Carbohydrate 19.9 antigen serum levels in liver disease.

BACKGROUND: Carbohydrate 19.9 antigen (CA19.9) has been used in the diagnosis and followup of gastrointestinal tumours. The aim of this prospective longitudinal study was the evaluation of CA19.9 levels in patients with chronic hepatitis and hepatic cirrhosis hepatitis C virus and B virus correlated. MATERIALS AND METHODS: 180 patients were enrolled, 116 with HCV-related chronic liver disease (48% chronic hepatitis, 52% cirrhosis) and 64 with HBV-related chronic liver disease (86% chronic hepatitis, 14% cirrhosis). Patients with high levels of CA19.9 underwent abdominal ecography, gastroendoscopy, colonoscopy, and abdominal CT scan. RESULTS: 51.7% of patients with HCV-related chronic liver disease and 48.4% of those with HBV-related chronic liver disease presented high levels of CA19.9. None was affected by pancreatic or intestinal neoplasia, cholestatic jaundice, or other diseases potentially able to induce Ca19.9 elevations. CA19.9 levels were elevated in 43.3% of HCV chronic hepatitis, in 56.3% of HCV cirrhosis, in 45.1% of HBV chronic hepatitis, and in 58% of HBV cirrhosis. CONCLUSIONS: CA19.9 commonly increases in the serum of patients with chronic viral hepatitis. Elevation of CA 19.9 is not specific for neoplastic disease and is related to the severity of fibrosis and to the viral aetiology of hepatitis.

Systemic therapies in hepatocellular carcinoma: present and future.

Hepatocellular carcinoma (HCC) is now the third leading cause of cancer deathsworldwide and is generally presented at an advanced stage, limiting patients' quality of life. The conventional cytotoxic systemic therapy has proved to be ineffective in HCC, since its induction several decades ago. Today it is possible to use our knowledge of molecular hepatocarcinogenesis to provide a targeted therapy. Sorafenib has demonstrated large improvements in overall survival in HCC. This review describes the molecular mechanisms and potential therapeutic targets, focusing on sorafenib, sunitinib, tivantinib, antiangiogenic agents, and current and future immunotherapies. Thus, it will be necessary in the future to classify HCCs into subgroups according to their genomic and proteomic profiling. The identification of key molecules/receptors/signaling pathways and the assessment of their relevance as potential targets will be the main future challenge potentially influencing response to therapy. Defining molecular targeted agents that are effective for a specific HCC subgroup will hopefully lead to personalized therapy.

Hepatocellualar carcinoma serum markers.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. In most cases, HCC is diagnosed at a late stage. Therefore, the prognosis of patients with HCC is generally poor. The recommended screening strategy for patients with cirrhosis includes the determination of serum α-fetoprotein (AFP) levels and an abdominal ultrasound every 6 months to detect HCC at an earlier stage. AFP, however, is a marker characterized by poor sensitivity and specificity, and abdominal ultrasound is highly dependent on the operator's experience. In addition to AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3), des-γ-carboxy prothrombin (DCP), glypican-3 (GPC-3), osteopontin (OPN), and several other biomarkers (such as squamous cell carcinoma antigen-immunoglobulin M complexes [SCCA-IgM], alpha-1-fucosidase [AFU], chromogranin A [CgA], human hepatocyte growth factor, insulin-like growth factor) have been proposed as markers for the early detection of HCC. For these markers, we describe the mechanisms of production, and their diagnostic and prognosis roles. None of them is optimal; however, when used together, their sensitivity in detecting HCC is increased. Recent research has shown that some biomarkers have mitogenic and migratory activities in the angiogenesis of HCC and are a factor of tumor growth.

Prognostic and diagnostic value of des-γ-carboxy prothrombin in liver cancer.

Des-γ-carboxy prothrombin (DCP) is an abnormal prothrombin induced by the absence of vitamin K2 that is increased in the serum of patients with hepatocellular carcinoma (HCC). In hepatoma cells, genetic alterations, membrane receptors, the inability to uptake labeled low-density lipoprotein, cytoskeletal changes and hepatocyte cytoplasmic transfers involved in vitamin K metabolism could play an important role in producing detectable DCP serum levels. Serum DCP was found to have a sensitivity ranging from 48% to 62%, a specificity of 81% to 98% and a diagnostic accuracy of 59% to 84% for detecting HCC. Plasma DCP does not correlate with α-fetoprotein (AFP) levels. However, when used together, the DCP and AFP assays increase the sensitivity of detecting HCC in more than 85% of patients. The specificity of the DCP assay appears to be superior to that of AFP. These biomarkers can complement ultrasound for early HCC detection, but neither DCP nor AFP is optimal. For small HCC, a high preoperative DCP level appears to be indicative of tumor recurrence. Recently, there has been attention given to DCP because of its role in detecting HCC recurrence after living donor liver transplant. More recent research has demonstrated that DCP stimulates human vascular endothelial cell growth and migration. All the data presented above demonstrate the importance of DCP in formulating a prognosis for patients with HCC.

A multidisciplinary therapeutic approach for reducing the risk of psychiatric side effects in patients with chronic hepatitis C treated with pegylated interferon α and ribavirin.

GOALS: To evaluate the effectiveness of psychiatric counseling in reducing the rate of development of psychiatric side effects of antiviral therapy with interferon-α and ribavirin among study participants compared with standard clinical monitoring alone. BACKGROUND: Interferon-α is used to treat chronic hepatitis C. Interferons may induce adverse events that usually, but not always, reverse within a few days after the end of therapy. STUDY: Two hundred eleven patients with chronic hepatitis C, genotype 1b were treated with peginterferon and ribavirin for 48 weeks in a prospective trial. Two groups were randomly created. Group A was interviewed by a team of gastroenterologists, psychiatrists, and psychologists and treated with psychotherapy once a month. Group B was monitored once a month according to a conventional protocol that did not include psychotherapy. SVR (sustained viral response), severe psychiatric symptom onset, and mood progression were assessed (P calculated using Fisher exact test, Friedman test, Dunn posttest, and Mann-Whitney U-test). RESULTS: At baseline, there was no difference in depressive symptoms or liver histologic score between the 2 groups. The onset rate of severe psychiatric manifestations was 4.7% (Group A) and 16.1% (Group B) between the 24th and 36th weeks (P<0.01). Fifteen participants in Group A and 39 in Group B required antidepressants and benzodiazepines (P<0.05). CONCLUSIONS: Patients can develop depressive symptoms during interferon therapy. Multidisciplinary medical treatment with psychiatric counseling provided during the treatment of chronic hepatitis C may contribute to the decrease or prevent the higher rates of depression associated with interferon treatment.

Epoetin alpha improves the response to antiviral treatment in HCV-related chronic hepatitis.

BACKGROUND: The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response. AIM: We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response. METHODS: Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 µg once weekly and ribavirin 1,000-1,200 mg/day; 174 were responders. Forty individuals completed treatment with no hemoglobin reduction; 134 developed anemia during therapy. Anemic responders were distributed randomly into two groups: group 1 continued therapy with epoetin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only. RESULTS: Patients in group 1 achieved better control of hemoglobin levels (13.8 ± 1.2 g/dl at the end of therapy) than those in group 2 (11.5 ± 0.8 g/dl). Sustained virological response was 59.7% in group 1 compared with 34.4% in group 2 (p<0.01). CONCLUSIONS: In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment, administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence.