Background/Aims: To investigate host-and virusrelated factors predictive of early and sustained a... more Background/Aims: To investigate host-and virusrelated factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. Methods: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region. Results: Mean pre-treatment HCV-RNA level (~10~ genome equivalents/mlfSD) was lower in sustained responders (3854+_7142) than in relapsers (9587+_10163) or in non-responders (5709f6618). HCV subtype lb was highly prevalent (82%), while types la, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of lb was much lower A
Nutcracker esophagus and non-specific motility disorders are the main causes of non-cardiac chest... more Nutcracker esophagus and non-specific motility disorders are the main causes of non-cardiac chest pain (NCCP), with gastroesophageal reflux in 60% of cases. Achalasia and diffuse esophageal spasm are the most frequent anomalies described in patients with dysphagia. The goal of this study was to evaluate the occurrence of esophageal body and lower esophageal sphincter motor abnormalities in patients with dysphagia, NCCP, or both. This study is a retrospective analysis of 716 patients with NCCP and/or dysphagia tested between January 1994 and December 2010. 1023 functional studies were performed, 707 of which were esophageal manometries, 225 esophageal pH-meters, and 44 bilimetries. We divided the patients into three groups: group 1 was composed of patients affected with dysphagia, group 2 with NCCP and group 3 with NCCP and dysphagia. Manometric anomalies were detected in 84.4% of cases (p<0.001). The most frequent esophageal motility alteration was achalasia (36%). The lower esophageal sphincter was normal in 45.9% of patients (p<0.001). In all 3 groups, 80.9%, 98.8%, and 93.8, respectively, of patients showed normal upper esophageal sphincter (p=0.005). Our data differs from those of other studies because they were collected from and analyzed by a single tertiary level referral center by a single examiner. This could have eliminated the variability found in different hands and different experiences. The high percentage of symptomatic patients with non-pathologic esophageal motility pattern suggests an unclear origin of the disease, with possible neuromuscular involvement. As a result, these patients may need more-detailed diagnostic studies.
The maximum resting pressure in the anal canal is greatly raised after hemorrhoidectomy. This inc... more The maximum resting pressure in the anal canal is greatly raised after hemorrhoidectomy. This increase is likely to be the cause of postoperative pain, which is still the most troublesome early problem after hemorrhoidectomy. This study was designed to compare, after hemorrhoidectomy, the effects of intrasphincter injection of botulinum toxin vs. application of glyceryl trinitrate ointment in improving wound healing and reducing postoperative pain at rest or during defecation. Thirty patients with hemorrhoids of third and fourth degree were included in the study and randomized in two groups. Anorectal manometry was performed preoperatively and 5 and 40 days after hemorrhoidectomy. One group received one injection containing 20 IU of botulinum toxin, whereas the other an application of 300 mg of 0.2 percent glyceryl trinitrate ointment three times daily for 30 days. Five days after hemorrhoidectomy, maximum resting pressure was significantly reduced compared with baseline values in both groups (85 +/- 15 vs. 68 +/- 11 mmHg for the group treated with botulinum toxin, 87 +/- 11 vs. 78 +/- 11 mmHg for the group treated with glyceryl trinitrate ointment). Overall analysis of postoperative pain at rest showed a significant reduction in the botulinum toxin group vs. glyceryl trinitrate group, whereas pain during defecation and time of healing were similar. Adverse effects, such as headaches, were observed only in the glyceryl trinitrate group. Forty days after hemorrhoidectomy in the glyceryl trinitrate group, maximum resting pressure values were similar to preoperative ones, whereas the values were still reduced in the botulinum toxin group. A single intrasphincter injection of botulinum toxin was more effective and safer than repeated applications of glyceryl trinitrate in reducing early postoperative pain at rest but not during defecation.
POSTERS was unreliable in 15 obese patients(8.9%). 54 patients (37.5%) had an histological and 90... more POSTERS was unreliable in 15 obese patients(8.9%). 54 patients (37.5%) had an histological and 90 (62.5%) a clinical diagnosis of cirrhosis. All patients underwent endoscopy. LS and SS were measured under US control. Results: In the subgroup with haemodinamic evaluation, we found a significant correlation between HVPG value and SSM(Linear regression analysis: r = 0.671; p = 0.009). 9 of them had the highest SS value(75 kPa). Mean HVPG was significant different between patients with SSM lower or equal 75 kPa(12.5 mmHg vs 19.1 mmHg, p = 0.013) without significant differences for bilirubin, albumin or INR values(p=ns). All 9 patients with SSM = 75 kPa had large esophageal varices(6 F2, 3 F3). In the whole cohort of patients, 80 (55.6%) had EV and 28 (19.4%) had large EV(F2 or F3). The AUROCs of LS and SS were almost the same(0.76 vs 0.73) for the prediction of EV but SSM was significantly better than LSM to predict large EV(AUROCs:0.84 vs 0.72). The best cut-offs of LS and SS for the diagnosis of cirrhosis with EV were 21 kPa(Sens. 71%, Spec. 72%) and 47 kPa(Sens. 79%, Spec. 70%) respectively. Twenty-four patients with a LSM <21 kPa had EV and 6 of them had large EV. Seventeen patients with SSM <47 had varices but none of them had a diagnosis of large varices(NPV = 100%). Conclusion: The stiffness of the spleen correlates with portal hypertension. Hence the measurement of SS in patients with cirrhosis adds to the accuracy of TE as a non-invasive tool to predict the presence of esophageal varices.
No significant correlation was found between folate and vitamin B 12 and bone mineral densities a... more No significant correlation was found between folate and vitamin B 12 and bone mineral densities at both neck of femur and lumbar spine. Conclusions: Results from this study suggest hyperhomocysteinemia is associated with low bone mineral density and may represent a risk factor for osteoporosis not only in general population but also in patients with primary biliary cirrhosis.
Background and aimsDrug-induced liver injury (DILI) is the most common cause of death from acute ... more Background and aimsDrug-induced liver injury (DILI) is the most common cause of death from acute liver failure, and accounts for approximately 13% of cases of acute liver failure in the United States. The clinical presentation of DILI covers a wide spectrum, from asymptomatic liver test abnormalities to symptomatic acute liver disease, prolonged jaundice and disability, or overt acute or subacute
Background/Aims: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertensio... more Background/Aims: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertension are poorly known. Methods: We performed a randomized controlled trial in 102 HCV patients with compensated cirrhosis and portal hypertension: 51 received 1 lg/ kg/week of Pegylated-interferon a-2b and 51 Pegylated-interferon plus 800 mg/day of ribavirin up to 52 weeks.
PurposeWe established the efficacy and safety of sublingual apomorphine compared with oral silden... more PurposeWe established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED).
To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short a... more To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short and longterm survival evaluating potential predictors of early mortality.
While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with bot... more While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated. To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy. PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologically proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis. Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0%vs 58.7%, P= 0.03), had lower transaminase levels (3.3 +/- 2.0 vs 3.8 +/- 2.5 u.l.n., P= 0.004), and had higher rate of alcohol intake (38.3%vs 22.5%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34-2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41-2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69-1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76-1.95). In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.
Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical pattern... more Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical patterns. It can occasionally be diagnosed in asymptomatic subjects. Our aim was to define the relationship among symptoms at diagnosis, serological markers [tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) anti-actin antibodies (AAA)] and degree of mucosal damage. A total of 68 consecutive adult patients with CD were enrolled. Intestinal biopsies were scored according to the Marsh classification modified by Oberhuber: I-II minimal lesions or absent villous atrophy; IIIA partial villous atrophy; IIIB-C total villous atrophy (TVA). HLA-typing was done for all patients. No association between clinical presentation and severity of mucosal damage was found. Presence of EMA or tTGA was significantly associated with more severe mucosal damage (P \ 0.001). Of 12 patients, 11 with AAA were also positive for TVA. The severity of mucosal damage is the main factor governing the detectability of serological markers of CD. The sensitivity of serological testing is questionable in patients with minimal lesions.
European Journal of Gastroenterology & Hepatology, 1997
The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic h... more The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate. The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C. A retrospective cohort study was carried out on 329 consecutive Caucasian patients with cirrhosis followed for a mean period of 5 years at seven tertiary care university hospitals. Inclusion criteria were biopsy-proven cirrhosis, anti-HCV positivity, abnormal serum aminotransferase levels and absence of complications of cirrhosis. The yearly incidence of hepatocellular carcinoma was 2.3% for 136 untreated patients and 1.0% for 193 patients treated with interferon alfa. The yearly incidence of hepatic decompensation was 5.7 for untreated and 1.5 for the treated patients. Fourteen (7%) of 193 treated patients showed sustained aminotransferase normalization and none of them developed complications of cirrhosis. At enrollment, untreated patients were older and had more severe liver disease than patients treated with interferon. After adjustment for clinical and serologic differences at entry between treated and untreated patients, the 5-year estimated probability of the occurrence of hepatocellular carcinoma was 2.1% and 2.7% and of decompensation was 7% and 11% for treated and untreated cases, respectively. This analysis did not detect any significant benefit of interferon alfa on morbidity in patients with compensated cirrhosis type C, although it suggests a reduction in complications of cirrhosis for those with a sustained response to therapy, and it indicates the need for better therapies.
Background: Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and ... more Background: Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and clinical outcomes of patients suffering from drug-induced autoimmune hepatitis. Methods: All patients with drug-induced liver injury admitted between 2000 and 2011 were retrospectively studied. Diagnoses of drug-induced autoimmune hepatitis and idiopathic autoimmune hepatitis were made according to simplified criteria. After discharge, all patients had regular follow-up and were contacted to update outcomes. Results: Among 10,270 in-hospital patients, 136 (1.3%) were diagnosed with drug-induced liver injury. Among them, 12 (8.8%) were diagnosed as drug-induced autoimmune hepatitis (41.7% males, age range 17-73); 8 (66.7%) were with jaundice at admission. Liver biopsies showed a pattern compatible with drug-induced autoimmune hepatitis, featured by severe portal inflammation and lymphoplasmacytic infiltrate. Drug-induced autoimmune hepatitis group had a shorter duration of drug intake, and higher values of transaminases and gamma globulins. All patients received immunosuppressive therapy with subsequent clinical remission, and five achieved a steroid-free long-term remission. Conclusions: A diagnosis of drug-induced autoimmune hepatitis was quite rare in our cohort, and clinical pattern was similar to idiopathic autoimmune hepatitis. Severe portal inflammation, prominent portalplasma cells, rosette formation and severe focal necrosis were significantly more frequent in drug-induced autoimmune hepatitis as compared to drug-induced liver injury.
Coeliac disease (CD) is found in 5-10% of patients with chronically abnormal liver tests and no o... more Coeliac disease (CD) is found in 5-10% of patients with chronically abnormal liver tests and no obvious cause of liver disease. In this population the efficacy of screening for CD by anti-tissue transglutaminase (anti-tTG) may be impaired by the high rate of positive anti-tTG found in chronic liver disease. To evaluate the prevalence of coeliac disease and the role of anti-tTG in patients with non-viral, non-autoimmune chronic and no obvious cause of liver damage. Out of 2,512 consecutive patients with abnormal liver tests, 168 (118 men, 50 women; mean age 40.7 +/- 12.6 years) were defined, on the basis of clinical data and liver biopsy, as NAFLD or cryptogenic chronic hepatitis. All were tested by recombinant IgA and IgG anti-tissue transglutaminase. Patients with a positive serology underwent endoscopy with duodenal biopsies. NAFLD was diagnosed in 121 patients, in 6 associated with cirrhosis, while 47 patients were considered as cryptogenic hepatitis in the absence of steatosis. Anti-tTG were positive in 20/168 patients (3 IgA alone; 11 IgG alone; 6 both IgA and IgG). Coeliac disease was found at endoscopy and confirmed by histopathology only in the 6 patients (3.6%) with both IgA and IgG anti-tTG positivity. Four of the patients with CD had NAFLD (3.3%), in 2 of them associated with cirrhosis; while 2 of those with cryptogenic hepatitis (4.2%) had CD. The prevalence of CD in patients with chronically abnormal liver tests of unexplained etiology is 4%, with no relation with the degree of liver steatosis. Screening should be done by testing for IgA and IgG antibodies and then evaluating by endoscopy and biopsy only patients positive for both.
Clinical Medicine Insights: Gastroenterology, 2014
BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are frequently associated with altered liv... more BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. MATERIALS AND METHODS: A retrospective review was undertaken of all consecutive IBD in-and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gammaglutamyl transpeptidase (GGT), or total bilirubin. RESULTS: A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. CONCLUSIONS: The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD.
Background/Aims: To investigate host-and virusrelated factors predictive of early and sustained a... more Background/Aims: To investigate host-and virusrelated factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. Methods: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region. Results: Mean pre-treatment HCV-RNA level (~10~ genome equivalents/mlfSD) was lower in sustained responders (3854+_7142) than in relapsers (9587+_10163) or in non-responders (5709f6618). HCV subtype lb was highly prevalent (82%), while types la, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of lb was much lower A
Nutcracker esophagus and non-specific motility disorders are the main causes of non-cardiac chest... more Nutcracker esophagus and non-specific motility disorders are the main causes of non-cardiac chest pain (NCCP), with gastroesophageal reflux in 60% of cases. Achalasia and diffuse esophageal spasm are the most frequent anomalies described in patients with dysphagia. The goal of this study was to evaluate the occurrence of esophageal body and lower esophageal sphincter motor abnormalities in patients with dysphagia, NCCP, or both. This study is a retrospective analysis of 716 patients with NCCP and/or dysphagia tested between January 1994 and December 2010. 1023 functional studies were performed, 707 of which were esophageal manometries, 225 esophageal pH-meters, and 44 bilimetries. We divided the patients into three groups: group 1 was composed of patients affected with dysphagia, group 2 with NCCP and group 3 with NCCP and dysphagia. Manometric anomalies were detected in 84.4% of cases (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The most frequent esophageal motility alteration was achalasia (36%). The lower esophageal sphincter was normal in 45.9% of patients (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). In all 3 groups, 80.9%, 98.8%, and 93.8, respectively, of patients showed normal upper esophageal sphincter (p=0.005). Our data differs from those of other studies because they were collected from and analyzed by a single tertiary level referral center by a single examiner. This could have eliminated the variability found in different hands and different experiences. The high percentage of symptomatic patients with non-pathologic esophageal motility pattern suggests an unclear origin of the disease, with possible neuromuscular involvement. As a result, these patients may need more-detailed diagnostic studies.
The maximum resting pressure in the anal canal is greatly raised after hemorrhoidectomy. This inc... more The maximum resting pressure in the anal canal is greatly raised after hemorrhoidectomy. This increase is likely to be the cause of postoperative pain, which is still the most troublesome early problem after hemorrhoidectomy. This study was designed to compare, after hemorrhoidectomy, the effects of intrasphincter injection of botulinum toxin vs. application of glyceryl trinitrate ointment in improving wound healing and reducing postoperative pain at rest or during defecation. Thirty patients with hemorrhoids of third and fourth degree were included in the study and randomized in two groups. Anorectal manometry was performed preoperatively and 5 and 40 days after hemorrhoidectomy. One group received one injection containing 20 IU of botulinum toxin, whereas the other an application of 300 mg of 0.2 percent glyceryl trinitrate ointment three times daily for 30 days. Five days after hemorrhoidectomy, maximum resting pressure was significantly reduced compared with baseline values in both groups (85 +/- 15 vs. 68 +/- 11 mmHg for the group treated with botulinum toxin, 87 +/- 11 vs. 78 +/- 11 mmHg for the group treated with glyceryl trinitrate ointment). Overall analysis of postoperative pain at rest showed a significant reduction in the botulinum toxin group vs. glyceryl trinitrate group, whereas pain during defecation and time of healing were similar. Adverse effects, such as headaches, were observed only in the glyceryl trinitrate group. Forty days after hemorrhoidectomy in the glyceryl trinitrate group, maximum resting pressure values were similar to preoperative ones, whereas the values were still reduced in the botulinum toxin group. A single intrasphincter injection of botulinum toxin was more effective and safer than repeated applications of glyceryl trinitrate in reducing early postoperative pain at rest but not during defecation.
POSTERS was unreliable in 15 obese patients(8.9%). 54 patients (37.5%) had an histological and 90... more POSTERS was unreliable in 15 obese patients(8.9%). 54 patients (37.5%) had an histological and 90 (62.5%) a clinical diagnosis of cirrhosis. All patients underwent endoscopy. LS and SS were measured under US control. Results: In the subgroup with haemodinamic evaluation, we found a significant correlation between HVPG value and SSM(Linear regression analysis: r = 0.671; p = 0.009). 9 of them had the highest SS value(75 kPa). Mean HVPG was significant different between patients with SSM lower or equal 75 kPa(12.5 mmHg vs 19.1 mmHg, p = 0.013) without significant differences for bilirubin, albumin or INR values(p=ns). All 9 patients with SSM = 75 kPa had large esophageal varices(6 F2, 3 F3). In the whole cohort of patients, 80 (55.6%) had EV and 28 (19.4%) had large EV(F2 or F3). The AUROCs of LS and SS were almost the same(0.76 vs 0.73) for the prediction of EV but SSM was significantly better than LSM to predict large EV(AUROCs:0.84 vs 0.72). The best cut-offs of LS and SS for the diagnosis of cirrhosis with EV were 21 kPa(Sens. 71%, Spec. 72%) and 47 kPa(Sens. 79%, Spec. 70%) respectively. Twenty-four patients with a LSM <21 kPa had EV and 6 of them had large EV. Seventeen patients with SSM <47 had varices but none of them had a diagnosis of large varices(NPV = 100%). Conclusion: The stiffness of the spleen correlates with portal hypertension. Hence the measurement of SS in patients with cirrhosis adds to the accuracy of TE as a non-invasive tool to predict the presence of esophageal varices.
No significant correlation was found between folate and vitamin B 12 and bone mineral densities a... more No significant correlation was found between folate and vitamin B 12 and bone mineral densities at both neck of femur and lumbar spine. Conclusions: Results from this study suggest hyperhomocysteinemia is associated with low bone mineral density and may represent a risk factor for osteoporosis not only in general population but also in patients with primary biliary cirrhosis.
Background and aimsDrug-induced liver injury (DILI) is the most common cause of death from acute ... more Background and aimsDrug-induced liver injury (DILI) is the most common cause of death from acute liver failure, and accounts for approximately 13% of cases of acute liver failure in the United States. The clinical presentation of DILI covers a wide spectrum, from asymptomatic liver test abnormalities to symptomatic acute liver disease, prolonged jaundice and disability, or overt acute or subacute
Background/Aims: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertensio... more Background/Aims: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertension are poorly known. Methods: We performed a randomized controlled trial in 102 HCV patients with compensated cirrhosis and portal hypertension: 51 received 1 lg/ kg/week of Pegylated-interferon a-2b and 51 Pegylated-interferon plus 800 mg/day of ribavirin up to 52 weeks.
PurposeWe established the efficacy and safety of sublingual apomorphine compared with oral silden... more PurposeWe established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED).
To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short a... more To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short and longterm survival evaluating potential predictors of early mortality.
While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with bot... more While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated. To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy. PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologically proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis. Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0%vs 58.7%, P= 0.03), had lower transaminase levels (3.3 +/- 2.0 vs 3.8 +/- 2.5 u.l.n., P= 0.004), and had higher rate of alcohol intake (38.3%vs 22.5%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34-2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41-2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69-1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76-1.95). In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.
Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical pattern... more Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical patterns. It can occasionally be diagnosed in asymptomatic subjects. Our aim was to define the relationship among symptoms at diagnosis, serological markers [tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) anti-actin antibodies (AAA)] and degree of mucosal damage. A total of 68 consecutive adult patients with CD were enrolled. Intestinal biopsies were scored according to the Marsh classification modified by Oberhuber: I-II minimal lesions or absent villous atrophy; IIIA partial villous atrophy; IIIB-C total villous atrophy (TVA). HLA-typing was done for all patients. No association between clinical presentation and severity of mucosal damage was found. Presence of EMA or tTGA was significantly associated with more severe mucosal damage (P \ 0.001). Of 12 patients, 11 with AAA were also positive for TVA. The severity of mucosal damage is the main factor governing the detectability of serological markers of CD. The sensitivity of serological testing is questionable in patients with minimal lesions.
European Journal of Gastroenterology & Hepatology, 1997
The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic h... more The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate. The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C. A retrospective cohort study was carried out on 329 consecutive Caucasian patients with cirrhosis followed for a mean period of 5 years at seven tertiary care university hospitals. Inclusion criteria were biopsy-proven cirrhosis, anti-HCV positivity, abnormal serum aminotransferase levels and absence of complications of cirrhosis. The yearly incidence of hepatocellular carcinoma was 2.3% for 136 untreated patients and 1.0% for 193 patients treated with interferon alfa. The yearly incidence of hepatic decompensation was 5.7 for untreated and 1.5 for the treated patients. Fourteen (7%) of 193 treated patients showed sustained aminotransferase normalization and none of them developed complications of cirrhosis. At enrollment, untreated patients were older and had more severe liver disease than patients treated with interferon. After adjustment for clinical and serologic differences at entry between treated and untreated patients, the 5-year estimated probability of the occurrence of hepatocellular carcinoma was 2.1% and 2.7% and of decompensation was 7% and 11% for treated and untreated cases, respectively. This analysis did not detect any significant benefit of interferon alfa on morbidity in patients with compensated cirrhosis type C, although it suggests a reduction in complications of cirrhosis for those with a sustained response to therapy, and it indicates the need for better therapies.
Background: Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and ... more Background: Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and clinical outcomes of patients suffering from drug-induced autoimmune hepatitis. Methods: All patients with drug-induced liver injury admitted between 2000 and 2011 were retrospectively studied. Diagnoses of drug-induced autoimmune hepatitis and idiopathic autoimmune hepatitis were made according to simplified criteria. After discharge, all patients had regular follow-up and were contacted to update outcomes. Results: Among 10,270 in-hospital patients, 136 (1.3%) were diagnosed with drug-induced liver injury. Among them, 12 (8.8%) were diagnosed as drug-induced autoimmune hepatitis (41.7% males, age range 17-73); 8 (66.7%) were with jaundice at admission. Liver biopsies showed a pattern compatible with drug-induced autoimmune hepatitis, featured by severe portal inflammation and lymphoplasmacytic infiltrate. Drug-induced autoimmune hepatitis group had a shorter duration of drug intake, and higher values of transaminases and gamma globulins. All patients received immunosuppressive therapy with subsequent clinical remission, and five achieved a steroid-free long-term remission. Conclusions: A diagnosis of drug-induced autoimmune hepatitis was quite rare in our cohort, and clinical pattern was similar to idiopathic autoimmune hepatitis. Severe portal inflammation, prominent portalplasma cells, rosette formation and severe focal necrosis were significantly more frequent in drug-induced autoimmune hepatitis as compared to drug-induced liver injury.
Coeliac disease (CD) is found in 5-10% of patients with chronically abnormal liver tests and no o... more Coeliac disease (CD) is found in 5-10% of patients with chronically abnormal liver tests and no obvious cause of liver disease. In this population the efficacy of screening for CD by anti-tissue transglutaminase (anti-tTG) may be impaired by the high rate of positive anti-tTG found in chronic liver disease. To evaluate the prevalence of coeliac disease and the role of anti-tTG in patients with non-viral, non-autoimmune chronic and no obvious cause of liver damage. Out of 2,512 consecutive patients with abnormal liver tests, 168 (118 men, 50 women; mean age 40.7 +/- 12.6 years) were defined, on the basis of clinical data and liver biopsy, as NAFLD or cryptogenic chronic hepatitis. All were tested by recombinant IgA and IgG anti-tissue transglutaminase. Patients with a positive serology underwent endoscopy with duodenal biopsies. NAFLD was diagnosed in 121 patients, in 6 associated with cirrhosis, while 47 patients were considered as cryptogenic hepatitis in the absence of steatosis. Anti-tTG were positive in 20/168 patients (3 IgA alone; 11 IgG alone; 6 both IgA and IgG). Coeliac disease was found at endoscopy and confirmed by histopathology only in the 6 patients (3.6%) with both IgA and IgG anti-tTG positivity. Four of the patients with CD had NAFLD (3.3%), in 2 of them associated with cirrhosis; while 2 of those with cryptogenic hepatitis (4.2%) had CD. The prevalence of CD in patients with chronically abnormal liver tests of unexplained etiology is 4%, with no relation with the degree of liver steatosis. Screening should be done by testing for IgA and IgG antibodies and then evaluating by endoscopy and biopsy only patients positive for both.
Clinical Medicine Insights: Gastroenterology, 2014
BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are frequently associated with altered liv... more BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. MATERIALS AND METHODS: A retrospective review was undertaken of all consecutive IBD in-and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gammaglutamyl transpeptidase (GGT), or total bilirubin. RESULTS: A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. CONCLUSIONS: The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD.
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Papers by Piero Almasio