Detection of hepatitis C virus (HCV) RNA in the peripheral blood mononuclear cells of HCV-infected patients following sustained virologic response.

It is unclear whether direct-acting antiviral drugs (DAAs) result in the complete eradication of HCV infection or whether some quantities of the virus may persist after achieving a sustained virologic response (SVR). Aim The aim of this work was to study the possibility of the persistence of HCV RNA in peripheral blood mononuclear cells (PBMCs) after achieving SVR following DAA treatment. This study included 100 patients infected with HCV genotype 4, who were candidates for receiving DAAs and who achieved SVR during follow-up, as determined at 12 and/or 24 weeks following the end of treatment. All patients were subjected to demographic, biochemical and hematological assessments. Detection of HCV RNA in the serum and PBMCs and determination of the HCV genotype were performed with real-time PCR. We detected HCV RNA in the PBMCs of 20 out of 100 (20%) patients infected with HCV genotype 4, who achieved SVR. However, the persistent viral load in the PBMCs was very low (range: 400-900 U/mL; mean ± SD: 645.45 ± 153 U/mL). Multiple logistic regression analysis showed that only the higher posttreatment levels of aspartate transaminase (AST) were significantly predictive of HCV RNA persistence in the PBMCs (OR: 1.29; 95% CI: 1.08-1.55). Additionally, according to the Cox proportional hazard model, liver cirrhosis was the only significant risk factor for the persistence of HCV infection in PBMCs (HR: 5.8; 95% CI: 1.3-26.1; P < 0.02). Our results indicated the persistence of HCV RNA in some HCV patients who achieved SVR after treatment with DAAs.

Long-term follow-up of living liver donors: A single-center experience.

Living donors are healthy individuals who are exposed to a major surgical procedure during which a major part of their liver is resected. Data on the long-term consequences of living liver donation are scarce. This study examined clinical, laboratory, and long-term health-related quality of life (HRQoL) in 237 living liver donors and 239 matched controls during 48-168 months of postdonation follow-up. We used the 36-item short-form health survey (SF-36), version 1. The scores for the four following subscales were higher in nondonors than in donors: physical functioning (p = 0.009), role limitations due to physical health (p = 0.002), energy/fatigue (p < 0.001), and bodily pain (p < 0.001). The scores on the eight subscales of the SF-36 were higher in donors with living recipients than in donors whose recipients died (p < 0.001). Our results suggest that living donor right hepatectomy is safe and results in a postdonation HRQoL similar to that of nondonors in those donors whose recipients are healthy, whereas donors whose recipients die have a lower HRQoL that is significantly negatively correlated with the time since recipient death and improves over time.

Curcumin activation of nuclear factor E2-related factor 2 gene (Nrf2): Prophylactic and therapeutic effect in nonalcoholic steatohepatitis (NASH).

BACKGROUNDS: Modern dietary habits have been associated with Nonalcoholic Steatohepatitis (NASH). Curcumin is a natural herbal found to suppress cellular oxidative states and could be beneficial in NASH. This study investigates the effect of curcumin in an animal model of NASH. MATERIALS AND METHODS: Fifty rats were allocated into five groups. Control, High Fat Diet (HFD), curcumin prophylactic (CP) and therapeutic (CT) groups. HFD regimen was given for 16 weeks. Curcumin was given along with HFD (prophylactic) or after establishment of the model for two weeks (therapeutic). Livers and blood samples were harvested for histological, biochemical, and molecular studies. KEY FINDINGS: Livers from HFD groups showed vascular, inflammatory, cellular degenerative and fibrotic changes. The hepatic damage was reflected by the increased serum liver enzymes. HFD groups showed excessive fibrotic change. Interestingly, curcumin administration as prophylactic or therapeutic significantly preserved and/or restored liver structure. This was evidenced by the normalization of the liver enzymes, preservation and/or reversibility of cellular changes and the decrease of the stage of fibrosis. Nuclear factor E2-related factor 2 gene (Nrf2) expression showed no changes in the HFD groups, however it showed upregulation in curcumin treated groups. Thus, the protective and therapeutic effect of curcumin could be induced through upregulation of the Nrf2 gene. Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers. SIGNIFICANCE: Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers.

The effects of electrical and thermal boundary condition on the simulation of radiofrequency ablation of liver cancer for tumours located near to the liver boundary.

Effects of different boundary conditions prescribed across the boundaries of radiofrequency ablation (RFA) models of liver cancer are investigated for the case where the tumour is at the liver boundary. Ground and Robin-type conditions (electrical field) and body temperature and thermal insulation (thermal field) conditions are examined. 3D models of the human liver based on publicly-available CT images of the liver are developed. An artificial tumour is placed inside the liver at the boundary. Simulations are carried out using the finite element method. The numerical results indicated that different electrical and thermal boundary conditions led to different predictions of the electrical potential, temperature and thermal coagulation distributions. Ground and body temperature conditions presented an unnatural physical conditions around the ablation site, which results in more intense Joule heating and excessive heat loss from the tissue. This led to thermal damage volumes that are smaller than the cases when the Robin type or the thermal insulation conditions are prescribed. The present study suggests that RFA simulations in the future must take into consideration the choice of the type of electrical and thermal boundary conditions to be prescribed in the case where the tumour is located near to the liver boundary.

Magnesium sulfate versus esomeprazole impact on the neonates of preeclamptic rats.

OBJECTIVE: Preeclampsia represents a major complication of pregnancy, associated with greater maternal and fetal complications. We compared the effects of esomeprazole (a proton pump inhibitor) and magnesium sulfate (MgSO4) on the deleterious effects observed on the mother and neonates in experimentally induced preeclampsia in rats. STUDY DESIGN: Preeclampsia was induced in pregnant rats with NG-nitro-l-arginine methyl ester (L-NAME) starting from day 10-till end of pregnancy. Pregnant rats were divided into four groups: control pregnant; untreated preeclampsia; preeclamptic rats treated with MgSO4 and preeclamptic treated with esomeprazole. Treatment was started on day 14 and continued until end of pregnancy. Systolic blood pressure, gestation duration, the total number of pups/fetal resorption, pups birth weight, and histopathology examination of the pup's organs were recorded. RESULTS: In comparison with the L-NAME group, the MgSO4 and esomeprazole treatment reduced the values of systolic blood pressure; MgSO4 normalized gestational duration while esomeprazole prolonged it (post-term pregnancy); both restored number of delivered pups; with no statistical differences between the numbers of died pups between the four groups studied while with esomeprazole, out of 10 pregnant females, 2 of them had complete intrauterine fetal resorption; esomeprazole normalized birth weight and histological structure of fetal liver, kidney, and brain. On the other side, MgSO4 treatment gave rise to lower than normal birth weight and minimal tissue damage. CONCLUSION: Esomeprazole and MgSO4 improved systolic blood pressure, prevented preterm labor and restored numbers of pups delivered and fetal weight. Esomeprazole prolonged gestational period post-term with subsequent improving reproductive outcome.

Predicting portal hypertension and variceal bleeding using non-invasive measurements of metabolic variables.

BACKGROUND & AIM: This study assessed the involvement of metabolic factors (anthropometric indices, insulin resistance (IR) and adipocytokines) in the prediction of portal hypertension, esophageal varices and risk of variceal bleeding in cirrhotic patients. MATERIAL AND METHODS: Two prospective and retrospective cohorts of cirrhotic patients were selected (n = 357). The first prospective cohort (n = 280) enrolled consecutively in three centers, underwent upper gastrointestinal endoscopy, seeking evidence of esophageal varices. Clinical, anthropometric, liver function tests, ultrasonographic, and metabolic features were recorded at the time of endoscopy, patients were followed-up every 6 months until death, liver transplantation or variceal bleeding. The second retrospective cohort (n = 48 patients) had measurements of the hepatic venous pressure gradient (HVPG). Statistical analyses of the data were with the SPSS package. RESULTS: The presence of esophageal varices was independently associated with lower platelet count, raised HOMA index and adiponectin levels. This relationship extended to subset analysis in patients with Child A cirrhosis. HOMA index and adiponectin levels significantly correlated with HVPG. Beside Child-Pugh class, variceal size and glucagonemia, HOMA index but not adiponectin and leptin plasma levels were associated with higher risk of variceal bleeding. CONCLUSION: In patients with cirrhosis, HOMA score correlates with HVPG and independently predict clinical outcomes. Three simple markers i.e. platelet count, IR assessed by HOMA-IR and adiponectin significantly predict the presence of esophageal varices in cirrhotic patients.

Association between metabolic abnormalities and hepatitis C-related hepatocellular carcinoma.

BACKGROUND AND AIM: Metabolic syndrome is recognised as a potential risk factor for the development of hepatocellular carcinoma (HCC). The association between metabolic factors and hepatitis C (HCV)-related HCC has not yet been well clarified. This study was conducted to elucidate the role of metabolic factors in HCV-related HCC. MATERIAL AND METHODS: We recruited 147 HCC patients and compared them with 147 matched CHC patients and 320 controls. The plasma levels of homeostasis model assessment-IR (HOMA-IR), adiponectin and lipids for all participants were assessed. RESULTS: The HCC group showed significantly higher levels of insulin, glucose, HOMA-IR and adiponectin as well as lower levels of total cholesterol, HDL-C, LDL-C, and triglycerides compared with the matched CHC patients and controls. HOMA-IR did not correlate with pathologic features of HCC, whereas serum adiponectin levels correlated positively with the size of tumour nodules (P = 0.009). Based on stepwise logistic regression analysis, age (OR: 1.456, 95% CI: 1.072-1.979, P < 0.01), HOMA-IR (OR: 2.50, 95% CI: 1.70-3.69, P = 0.001), and adiponectin (OR: 1.585, 95% CI: 1.269-1.980, P = 0.001) were independently associated with HCC. CONCLUSIONS: Metabolic abnormalities are closely associated with the occurrence and development of HCV-related HCC. Patients with CHC and high serum adiponectin levels face a higher risk of developing liver cancer. Insulin resistance, as measured by HOMA-IR, is significantly associated with HCV-related HCC.

Insulin resistance impairs viral dynamics independently of ethnicity or genotypes.

BACKGROUND AND AIM: Data concerning the influence of insulin resistance (IR) and ethnicity on early phases of viral kinetics after initiation of peginterferon plus ribavirin in treatment-naive, chronic hepatitis C (CHC) patients are limited. METHODS: A total of 263 nondiabetic CHC patients treated with peginterferon plus ribavirin were enrolled for analysis from an Egyptian and Spanish center. IR was evaluated by homeostasis model assessment (HOMA)-IR. Hepatitis C virus (HCV) RNA levels were measured at baseline, 48 hours, 2, 4, and 12 weeks after treatment initiation. Sustained virological response (SVR) was examined 24 weeks after therapy discontinuation. RESULTS: Baseline HOMA-IR strongly influenced 48 hours viral dynamics. HCV-RNA decay observed at 48 hours after the first injection of peginterferon was significantly lower (0.91±0.51 log) in patients with HOMA ≥2 compared with those with HOMA <2 (1.8±0.95 log, P=0.005) this effect was independent of stage of liver fibrosis, HCV genotype, and ethnicity. These differences remained with several cutoffs such as HOMA >3 or HOMA >4. Multivariate analysis identified baseline insulin levels as the main independent variable affecting the 48-hour response in addition to baseline HCV-RNA. The difference in early viral kinetics between patients with HOMA ≥2 or <2 is associated with a significant difference in the percentage of patients achieving both rapid virological response and SVR. CONCLUSIONS: IR is a major determinant of the early viral kinetic response to peginterferon plus ribavirin, which has a great impact on subsequent rapid virological response and SVR in CHC patients. This suggests that strategies to improve IR may have a positive effect on SVR and may be early monitored.

Serum lipids and chronic hepatitis C genotype 4: interaction and significance.

BACKGROUND & AIM: Metabolic abnormalities are common in chronic hepatitis C infection (CHC). However, the genotypic differences of these disarrangements in patients infected with CHC genotype 4 (HCV-4) and its association with liver histology and viral loads remain unknown. MATERIAL AND METHODS: We consecutively enrolled 183 HCV-4 patients and 106 healthy matched controls; to compare metabolic profiles and assess pattern of association of HCV RNA levels as well as histological factors with the serum lipid profile. RESULTS: HCV-4 infection is associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) index, despite that, a favourable lipid pattern, consisting of an elevation in HDL- C and a reduction in serum cholesterol (TC), LDL-C and triglyceride (TG) levels, in comparison with normal matched adults. Significant fibrosis was independently associated with HOMA-IR, portal/periportal inflammation grade, serum cholesterol and age. Univariate association was elucidated between lower LDL-C and TC and Metavir activity score and between higher TG and TC and steatosis. In multivariate analysis, severe hepatitis activity, milder hepatic fibrosis, and triglyceride levels are associated with higher HCV RNA levels. CONCLUSION: HCV-4 is associated with wide metabolic changes. A proportional relationship is found between serum lipid profiles and hepatitis C viral load and liver histology in patients with HCV-4.

Management of hepatitis C virus genotype 4: recommendations of an international expert panel.

HCV has been classified into no fewer than six major genotypes and a series of subtypes. Each HCV genotype is unique with respect to its nucleotide sequence, geographic distribution, and response to therapy. Genotypes 1, 2, and 3 are common throughout North America and Europe. HCV genotype 4 (HCV-4) is common in the Middle East and in Africa, where it is responsible for more than 80% of HCV infections. It has recently spread to several European countries. HCV-4 is considered a major cause of chronic hepatitis, cirrhosis, hepatocellular carcinoma, and liver transplantation in these regions. Although HCV-4 is the cause of approximately 20% of the 170 million cases of chronic hepatitis C in the world, it has not been the subject of widespread research. Therefore, this document, drafted by a panel of international experts, aimed to review current knowledge on the epidemiology, natural history, clinical, histological features, and treatment of HCV-4 infections.