Aberrant cytokine and VCAM-1 expression in patients with viral and non-viral related liver cirrhosis.

The study aim was to compare the alterations in the expression levels of proinflammatory and chemotactic cytokines as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17A and IL-8, the down regulatory cytokine IL-10, in addition to the vascular cell adhesion molecule-1 (VCAM-1) gene in different groups of patients with cirrhosis due to various etiologies. This case-control study included 84 patients suffering from cirrhosis of viral and non-viral etiologies and 20 sex and age-matched healthy controls. All patients were subjected to detailed history taking, clinical examination, and liver function assessment. The expression levels of TNF-α, IL-17A, IL-8, IL-10, and VCAM-1 were assessed in peripheral blood mononuclear cells by real-time PCR. Patients with cirrhosis showed marked changes in the tested gene expression levels relative to the control group. Higher expression levels of all genes except IL-10 were seen in patients of the viral than in the non-viral groups. Most of the significant correlations of liver function parameters were observed with TNF-α in both the viral and non-viral groups, followed by IL-17A. Increased TNF-α and IL-17A presented potential risk factors for disease progression to cirrhosis of Child class C.

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression.

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.

Increased frequency and FOXP3 expression of human CD8+CD25High+ T lymphocytes and its relation to CD4 regulatory T cells in patients with hepatocellular carcinoma.

The mechanism of action of CD8+CD25High+FOXP3+ T cells in hepatocellular carcinoma (HCC) has not been fully understood. Herein, the role of CD8+CD25High+FOXP3+ T cells in HCC was compared with that of CD4+CD25High+FOXP3+ regulatory T cells (conventional Tregs). Thirty-five patients with HCC and twenty age and sex-matched healthy adults (controls) were enrolled. The percentage of CD8+CD25High+FOXP3+ T cells and conventional Tregs in peripheral blood was measured by flow cytometry. Our results revealed that the percentage of peripheral CD8+CD25High+FOXP3+ T cells in HCC patients was significantly higher than controls (P = 0.005). The conventional Tregs showed the same trend with a higher level in HCC than controls (P < 0.0001). FOXP3 expression of CD8+CD25High+ T cells is higher than that of CD8+CD25low+ and CD8+CD25Negative T cells. The percentage of CD8+CD25High+FOXP3+ T cells positively correlated with that of conventional Tregs in HCC patients but not in controls. The higher alpha-fetoprotein positively correlated with the higher CD8+CD25High+FOXP3+ T cells and conventional Tregs (R2 = 0.481, P < 0.0001 and R2 = 0.249, P = 0.001, respectively). The frequency of both CD8+CD25High+FOXP3+ T cells and conventional Tregs was significantly increased in HCC with multiple lesions compared with those with one or two lesions. In conclusion: CD8+CD25High+FOXP3+ T cells similar to conventional Tregs might be used as biomarkers of HCC progression. Therapy targeting the peripherally expanded CD8+CD25High+FOXP3+ T cells may provide a novel perspective for HCC treatment.

Frequency and Implications of myeloid-derived suppressor cells and lymphocyte subsets in Egyptian patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND AND AIM: Myeloid-derived suppressor cells (MDSCs) play a pivotal role in tumor immunity and induction of immune tolerance to a variety of antitumor effectors, including T lymphocytes. Herein, we tried to evaluate the frequency and clinical significance of MDSCs and different lymphocyte subsets in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: Four groups were enrolled; chronic HCV (CHC; n = 40), HCV-related liver cirrhosis (n = 40), HCV-related HCC (HCV-HCC; n = 75), and healthy control group (n = 20). The percentage of peripheral lymphocytes subsets and total MDSCs with their main two subsets; monocytic (M-MDSCs) and granulocytic (G-MDSCs) was evaluated by flow cytometry. RESULTS: The frequency of total MSDCs and M-MDSCs was significantly elevated in HCV-HCC especially patients with advanced stage HCC compared with those with early-stage HCC. The frequency of total MSDCs and M-MDSCs was positively correlated with ALT, AFP, and HCV viral load and negatively correlated with CD8+ T-cell frequency. CD4 + T cells were significantly decreased in HCV-HCC patients. The frequency of CD4 + T cells and CD8 + T cells was negatively correlated with AFP and AST, but not with albumin or HCV viral load. CONCLUSION: Taken together, our data suggest that MDSCs, M-MDSCs, and lymphocyte subsets are associated with the development and progression of HCV-related HCC.

Efficacy of ombitasvir/paritaprevir/ritonavir/ribavirin in management of HCV genotype 4 and end-stage kidney disease.

BACKGROUND: Till now, pooled data about the safety and efficacy of different direct-acting antiviral (DAAs) regimens in different renal situations are still under evaluation. AIM: To evaluate a real-life experience of the efficacy and safety of ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r plus RIB) in patients with end-stage kidney disease (ESKD). PATIENTS AND METHODS: Between January 2017 and January 2018, an open-label multicenter prospective study was designed to enroll all consecutive patients with proven CHC genotype 4 infections and concomitant ESKD based on estimated glomerular filtration rate (eGFR) with (HD group) or without hemodialysis (non-HD group). Patients were given a co-formula of OBV/PTV/r (25/150/100 mg) once-daily plus RIB was given for 12 weeks. Sustained virologic response (SVR 12) was the primary endpoint. RESULTS: A total of 110 patients were enrolled. An overall SVR 12 was reported in 104 (94.5%) patients, and treatment failure were reported in 6 patients [2 patients (1.8%) were relapsed, and 4 patients (3.6%) patients were non-responders]. SVR12 was 96% in HD and 91.4% in non-HD patients (P = 0.286). There were no reported serious adverse events. Anemia was reported in 66.6% (n = 50) in HD group and in 31.4% (n = 11) in non-HD group. CONCLUSION: Although it is still challenging, achievement of SVR12 in patients with chronic HCV and concomitant end-stage kidney disease in the era of DAAs became possible with a 12 weeks course of a co-formula of ombitasvir/paritaprevir /ritonavir plus ribavirin. CLINICALTRIALS. GOV ID: NCT03341988.

Rifaximin versus metronidazole in management of acute episode of hepatic encephalopathy: An open labeled randomized clinical trial.

BACKGROUND AND STUDY AIMS: Many regimens are tried in managing overt hepatic encephalopathy (HE). We investigated the efficacy of rifaximin versus metronidazole in management of an acute episode of HE on top of cirrhosis. PATIENTS AND METHODS: An open label prospective controlled trial was conducted on patients with an acute episode of HE on top of cirrhosis who were randomly divided into metronidazole-group (M-group) and rifaximin-group (R-group) with 60 patients in each. The main outcome measure was the clinical improvement of HE, duration of hospital stay and the changes in the level of serum ammonia after 3 days of starting therapy. RESULTS: Both M-group and R-group were comparable as regards age and sex (mean age 51 ±â€¯11 years and 49 ±â€¯12; male/female ratio 45:15 and 50:10, respectively). Forty-six patients (76.7%) in M-group compared with forty-five (75%) in R-group showed clinical improvement (p = 0.412). Hospital stays were comparable between both group; 4.2 ±â€¯2.1 and 3.9 ±â€¯1.7 for M-group and R-group; respectively (p = 0.435). There was no significant difference of venous ammonia levels (Mean of delta 160.77 ±â€¯185.34 µg/dL and 207.95 ±â€¯218.43 µg/dL with p 0.664 and 0.974 in M-group and R-group, respectively). No adverse events were reported throughout the whole study. CONCLUSION: Rifaximin and metronidazole are equally effective in management of acute episode of overt HE, therefore, re-auditing of treatment protocols of HE are warranted especially in limited resource settings.

Button hole hernioplasty: A new technique for treatment of umblical hernia in cirrhotic patients. A prospective follow up study.

BACKGROUND: Surgical treatment of umbilical hernia in cirrhotic patients is still an interesting topic in many studies to achieve the best method of treatment. These patients are liable to many surgical and medical risks. AIMS: to evaluate the surgical outcome as well as the postoperative course of Button hole hernioplasty as a simple, safe, and effective new technique for hernia repair in cirrhotic patients. METHODS: Forty cirrhotic patients with uncomplicated umbilical hernia were included in this study through collaboration between Departments of General Surgery and Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut, during one year period. Patients were categorized according to the severity of liver cirrhosis into three groups (A, B, and C). Patients were subjected to an elective hernioplasty after adjustment of the disturbed medical and biochemical factors. RESULTS: There was a significant difference in operative time, hospital stay, and prothrombine (time and concentration) among the three groups (p < 0.05). The three parameters were longest in group C when compared to the other two groups. No severe complications were recorded except in only one case. Also, no recurrence, no morbidities or deaths were recorded after 6 months follow-up. CONCLUSIONS: Button hole hernioplasty is a new simple surgical technique for treatment of umbilical hernia in cirrhotic patients with no significant complications.

Incidence, causes, and outcomes of renal failure among cirrhotic patients.

BACKGROUND/AIMS: To evaluate the incidence, risk factors of RF among cirrhotic and its impact on patient's outcome. MATERIALS AND METHODS: A total of 573 cirrhotic patients were evaluated for renal failure (RF) and its causes, 212 patients (37%) were enrolled. RESULTS: Majority of the patients had post hepatitis C liver disease (n=190, 89.6%) with Child-Pugh score C (88.2%), HCC was in 21.2% of cases baseline characteristics. Infections were observed in 45.8% (n=97) of patients whereas, spontaneous bacterial peritonitis (SBP) was the most type of infection (19.3%) among cirrhotic patients with renal failure, followed by pneumonia (9.9%). Infection-induced represents 30.2% followed by hypovolemia (29.7%), whereas HRS was in 11.3%. Reversibility of the condition was seen in 81 patients (38.2%), whereas mortality was seen in 58 (27.4%) patients of RF. The reversibility was more common in the patients with infection, followed by hypovolemia. Mortality was higher in the patients with HRS followed by parenchymal renal disease. CONCLUSION: Infection-induced and hypovolemic-induced RF represent the most common and also the most correctable causes and must be considered in management protocols for early detection and treatment that will serve for a better prognosis.

Multidisciplinary decision making in the management of hepatocellular carcinoma: A hospital-based study.

BACKGROUND/AIMS: To evaluate the short-term outcome of the decision taken by the Hepatoma Board for the treatment of Hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a prospective descriptive study involving 74 patients with HCC diagnosed by the known criteria. The decisions taken by the Hepatoma Board for the 74 patients were as follows: 1- surgical resection (7 patients), 2- local ablative therapy (LAT) (22 patients), 3- conventional transarterial chemoembolization (TACE) (24 patients), and 4- palliative supportive care (21 patients). RESULTS: The short-term mortality rate was 25.7% of the total patients. The success rate was nearly equal in LAT (68.2%) and surgery (71.4%), whereas the success rate was approximately 33.3% in TACE. There was no difference in the mean total bilirubin level before and after LAT, surgery, or TACE (p>0.05 for each). There was a significant decrease in the mean serum albumin level after TACE (p=0.000). There was a decrease in the mean alpha fetoprotein level after surgery and LAT (p=0.033) for surgery and (p=0.048) for LAT. CONCLUSION: The management of HCC is better performed through a multidisciplinary team decision. Surgery has comparable outcome to LAT but is more invasive. According to our local experience, conventional TACE has a success rate of 33.3%.

Human fascioliasis: a re-emerging disease in upper Egypt.

In recent years, the number of humans infected with Fasciola has risen rapidly. Diagnosis is based mainly on detection of eggs in stool analysis. The rate of infection in Egypt is unknown. In this retrospective study, we describe 23 cases of hepatic fascioliasis, and only 2 of these cases showed eggs in stools. The symptoms of infection, such as pyrexia of unknown origin, epigastric pain, and abdominal distension, were suggestive. Imaging techniques, including abdominal ultrasonography and computed tomography, were very helpful in detecting hepatic changes. An indirect hemagglutination assay proved to be of value for diagnosis. Treatment using a 2-day triclabendazole regimen cured the infection and signs of hepatic involvement disappeared. Combining both imaging techniques and laboratory tests is essential for diagnosis of fascioliasis in the early stage.