MicroRNAs and clinical implications in hepatocellular carcinoma.

AIM: To assess the role of some circulating miRNAs (miR-23a, miR-203, miR338, miR-34, and miR-16) as tumor markers for diagnosis of hepatocellular carcinoma (HCC). METHODS: One hundred and seventy-one subjects were enrolled, 57 patients with HCC, 57 patients with liver cirrhosis (LC) and 57 healthy subjects as control group. Severity of liver disease was assessed by Child Pugh score. Tumor staging was done using Okuda staging system. Quantification of Micro RNA (miR-23a, miR-203, miR338, miR-34, and miR-16) was performed. RESULTS: All studied miRNA showed significant difference between HCC and cirrhotic patients in comparison to healthy control. miR-23a showed statistically significant difference between HCC and cirrhotic patients being higher in HCC group than cirrhotic. miR-23a is significantly higher in HCC patients with focal lesion size equal or more than 5 cm, patients with multiple focal lesions and Okuda stage III. At cutoff value ≥ 210, miR-23a showed accuracy 79.3% to diagnose HCC patients with sensitivity 89.47% and specificity about 64.91%. At cut off level ≥ 200 ng/mL, serum alpha fetoprotein had 73.68% sensitivity, 52.63% specificity, 43.75% PPV, 80% NPV for diagnosis of HCC. CONCLUSION: MicroRNA 23a can be used as a screening test for early detection of HCC. Also, it is related to larger size of tumour, late Okuda staging and multiple hepatic focal lesions, so it might be a prognostic biomarker.

Role of procalcitonin in diagnosis of bacterial infection in trans-arterial chemoembolisation treated hepatocellular carcinoma patients.

BACKGROUND AND STUDY AIM: Trans-arterial chemoembolisation (TACE) became the treatment of choice for multinodular hepatocellular carcinoma. The use of prophylactic antibiotics following intervention is controversial. This study aimed to assess the role of serum procalcitonin level in early diagnosis of bacterial infection following TACE to optimise antibiotic intake in those patients. PATIENTS AND METHODS: This study was carried on HCC patients diagnosed according to AASLD who underwent TACE and developed post interventional fever within 48 h. Laboratory investigations including CBC, neutrophil count, C-reactive protein and ESR (pre and after intervention) were done. Cultures were done according to the suspected site of infection. Serum procalcitonin was done for all the included patients before and after TACE. RESULTS: Forty two TACE treated patients were included with post interventional fever within 48 h. Their ages ranged between 45 and 65 (mean 53.83 ± 5.23). All patients received antibiotic prophylaxis started 24h pre intervention and for 5 days after according to the local protocol. Five patients (11.9%) had positive blood cultures post intervention. The analysis of laboratory results showed statistical significant correlation between procalcitonin levels and positive cultures, post interventional CRP and TLC and pre interventional INR and bilirubin, while there was statistical significant correlation between CRP and post interventional temperature, total leucocytic count and site of focal lesion. CONCLUSION: Procalcitonin seems to be a promising marker for diagnosis of sepsis in TACE treated HCC patients to optimise the unnecessary use of antibiotics.

Expression of Toll like receptors 3 & 7 in peripheral blood from patients with chronic hepatitis C virus infection and their correlation with interferon-alpha.

Toll-like receptor 3 (TLR3) and Toll-like receptor 7 (TLR7) are pathogen- recognition receptors that are expressed on innate immune cells. They recognize viral RNA which induces their activation with subsequent increase in IFN-alpha transcription. It has been postulated that HCV may cause down regulation of these receptors as one of immune evading mechanisms that participate in viral persistence. The aim of this work is to investigate the expression of Toll-like receptors 3 (TLR3) and 7 (TLR7) in peripheral blood from patients with chronic hepatitis C infection and correlate their expression to the peripheral blood expression of interferon-alpha (IFN-alpha), viral load and histopathology of the liver. IFN-alpha, TLR3 and TLR7 expression in peripheral blood from patients with chronic hepatitis C infection (n = 30) and from healthy controls (n = 20) were measured by real time polymerase chain reaction. Viral load and Liver biopsy were done for all patients. The results showed lower expression of TLR3 and TLR7 in patients than controls, and levels of expression correlated positively with IFN-alpha expression. No correlation was found between TLR3 and TLR7 and viral load or histopathological staging and grading of the liver tissue. In conclusion, HCV may induce down regulation of TLRs (TLR3 and TLR7) expression on innate immune cells with subsequent decrease in INF-alpha production suggesting that new therapies that aim to increase the expression level of TLRs may help in treatment of HCV infection.

Serum leptin level and its association with fatigue in patients with chronic hepatitis C virus infection.

BACKGROUND AND STUDY AIM: Fatigue is one of the most common presenting symptoms of chronic hepatitis C virus (HCV) infection. Its pathogenesis has been poorly investigated. Serum leptin levels are increased in cirrhosis and are suggested to have a role in the mediation of fatigue. This study was designed to assess possible association of serum leptin levels with fatigue and severity of liver disease in Egyptian patients with chronic hepatitis C infection. PATIENTS AND METHODS: Seventy patients and 20 control subjects participated in the study. They were subjected to clinical and laboratory assessment, the determination of serum leptin level by ELISA and the assessment of fatigue using the multidimensional assessment of fatigue (MAF) scale. Respondents are asked to reflect on fatigue patterns for the past week. The MAF is a revision of the Piper Fatigue Scale. RESULTS: Fatigue was present in all patients (100%) and 13 subjects of the control group (65%). There was a highly significant statistical difference between cases and controls regarding the presence and severity of fatigue. Serum leptin level was significantly higher in cases (24.9±28) in comparison to the control subjects (14.8±8). Serum leptin was not related to severity of liver disease as assessed by the Child Pugh classification. Serum leptin levels were directly correlated to the severity of fatigue (p<0.01) in patients but not in the control subjects. CONCLUSION: Fatigue is highly prevalent in Egyptian patients with chronic HCV infection. Leptin might play a role in the mediation of fatigue in those patients drawing attention to biological basis of one of the most common symptoms facing clinician dealing with this problem.

Clinical spectrum of fever of unknown origin among adult Egyptian patients admitted to Ain Shams University Hospitals: a hospital based study.

This prospective study was designed to analyze the clinical spectrum of fever of unknown origin (FUO) among adult Egyptian patients admitted to Ain Shams University Hospitals during the period from May 2009 till the end of December 2010. All Egyptian patients fulfilling the criteria of FUO admitted during this period were followed up till reaching the diagnosis. 93 patients were included in the study. They were 48 (51.6%) females and 45 (48.4%) males, their ages ranged from 15 to 65 years (34.39 +/- 13.6). Infections were the commonest cause of FUO (41.94%) followed by malignancies (30.11%). While autoimmune diseases represented 15.05% and in 12.9% of patients the diagnosis was not established. Brucellosis and infective endocarditis were the commonest infections, while hematological malignancies were the commonest oncological diseases. Systemic lupus erythematosus (SLE) was the commonest auto-immune disease. Brucellosis, infective endocarditis, hematological malignancies and SLE must be considered in the differential diagnosis of adult FUO in Egypt.

Serum interleukin-18: does it have a role in the diagnosis of hepatitis C virus related hepatocellular carcinoma?

BACKGROUND AND STUDY AIMS: Early diagnosis of hepatocellular carcinoma (HCC) is the only hope for cure. Although the role of alpha foetoprotein (AFP) in the diagnosis of advanced HCC is well recognised, at least one-third of cases will be missed unless another diagnostic tool is used. Increased levels of circulating interleukin-18 (IL-18) have been observed in patients with several cancer types and were described in patients with chronic hepatitis. The aim of this study is to assess the role of serum IL-18 level in the diagnosis of hepatitis C virus (HCV)-related HCC. PATIENTS AND METHODS: A total of 75 subjects categorised into four groups, including 25 patients with HCV-related HCC and AFP above 200ng/ml, 25 patients with HCV-related HCC and AFP below 200ng/ml, 15 patients with HCV-related chronic liver disease and 10 healthy controls, were enrolled. HCC was diagnosed according to guidelines of the American Association for the Study of Liver Diseases. AFP and IL-18 were assessed in all subjects. RESULTS: AFP and IL-18 levels are significantly higher in patients with HCC than in disease control and healthy control subjects. IL-18 level is not correlating with the size or the number of hepatic focal lesions neither with the presence of lymphovascular invasion or abdominal lymphadenopathy. The best cut-off value of IL-18 for the diagnosis of HCC is 500pg/ml with 84% sensitivity and 86.7% specificity and the area under receiver operating characteristic curve is 0.675. CONCLUSION: Serum IL-18 level is a suitable marker for the diagnosis of HCV-related HCC complementary to AFP, especially in cases with AFP level less than the diagnostic value.

Liver metastases in Egyptian patients with colorectal cancer: incidence and clinico-pathological predictors.

Carcinoma of the large bowel is the fourth commonest cancer worldwide. The most frequent site for metastasis is the liver. Overall 30% of patients develop liver metastasis during the course of their illness; of these, 23% to 47% are synchronous lesions. These data are based on western studies. No data are published on patients with colorectal cancer from Egypt. We aimed to assess the incidence of colorectal liver metastasis in Egyptian patients and to evaluate the differences in the clinicopathological features and tumor behavior in patients with and without liver metastasis. One hundred forty eight patients were prospectively enrolled in the study. Patients were classified into metastatic group (n=78) and non metastatic group (n=70). In the two groups macroscopic features compared including: tumor size (2 cm, 2-5 cm, and >5 cm), site of primary tumor, side of liver involved, clinical symptoms and liver profile. Carcino-embryonic antigen (CEA) and cancer antigen (CA19.9) levels were recorded. At microscopy, tumor differentiation, invasion and nodal status were evaluated. No difference was found in the distribution of the primary site and size of the tumor. Jaundice, hepatomegaly and ascites were significantly higher in patients with liver metastases. Patients with liver metastasis had higher levels of CEA, CA19.9, higher frequency of vascular invasion and nodal involvement.