Efficacy and safety of tenofovir, entecavir, and telbivudine for chronic hepatitis B in heart transplant recipients.

BACKGROUND: Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. METHODS: In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB. RESULTS: Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0-4). Glomerular filtration rate (GFR) was <50 mL/min in 7 patients (54%). Two patients were started on de novo ETV before transplant. Eleven previously treated patients were switched to TDF (n = 9) or LdT (n = 2). Median treatment duration was 33 months (range 1-71). HBV DNA remained suppressed in 6 patients and became undetectable in 5. Aminotransferases went down to the normal range in all patients, with a single flare in 1 patient. One patient lost hepatitis B surface antigen. No cases occurred of hepatic decompensation, hepatocellular carcinoma, or liver-related death. The GFR remained largely stable, and no cases of TDF-related hyper-phosphaturia were observed. CONCLUSIONS: This study indicates that newer antivirals are effective and safe in HTR with CHB.

Primary sclerosing cholangitis in patient with celiac disease complicated by cholecystic empyema and acute pancreatitis.

BACKGROUND: The association of celiac disease and sclerosing cholangitis is a well known, although unusual, pathologic feature of autoimmunity. METHODS: A 64 year old patient presenting with sub-acute cholangitis and pancreatitis, treated with cholecystectomy and endoscopic sphincterotomy. The post-operative course, complicated by cholestatic jaundice, and subsequent clinical complications are described, showing how the diagnosis of sclerosing cholangitis was outlined after the Endoscopic Retrograde Cholangio-Pancreatography (ERCP) and confirmed by liver biopsy. Long term treatment with Ursodeoxycholic acid has gradually normalized bilirubin values, while cholestasis enzymes are gradually decreasing. After 18 months bleeding from oesophageal varices ensued, which was controlled through endoscopic ligation. CONCLUSIONS: The diagnosis of primary sclerosing cholangitis should be taken into account when cholangitis is associated with other immunity derangements and segmentary dilatations of the intra-hepatic bile ducts, but no dilatation of the main bile duct is noticed at imaging or endoscopy. Recovery of hepatic function should be always attempted before bringing the patient to surgery, in order to avoid postoperative hepatic decompensation.

Outcome of treatment with pegylated interferon and ribavirin in heart transplant recipients with chronic hepatitis C.

BACKGROUND/AIM: The combination of pegylated interferon (PEG-IFN) and ribavirin (RBV) is the current treatment for chronic hepatitis C (CHC). The treatment is thought to suppress viral replication and induce viral clearance via immunomodulatory effects. For this reason, concern exists for the use of this treatment in recipients of a solid organ transplantation. We sought to evaluate the safety and efficacy of PEG-IFN/RBV in heart transplant recipients with CHC. METHODS: From June 2005 to September 2009, we treated three CHC patients with heart transplantation. PEG-IFN alpha2b and RBV doses and treatment duration were set according to the hepatitis C virus (HCV) genotype and body weight as per current recommendations. Dose reductions were dictated by individual patient tolerability. Cardiac safety was monitored by clinical examinations, echocardiography, and measurement of troponin I and B-type natriuretic peptide, as well as endomyocardial biopsies. RESULTS: All three patients, displayed HCV genotype 1b infection, viral loads of >5 logs, and a Scheuer fibrosis score ≥ 2. Two of them completed the prescribed treatment course becoming sustained virological responders. The other patient had an initial complete virological response, but subsequently experienced a viral breakthrough after reduction of PEG-IFN and withdrawal of RBV due to severe anemia. We observed no cardiovascular adverse events nor rejection episodes. Posttreatment clinical history and examination, electrocardiography, and echocardiography did not show any sign of graft dysfunction. CONCLUSIONS: Treatment with PEG-IFN/RBV may be safely offered to stable heart transplant recipients with CHC and signs of liver disease progression. Close monitoring of treatment safety is mandatory.

Molecular epidemiology of a clonal outbreak of multidrug-resistant Acinetobacter baumannii in a university hospital in Italy.

This study investigated the molecular epidemiology of a clonal outbreak of multidrug-resistant Acinetobacter baumannii that occurred between June 2003 and June 2004 in a tertiary-care hospital in Naples, Italy. A. baumannii was isolated from 74 patients, of whom 38 were infected and 36 were colonised. Thirty-three patients had ventilator-associated pneumonia, three had hospital-acquired pneumonia, and two had sepsis. Genotypic analysis of 45 available A. baumannii isolates revealed two distinct pulsed-field gel electrophoresis (PFGE) patterns. Of these, PFGE pattern 1 was represented by isolates from 44 patients and was identical to that of an epidemic A. baumannii clone isolated in another hospital of Naples during 2002. All A. baumannii isolates of PFGE type 1 showed identical multiresistant antibiotypes, characterised by resistance to all antimicrobial agents tested, including carbapenems, with the exception of colistin. In these isolates, inhibition of OXA enzymes by 200 mM NaCl reduced the imipenem MIC by up to four-fold. Molecular analysis of antimicrobial resistance genes showed that all A. baumannii isolates of PFGE type 1 harboured a class 1 integron containing the aacA4, orfX and bla(OXA-20) gene cassettes, an ampC gene and a bla(OXA-51)-like allele. Moreover, a bla(OXA-58)-like gene surrounded by the regulatory elements ISAba2 and ISAba3 was identified in a 30-kb plasmid from A. baumannii isolates of PFGE type 1, but not PFGE type 2. Thus, selection of a single A. baumannii clone producing an OXA-58-type carbapenem-hydrolysing oxacillinase was responsible for the increase in the number of A. baumannii infections that occurred in this hospital.

Role of immunosuppressive regimen on the incidence and characteristics of cytomegalovirus infection in heart transplantation: a single-center experience with preemptive therapy.

OBJECTIVE: This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. PATIENTS AND METHODS: Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo = 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n = 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. RESULTS: The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P = .004 and P = .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P = .001 and P = .008). CONCLUSIONS: The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.

Hepatic cryptococcosis in a heart transplant recipient.

Cryptococcosis primarily occurs in patients with impaired immune response. While pulmonary and/or cerebral involvement are more often described, there is limited experience of its presence in other sites. We present a case of hepatic cryptococcosis with possible pulmonary involvement in a 54-year-old male heart transplant recipient. Two months after heart transplantation, he developed a persistent, moderate dyspnea with fever and signs of liver damage. Diagnosis was made with liver biopsy for a concurrent reactivation of chronic hepatitis B virus (HBV) infection already present before transplant. Along with a mild chronic HBV hepatitis with fibrosis, we observed sinusoidal dilation and groups of bright, rounded, colorless cells with a central nucleus suggestive of cryptococci. Periodic acid-Schiff stain clearly showed encapsulated yeasts, which supported the diagnosis. Cryptococcal antigen was positive in serum and negative in the cerebrospinal fluid. Computed tomography scan of the chest demonstrated a mild interstitial infiltrate. The patient promptly responded to reduction of immunosuppressive therapy and antifungal treatment with amphotericin B lipid complex and flucytosine followed by maintenance treatment with fluconazole. Cryptococcosis should always be considered in the differential diagnosis in immunocompromised hosts with dyspnea and signs of extrapulmonary involvement. Diagnosis of extrapulmonary and extraneural cryptococcosis is difficult and often fortuitous; a histopathological examination of tissues involved is probably warranted.

Streptococcus bovis endocarditis and its association with chronic liver disease: an underestimated risk factor.

Clinical and epidemiological characteristics of Streptococcus bovis endocarditis were prospectively studied among 199 patients with definite endocarditis. Thirty patients (15.1%) had S. bovis endocarditis. Compared with patients with non-S. bovis endocarditis, these 30 patients were older (mean age, 58.6+/-12.4 years vs. 46.0+/-17.0 years; P<.001) and had higher rates of bivalvular involvement (43.3% vs. 7.7%; P<.001), embolism (73.3% vs. 40.2%; P=.002), and diskitis (23.3% vs. 0.6% P<.001). In patients with S. bovis biotype I (S. bovis I) endocarditis, advanced liver disease was present in 56.7%, compared with 15.3% of patients with non-S. bovis endocarditis (P<.001), and colonic adenoma was present in 46.7%. The in-hospital mortality rate (16.7%) was correlated with delayed diagnosis and advanced liver diseases. In our city, S. bovis I endocarditis is frequently correlated with liver diseases; diskitis may be the first sign of the disease.

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

Efficacy and limitations of preemptive therapy against cytomegalovirus infections in heart transplant patients.

OBJECTIVES: Cytomegalovirus (CMV) disease often represents a serious complication that promotes opportunistic infections in heart transplant recipients. In this study we evaluated the impact of preemptive gancylovir therapy, guided by pp65 antigenemia on the morbidity associated with viral reactivation. PATIENTS AND METHODS: We have performed a CMV infection surveillance program since March 1999, with antigenemia pp65 determinations weekly for the first 2 months biweekly in the third months, and monthly to the sixth month. Patients with pp65 antigenemia value >/= 10 positive cells per 2 x 10(5) polymorphonuclear cells (PMN) were treated with intravenous gancyclovir followed by 1 month of oral gancyclovir. RESULTS: Among the 107 patients who underwent the virological monitoring, 80 were pp65 antigenemia-positive with preemptive therapy administered in 48 cases. Five patients displayed symptomatic CMV disease (4.7% vs 18% rate in the period of 1988 to 1998 before the introduction of virologic monitoring; P <.01). We observed only one case of gancyclovir-resistant pneumonia which was successfully treated with foscarnet. CMV recurrence in 10 patients required a second cycle of gancyclovir treatment. Our experience included 13 opportunistic infections (12.7%) with 11 antigenemia-positive. CONCLUSIONS: Preemptive therapy drastically reduces the incidence of CMV disease and the associated morbidity. Compared to universal prophylaxis, this approach may avoid unnecessary pharmacologic treatment in more than 50% of transplant recipients. Indeed, preemptive therapy does not fully prevent CMV disease, because it may manifest at the first antigenemia determination, and furthermore may select gancyclovir-resistant strains.

First definite case of aortic valve endocarditis due to Moraxella phenylpyruvica.

Described here is the first definite case of endocarditis due to Moraxella phenylpyruvica, which occurred in a 50-year-old male with a bicuspid aortic valve. The diagnosis was delayed because of the confounding positivity of the Widal and Wright tests. The patient was cured with surgical valve replacement and antibiotic treatment.

Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis.

The pathogenesis of thrombocytopenia in chronic hepatitis is not well known. This study evaluated the relationship between liver injury, serum thrombopoietin, splenomegaly and thrombocytopenia in chronic viral hepatitis. Two hundred and nine patients were enrolled, 85 with splenomegaly and 124 without. Thrombocytopenia was present in 71% and 23% of patients with or without splenomegaly respectively. In subjects with low platelet count, those with splenomegaly showed significantly lower platelet numbers than those without splenomegaly. The spleen size correlated with portal hypertension. An inverse correlation between spleen size and platelet count was observed (r = -0.54; P < 0.0001). In patients without splenomegaly, thrombocytopenia was associated with the grade of fibrosis; platelet counts were the highest in patients with fibrosis 0-2, lower in those with grade 3 (P < 0.008) and lowest in those with grade 4 (P < 0.05). These findings were independent of demographic and biochemical characteristics, hepatic necroinflammatory activity, portal hypertension and splenomegaly. Patients with normal platelet counts showed higher thrombopoietin levels than those with low platelet counts (P < 0.0001). An inverse correlation between thrombopoietin levels and fibrosis grade was observed (r = - 0.50; P < 0.0001). Median thrombopoietin levels were 58 and 27 pg/ml for fibrosis grade 0-1 and grade 4 respectively (P < 0.001). These data indicate that advanced hepatic fibrosis, causing an altered production of thrombopoietin and portal hypertension, plays the central role in the pathogenesis of thrombocytopenia in chronic viral hepatitis.

Relationship between genotypes of hepatitis C virus and histopathological manifestations in chronic hepatitis C patients.

OBJECTIVE: The aim of this study was to assess the relationship between HCV genotype and histological liver injury. DESIGN: Prospective study on a cohort of patients with biopsy proven chronic hepatitis C. SETTING: University medical centre. PARTICIPANTS: Enrolled were 324 consecutive patients (male 197, median age 52 years, range 19-68; chronic hepatitis, 224; cirrhosis, 100). METHODS: HCV genotype was determined by the INNO LiPA assay and HCV RNA levels by the bDNA assay. The histological features were scored according to the histology activity index. RESULTS: The distribution of HCV genotypes was 1a, 4.6%; 1b, 52.4%; 2a/c, 27%; 3a, 8%; 4, 2%; mixed, 6%. Serum HCV RNA levels were similar for all genotypes. There was no difference in the distribution of HCV genotypes between patients with chronic hepatitis and those with cirrhosis. Patients with genotype 1b and those with type 2a/c showed a similar prevalence of cases of cirrhosis (33% versus 31%, respectively). In addition, in a subgroup of 102 patients with an established date of infection, the progression to cirrhosis occurred with a similar length of time for HCV type 1b and 2a/c (median 16 versus 15 years, respectively). Patients with HCV genotype 2a/c or mixed genotype showed a higher histology activity index than those with type 1b (P< 0.01), whereas there was no difference in the fibrosis score for the different genotypes. Patients with genotype 3a showed a significantly higher prevalence of steatosis compared to those infected with other genotypes. Alanine aminotransferase (ALT) values were higher in patients with HCV type 2a/c, 3a and mixed genotype than those with type 1 (P < 0.002). CONCLUSIONS: The data indicate that there is no association between a particular HCV genotype and the progression to cirrhosis, and that specific genotypes are associated with distinct histopathological and biochemical manifestations although none of them is correlated with an increase of the fibrosis stage.

Dual or single hepatitis B and C virus infections in childhood cancer survivors: long-term follow-up and effect of interferon treatment.

We conducted a long-term prospective study of 89 cancer survivor children who had acquired hepatitis B virus (HBV) and/or hepatitis C virus (HCV) during treatment for neoplasia, the aim being to evaluate the natural history of the diseases and the effect of interferon (IFN) treatment. Patients were followed up for a median period of 13 years (range, 8 to 20); 46 were infected by HBV, 11 by HCV, and 32 coinfected by HBV and HCV. A spontaneous clearance of hepatitis B surface antigen (HBsAg) occurred more frequently in coinfected patients (19%) than in the HBV-infected (2%; P =.004), with an annual seroconversion rate of 2.1% and 0.2%, respectively (P =.008). Loss of hepatitis Be antigen (HBeAg) occurred in 44% of coinfected and in 28% of HBV-infected patients. Clearance of serum HCV-RNA was observed in 34% and 9%, respectively, of coinfected and HCV-infected patients. Seventeen HBV-infected, 4 HCV-infected, and 16 coinfected patients received alpha-IFN treatment. In the HBV group, 6 patients (35%) cleared serum HBV DNA and seroconverted to anti-HBe; in the HCV-group, none cleared HCV-RNA. In the coinfected group, 1 patient cleared both HBV DNA and HCV-RNA, 6 patients cleared serum HCV-RNA alone, and 1 only HBV DNA and HBeAg. Overall, the diseases showed a mild histological course with no evidence of liver cirrhosis. A reciprocal interference on viral replication between HBV and HCV may occur in coinfected patients. Treatment seems to be effective for selected cases and is justified in view of the uncertain prognosis of the disease in these patients.

HCV RNA levels in serum, liver, and peripheral blood mononuclear cells of chronic hepatitis C patients and their relationship to liver injury.

OBJECTIVE: We sought to evaluate the relationship between HCV RNA levels in serum, liver, and peripheral blood mononuclear cells (PBMC) and the degree of liver injury in chronic hepatitis C (CHC) patients. METHODS: Thirty-six consecutive CHC patients were included in the study. The liver damage was evaluated by the histological activity index (HAI) score. The HCV RNA levels in the three compartments studied were assessed by bDNA assay. Nineteen patients were treated with alpha-interferon 2b (IFN). RESULTS: Serum and liver HCV RNA levels in CHC patients were significantly associated with an increasing HAI score irrespective of the HCV genotypes. Cirrhotic patients showed higher HCV RNA levels than the CHC patients with HAI score 1-4 (p < 0.05), but had lower levels than the group with HAI score > 8 (p < 0.03). Patients with HAI score 1-4 showed the lowest levels of HCV RNA in PBMC. There was a strong relation (r = 0.78; p < 0.001) between serum and liver HCV RNA levels, but not between either serum or liver HCV RNA levels and those of PBMC. Seven patients showed a response to IFN and three of these had a sustained response. Pretreatment levels of HCV RNA in PBMC of the IFN responder patients were lower than those of the nonresponder patients (p < 0.02). CONCLUSIONS: The data indicate a relation between serum or liver HCV RNA levels and the degree of liver injury in CHC patients, and show that serum HCV RNA level mirrors the hepatic viral burden.

Ethnic differences in red blood cell sodium/lithium countertransport and metabolic correlates of hypertension: an international collaborative study.

Arterial hypertension is frequently associated with metabolic abnormalities. An abnormal activity of the erythrocyte sodium/lithium countertransport (Na/Li CT), an ion transport system under strong genetic control, is also found in people with hypertension and concomitant metabolic abnormalities. However, little information exists with regard to these clinical associations in different racial groups. The aim of this international collaborative study was to investigate Na/Li CT and the metabolic correlates of hypertension in two comparable samples of normotensive and hypertensive populations in the cities of Naples, Italy, and Shanghai, China, using identical, carefully standardized techniques. Blood pressure, anthropometric and metabolic variables, Na/Li CT, and 24-h urinary Na and K excretion were measured in untreated essential hypertensive (HPT) and normotensive (NT) individuals selected by age (35-60 years), body mass index (BMI; < 30 kg/m2), and blood pressure (BP; HPT, DBP > or = 95 mm Hg; NT, DBP < 90 mm Hg). The analysis of variance with adjustment for age was used to compare the groups. In the Neapolitan population, hypertensive individuals had higher serum triglyceride (P < .05) and uric acid levels (P < .001) than the normotensive group and also had a reduced glucose tolerance (P < .01) and an enhanced insulin response to the oral glucose tolerance test (OGTT) (P < .05). No such differences were seen between normotensive and hypertensive Chinese participants. The Neapolitan population (both NT and HPT) had a higher BMI (P < .01) than their Chinese peers. In the comparison of hypertensive patients in Shanghai and in Naples, the Neapolitans were heavier (P < .001), had a lower HDL/total cholesterol ratio (P < .01), an elevated fasting blood glucose (P < .05), and also a higher glucose (P < .001) and insulin response (P < .001) to OGTT. By contrast, they showed a significantly lower urinary Na/K ratio (P < .001). Na/Li CT was significantly increased in HPT both in Naples (286 +/- 24 v 224 +/- 13 micromol/L RBC x h; P < .05, M +/- SE) and in Shanghai (388 +/- 45 v 265 +/- 30 micromol/L RBC x h; P < .05). Furthermore, Na/Li CT was significantly and inversely associated with HDL cholesterol both in the Neapolitan (P < .01) and in the Chinese (P < .05) population, whereas it was directly correlated with serum triglyceride (P < .001) and serum uric acid (P = .001) only in the Neapolitan population. These results indicate that essential hypertension is associated with a higher prevalence of obesity, impaired glucose tolerance, and hyperinsulinemia in Naples than in Shanghai; and Na/Li CT is linked to both high blood pressure and metabolic abnormalities in the Italian sample, whereas it is an isolated marker of hypertension in the Chinese sample.

Red blood cell sodium-lithium countertransport and risk of future hypertension: the Olivetti Prospective Heart Study.

An elevated red blood cell (RBC) sodium-lithium countertransport (Na-Li CT) is associated with high blood pressure (BP) in cross-sectional investigations; however, its value as a predictor of future hypertension, and thus of cardiovascular risk, has not been defined. The present study evaluated the association between Na-Li CT and risk of future hypertension in a sample of 106 untreated normotensive middle-aged men participating in the Olivetti Prospective Heart Study in southern Italy. BP, anthropometric and metabolic variables, and RBC Na-Li CT were measured at baseline in 1987 and at a follow-up visit in 1994 through 1995. Na-Li CT was stable over time (r=0.85) and was significantly associated to systolic BP in both visits. Of the 106 initially normotensive participants, 14 were found to be hypertensive at the 8-year follow-up examination. Eleven of these 14 hypertensives were in the highest tertile of systolic BP at baseline, and 9 of 11 also had an elevated baseline Na-Li CT. In multiple logistic regression analysis, baseline BP, Na-Li CT, and age were all significant predictors of the risk of future hypertension. Individuals with baseline systolic BP in the highest tertile had a 60% risk of developing hypertension if their Na-Li CT was also high, whereas their risk was only 5% if Na-Li CT was in the two lowest tertiles (P=0.003). RBC Na-Li CT was a valuable predictor of subsequent hypertension in middle-aged men with a high-normal BP level for their age.

Effects of long-term course of alpha-interferon in patients with chronic hepatitis C associated to mixed cryoglobulinaemia.

OBJECTIVE: To evaluate the efficacy of a long-term course of alpha-interferon (alpha-IFN) in the treatment of HCV-related mixed cryoglobulinaemia and to determine the impact of cryoglobulinaemia on therapeutic response to IFN in chronic hepatitis C (CHC) patients. DESIGN: Prospective controlled study. SETTING: University Medical Centre. PARTICIPANTS: Ninety consecutive CHC patients, 50 with cryoglobulinaemia (25 symptomatic and 25 asymptomatic; median cryocrit, 8%; chronic persistent hepatitis (CPH) 7, chronic active hepatitis (CAH) 27, cirrhosis 16) and 40 without cryoglobulinaemia (CPH 6, CAH 20, cirrhosis 14). HCV genotypes in the cryoglobulinaemic and non-cryoglobulinaemic groups were: 1b 40% and 45%; 2a 40% and 30%; others 20% and 25%, respectively. INTERVENTIONS: Twelve-month course of alpha-IFN 2a, 3 MU, three times weekly. MAIN OUTCOME MEASURES: Disappearance of cryoglobulinaemia and related syndrome, clearance of serum HCV RNA and normalization serum transaminase levels at the end of treatment (response) and after 12 months follow-up (sustained response). RESULTS: Overall, cryoglobulinaemic patients showed a similar response to IFN to those without cryoglobulinaemia (44% vs. 42.5%, respectively). In the cryoglobulinaemic group, symptomatic patients showed a lower response rate than asymptomatic patients (28% vs. 60%, respectively; P<0.05). HCV genotype 2a/c, absence of cirrhosis and a low cryocrit (<9%) were predictive factors of high response rate to IFN. Sustained response in non-cryoglobulinaemic patients (22.5%) tended to be higher than in patients with symptomatic cryoglobulinaemia (4%), as well as among patients carrying genotype 2a/c (67% vs. 10%, respectively; P<0.02). IFN was effective in controlling purpura (80%) but was moderately effective on severe haematuria/proteinuria, renal insufficiency and neuropathy. CONCLUSIONS: A 12-month course of alpha-IFN is effective treatment for HCV-related cryoglobulinaemia. However, patients with CHC associated to symptomatic cryoglobulinaemia have a lower response rate to IFN.

Epidemiology, clinical spectrum and prognostic value of mixed cryoglobulinaemia in hepatitis C virus patients: a prospective study.

A prospective study was undertaken to evaluate the prevalence, incidence, clinical spectrum and prognostic value of mixed cryoglobulinaemia in HCV infection. Four-hundred and thirty-two consecutive patients with chronic liver disease, 303 HCV-related, 81 HBV-related, 14 nonB-nonC related, and 34 of non-viral aetiology were studied. Cryoglobulinaemia was detected in 139 (46%) of the HCV-related chronic hepatitis patients, in 4 (5%) of the HBV-related and in none of the chronic hepatitis patients of any other aetiology. Cryoglobulinaemia was associated with liver cirrhosis, the duration of liver disease and predominantly with the female sex. HCV and anti-HCV antibodies were present in all the cryoprecipitates. All the HCV genotypes were associated with cryoglobulinaemia. In a high percentage of patients, the amount of cryoglobulinaemic was low and about half of the cryoglobulinaemic patients showed a clinical syndrome. The incidence per year of cryoglobulinaemia (6%) and of related signs was low. A higher incidence of malignant lymphoproliferative diseases was observed in type II cryoglobulinaemia. The presence of a cryoglobulinaemia-related clinical syndrome plays a role in the prognosis of patients with chronic hepatitis C.