patient completed the treatment period. As a result of the switch, 4 of these 16 (25%) patients also obtained a SVR. Thus, the overall SVR rate of this study was 22/61 (36.1%). CONCLUSIONS: These results suggest that an early retreatment with leukocyte IFN-alpha may be a safe and valid therapeutic option among difficult-to-treat HCV cirrhotic patients who cannot tolerate PEG-IFNs.

Fatal hepatitis during Epstein-Barr virus reactivation.

Fulminant hepatitis by Epstein-Barr virus is a rare event which is predominantly due to primary infection. We report a rare case of fatal hepatic failure due to Epstein-Barr virus reactivation in a 19-year-old boy who was taking oral steroids. Transaminase peak and the fulminant course of the disease began soon after steroid interruption. Epstein-Barr virus reactivation was diagnosed on the basis of past clinical history of heterophile-positive infectious mononucleosis, a high titer of IgG anti Epstein-Barr virocapsidic antigen, slight elevation of anti-virocapsidic IgM, a high titer of anti-EA IgG antibodies and elevated viral load in serum measured by polymerase chain reaction. It is concluded that Epstein-Barr virus should be considered as a possible etiological agent of fulminant hepatitis.

Leucocyte interferon-alpha retreatment for chronic hepatitis C patients previously intolerant to other interferons.

The activity and tolerability of a retreatment cycle with leucocyte interferon-alpha (IFN-alpha) (6 million units (MU) three times weekly for 12 months) was evaluated in a group of 22 hepatitis C patients who had been intolerant to a previous course of lymphoblastoid IFN-alpha. Seven patients (31%) discontinued the new therapy owing to either a lack of response (six patients) or to severe leucopenia (one patient). Fifteen patients (68%) completed the 12-month treatment: all had a biochemical response and 10 (45%) also had disappearance of serum HCV RNA (complete response). Mild adverse reactions (fever, headaches and diarrhoea) were seen in these patients during retreatment. After 12 months of follow-up, 11 patients (50%) still maintained the biochemical response (long-term response); seven of these patients (32%) were also negative for serum HCV RNA. Biochemical and complete responses, at the end of both treatment and follow-up, were similar to those seen with lymphoblastoid IFN-alpha. The full dose of leucocyte IFN-alpha, when used in patients previously intolerant to the same dosage of lymphoblastoid IFN-alpha, was better tolerated: only one of the 15 patients who completed the 12-month treatment had a severe adverse event leading to withdrawal vs 22 of 68 patients treated with lymphoblastoid IFN-alpha. Furthermore, there were no manifestations of serological or clinical autoimmunity caused by leucocyte IFN-alpha, even in patients with autoantibodies associated with previous IFN therapy.

Acute hepatitis E in Catania (eastern Sicily) 1980-1994. The role of hepatitis E virus.

Between 1980 and 1994, 540 patients with acute viral hepatitis were admitted to hospital at the Department of Infectious Diseases of Catania (eastern Sicily). Twenty-five patients out of 540 were assessed as having non-A, non-B, non-C hepatitis. These subjects were studied for anti-HEV IgM and IgG seroprevalence by testing serial serum samples collected 1, 4, 12 and 24 weeks after the onset of acute disease. Fourteen of 25 samples (56%) seroconverted to anti-HEV IgG antibodies. No sample was positive for anti-HEV IgG at week 1, ten samples were positive at week 4 and the remainder at week 12. Anti-HEV reactivity was maintained until week 24 in all cases. In 11 of the 14 patients seroconverting to anti-HEV, the presence of IgM anti-HEV was found, which appeared in the sample from week 1 and gradually disappeared thereafter. Identified risk factors for HEV transmission included travel in the tropics and shellfish ingestion (anti-HEV positive versus anti-HEV negative: p < 0.05). HEV-related hepatitis is not yet a major public health problem in Sicily but, from our data, the trend of its incidence is clearly upwards. The high incidence of faecally-orally transmitted diseases in Sicily, the crucial position of Sicily in the middle of the Mediterranean Sea (where HEV largely circulates) and the increase of migration from developing countries are all factors which should increase awareness for a more active surveillance of the spread of HEV in our area.

[A case of severe thrombocytopenia in infectious mononucleosis]. / Su un caso di grave piastrinopenia in corso di mononucleosi infettiva.

The authors discuss a case of thrombocytopenia with bleeding occurred in a young woman with infectious mononucleosis admitted to the Infectious Disease Department of University of Catania. It is reported the pathogenetic hypothesis of virus-induced thrombocytopenia and therapy.

[Long-term study of anti-HCV reactivity using 3d generation recombinant immunoblot assay in acute post-transfusion hepatitis]. / Studio "long-term" della reattività anti HCV nella epatite acuta post-trasfusionale con Recombinant Immuno Blot Assay di terza generazione.

Twenty-five patients with post-transfusional C hepatitis have been tested retrospectively by IIIrd generation Recombinant Immuno Blot Assay (RIBA) in order to evaluate long-term anti HCV antibodies dynamics. The test was performed 1, 15, 70 and 140 days after the onset of the disease. Fifteen patients recovered and 10 became chronic. In the 15th day anti C33 and anti C22 were found in 76% of subjects, anti NS5 in 68% and anti C100 in 32%. In the 70th day, 96%, of patients had anti C22, 92% had anti C33 and anti NS5 and 52% showed anti C100. In the 140th day, all patients were positive for anti C33, and C22 and anti NS5, while anti C100 was present in 64%. Five-six years after the acute disease, all chronically progressed patients had a complete antibody pattern by RIBA III, while anti C22 was the only positive persisting antibody, among the recovered patients. Anti C22, anti C33 and anti NS5 shorten the serological "window-phase" during acute hepatitis, but no further improvement in diagnostic precocity seems to be guaranteed by third generation RIBA. The precocious appearance of complete RIBA III pattern during acute hepatitis may represent a herald for a chronic evolution of the disease.

[Hemodynamic and metabolic effects of noradrenaline infusion in a case of hyperdynamic septic shock]. / Effetti emodinamici e metabolici della infusione di noradrenalina in un caso di shock settico iperdinamico.

AIM: To evaluate the effect of noradrenaline infusion in a case of hyperdynamic septic shock refractory to volume loading, dopamine and dobutamine, on hemodynamic parameters, oxygen transport, lactate and pyruvate levels. DESIGN: Description of a clinical case. SETTING: Postsurgical Intensive Care Unit in a University Hospital. PATIENT: A 48-year-old woman with symptoms of peritonitis due to Enterobacter Agglomerans and refractory hyperdynamic septic shock. INTERVENTIONS: Administration of noradrenaline in doses ranging from 0.03 to 0.14 micrograms/kg/min. MEASUREMENTS AND RESULTS: Before and after noradrenaline infusion the following were evaluated: hemodynamic (parameters) and oxygen transport acid-base status, arterial blood levels of lactate and pyruvate, and lactate/pyruvate ratio. During the administration of noradrenaline an increase was observed over time in oxygen consumption (from 110 +/- 16 to 164 +/- 19 mL/min/m2; p < 0.01), peripheral vascular resistance (from 509 +/- 95 to 1172 +/- 384 dynes.sec.cm-5, p < 0.01) and the oxygen extraction index (from 12.9 +/- 2.1 to 21.2 +/- 2.9%, p < 0.01), together with reduced lactate (from 24.4 +/- 1.5 to 4.9 +/- 5.1 mmol/L) and pyruvate levels (from 945 +/- 62 to 357 +/- 174 mumol/L; p < 0.01) and a reduced lactate/pyruvate ratio (from 26.2 +/- 1.2 to 11.8 +/- 5.9, p < 0.01). No significant increases were found in cardiac output and oxygen delivery. CONCLUSIONS: In the case observed here the infusion of noradrenaline induced an increase in oxygen consumption and the oxygen extraction index associated with a reduction in the lactate/pyruvate ratio and the normalisation of the acid-base status. These changes were not associated with an increase in oxygen which remained delivery > or = 600 mL/min/m2.