Hematological ratios in patients with acute decompensation and acute-on-chronic liver failure: prognostic factors.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterized by the presence of intense systemic inflammation. Leucocyte quantification can serve as an indirect indicator of systemic inflammation. In our study, we investigated the predictive value of hematological ratios (neutrophils to lymphocytes, monocyte to lymphocytes, platelets to lymphocytes, lymphocytes to C-reactive protein, and neutrophils to lymphocytes and platelets) in acute decompensation (AD) and ACLF patients and their relation to disease severity and early mortality. PATIENTS AND METHODS: We included 60 patients with ACLF and AD, and 30 cirrhotic controls. Clinical data were collected, and survival was followed for 1 and 6 months. Blood samples were analyzed at admission for differential leucocytes and assessed for liver and renal function tests. The leukocyte ratios were calculated and compared, and their correlation with liver function indicators and prognosis was assessed. RESULTS: All ratios were significantly higher in AD and ACLF patients compared to control (except for lymphocyte to C-reactive protein ratio which was significantly lower), and were positively correlated with Child-Pugh score, model for end-stage liver disease (MELD)-Na, and ACLF severity scores. Multivariate regression revealed that neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, and MELD-Na were independent prognostic factors of 1-month and 6-month mortality. A unique prognostic nomogram incorporating MELD-Na, neutrophil to lymphocyte ratio, and monocyte to lymphocyte ratio could be proposed for predicting prognosis in AD and ACLF patients. CONCLUSIONS: Cheap, easy, and noninvasive hematological ratios are introduced as a tool for early identification and risk stratification of AD and ACLF patients.

Efficacy of lubiprostone for functional constipation treatment in adolescents and children: Randomized controlled trial.

OBJECTIVES: Adolescent and pediatric functional constipation (FC) is a common clinical problem. Currently, data on lubiprostone for the treatment of pediatric FC are scarce. This study investigated the efficacy and safety of lubiprostone in the treatment of pediatric FC. METHODS: In a single-blinded, randomized controlled study, we included 280 patients aged 8-18 years with FC. Patients were randomized either to a weight-based lubiprostone dose (n = 140) or conventional laxatives (n = 140), including lactulose, bisacodyl, or sodium picosulfate, for 12 weeks, followed by 4 weeks posttreatment follow-up. RESULTS: Improvement in constipation was achieved in 128 (91.4%) patients in the lubiprostone group, and in 48 (34.3%) patients of the conventional therapy group (p < 0.001) and was sustained after treatment discontinuation. One quarter of the lubiprostone group experienced the first spontaneous bowel motion within 48 h after dose initiation. A total of 75.7% of the lubiprostone group could achieve and sustain Bristol stool form of 3 or 4 during the last 4 weeks of therapy and through the 4 weeks of follow-up versus 50 (35.7%) patients in the conventional therapy group (p < 0.001). No life-threatening adverse drug reactions were encountered, and no treatment-related discontinuation. Mild self-limited colicky abdominal pain and headache were the most prevalent side effects in the lubiprostone group. CONCLUSIONS: Lubiprostone is an effective and well-tolerated pharmacotherapy for youthful age and pediatric age groups, which may alter the paradigm of pediatric FC treatment.

Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial.

Background: Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients. Material and methods: We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40 mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL. Results: Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups (P < 0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan (P < 0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively (P < 0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding. Conclusion: Short course of vonoprazan 20 mg/day is safe and superior to pantoprazole 40 mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.

Vibration Controlled Transient Elastography in Screening for Silent Liver Diseases.

OBJECTIVES: The objective of this study was to screen for significant hepatic fibrosis or steatosis in asymptomatic, apparently healthy subjects by using Vibration-controlled transient elastography and controlled attenuation parameter (CAP). METHODS: Prospectively, 433 asymptomatic apparently healthy adults were included. Fibroscan/CAP examination was performed for all of them. Subjects with liver stiffness measurement > 6 kPa or CAP >248 dB/m were further evaluated to assess underlying chronic liver disease. RESULTS: According to fibroscan/CAP examination, subjects were classified into four subgroups: normal (119) with CAP score of 215.85 ± 24.81 dB/m and fibrosis score of 4.47 ± 0.81 kPa, subjects with steatosis only 133 with CAP score of 309.41 ± 42.6 dB/m and fibrosis score of 4.74 ± 0.82 kPa, subjects with both steatosis and fibrosis 95 with CAP score of 318.20 ± 39.89 dB/m and fibrosis score of 7.92 ± 2.58 kPaand subjects with fibrosis only 86 with CAP score of 213.48 ± 22.62 dB/m and fibrosis score of 6.96 ± 1.11 kPa. S0 was present in 205 (47.3%), S1 in 48 (10.2%), S2 in 16 (3.7%) and S3 in 168 (38.8%) of studied subjects, whereas F0-1 was present in 371 (85.7%), F2 in 44 (10.16%), F3 in 16 (3.7%) subjects and F4 in only one (0.23%) subject. Subjects with both steatosis and fibrosis showed significantly higher transaminases, triglycerides and total cholesterol levels than other subgroups. CONCLUSIONS: Most asymptomatic, apparently healthy subjects (72%) have significant steatosis and fibrosis. Liver stiffness measurement and CAP might represent promising first-line noninvasive procedures to screen for silent liver diseases in the general population.

ß-arrestin-2 predicts the clinical response to ß-blockers in cirrhotic portal hypertension patients: A prospective study.

BACKGROUND: Portal hypertension, a common complication associated with liver cirrhosis, can result in variceal bleeding, which greatly impacts patient survival. Recently, ß-arrestin-2 has been shown to predict the acute hemodynamic response to nonselective ß-blocker therapy for cirrhotic portal hypertension. However, more data is needed on the long-term effects of and changes in ß-arrestin-2 following nonselective ß-blocker therapy. AIM: To investigate the expression and role of ß-Arrestin-2 in predicting the long-term response to nonselective ß-blockers in cirrhotic portal hypertensive patients. METHODS: We prospectively enrolled 91 treatment-naïve patients with cirrhotic portal hypertension. Baseline clinical and laboratory data were obtained. Gastroscopy was performed for grading and treating varices and obtaining gastric antral biopsies. We measured the serum and antral expression of ß-arrestin-2 and obtained Doppler measurement of the portal vein congestion index. Treatment with nonselective ß-blockers was then started. The patients were followed up for 18 mo, after which they have undergone a repeat antral biopsy and re-evaluation of the portal vein congestion index. RESULTS: A higher serum level and antral expression of ß-arrestin-2 was associated with longer bleeding-free intervals, greater reduction in the portal vein congestion index, and improved grade of varices. Among patients with a low ß-arrestin-2 expression, 17.6% were nonselective ß-blocker responders, whereas, among those with high expression, 95.1% were responders (P < 0.001). A serum ß-arrestin-2 value ≥ 2.23 ng/mL was associated with a lower likelihood of variceal bleeding (90% sensitivity and 71% specificity). ß-arrestin-2 expression significantly decreased after nonselective ß-blocker therapy. CONCLUSION: ß-arrestin-2 expression in cirrhotic portal hypertension predicts the clinical response to long-term nonselective ß-blocker treatment. Serum ß-arrestin-2 is a potential noninvasive biomarker for selecting the candidate patients for nonselective ß-blockers.

Post-COVID-19 Syndrome Clinical Manifestations: A Systematic Review.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic health problem that causes a wide spectrum of clinical manifestations and considerable mortality rates. Unfortunately, recovered patients who survive COVID-19 may continue to report a wide variety of clinical manifestations of multisystem affection such as pulmonary embolism, deep vein thrombosis, acute myocardial infarction, depression, anxiety, myalgia, dyspnea, and fatigue. OBJECTIVE: We aimed to summarize the current literature regarding the prevalence of post-COVID- 19 manifestations. METHODS: We conducted a systematic review of post-COVID-19 manifestations by searching MEDLINE via PubMed, Scopus, Web of Science (WOS), EBSCO, Wily, and World health organization (WHO) databases. Screening, study selection, data extraction, data synthesis, and quality assessment were made by two independent reviewers. RESULTS: Of 1,371 references, 817 references remained after removing duplicates. Reviews, case reports, commentaries, and any article containing non-original information were excluded. According to the eligibility criteria for this systematic review, 12 studies were included for qualitative synthesis. The overall prevalence of post-COVID-19 manifestations ranged from 35% to 90.5%. Fatigue, dyspnea, neuropsychological disorders, and pain were the most frequent post-COVID-19 symptoms. CONCLUSION: This systematic review showed that 35% to 90.5% of recovered patients who survive COVID-19 continue to have a wide variety of clinical manifestations, including fatigue, dyspnea, neuropsychological disorders, and pain as the most frequent post-COVID-19 symptoms.

Colorectal cancer in Arab world: A systematic review.

BACKGROUND: The incidence of colorectal cancer (CRC) is increasing among young individuals in the Arab world as well as in other regions of the world. AIM: To explore the incidence and prevalence of CRC in the Arab world. METHODS: The PubMed, Scopus, Web of Science, EBSCO and Wiley databases were searched to retrieve relevant articles irrespective of the language or the publication year. The search terms were "("colon OR rectum OR sigmoid OR rectal OR colonic OR colorectal") AND ("cancer OR malignancy OR malignant OR neoplasm") AND ("Jordan" OR "United Arab Emirates" OR "Bahrain" OR "Tunisia" OR "Algeria" OR "Djibouti" OR "Saudi Arabia" OR "Sudan" OR "Syria" OR "Somalia" OR "Iraq" OR "Oman" OR "Palestine" OR "Qatar" OR "Comoros" OR "Kuwait" OR "Lebanon" OR "Libya" OR "Egypt" OR "Morocco" OR "Mauritania" OR "Yemen"). Reviews, meta-analyses, and articles containing nonoriginal data were excluded. Retrieved articles were screened, and relevant data were extracted. Descriptive statistics were used for data analysis. RESULTS: Nine studies were included. Five of the studies provided information regarding the prevalence of CRC. The prevalence of CRC was 0.72% in Saudi Arabia and 0.78% in the United Arab Emirate, while in Egypt, it ranged from 0.4% to 14%. Four studies showed information regarding the incidence. The annual incidence rate of CRC in Qatar was 7.5/100000/year. In Egypt, the crude incidence rate (CIR) in males was 3.1 for colon cancer and 1 for rectal cancer, while in females, it was 2.3 for colon cancer and 0.8 for rectal cancer. The age-standardized rate for CRC incidence in 2003 was 36.90 for males, 26.50 for females, and 30.49 for both sexes in Saudi Arabia. In 2016, the CIRs in Saudi Arabia were 3.6 and 2.1 in females for colon cancer and rectal cancer, respectively, while in males, it was 3.3 and 2.8 for colon cancer and rectal cancer, respectively. One study in Egypt revealed that 25% of CRC cases occurred among individuals younger than 40 years old. CONCLUSION: There is a considerable prevalence of CRC in some Arab countries. More studies are needed to explore the incidence and prevalence of CRC in the rest of the Arab world.

Efficacy of Lactoferrin with Standard Triple Therapy or Sequential Therapy for Helicobacter pylori Eradication: A Randomized Controlled Trial.

BACKGROUND: Bovine lactoferrin addition to regimens of Helicobacter pylori treatment has been tried, with conflicting results. AIM: To assess the effect of bovine lactoferrin in addition to the anti-H. pylori treatment. METHODS: We enrolled 400 H. pylori-infected patients who were randomized into 4 equal groups: (A): proton-pump-based triple therapy (PpTT) for 2 weeks, (B): sequential therapy for 2 weeks, (C): proton-pump-based triple therapy plus bovine lactoferrin for 2 weeks, and (D): sequential therapy plus bovine lactoferrin for 2 weeks. RESULTS: In the per-protocol analysis, the success in groups A, B, C, and D were 70.3%, 82.8%, 85.6%, and 94.5%, respectively (P < .001). The treatment success rate for the sequential therapy plus bovine lactoferrin regimen was significantly higher than that with sequential therapy alone (94.5% vs. 82.8%, P = .013). The same applied for proton-pump-based triple therapy (85.6% vs. 70.3%, P = .014). The addition of bovine lactoferrin and the presence of endoscopic corpus gastritis were independent predictors for successful eradication of H. pylori. CONCLUSION: Bovine lactoferrin could hasten the effectiveness of the proton-pump-based triple therapy or sequential therapy for H. pylori eradication.

Direct antiviral drugs in the treatment of hepatitis C-infected rheumatoid arthritis Egyptian cohort: safety and clinical impact.

BACKGROUND AND AIM: Data about the safety and efficacy of direct-acting antivirals (DAAs) in the treatment of hepatitis C virus (HCV) patients with concomitant rheumatoid arthritis (RA) are scarce. We assessed the impact and safety of DAAs treatment of hepatitis C on rheumatoid arthritis disease activity. PATIENTS AND METHODS: Prospectively, we enrolled 65 patients with RA and HCV. A clinico-laboratory evaluation was done at baseline, including liver assessment and RA disease activity score-28 (DAS28). At 12 weeks of post-DAAs treatment, sustained virologic response (SVR12) and DAS28 were reevaluated. RESULTS: The SVR12 was achieved in 59 (90.8%) patients. RA control was achieved in 47 (79.9%) patients. The post SVR12 DAS28 score was significantly lower than the baseline (3.32 ± 0.93 vs. 4.37 ± 0.90; P < 0.001). There was a significant decline in the mean values of serum anticyclic citrullinated peptide, rheumatoid factor, erythrocyte sedimentation rate and C-reactive protein after achieving an SVR12 (30.47 ± 12.37 vs. 57.61 ± 15.91 U/ml; 29.78 ± 19.58 vs. 55.14 ± 16.89 IU/ml; 17.13 ± 10.84 vs. 29.68 ± 14.32 mm/h and 5.76 ± 1.57 vs. 11.44 ± 4.13 mg/l, respectively; P < 0.05). RA activity and antirheumatic drugs were stepped-down [12 (20.3%) and 35 (59.3%) patients showed good and moderate RA response, respectively]. The baseline viral load, absence of cirrhosis and SVR12 were the only predictors of disease control (P < 0.05). No drug-related adverse events or drug-related discontinuation. CONCLUSIONS: Unlike interferon, HCV elimination by DAAs significantly improves RA activity and treatment outcome with high safety and efficacy.

Liver stiffness as a predictor of hepatocellular carcinoma behavior in patients with hepatitis C related liver cirrhosis.

BACKGROUND: Risk stratification and prognostication of hepatocellular carcinoma (HCC) help to improve patient outcome. Herein we investigated the role of liver stiffness measurement (LSM) in the prediction of HCC behavior. METHODS: Totally 121 naïve patients with HCC were included. HCC radiological evaluation and staging were done. LSM was measured using virtual touch quantification. Patients were divided into early to intermediate HCC (BCLC-0, A and B) and late HCC (BCLCC and D). HCC was treated according to the BCLC stage. HCC recurrence-free interval was estimated. RESULTS: The mean LSM inside the tumor was significantly lower than the peri-tumoral area and the cirrhotic non-cancerous liver parts (P < 0.001). In late HCCs stage, the mean LSM inside the tumor and in the peri-tumoral tissue was lower than the corresponding values in the early to intermediate HCCs stage (P < 0.001). LSM inside the tumor and in the peri-tumoral tissue negatively correlated with serum AFP, tumor vascular invasion, and stage (P < 0.05). The recurrence-free interval was directly correlated to LSM inside the tumor and inversely to LSM in cirrhotic non tumorous liver part. Kaplan-Meier analysis showed that the recurrence-free interval was significantly longer in patients with LSM inside the tumor of ≥1.25 m/s compared to those with LSM inside the tumor of <1.25 m/s. CONCLUSIONS: LSM can serve as a potential non-invasive predictor for HCC clinical behavior and the recurrence-free interval following loco-regional treatments.

Hepatocellular Carcinoma Occurrence/Recurrence after Direct-Acting Antivirals for Hepatitis C in Egyptian Cohort: Single-Center Experience.

BACKGROUND: Conflicting data have been published about the risk of hepatocellular carcinoma (HCC) following direct-acting antivirals (DAAs). We investigated the incidence of HCC occurrence/recurrence after DAAs therapy. PATIENTS AND METHODS: Retrospectively, we analyzed data of 392 patients with F3-4 fibrosis and cirrhosis treated by DAAs during the period from August 2015 to May 2018. In HCC-experienced patients, HCC treatment modality, and the duration between HCC management and DAAs initiation were recorded. In all patients, pretreatment clinicolaboratory evaluation, and imaging before, during and after DAAs were done. RESULTS: De novo HCC occurred in 7.6% of naïve patients, while recurrence appeared in 28% of patients with previous HCC. Pretreatment alpha-fetoprotein was an independent predictor of HCC occurrence, while the time between HCC ablation and the beginning of DAAs was the only predictor of HCC recurrence (p < 0.001). Half of the patients who started DAAs before 6 months had HCC recurrence, while patients who started DAAs at ≥6 months had no recurrence (p< 0.0001). CONCLUSIONS: Although HCC occurrence after DAAs was not high, recurrence was apparently high. Pretreatment alpha-fetoprotein is a predictor for de novo HCC. The time between HCC ablation and DAAs was the strongest predictor of recurrence.

Role of the von Willebrand factor and the VITRO score as predictors for variceal bleeding in patients with hepatitis C-related cirrhosis.

BACKGROUND: Noninvasive methods have been established to detect clinically significant portal hypertension in liver cirrhosis with variable limitations. The von Willebrand factor (vEF) has been found to increase in liver cirrhosis. AIM: The aim of this study was to explore the vEF and VITRO (von Willebrand factor antigen/platelet ratio) score in the prediction of variceal bleeding in patients with portal hypertension. MATERIALS AND METHODS: Fifty patients with hepatitis C-related liver cirrhosis (25 patients with variceal bleeding and 25 without variceal bleeding) as well as 80 healthy controls were included. Laboratory investigations and upper gastrointestinal endoscopy were performed in all patients. Serum vEF was measured in the patient and the control group. The VITRO score was calculated. RESULTS: The mean levels of the vEF antigen and the VITRO score were higher in patients with variceal bleeding compared with patients without variceal bleeding and controls (P<0.001). At levels of at least 100.1 ng/ml and at least 0.732, the vEF and the VITRO score could predict variceal bleeding with a sensitivity and a specificity of 92 and 99.9% for the vEF and 80 and 68% for the VITRO score (area under the curve=0.982 and 0.843), respectively. Levels of vEF were correlated positively with esophageal varices grade. CONCLUSION: Serum vEF level and the VITRO score are potential noninvasive biomarkers for the prediction and risk stratification of variceal bleeding in hepatitis C-related liver cirrhosis.

Tolerability and effectiveness of generic direct-acting antiviral drugs in eradication of hepatitis C genotype 4 among Egyptian patients.

BACKGROUND: We investigated tolerability and effectiveness of generic, less expensive direct antiviral drugs in the treatment of hepatitis C virus genotype 4 (HCV GT-4) in an Egyptian cohort. PATIENTS AND METHODS: Retrospectively, we analysed data from 648 patients with HCV GT4 attending Alexandria Main University Hospital from January 2016 to May 2017 [488 treatment naïve/160 treatment-experienced/288 with chronic hepatitis/360 with cirrhosis]. Patients received generic sofosbuvir/ledipasvir (n = 168, treatment naïve = 136, treatment-experienced = 32) or sofosbuvir/daclatasvir (n = 480, treatment naïve = 352, treatment-experienced = 128) ± ribavirin. We assessed sustained virologic response 12 weeks after treatment, non-response, relapse, treatment discontinuation and drug adverse reactions. RESULTS: An overall sustained virologic response 12 weeks after treatment was achieved in 97.8%, non-response in 0.6%, relapse in 0.3% and discontinuation of treatment in 1.3% of patients. Sofosbuvir/ledipasvir ± ribavirin regimen attained an overall sustained virologic response 12 weeks after treatment in 96.4% of patients (100% of treatment-experienced vs 95.6% of treatment naïve, P = 0.28), vs 98.3% for sofosbuvir/daclatasvir ± ribavirin regimen (100% of treatment-experienced vs 97.7% of treatment naïve, P = 0.08). No severe drug adverse events or deaths were reported except anaemia due to ribavirin. CONCLUSION: Generic direct antiviral drugs used in treating Egyptian patients with HCV GT-4 demonstrated equal potency, safety and tolerability compared to original brands, with low cost which would help to provide treatment to a larger scale of patients.