Assessment of treatment response in hepatocellular carcinoma: a review of the literature

Hepatocellular carcinoma (HCC) has a high incidence all over the world. Even if the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and could have a key role in clinical management. Since 1950 several radiological response criteria have been applied; however, it was not until 2000 that specific criteria for HCC were introduced by the European Association for the Study of the Liver (EASL), and these were then standardized in 2010 with the development of the modified Response Evaluation Criteria for Solid Tumors (mRECIST) for HCC. The purpose of this brief review is to compare data in literature regarding the application an…

Primary biliary cirrhosis and hereditary hemorrhagic telangiectasia: When two rare diseases coexist

Primary biliary cirrhosis is a slowly progressive cholestatic autoimmune liver disease that mainly affects middle- aged women with an estimated prevalence ranging from 6.7 to 402 cases per million. Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that can affect many organs, including liver, with a prevalence of 1-2 cases per 10000. We describe the coexistence, for the first time to our knowledge, of these two rare diseases in a 50-year old Caucasian woman. In this setting, the relevance of an accurate medical history, the role of liver histology an…

Direct acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background & aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) after successful treatment of early hepatocellular carcinoma (HCC) has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We enrolled prospectively 163 consecutive patients with HCV-related cirrhosis and at first diagnosis of early Barcelona Clinic Liver Cancer (BCLC) 0/A HCC who had achieved a complete radiologic response after curative resection or ablation, subsequently treated with DAAs. DAA-untrea…

Progressive multi-organ expression of immunoglobulin G4-related disease: A case report.

A 63-year-old Caucasian man presented with a cholestatic syndrome, renal failure and arthralgias. A laboratory examination revealed high immunoglobulin G (IgG) and IgG4 levels (5.95 g/L; normal range: 0.08-1.4 g/L), pointing to a diagnosis of systemic IgG4-related disease, with definite radiological evidence of biliary and pancreatic expression, and plausible renal, articular, salivary and lacrimal glands involvement. Due to the rarity of the condition, there are currently no random control trials to point to the optimal therapeutic approach. The patient has been on steroid therapy with the subsequent introduction of azathioprine, with a complete resolution of all symptoms, a rapid reductio…

Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis C virus genotype 1.

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe > or =30%. Thirty nondiabetic, nonobese blood donors served as controls. …

Body Mass Index and Liver Stiffness Affect Accuracy of Ultrasonography in Detecting Steatosis in Patients With Chronic Hepatitis C Virus Genotype 1 Infection

Background & Aims: Few studies have evaluated the accuracy of ultrasonography in detecting steatosis in patients with chronic hepatitis C. We assessed its accuracy in detecting steatosis and factors that affect its diagnostic performance in consecutive patients with chronic hepatitis C virus genotype 1infection. Methods: We analyzed data from 515 patients with chronic hepatitis C, confirmed by liver biopsy, assessing anthropometric, biochemical, metabolic, virologic, and ultrasonography features. Transient elastography was performed to measure liver stiffness. Steatosis was identified with ultrasonography based on detection of a bright liver echo pattern. Results: Ultrasonography identified…

INSULIN RESISTANCE AND SEVERITY OF FIBROSIS IN HCV GENOTYPE 1 CHRONIC HEPATITIS.

Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C .

Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients.One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI.TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating ch…

Il supporto della SISV alla realizzazione di un manuale nazionale per il monitoraggio degli habitat della Direttiva 92/43/EEC in Italia

A partire dall’entrata in vigore della Direttiva 92/43/EEC, la sorveglianza dello stato di conservazione degli habitat elencati nell’Allegato I ed il relativo monitoraggio periodico a intervalli di sei anni sono diventati un obbligo per tutti i paesi membri dell’UE, in base a quanto previsto negli Articoli 11 e 17. Nel 2011 è stato pubblicato un documento che fornisce le linee guida di riferimento europee per il monitoraggio di habitat e specie (Evans & Arvela 2011). Su questa base metodologica, la Società Italiana di Scienza della Vegetazione (SISV), avvalendosi di un ampio gruppo di soci esperti, ha avviato un dibattito interno su principi, criteri, parametri e strumenti per il monitoragg…

Treatment of hepatocellular carcinoma: present and future

Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesi…

The SISV support to the implementation of a national manual for monitoring the Habitats of the 92/43/EEC Directive in Italy.

The 4th National Report ex Art. 17 of the 92/43/EEC Directive in Italy (period 2013-2018) will try to fill a number of gaps still affecting the former versions of the Italian Reports, where territorial data were still missing for large parts of the country and the assessment was mostly based on the use of the expert opinion. Similar inconsistencies also emerged in other European countries (State of nature in the EU, EEA 2015). In order to reach this aim, a nationally shared protocol for monitoring the vegetation-based Annex I Habitats is currently under development. The most prominent issues addressed by the ongoing project are: i) fixing standardized, updated and scientifically grounded me…

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems

Summary Background  A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. Aim  To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. Methods  We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. Results  One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated p…

Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection.

OBJECTIVES: Metabolic factors may affect the course of chronic hepatitis C (CHC). Insulin resistance (IR) determines steatosis, but its direct role in affecting progression of hepatic fibrosis is less clear. We aimed to assess whether increasing degrees of IR, up to overt diabetes, are linked to steatosis and higher stages of fibrosis in patients with CHC resulting from genotype 1 HCV (G1-HCV). METHODS: Two hundred one consecutive patients with G1-HCV infection were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, by the homeostasis model assessment (HOMA). Nondiabetic patients were defined as insulin resistant if HOMA-IR was >2.7. All biopsies were …

Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort

Background: Natural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans. Objectives: We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy. Methods: Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All subjects were treated with Ursodeoxycholic acid at a dose of 15 mg/kg. HLA class II DRB1 alleles were compared with those of 237 healthy control subjects. IL28B genotyping for IL28B rs12979860 C/T and rs80899917 G/T was …

Focal lymphocytic aggregates in chronic hepatitis C: occurrence, immunohistochemical characterization, and relation to markers of autoimmunity.

Intrahepatic lymphocytic aggregates are observed in chronic hepatitis C as well as in autoimmune chronic hepatitis. Autoantibodies and autoimmune manifestations may occur in hepatitis C. It has been suggested that the lymphocytic aggregates play a role in the liver injury of chronic hepatitis C by an immune-mediated mechanism. We studied the occurrence of intrahepatic lymphocytic aggregates and of autoantibodies in a consecutive series of 128 patients with chronic hepatitis C. For the phenotypic characterization of the lymphocytic aggregates cryostat sections and microwaved paraffin embedded sections were immunostained with monoclonal antibodies directed against T cell subsets, B cells, kil…

Mortality in patients with hepatocellular carcinoma predicted by six scoring systems: None is the winner

Antimitochondrial antibody -M2 positive autoimmune hepatitis during standard of care for chronic hepatitis C

The current standard of care (SoC) for chronic hepatitis C, i.e. the combination of a pegylated-interferon (PEG-IFN) with ribavirin (RBV), may activate underlying autoimmune conditions. Particularly, interferon (IFN) has been known to induce or exacerbate autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in hepatitis C virus patients. We describe a severe, acute-onset antimitochondrial antibody (AMA)-M2 positive AIH appearing during the last weeks of SoC in a woman with chronic hepatitis C and no previous history of autoimmunity, and resolving on protracted steroids. In this context, the relevance of the characterization of the immunoglobulin isotype of portal plasma cells for …

Quantification of fibrosis in chronic hepatitis C: Performance of Transient Elastography and Acoustic Radiation Force Impulse using Collagen Proportionate Area as reference

Liver eosinophilic infiltrate is a significant finding in patients with chronic hepatitis C.

Eosinophilic infiltrate of liver tissue is described in primary cholestatic diseases, hepatic allograft rejection and drug-induced liver injury, but its significance and its implications in chronic hepatitis C are unknown. The aim of this study was to investigate the clinical significance of eosinophilic liver infiltrate in patients with chronic hepatitis C. We retrospectively evaluated 147 patients with chronic hepatitis C. The presence of eosinophilic infiltrate was investigated in liver biopsies, and a numeric count of eosinophilic leucocytes in every portal tract was assessed. An eosinophilic infiltrate of liver tissue (> or =3 cells evaluated in the portal / periportal spaces) was obse…

Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: a retrospective cohort study.

Abstract 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% m…

Hyperferritinemia is a risk factor for steatosis in chronic liver disease.

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty l…

Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules

Background & Aims The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned because of the risk of a false positive diagnosis in cases of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS Liver Imaging Reporting and Data System [LI-RADS®]) to classify lesions at risk of HCC investigated by CEUS. The aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. Methods A total of 1,006 nodules from 848 patients with chronic liver disease at risk of HCC were collected in five Italian centers and retrospectively analyzed. Nodules were classified as LR-5, (HCC) …

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background & Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAA…

Successful intravenous immunoglobulin treatment for steroid-resistant eosinophilic enteritis in a patient with systemic lupus erythematosus.

Eosinophilic gastroenteritis is a rare condition of unknown etiology characterized by eosinophilic infiltration of the bowel. Corticosteroids are the mainstay of EG therapy. Although rare, steroid-resistant EG could be a life-threatening condition with tissue destructive evolution. Associations of eosinophilic gastroenteritis with systemic lupus erythematosus have rarely been reported. In this report we describe a case of successful IVIG treatment in a patient with systemic lupus erythematosus and steroid-refractory eosinophilic gastroenteritis. Eosinophilic gastroenteritis is a rare condition of unknown etiology characterized by eosinophilic infiltration of the bowel. Corticosteroids are t…

Antimitochondrial antibody -M2 positive autoimmune hepatitis during standard of care for chronic hepatitis C.

The current standard of care (SoC) for chronic hepatitis C, i.e. the combination of a pegylated-interferon (PEG-IFN) with ribavirin (RBV), may activate underlying autoimmune conditions. Particularly, interferon (IFN) has been known to induce or exacerbate autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in hepatitis C virus patients. We describe a severe, acute-onset antimitochondrial antibody (AMA)-M2 positive AIH appearing during the last weeks of SoC in a woman with chronic hepatitis C and no previous history of autoimmunity, and resolving on protracted steroids. In this context, the relevance of the characterization of the immunoglobulin isotype of portal plasma cells for …

A methodological protocol for Annex I Habitats monitoring: the contribution of Vegetation science.

The methodological foundations of the recently published Manual for Annex I Habitats monitoring in Italy, edited by the Italian Institute for Environmental Protection and Research (ISPRA) with the scientific support of the Italian Society for Vegetation Science (SISV), are here presented, discussed and related to the most consolidated and acknowledged scientific advances in the field of Vegetation science. The proposed methodologies aim at offering simple, yet effective, protocols and procedures towards a harmonized data collection, by way of standardized and shared technical tools, resulting in comparable evaluations of the conservation status of Annex I Habitats. The methodological framew…