Vol. 11 Issue 3
On the cover: 1. T-Scan showing a cardiac mass (arrow). 2. Liver needle biopsy (A) and left ventricle biopsy (B-C).
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer deaths in men. Due to differences in the prevalence of viral hepatitis, the incidence of HCC in low and middle income countries is much higher than that of high income countries. Strategies to limit the impact of HCC include primary prevention against new cases of viral hepatitis, secondary prevention of HCC in susceptible individuals, and early HCC detection. Universal hepatitis B vaccination has resulted in dramatic reduction in incident cases of chronic hepatitis B and HCC in children and adolescents, and the full effect is expected in the next 20 years. The key hurdle for universal vaccination is the cost and the accessibility in low and middle income countries. Randomized controlled trials and meta-analyses showed that successful treatment of chronic hepatitis B and C can reduce the risk of HCC and cirrhotic complications. HCC surveillance by regular ultrasound examination and alpha fetoprotein testing leads to early cancer detection and offers the opportunity for curative treatment. Since all these measures are costly and require manpower and infrastructure support, the implementation should rely on the liaison among healthcare providers and policymakers. The cost-effectiveness of various strategies should also be studied based on local situations.
Elevated serum ferritin, or hyperferritinemia, is a common finding on routine bloodwork and often prompts referral for further evaluation. In the following review, we outline the various causes of hyperferritinemia and point out that, in the majority of cases, this does not represent true iron overload. Despite much research interest in this area, the precise mechanism of hyperferritinemia and its impact on disease severity in various clinical conditions continues to be debated. While some research suggests that iron reduction in cases of hyperferritinemia is of benefit, the decision to treat such patients should be individualized, and may be influenced by the presence of other features of iron overload.
Acute kidney injury (AKI) is an important marker of morbidity and mortality in critically ill cirrhotic patients. The most common causes of AKI in cirrhotic patients include prerenal or hepatorenal syndrome (HRS). Diagnosis of AKI may be delayed by the lack of clinical, biochemical, and radiological markers with proven sensitivity and specificity in cirrhotic patients. In this review, we discuss the epidemiology, pathophysiology, diagnosis, and therapies for AKI in cirrhotic patients admitted to an intensive care unit (ICU).
Background and aims. Effective assessing the prognosis of patients with end-stage liver disease is always challenging. This study aimed to investigate the accuracy of different models in predicting short-term prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). Material and methods. We retrospectively evaluated survival of a cohort of patients with at least 3-month follow up. The receiver-operating-characteristic curves (ROC) were drawn for Child-Turcotte-Pugh (CTP) classification, King's College Hospital (KCH) criteria, model for end-stage liver disease (MELD), MELD combined with serum sodium (Na) concentration (MELDNa), integrated MELD (iMELD) and logistic regression model (LRM). Results. Of the 273 eligible patients, 152 patients (55.7%) died within 3-month follow up. In cirrhotic patients (n = 101), the AUCs of LRM (0.851), MELDNa (0.849), iMELD (0.845) and MELD (0.840) were all significantly higher than those of KCH criteria (0.642) and CTP (0.625) (all p < 0.05), while the differences among LRM, MELD, MELDNa and iMELD were not significant, and the most predictive cutoff value was 0.5176 for LRM, 30 for MELDNa, 47.87 for iMELD and 29 for MELD, respectively. In non-cirrhotic patients (n = 172), the AUC of LRM (0.897) was significantly higher than that of MELDNa (0.776), iMELD (0.768), MELD (0.758), KCH criteria (0.647) and CTP (0.629), respectively (all p < 0.05), and the most predictive cutoff value for LRM was -0.3264. Conclusions. LRM, MELD, MELDNa and iMELD are with similar accuracy in predicting the shortterm prognosis of HBV-ACLF patients with liver cirrhosis, while LRM is superior to MELD, MELDNa and iMELD in predicting the short-term prognosis of HBV-ACLF patients without liver cirrhosis.
Background. In the follow up of chronic hepatitis B infection (HBV), a significant correlation between quantitative HBsAg titer measurement and HBV DNA level, and moreover with intrahepatic covalently closed circular DNA was already shown. However, besides their impact on long-term follow up, they are really expensive methods, and not available widespread. We aimed to investigate the utility of qualitative measurement of HBsAg titer in prediction of virologic response at the end of the first year of anti-viral treatment in chronic HBV infection. Material and methods. A total of 70 patients receiving anti-viral therapies for chronic HBV infection were included into the study. The patients were evaluated according to Hbe Ag status and response to treatment. The determinations used in the study (biochemical, virologic responses, primary non-response) were accepted as it was described in AASLD. Results. Qualitative HBsAg titer increased significantly in both HBeAg positive and negative patients (p values 0.002 and < 0.000). Increasing of HBsAg titer in first three months is more dramatic in responder group, however the difference was disappeared at the sixth and twelve moths on follow up. Similarly, a fast increasing in anti-HBe titer in HBeAg negative chronic HBV patients was related with higher response at the end of first year therapy. However, the changings at the 12th month of anti-viral treatment were similar in both responder and non-responder groups. Conclusion. In conclusion, the fast increase in qualitative measurement of HBsAg titer seemed to be a predictor of higher anti-viral medication success in chronic HBV patients. However, this meaningful increasing was disappeared on the follow up, particularly after the six months examination.
Background and aims. Despite effective vaccine available, hepatitis A remains a significant cause of morbidity and mortality worldwide including acute liver failure, transplantation and death. Vaccination rates for hepatitis A in the general population are low. Rates of hepatitis A vaccination in healthcare personnel (HCP) are unknown. We studied vaccination rate to hepatitis A in a cohort of HCP at a large US academic center. Material and methods. An anonymous survey was circulated between 499 HCP at-risk of hepatitis A exposure at our Institution. Results were corrected for non-response rate and compared with the general US population using the 2007 CDC-National Immunization Survey. Rate of hepatitis A vaccination was compared with Institutional rate of vaccination for the Influenza 2009-2010 season. Results. Rate of vaccination for hepatitis A in HCP was 28.8% (response rate 41.4%; 207/499), with 58.9% having completed the full series and 24.7% being tested for post-vaccination immunity. Acceptance rate among non-vaccinated subjects was 70.7%. HCP hepatitis A vaccination rate was statistically greater than the national general population (28.8 vs. 12.1%, p ≤ 0.031). A statistically significant greater vaccination rate was found among USborn responders vs. foreign-born HCP (34.3 vs. 19.3%, p = 0.0324). Vaccination for hepatitis A was statistically inferior to that of Influenza (28.8 vs. 90%; P = 0.01). Conclusions. HCP have statistically higher vaccination rate for hepatitis A than the general population, but overall protection remains suboptimal with vaccination rate below those for mandatory vaccines. Further studies to determine whether hepatitis A vaccine is cost-effective in HCP are recommended.
Background and rationale for the study. Hepatitis B (HB) is one of the most prevalent occupational infections in health attendance environments. According to the Brazil Ministry of Health, health professionals must be vaccinated against the hepatitis B virus (HBV) and provide laboratory proof of immunization. Aims. To evaluate the seroprevalence of HBV infection and to analyze the response to vaccine by measuring serum antibodies against HBV surface antigen (anti-HBs) levels in a sample of students and health professionals at the Federal University of Bahia. Results. As part of this cross-sectional study, a campaign against occupational HB was launched in 2007 and vaccination and blood samples were collected for analysis of the following serological markers: HBV surface antigen (HBsAg) and anti-HBs (measured by enzyme-linked immunoassay) and total antibodies against HBV core antigen (anti-HBc). The study sample comprised 766 people. Global seropositivity for HBV was 1.7%: 0.5% in the students and 8.8% in the professionals. In a group of volunteers, a serological profile compatible with postvaccine immunity was shown by 95% of volunteers with proof of vaccination and by 81.8% of volunteers without proof of vaccination. Conclusions. In conclusion, this study shows that it is important to promote vaccination campaigns and improve knowledge and awareness about HB among health care workers and higher education students.
Introduction. Hepatitis C virus genotype 4 is predominant in the Middle East and Northern Africa, even if it has recently spread to Southern Europe. Data about the treatment of post-liver transplantation (LT) genotype 4 hepatitis C recurrence are scarce. We report a retrospective analysis of post-LT genotype 4 hepatitis C treatment in 9 Italian transplant centres, focusing on the overall survival rates and treatment outcome. Results. Among 452 recipients, we identified 17 HCV genotype 4 patients (16 males, 1 female) transplanted between 1998 and 2007. All patients received combined antiviral treatment with conventional doses of interferon (recombinant or pegylated) and ribavirin after histological diagnosis of hepatitis C recurrence. The observed overall survival after LT was 100% at 1 year and 83.3% at 5 years. More than 1/3 (35.3%) of patients achieved a sustained virological response (SVR) and 40% (data available in 15 subjects) an early virological response (EVR), which was significantly associated with the achievement of SVR (overall accuracy: 85.7%; predictive values of EVR absence/presence 80/88.8%; chi-square p < 0.05). Conclusion. In conclusion, in post-LT genotype 4 hepatitis C treatment, SVR rates are similar to genotype 1. Patients who don't show an EVR are not likely to achieve a SVR.
Background. Liver transplantation is often associated with metabolic derangements. Adipocyte fatty-acidbinding protein 4 (AFABP4) integrates inflammatory and metabolic responses. It has also been associated with metabolic syndrome in animal models and clinical studies in the general population. Aim. To determine the role of AFABP4 in post-transplant metabolic syndrome. Material and methods. Consecutive patients followed for at least 6 months after liver transplantation were tested for insulin resistance by homeostasis model assessment (HOMA). Serum levels of AFABP4 were tested by an enzyme-linked immunosorbent assay. Results. The study group included 76 patients (64.5% male, mean age 56.3 ± 12.4 years). Hypertension was present in 56.5%, hyperlipidemia in 69.7%, diabetes mellitus in 23.6%. Half of the patients met at least 3 criteria for metabolic syndrome. Serum AFABP4 levels (p < 0.0001), HOMA index ≥ 2.5 vs. < 2.5 (p < 0.0002) and BMI ≥ 30 vs. < 30 (p < 0.0006) were significantly higher in patients with metabolic syndrome. Within the metabolic syndrome subgroup, AFABP4 levels significantly correlated with age, aspartate aminotransaminase level, waist circumference, and HOMA index. High AFABP4 significantly increased the odds of acquiring metabolic syndrome (OR 1.04, 95% CI 1.007-1.074, p = 0.017). On multiple logistic regression analysis, independent predictors of high AFABP4 were cryptogenic liver disease, steroid administration, high HOMA index, and a high degree of fatty infiltration. Conclusion. Prevalence of metabolic syndrome is significantly higher in liver transplant recipients than in the general population. AFABP4 may serve as a circulating biomarker in the clinical prediction/diagnosis of metabolic syndrome in patients post-liver transplantation.
Background & aims. Some phytochemicals present in coffee have a potential antioxidant role which seems to protect the human body against cardiovascular diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a common disease with limited therapeutic options. This study investigated the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with nonalcoholic fatty liver disease. Material and methods. We performed a case-control study at the University Hospital, Mexico City. Anthropometric, metabolic, dietary and biochemical variables of all patients were determined and compared. The presence of nonalcoholic fatty liver disease was established by ultrasonography. All patients completed a dietary questionnaire in order to determine their of coffee consumption. Catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured in all of the patients. Results. Seventy-three subjects with and 57 without nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty liver disease had significantly higher body mass index, blood glucose, homeostasis model of assessment–insulin resistance and insulin values in comparison to patients without nonalcoholic fatty liver disease. On the one hand, there was a significant difference in coffee intake between the groups (p < 0.05, for all comparisons). There was no significant difference between groups in catalase (0.39 ± 0.74 vs. 0.28 ± 0.69 nM/min/mL), superoxide dismutase (5.4 ± 3.45 vs. 4.7 ± 2.1 U/mL) or thiobarbituric acid-reactive substances (4.05 ± 1.87 vs. 3.94 ± 1.59 μM/mL). Conclusions. A high intake of coffee has a protective effect against nonalcoholic fatty liver disease however there was no significant difference in the antioxidant variables analyzed.
Background. Pro-inflammatory cytokine production is directly inhibited by acetylcholine (ACh), and a relationship between total circulating ACh hydrolytic capacity and inflammatory reactions has been previously reported. Butyrylcholinesterase (BChE) is the major ACh hydrolyzing enzyme in plasma, and the aim of our study was to evaluate its association with low-grade systemic inflammation. Material and methods. A total of 4,077 patients clinically managed in the Cardiology, Hypertension, and Digestive Medicine Units were included in our study. Three subclinical chronic inflammatory degrees were established in accordance with the high-sensitivity C-reactive protein (hsCRP) concentrations proposed, for low (< 1 mg/L), average (1-3 mg/L), and high (> 3-10 mg/L) cardiovascular disease risk estimation. Results. In male patients with subclinical chronic inflammation and hsCRP concentrations < 1 mg/L, a significant positive correlation was observed between BChE and hsCRP (p < 0.02); however, for hsCRP concentrations > 3 mg/L, the correlation between these variables in both sexes becomes significantly negative (p < 0.001), as in patients with acute inflammation (hsCRP > 10 mg/L). In all cases significant positive correlations were obtained between the BChE activities and albumin concentrations (p < 0.001). Conclusions. The liver production of BChE and albumin occurs in a coupled fashion, and these biochemical variables may be considered as negative inflammatory reactants, whose serum levels are inversely associated with the increasing degree of subclinical inflammation.
Introduction. Identifying liver fibrosis is important to evaluate the severity of liver damage and to establish a prognosis. Utility of non-invasive markers of liver fibrosis has been proved in adults but there are few reports in children. The aim of this study was to evaluate Fibrotest® score and APRI suitability to identify children with liver fibrosis. Material and methods. 68 children with chronic liver disease requiring liver biopsy were prospectively included from three 3rd-level pediatric hospitals. The same pathologist evaluated all liver biopsies; fibrosis degree was determined by METAVIR score. Serum samples were obtained to determine Fibrotest® and APRI. AUROC were used to determine cut-off and differentiate between advanced fibrosis (METAVIR F3, F4) and no fibrosis (F0). Results. 68 biopsies were evaluated; METAVIR > F3 was identified in 26 (38%). Non invasive liver fibrosis markers to differentiate between advanced and no fibrosis were: Fibrotest® AUROC = 0.90 (95% CI 0.77-1.00) (cut-off value 0.35) sensitivity 88.00% (95% CI 68-96) and specificity 80% (95% CI 29-98); and for APRI AUROC = 0.97 (95% CI 0.92-1.00) (cut-off value 0.82), sensitivity 88% (95% CI 68-96) and specificity = 100% (95% CI 46-100). Conclusion. These results suggest the utility of Fibrotest® and APRI to identify advanced fibrosis; they can be recommended to select patients for liver biopsy and during patient follow-up.
Aim. To perform an updated meta-analysis comparing β-blockers (BB) with endoscopic variceal banding ligation (EVBL) in the primary prophylaxis of esophageal variceal bleeding. Material and methods. Randomized controlled trials were identified through electronic databases, article reference lists and conference proceedings. Analysis was performed using both fixed-effect and random-effect models. Heterogeneity and publication bias were systematically taken into account. Main outcomes were variceal bleeding rates and all-cause mortality, calculated overall and at 6, 12, 18 and 24 months. Results. 19 randomized controlled trials were analyzed including a total of 1,483 patients. Overall bleeding rates were significantly lower for the EVBL group: odds ratio (OR) 2.06, 95% confidence interval (CI) [1.55-2.73], p < 0.0001, without evidence of publication bias. Bleeding rates were also significantly lower at 18 months (OR 2.20, 95% CI [1.04-4.60], P = 0.04), but publication bias was detected. When only high quality trials were taken into account, results for bleeding rates were no longer significant. No significant difference was found for either bleedingrelated mortality or for all-cause mortality overall or at 6, 12, 18 or 24 months. BB were associated with more frequent severe adverse events (OR 2.61, 95% CI 1.60-4.40, P < 0.0001) whereas fatal adverse events were more frequent with EVBL (OR 0.14, 95% CI 0.02-0.99, P = 0.05). Conclusion. EVBL appears to be superior to BB in preventing the first variceal bleed, although this finding may be biased as it was not confirmed by high quality trials. No difference was found for mortality. Current evidence is insufficient to recommend EVBL over BB as first-line therapy.
Background. Eplerenone is a selective mineralocorticoid receptor (MR) antagonist, and its potential protective role in cardiovascular injury has been reported by several studies. However, whether and how this drug can ameliorate hepatic injury in rats is unknown. Material and methods. The present study was conducted to investigate effect of eplerenone against liver injury induced by carbon tetrachloride (CCl4) in rats. The biochemical liver function tests and oxidative stress parameters including malondialdehyde (MDA), reactive oxygen species (ROS), in addition to the reduced glutathione (GSH) levels were evaluated. Moreover, serum tumor necrotic factors (TNF-α) level and histopathological changes were examined. Results. Our results show that pre-treatment with eplerenone (4 mg/kg per day for 4 weeks) revealed attenuation in serum activities of alanine aminotransferase (ALT), aspartate aminotransferase, (AST), alkaline phosphatase (ALP) and bilirubin levels that were enhanced by CCl4. Further, pre-treatment with eplerenone inhibited the elevated hepatic MDA content and restored hepatic GSH to its normal level. The enhanced hepatic ROS production in CCl4-treated group was markedly decreased by eplerenone administration. Eplerenone pre-treatment significantly attenuated the inflammatory responses caused by CCl4 as evident by the decreased serum TNF-α level. Histopathological studies showed that eplerenone alleviated the liver damage and reduced the lesions caused by CCl4. Conclusion. Collectively, the present study provides a proof to hepatoprotective actions of eplerenone via reducing oxidative stress and inflammatory responses in CCl4-induced liver damage in rat model.
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver.1,2 The most common extrahepatic metastatic sites are lung, abdominal lymph nodes and bone, while its cardiac metastasis is rare.2,3 Metastasis of HCC into the cardiac cavity is mostly caused by direct tumor invasion of vena cava inferior with continuous extension into the right cardiac cavity.4,5 Right heart metastasis without invasion of inferior vena cava, which may be caused by hematogenous spread of cancer cells, is rarely reported.6,7 This paper announces an unusual case of isolated involvement of left ventricle (LV) together with myocardial invasion of HCC. Our patient is known to be the first case with isolated HCC metastasis to the left ventricle. Strikingly, the patient was young and non-cirrhotic with negative serum HBsAg, and anti-HCV results.
Here we report a rare case of living Fasciola hepatica in biliary tract. The patient was in acute phase of infection and treated successfully with 10 mg/kg oral triclabendazole after the fluke was extracted using endoscopic retrograde cholangiopancreatography (ERCP).
Alcoholic liver disease (ALD) covers a wide spectrum of pathology ranging from fatty liver disease to acute steatohepatitis to cirrhosis and/or hepatocellular carcinoma. Alcoholic foamy degeneration (AFD) is an uncommon, potentially life-threatening condition that is part of the spectrum of ALD. It is characterized by extensive microvesicular steatosis in the perivenular areas. Since the first description in 1983, few case reports have been described. Here, we report 2 cases of AFD in patients with a previous history of chronic alcohol abuse and histological diagnosis of AFD with typical clinical, biochemical and histological features. In both cases we provide data on the hepatic hemodynamic status, and in one of them we report liver elastography results, which are features that have not been described previously. In both cases there was rapid resolution of biochemical and clinical abnormalities after complete abstinence, which is the mainstay of treatment for AFD.
Antiviral therapy in patients suffering from chronic hepatitis C virus (HCV) infection and rare comorbidities cannot be easily started, as it can reduce the likelihood of a good therapeutic response with an increased frequency of side effects. We report two patients presenting unusual comorbidities associated with chronic C hepatitis: one with the Ehlers-Danlos Syndrome (EDS), a rare genetic disease caused by a defect in collagen synthesis, the other one with the Charcot Marie Tooth (CMT) disease, an uncommon but severe form of demyelinating peripheral neuropathy. Both patients were successfully treated with pegylated Interferon (Peg-IFN) and ribavirin (RBV) combined therapy, with the achievement of a sustained viral response (SVR) and a low occurrence of adverse effects. Up to now there are no reports of patients suffering from chronic C hepatitis associated with these uncommon but severe comorbidities treated with antiviral therapy. In conclusion, in such clinical situations, anti-HCV therapy may be started and tailored, especially if the patient is highly motivated and if optimal predictors of response (i.e. young age, favourable genotype and low baseline viraemia) do exist.