Elastography for hepatic fibrosis severity in chronic hepatitis B or C.

AIMS: To assess the value of transient elastography for predicting significant fibrosis or cirrhosis in chronic hepatitis B or C (CHB or CHC) patients. METHODS: 75 patients (CHB: 45, CHC: 32) were included. All underwent elastography and liver biopsy concurrently. Biopsies were evaluated using Ishak's classification. Fibrosis was mild, moderate or severe/cirrhosis when scores were 0-1 (n = 30), 2-3 (n = 20), 4-6 (n = 25), respectively. RESULTS: Median liver stiffness values were higher in patients with severe fibrosis or cirrhosis than in those with moderate or mild fibrosis (14.8 vs. 6.4 vs. 5.3 kPa, p < 0.001). The diagnostic accuracy of elastography for severe fibrosis and cirrhosis was excellent [area under the receiver operating characteristic (AUROC) curve 0.938 vs. 0.948], but it was not optimal for mild fibrosis (AUROC 0.78). Values of 7.5, 9.0 and 12 kPa had a sensitivity and specificity for severe fibrosis/cirrhosis of 96, 84 and 60%, and 76, 90 and 94%, respectively. The median stiffness value in cirrhotic patients (score 5-6) was 16.6 kPa (7.7-48). No differences in accuracy of elastography between CHB or CHC patients were found. Cutoff was 12.5 kPa for cirrhosis; 10/75 patients (13%) were misclassified. CONCLUSION: Transient elastography has an excellent diagnostic accuracy for severe fibrosis and cirrhosis in CHB and CHC, but the cutoffs need further evaluation.

Endoscopic treatment for high-risk bleeding peptic ulcers: a comparison of epinephrine alone with epinephrine plus ethanolamine.

BACKGROUND: Among the various methods of combined endoscopic therapy for high-risk bleeding peptic ulcers the use of adrenaline followed by injection of ethanolamine is minimally demanding in terms of the endoscopic skills and instrumentation but has not been adequately studied. The aim of the present study is to determine whether the injection of ethanolamine in combination with epinephrine compared to injection of epinephrine alone reduces rebleeding rates, need for surgery and overall mortality of patients with bleeding ulcers. METHODS: Patients with ulcers and endoscopic features indicative of a high risk for spontaneous recurrent bleeding were included. High risk was defined by the Forrest classification. Patients were assigned to injection of epinephrine alone (n = 284) or epinephrine plus ethanolamine (n = 131). RESULTS: Initial hemostasis was achieved in 96% of patients in both groups. We detected significant difference in rates of recurrent bleeding, 16.4% vs. 8.7%, for epinephrine and epinephrine plus ethanolamine respectively (P<0.05). When patients were stratified according to Forrest criteria, no significant difference could be found, although there was a trend towards less recurrent bleeding in the case of dual injection therapy in all patient subgroups. There was no significant difference in the proportions of patients who required surgery, 7.7% vs. 7.6% respectively. Mortality was equal (3.2 vs. 3.1%) in the two groups. No major complications from endoscopic treatment were observed in either group. CONCLUSION: Adding ethanolamine to epinephrine for injection treatment of bleeding peptic ulcers decreases bleeding recurrence rates and represents a safe endoscopic treatment for high-risk bleeding ulcers.

Substitution treatment or active intravenous drug use should not be contraindications for antiviral treatment in drug users with chronic hepatitis C.

INTRODUCTION AND AIMS: International guidelines and routine clinical practice express concerns about antiviral treatment in intravenous drug users (IDUs). We analysed the effect of IDU and/or substitution therapy on chronic hepatitis C (CHC) treatment adherence and response. PATIENTS AND METHODS: Intravenous drug users with CHC were divided into three groups: (A) patients on a substitution programme; (B) active users; and (C) past IDUs. Patients were treated according to the standard of care and followed by a specialist team. RESULTS: A total of 175 patients (mean age 39.4±8.8) were included. One hundred and forty-four (65%) were adherent to therapy (completing treatment and 6 months of follow-up). Twenty-two patients (36%) discontinued because of side effects, 28 (46%) discontinued on their own and 11 (18%) completed treatment but did not present at follow-up. Of 142 patients with available treatment outcome, 99 (69.7%) achieved a sustained virological response (SVR), with no differences among the study groups. Patients with genotypes 2-3 and those who completed the treatment schedule had 2.78-fold (95% CI: 1.3-5.8) and 6.4-fold (95% CI: 2.6-15.6) higher probability of achieving SVR. CONCLUSION: Active use of illicit drugs and/or drug substitution do not affect the treatment outcome in patients with CHC as long as they are closely followed and remain adherent to the treatment.

Pylephlebitis: an overview of non-cirrhotic cases and factors related to outcome.

Pylephlebitis is a condition with significant morbidity and mortality. We review herein 100 relevant case reports published since 1971. Eighty-one patients were reported with acute pylephlebitis, while the remaining patients had chronic pylephlebitis. The most common predisposing infections leading to pylephlebitis were diverticulitis and appendicitis. Cultures from blood or other tissues were positive in 77%. The infection was polymicrobial in half of the patients and the most common isolates were Bacteroides spp, Escherichia coli and Streptococcus spp. Thrombosis was extended to the superior mesenteric vein (SMV), splenic vein, and intrahepatic branches of the portal vein (PV) in 42%, 12%, and 39%, respectively. Antibiotics were administered in all and anticoagulation in 35 cases. Patients who received anticoagulation had a favourable outcome compared to those who received antibiotics alone (complete recanalization 25.7% vs 14.8% (p > 0.05), no recanalization 5.7% vs 22.2% (p < 0.05), and death 5.7% vs 22.2% (p < 0.01)). Cases with complete recanalization had prompt diagnosis and management and two-thirds were recently published. Nineteen patients died; the majority of these (73.7%) died over the period 1971-1990. In conclusion, pylephlebitis remains an entity with high morbidity and mortality, but modern imaging modalities have facilitated an earlier diagnosis and have improved the prognosis. Anticoagulation has a rather beneficial effect on patients with pylephlebitis.

Interferon alpha-induced hashimoto thyroiditis followed by transient graves disease in a patient with chronic HCV infection.

The case of a 37-year-old man with chronic hepatitis C virus (HCV) infection is presented. The patient had received a 6-month course of antiviral therapy with peg interferon alpha-2a and ribavirin, with concomitant clearance of hepatitis C virus ribonucleic acid (HCV-RNA) from serum at the end of treatment. Three months after the treatment course he developed clinical and laboratory features of hypothyroidism along with high titers of thyroid peroxidase antibodies. Later on, while on treatment with levothyroxine, he developed all the clinical features of Graves disease along with increased levels of thyroid stimulating hormone (TSH)-receptor antibodies.This patient exhibited a rare sequence of immune-mediated thyroid disorders as a result of interferon alpha treatment. At the end of treatment, the patient developed Hashimoto thyroiditis, a typically Th1-response-mediated disease, followed sequentially after 6 months by Graves disease, a typically Th2-response-mediated disorder. Although both clinical entities have been described in patients receiving interferon-based regimens, to our knowledge, the changing pattern of immune-mediated thyroid disease in the same individual has not been reported in the literature.

Increased arterial stiffness and impaired endothelial function in nonalcoholic Fatty liver disease: a pilot study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease both in the general and pediatric population and has been associated with increased cardiovascular risk. Arterial function and early atherosclerotic changes are markers of cardiovascular disease and independent predictors of the corresponding risk. Through a global approach, we investigated the relationships between NAFLD and functional arterial changes and early atherosclerosis. METHODS: A total of 23 consecutive patients (mean age 55 ± 14 years, 11 males) with biopsy evidence of NAFLD and 28 control subjects matched for age, gender, body mass index, and other cardiovascular risk factors participated in the study. RESULTS: Compared to controls, NAFLD subjects had significantly higher carotid-femoral pulse wave velocity (PWV; 8.2 ± 1.3 m/s vs. 6.9 ± 1.3 m/s, P = 0.001), higher carotid intima-media thickness (IMT; 0.79 ± 0.18 mm vs. 0.67 ± 0.13 mm, P = 0.01), and reduced flow-mediated dilatation (FMD; 1.92 ± 2.11% vs. 4.8 ± 2.43%, P < 0.001). In multivariable analysis, presence of NAFLD was an independent determinant of both PWV and FMD, whereas leptin was an independent determinant of PWV (B = 0.036, P < 0.05), and adiponectin was independently associated with FMD (B = 0.104, P < 0.05). In addition, histological activity of liver disease expressed by the global Brunt Grade was associated independently with FMD (B = -1.054, P < 0.05). CONCLUSIONS: NAFLD is associated with arterial stiffness and endothelial dysfunction. Given the important independent prognostic role of these arterial indexes, these findings have important implications for increased cardiovascular risk in patients with NAFLD.

CagA and VacA polymorphisms are associated with distinct pathological features in Helicobacter pylori-infected adults with peptic ulcer and non-peptic ulcer disease.

Polymorphic variability in Helicobacter pylori factors CagA and VacA contributes to bacterial virulence. The presence of one CagA EPIYA-C site is an independent risk factor for gastroduodenal ulceration (odds ratio [OR], 4.647; 95% confidence interval [CI], 2.037 to 10.602), while the presence of the vacA i1 allele is a risk factor for increased activity (OR, 5.310; 95% CI, 2.295 to 12.287) and severity of gastritis (OR, 3.862; 95% CI, 1.728 to 8.632).

The burden of incidental findings in clinical practice in a tertiary care center.

BACKGROUND: To evaluate the prevalence and clinical burden of serendipitously discovered abnormalities in hospitalized patients, unrelated to their presenting symptoms and physical signs. METHODS: A total of 478 patients consecutively admitted in the Department of Medicine were enrolled in the study. In the end of first diagnostic work-up, the previously undetected imaging or endoscopic asymptomatic abnormalities termed as incidental findings (IFs) were recorded and some of them were further investigated. RESULTS: One hundred thirty eight (28.8%) patients had IFs. The most common IFs were located in the kidney and genitourinary system followed by liver and gallbladder. The most common method of detection of IFs was ultrasonography (US) of the abdomen. The patients with IFs compared with those without, were older (P=0.007), had no previous hospitalizations (P<0.001) and stayed longer in the hospital (P<0.001). The 25 (18.1%) patients with IFs were not evaluated further. One hundred seventy seven IFs discovered in 113 patients were further evaluated by medical specialists and additional tests were performed if warranted. In the end of the diagnostic work-up, in a total of 113 patients with IFs, 78.7% had insignificant and 21.2% potentially significant IFs. The latter group had higher rate of IFs compared with the former group, usually more than 3 (P=0.017). CONCLUSIONS: IFs were prevalent in a hospital population. Hospitalized patients with IFs were more than 60 years old and had no previous hospitalization. A large number of IFs were potentially significant deserving further clinical management.

Primary hepatic actinomycosis.

The clinical and imaging findings of primary hepatic actinomycosis are nonspecific and can mimic other diseases. This condition usually needs to be distinguished from other liver-occupying lesions, including malignancy. Review of the English language literature showed 67 cases of hepatic actinomycosis in immunocompetent, predominantly male patients. Infection was usually (75%) cryptogenic. The results of radiologic imaging showed that the lesion involved the right lobe in half of the cases, mimicked a liver tumor in 45%, and was single in two thirds of the cases. Hepatic actinomycosis coexisted with infections by common bacteria in 32% of cases reported. Diagnosis was usually achieved by microscopic examination of surgical or percutaneous specimens in 84.2% and 78.6%, respectively. Antibiotic therapy alone was used for treatment in approximately one half of cases and combined antibiotic treatment with surgical or percutaneous drainage procedure in the other half. The overall mortality rate was 7.6%. In conclusion, primary hepatic actinomycosis is a rare and usually cryptogenic infection. It is more common in men and immunocompetent subjects. It is well responsive to medical or combined medical and interventional treatment.

Serum apoptotic caspase activity in chronic hepatitis C and nonalcoholic Fatty liver disease.

BACKGROUND: Apoptotic caspases are substantially activated in liver and serum caspase activity has been suggested as a marker of early liver injury. AIM: To investigate whether serum levels of caspase-generated fragments of cytokeratin-18 are associated with the severity of histologic lesions in chronic hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease (NAFLD). METHODS: We included 134 patients with chronic HCV infection and 58 patients with NAFLD, who consecutively underwent liver biopsy, and 40 healthy controls. Caspase-generated cytokeratin-18 fragment levels were blindly measured in stored serum samples. RESULTS: Median cytokeratin-18 fragment levels were lower in HCV-positive patients with minimal/mild than patients with moderate/severe histologic lesions (174 U/L vs. 223 U/L, P<0.001) offering moderate accuracy for differentiation between the 2 groups (c-statistic: 0.74). Cytokeratin-18 fragments levels were lower in healthy subjects (148 U/L) than patients with simple fatty liver (174 U/L, P=0.013) than patients with nonalcoholic steatohepatitis (355 U/L, P<0.001) offering excellent diagnostic accuracy for differentiation between the 2 latter groups (c-statistic: 0.87). CONCLUSIONS: Serum apoptotic caspase activity is associated with the severity of liver histologic lesions in both chronic HCV infection and NAFLD, but it has excellent diagnostic accuracy in NAFLD and moderate accuracy in chronic HCV patients.

The burden and recent epidemiological changes of the main chronic liver diseases in a Greek referral tertiary centre.

OBJECTIVE: To investigate the burden and recent epidemiological changes of the main chronic liver diseases in a Greek referral tertiary centre. METHODS: We evaluated the main epidemiological characteristics of 1080 consecutive adult patients, seen at our outpatient liver clinic between 2002 and 2007, with chronic hepatitis B (HBV) and/or C (HCV) virus infection, alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD). Our patient population was divided into two groups in relation to the time of the first visit (period A: 2002-2004, period B: 2005-2007). RESULTS: Among our patient population, 86.1% had chronic HBV and/or HCV infection (chronic HCV alone: 44.9%), 9.2% NAFLD and 4.8% ALD. From period A to B, there was a decrease in chronic HBV cases (44.0 vs. 37.8%, P = 0.045) with immigrants being responsible for 35.5% of them and being more frequent in period B than A (39.7 vs. 30.5%, P = 0.046). In chronic hepatitis B, hepatitis B e antigen-positive patients, who were more frequent immigrants compared with hepatitis B e antigen-negative patients (65.5 vs. 29.5%, P = 0.001), increased from period A to B (8.0 vs. 17.6%, P = 0.045). Intravenous drug use was reported by 41.2% of HCV patients with its proportion increasing from period A to B (32.5 vs. 47.4%, P = 0.002). Decompensated cirrhosis was present in 67, 10, 11 and 3% of patients with ALD, HBV, HCV and NAFLD, respectively. CONCLUSION: At Greek tertiary centres, chronic viral hepatitis remains responsible for most chronic liver disease cases, but its epidemiology is changing owing to immigrants and intravenous drug users.

Efficacy of three different dosages of esomeprazole in the long-term management of reflux disease: a prospective, randomized study, using the wireless Bravo pH system.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is a chronic condition that usually requires long-term maintenance therapy with proton-pump inhibitors (PPIs). In clinical practice, patients receive PPIs at the lowest dose to control symptoms. However, it is not known whether this approach adequately controls acidic esophageal reflux. We sought to investigate the efficacy of three different dosages of esomeprazole in patients receiving maintenance therapy for GERD, using the Bravo pH system. METHODS: Patients with a previous history of erosive esophagitis A or B (LA classification) that was healed at the time of enrollment or endoscopy-negative reflux disease (ENRD), documented with an abnormal pH study, were randomized to receive maintenance therapy with esomeprazole 40 mg twice daily (group A), once daily (group B), or every other day (group C). Intraesophageal pH was monitored for two consecutive days using the Bravo wireless system, 30 days after randomization. The parameters subjected to analysis were percent of total time pH<4 and the De Meester score. RESULTS: The pH results from 73 patients (group A=24, group B=24, group C=25 patients) were subjected to final analysis. On the first day of the study, the mean (+/-s.d.) percent of total time pH <4 and the De Meester score were group A: 0.9(1.2) and 4.1(4.0); group B: 1.5(1.6) and 7.0(6.9); group C: 1.3(1.0) and 6.0(3.3), respectively (P=0.262 and 0.134, respectively). On the second day of the study, the corresponding values were group A: 0.7(1.0) and 3.9(5.9); group B: 1.5(1.8) and 6.4(6.6); group C: 7.0(4.4) and 29.4(19.4), respectively. The difference was statistically significant (P<0.0001 and <0.0001, respectively). Further analysis showed that patients not receiving PPI had a significantly higher mean percent of total time pH<4 and De Meester score as compared with patients on PPI once or twice daily (P<0.001 and <0.001 respectively). CONCLUSIONS: The administration of esomeprazole 40 mg every other day does not control acidic esophageal reflux on the day off PPI. Esomeprazole 40 mg once daily effectively controls reflux of acid in patients with history of mild esophagitis or ENRD, whereas doubling the dose does not seem to confer any further advantage.

Thrombotic risk factors and liver histologic lesions in non-alcoholic fatty liver disease.

BACKGROUND/AIMS: The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH. METHODS: We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n=39) or C (n=51). Thrombophilic factors were evaluated on the day of the liver biopsy. RESULTS: One or more thrombotic RFs were detected in 37% of NAFLD patients, and >or= 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; P

Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from benign steatosis to end-stage liver disease. The pathogenesis of non-alcoholic steatohepatitis (NASH) is currently thought to involve a multiple-hit process with the first hit being the accumulation of liver fat which is followed by the development of necroinflammation and fibrosis. There is mounting evidence that cytokines secreted from adipose tissue, namely, adipokines, are implicated in the pathogenesis and progression of NAFLD. In the current review, we explore the role of these adipokines, particularly leptin, adiponectin, resistin, tumor necrosis factor-a, and interleukin-6 in NASH, as elucidated in experimental models and clinical practice. We also comment on their potential use as noninvasive markers for differentiating simple fatty liver from NASH as well as on their potential future therapeutic role in patients with NASH.

Acute bilateral phrenic neuropathy following treatment with adalimumab.

The recombinant human IgG1 monoclonal antibody specific for human TNF-a adalimumab (Humira) has been recently introduced for the treatment of moderate/severe psoriasis. Neurological diseases have been rarely described as adverse events of anti-TNF agents. A case of acute respiratory failure due to diaphragmatic weakness following adalimumab therapy for psoriasis is described. A 65-year-old female patient presented with jaundice followed 2 days later by severe dyspnea and tachypnea which worsened when patient was lying flat, 1 week after the fourth dose of adalimumab. Isoniazid and vitamin B6 were co-administered with adalimumab. A symmetric elevation of diaphragms was shown on radiography and fluoroscopy. A pulmonary restrictive defect with a prominent decline of forced vital capacity (FVC) when the patient was on supine position was recorded. In the absence of specific limb electrophysiological abnormalities, acute bilateral symmetric phrenic neuropathy was diagnosed. The patient was a borderline candidate for mechanical ventilation for 3 weeks. Conservative treatment with oxygen was administered and both respiratory and liver disorder resolved 4 weeks following admission. A causal relationship of phrenal neuropathy with adalimumab is herein discussed.

Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease.

AIM: Retinol-binding protein-4 (RBP4) has been proposed as a new adipokine that regulates insulin action in muscles and the liver, and contributes to the pathogenesis of insulin resistance. As non-alcoholic fatty liver disease (NAFLD) is related to insulin resistance, we aimed to evaluate RBP4 levels in the serum and liver of patients with NAFLD. METHODS: Serum RBP4 was measured in 30 NAFLD patients and 30 matched healthy controls. RBP4 expression in the liver of NAFLD patients was shown by immunohistochemistry. RESULTS: Serum RPB4 was significantly lower in NAFLD patients compared with controls (25.15 vs 34.66 microg/mL, P < 0.001) and there was no correlation with metabolic parameters or insulin resistance. RBP4 liver tissue immunostaining was more extensive and intense in NAFLD liver compared with normal liver and the RBP4 immunohistochemical score was positively correlated with the grade of steatosis, grade of non-alcoholic steatohepatitis activity and stage of fibrosis. CONCLUSIONS: In NAFLD patients, serum RBP4 was significantly lower as compared with controls and did not correlate with insulin resistance. In contrast, RBP4 liver tissue expression was enhanced and correlated with NAFLD histology.