Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24‐week ...course of pegylated IFN (Peg‐IFN) alpha‐2b versus a 12‐week course of Peg‐IFN alpha‐2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg‐IFN alpha‐2b monotherapy (1.5 μg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6‐month posttreatment follow‐up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real‐time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent‐to‐treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow‐up; thus, sustained response rates with per‐protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg‐IFN alpha‐2b was well tolerated. Conclusion: Peg‐IFN alpha‐2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration. (Hepatology 2014;59:2101‐2109)
Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively.
To evaluate the incidence and the ...clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis.
The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed.
Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia 17/84 (20.2 %) and 10/45 (22.2%), respectively, followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05).
Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.
To evaluate the hepatitis B virus (HBV) and the hepatitis C virus (HCV) epidemiology in the general population of Northern Italy, a cohort of 965 subjects, all residents (including 47 immigrants), ...were anonymously tested for HBV and HCV infections.
Serum samples were assayed for anti-HCV and anti-HBV markers by enzyme-linked immunosorbent assay and for HCV-RNA by polymerase chain reaction, and the positive cases were genotyped. HBsAg-positive cases were assayed for HBeAg/anti-HBe, whereas HBsAg negatives were tested for both anti-HBc and anti-HBs.
The overall prevalence of anti-HCV was 2.6%, with a bimodal distribution characterized by the highest prevalence (12%) in subjects over 75 years old. None of the subjects under 25 years old was anti-HCV positive. Anti-HCV positivity was similar in males and females (2.4% vs. 2.7%). HCV-RNA was positive in 40% of cases and genotype 1 was the most common. The HBsAg prevalence was 1%, with a significant difference according to country of origin (0.8% in Italian subjects vs. 6.4% in immigrants, P=0.01). HBsAg positivity increased significantly with age (R2=0.57, P<0.02). The overall percentages for the prevalence of isolated anti-HBs, anti-HBs+/anti-HBc+, and isolated anti-HBc were 23.8%, 8.4%, and 4.2%, respectively.
Our study provides a new picture of HCV and HBV epidemiology in Northern Italy, with these features: (1) a cohort effect showing a reduction of HCV infection in the elderly, possible due to age-related mortality; (2) an unchanged overall prevalence of HBV infection, despite continuing immigration of subjects from endemic countries.
Patients hospitalized in the authors' institution for erysipelas or cellulitis between January 1995 and December 2002 were included in this retrospective review. Two hundred cases of soft tissue ...infections were hospitalized during the study period. The mean age of the patients was 58 years. The most commonly involved site was the leg (66%), followed by the arm (24%) and face (6%). Most patients (71%) had a recognized risk factor for soft tissue infection. Fever was present in 71% of cases, with a mean duration of 3 days. Blood cultures were positive in 3 out of 141 (2%) cases, whereas cutaneous swabs were positive in 73 out of 92 (79%) cases. On admission, white blood cells counts (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were elevated above normal levels in 100 out of 191 (50%) cases, 151 out of 176 (85%) cases, and 150 out of 154 (97%) cases, respectively. Patients with a hospital stay of more than 10 days had significantly higher CRP and ESR values than patients hospitalized for 10 days or less (
P<0.01). A single antibiotic was used as treatment in 115 cases, whereas in the remaining 85 cases a combination of two antibiotics was administered. The most commonly used antibiotics were amoxicillin-clavulanic acid as single agent and penicillin with clindamycin as combination therapy. The mean duration of hospitalization was 7 days for patients treated with a single antibiotic and 11 days for patients treated with an antibiotic combination. A recurrence of infection occurred in 34 (17%) patients. Soft tissue infections are common and have a high degree of morbidity and require prolonged hospitalization and antibiotic treatment. Microbiological diagnosis is difficult and treatment is based on empiric evidence. ESR and CPR levels on admission may predict the severity of the disease and duration of hospitalization.
The correlation between therapeutic response and liver fibrogenesis was studied in serum and liver specimens taken from 31 patients treated with alpha-interferon (IFN) (14 sustained responders and 17 ...non-responders) for chronic hepatitis C. Serum samples, collected before therapy, and at further 6-month intervals over 2 years, were tested for markers of liver neofibrogenesis. Serum N-terminal procollagen III peptide (PIIINP) displayed a significant and persistent decrease (P < 0.05) in sustained responders but not in non-responders; significantly lowered (P < 0.05) mean levels of C-terminal procollagen I peptide (PICP) were transiently observed in both patient groups, apparently as a result of IFN administration. Serum laminin (Lam) levels remained unchanged. One year after the cessation of treatment, liver biopsy re-testing showed an improvement in necro-inflammatory scores only in sustained responders, with the histological fibrosis scores remaining unaltered in both groups. IFN treatment seemed to exert an influence on serum levels of markers of hepatic connective tissue turnover even in patients that did not respond to therapy, while no effect was observed on preexistent liver fibrosis.
To investigate if the risk of liver enzyme elevation (LEE) in HIV/hepatitis B or C (HBV, HCV) co-infection is altered by HAART (two or more drugs).
Analysis comprised HIV-positive patients in the ...ICoNA study without acute hepatitis who had >or= 1 positive HCV antibody test and > 1 positive HBV surface antigen test. LEE was defined as > 5x baseline alanine aminotransferase (ALT) or > 3.5x baseline if the baseline was > 40 IU/l. Analysis used Poisson regression with generalized estimating equation correction to examine HBV or HCV co-infection, use of HAART, baseline ALT and demographics as LEE predictors.
Of the 5272 patients, 47.6% were co-infected with HCV/HBV; 29.9% were female and 39% were intravenous drug users. There were 275 episodes of LEE during 18 259 person-years follow up. Taking HAART did not significantly increase risk of LEE adjusted relative risk (RR), 1.19; 95% confidence interval (CI), 0.81-1.75; P = 0.37. Co-infection increased the risk of LEE (adjusted RR, 5.07; 95% CI, 3.47-7.48; P < 0.001), with no significant differences if taking HAART (adjusted RR, 4.99; 95% CI, 3.38-7.37) or not (adjusted RR, 6.02; 95% CI, 2.02-17.98) (P = 0.74 for interaction). Females were at lower risk of LEE than males (adjusted RR, 0.59; 95% CI, 0.42-0.83; P = 0.02).
HIV and HBV/HCV co-infection per se is associated with increased risk of LEE that is not modified by HAART. The recommendation for caution in HAART use in co-infected patients, simply based on a high rate of LEE in people on therapy, may be questionable.
To assess the risk of clinical progression (CP) according to the duration of time spent without complete viral load (VL) suppression compared with that associated with periods of stably suppressed ...viremia in HIV-infected people who started highly active antiretroviral therapy (HAART) when previously naïve to antiretrovirals.
A cohort study of patients having started HAART after enrollment in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA) and being followed for at least 6 months.
Person-years spent in different categories according to the VL level and the change in VL from the most recent value before the initiation of HAART were calculated. A multivariable Poisson regression model, including potential confounders, was constructed.
A total of 3023 patients were studied. The overall rate of CP was 13.4 per 1000 person-years. Evidence for a higher risk of CP was observed for people with a current VL >10,000 copies/mL. For each year longer spent on HAART with a VL >100,000 copies/mL, a 5-fold increased risk was observed (relative risk RR = 5.34, 95% confidence interval CI: 2.83 to 1.08; P = 0.0001). An increased risk of CP in patients with current suppression <1.5 log10 copies/mL (RR = 2.34, 95% CI: 1.16 to 4.74; P = 0.02) and in those with no suppression or a VL higher than their set point (RR = 2.39, 95% CI: 1.17 to 4.89; P = 0.02) was observed compared with those with suppression of >3 log10 copies/mL, although it was not significant. Longer duration on HAART with a VL suppressed below set point seemed to confer protection against CP.
Virologic failure to antiretroviral drugs is common. The risk of CP may remain low despite a low but detectable level of HIV viremia.
To investigate the prevalence of hepatitis G virus (HGV/GBV-C) in patients with liver disease and to confirm its hypothesized ability to cause liver damage, we studied 130 subjects; 61 had chronic ...hepatitis C virus infection and 69 had acute hepatitis of either defined etiology (n = 57) or of unknown origin (n = 12). Positivity for HGV/GBV-C RNA was detected in 10 of the 61 subjects with chronic hepatitis C (16.3%) and in 11 of the 57 subjects with acute hepatitis of defined etiology (19%), whereas we failed to detect HGV/ GBV-C viremia in subjects with hepatitis of nonestablished etiology. Patients exhibiting positivity for HGV/GBV-C RNA were found to be comparable to those exhibiting negativity for HGV/GBV-C RNA in terms of both liver function tests and Knodell's score (in liver biopsies); the affect of HGV/GBV-C infection on the biohumoral and histological activity in patients with chronic hepatitis C therefore appears to be minimal or absent. Similar clinical features were observed in patients with acute hepatitis of known etiology whether they were positive or negative for HGV/GBV-C RNA. However, long-term clinical studies are still required to clarify the actual impact of HGV/GBV-C co-infection. In our geographic, i.e., a region or north-east Italy, HGV/GBV-C infection appears to be strictly related to intravenous drug use, and this agent does not seem to be responsible for acute hepatitis of unknown etiology; other etiological agents are probably involved.
The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with ...interferon-alpha (IFN-alpha).
The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA), parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test.
None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-alpha. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA+ patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other autoantigens did not change during the course of treatment.
We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies (in particular, thyroid and pancreas) before and during IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease.
Background: the frequency and the impact of occult HBV infection in patients with chronic hepatitis C infection is still a matter of some controversy.
Objectives: our aim was to evaluate the ...prevalence of occult HBV infection and assess its impact on liver biochemistry, HCV viral titre, liver histology and on outcome of therapy in patients with chronic hepatitis C.
Study design: paired liver biopsies and serum samples were collected from 51 patients (84% IVDUS) with HBsAg negative chronic hepatitis C, and tested for HBV-DNA with nested PCR. Liver biopsies were further studied histologically, with morphometric analyses and immunostaining techniques. Twenty-five were treated with alpha Interferon and ribavirin and followed for at least 18 months.
Results: HBV DNA was detected in 29.4% of liver tissue specimens and in only one (1.9%) serum sample. Three liver specimens were positive for surface gene, nine for core gene, three for both and none for the X gene. No significant difference in mean transaminase values, HCV viral titre, HCV genotype, or grading and staging and morphometric analysis was observed in patients with or without HBV DNA. Moreover, all 51 liver specimens were negative for both HBsAg and HBcAg. Sustained response to combination therapy was achieved in 40% of patients with and in 53% of patients without HBV DNA in the liver specimens (
P=NS).
Conclusions: HBV DNA is frequently found in the liver of patients with chronic hepatitis C. However, the lack of any significant impact on HCV viral titre, liver enzymes, histological parameters and response to therapy, suggests that in most cases HBV DNA detected in the liver by PCR may be either an integrated or low level replicative form.
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