The Predictors of Hepatorenal Syndrome Development in HCV Cirrhotic Ascitic Egyptian Patients with Spontaneous Bacterial Peritonitis.

BACKGROUND & AIM: Spontaneous bacterial peritonitis is considered a precipitating factor for renal impairment in patients with liver cirrhosis. No specific study addressing this problem has been reported. This study aimed to detect the incidence and predictive factors of hepatorenal syndrome in these patients. MATERIALS AND METHODS: This study enrolled 121 hepatic cirrhotic patients with spontaneous bacterial peritonitis. History taking, clinical examination, and laboratory investigations including ascitic fluid analysis were carried out. Kidney function tests were repeated 3 days after the initiation of treatment. Patients were divided into 2 groups after one week of treatment during the follow-up period: Group I: patients without hepatorenal syndrome, and Group II: patients with hepatorenal syndrome. Multivariate analysis was performed to determine independent predictors of hepatorenal syndrome development. RESULTS: A total of 30 patients (24.8%) developed hepatorenal syndrome. Patients with hepatorenal syndrome had significantly lower sodium and albumin levels as well as higher creatinine, bilirubin, Child-Turcotte-Pugh score, portal vein diameter, Model for End-Stage Liver Disease score. Higher percentage of them had a history of recurrent spontaneous bacterial peritonitis and multiple therapeutic paracentesis of ascites. Multivariate analysis detected that serum bilirubin, Model for End-Stage Liver Disease-Sodium, and portal vein diameter were significant predictors of hepatorenal syndrome. Cutoff values were determined as 3.3 mg/dl for bilirubin, 15.9 mm for portal vein diameter, and 26 for Model for End-Stage Liver Disease-Sodium. CONCLUSION: Hepatorenal syndrome is a common complication of spontaneous bacterial peritonitis. In our study, high serum bilirubin, Model for End-Stage Liver Disease-Sodium, and portal vein diameter are predictors of the development of hepatorenal syndrome in patients with spontaneous bacterial peritonitis.

Irritable bowel syndrome in Egyptian medical students, prevalence and associated factors: a cross-sectional study.

Introduction: irritable bowel syndrome is a recurrent chronic gastrointestinal functional disorder. Despite it is not dangerous; it carries a significant feedback on self-confidence and quality of life. Medical students are expected to develop irritable bowel syndrome because they are subjected to stress due to over academic pressure. The objectives were to investigate irritable bowel syndrome prevalence, and to detect the related risk factors in this specific group of Egyptian people. Methods: this cross-sectional study performed in two faculties of medicine in Nile Delta, Egypt. It had been built on self-administered questionnaires including Rome III criteria for diagnosis of irritable bowel syndrome, as well as several questions for gathering socio-demographic information and manifestations suggesting irritable bowel syndrome. Results: fifty (27.5%) of 182 evaluated medical students achieved criteria of irritable bowel syndrome, 64% of them were mixed type. Irritable bowel syndrome had a significant relationship with coffee, milk products, fewer vegetables, and fruits intake (P=0.034, P=0.044, P<0.001 respectively). Depression, anxiety, and food intolerance were detected to be significantly related to irritable bowel syndrome (p<0.001, p=0.005, p=0.04) respectively. Conclusion: it was demonstrated that many Egyptian medical students were suffering from irritable bowel syndrome. Some dietary habits, anxiety, and depression of the students could be risk factors related to development of irritable bowel syndrome.

Treatment of Chronic Hepatitis C Virus Using Direct Acting Antivirals in Geriatric Egyptian Patients.

BACKGROUND & AIMS: There is high proportion of geriatric patients who acquired chronic hepatitis C virus infection. There is a shortage in evidence- based data as regards direct-acting antivirals in this group of patients. The aim was to assess safety, efficacy, and tolerability of direct acting antiviral drugs in Egyptian geriatric patients. METHODS: This prospective study was performed on 177 patients with chronic hepatitis C and administrated different regimens of direct acting antivirals. Patients were divided into two groups: Group I: patients below 65 years old (N = 143), and Group II: patients > 65 years old (N = 34). Pretreatment history taking, baseline characteristics, and investigations were done for both groups. Follow up was made to detect treatment efficacy and adverse effects. RESULTS: Geriatric group were found to have more comorbidities (diabetes mellitus, hypertension, and cardiomyopathy); also liver cirrhosis. Minor adverse effects occurred in both groups without significant difference included fatigue, insomnia, headache, and dizziness. Vomiting, diarrhea, and skin rash occurred in group II more than group I. Leucopenia, thrombocytopenia, jaundice, and significant anemia occurred without significant difference between both groups. Eighteen patients (25%) of 72 patients who took ribavirin had to reduce ribavirin dose or to stop it. The overall treatment response in the entire study was 97.7% without significant difference between both groups. CONCLUSION: Direct acting antivirals are recommended regardless the age. These drugs are effective and tolerable in elderly patients. Attention to other comorbidities, drug-drug interactions, and follow up are recommended.

Modifications of Medical Care of Chronic Liver Diseases During COVID-19 Pandemic: Necessity or Novelty?

In late 2019, coronavirus-2 (SARS-COV 2) infection emerged in Wuhan, China and spread to all countries making the first pandemic of the 21st century. It seems that this infection will persist which is long enough to obligate modifications in both lifestyle and health care systems. Because chronic liver diseases (CLD) are prevalent all over the world, it is expected to manage patients with CLD and COVID-19. The aim of this review was to shed light on the impact of COVID-19 pandemic on the management of patients with CLD and how to give medical care to CLD patients during COVID-19 pandemic.

Predictive and Prognostic Value of Ascitic Fluid Mannose Binding Lectin in Patients with Spontaneous Bacterial Peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis is a common bacterial infection of ascitic fluid, mainly in ascites due to liver cirrhosis. Mannose-binding lectin (MBL) can activate phagocytosis and the complement system. Spontaneous bacterial peritonitis was detected to be higher in MBL deficiency. This study aimed to assess ascitic fluid MBL in liver cirrhosis and spontaneous bacterial peritonitis. METHODS: Ninety patients with cirrhotic ascites were included. Forty five of them had SBP. Child- Pugh score, Model for End Stage Liver Disease (MELD) and its update (uMELD) scores were used to assess the severity of liver cirrhosis. Ascitic fluid samples were obtained for differentiation of leucocytic count, estimation of albumin, protein, glucose, and serum-ascitic albumin gradient. Ascitic fluid levels of MBL were measured for all patients. SBP was documented if polymorphonuclear leucocytic count ≥250/mm in ascitic fluid. RESULTS: Ascitic fluid MBL level was significantly lower in patients with SBP. MBL had a significant negative correlation with ascitic total leukocytic count (TLC), also with serum creatinine, bilirubin, PT, INR and MELD score among SBP patients. However, it had a significant positive correlation with ascitic protein and with platelets. According to multivariate analysis, fever, TLC, platelets, creatinine, MBL, glucose and polymorphs were independent predictors for SBP development. CONCLUSION: Ascitic fluid MBL could be a good predictive and prognostic marker in patients with cirrhosis and spontaneous bacterial peritonitis.

Platelet Count Improvement after Chronic Hepatitis C Treatment among Cirrhotic Patients Who Achieved Sustained Virological Response: Realworld Results from 2186 Patients in Egypt.

BACKGROUND AND AIMS: This study aimed to assess the changes in platelet counts of patients with liver cirrhosis due to chronic HCV, who achieved sustained virological response (SVR) after taking direct acting antivirals (DAAs) in a large cohort study in Egypt. METHODS: This multicenter observational retrospective study was carried out on 2500 chronic hepatitis C virus (HCV) infected patients who achieved (SVR) after treatment with direct acting antiviral drugs (DAA). HCV infection was confirmed by positive PCR for HCV RNA infection. SVR was defined as a negative PCR test for HCV-RNA 12 weeks after completion of DAA therapy. Platelets count was measured before therapy, during therapy, at the end of treatment, and 12 weeks after the end of the treatment. RESULTS: There were 2186 patients enrolled in the study; 1866 (85.4%) were treatment naïve. There were 1006 (46%) males and 1180 (54%) females. Mean age was 50.82± 11.66 years, 2142 (98%.0) patients achieved SVR, 2118 (96.9%) patients had Child -Pugh class A cirrhosis, and 68 (3.1%) had Child -Pugh class B liver cirrhosis. A significant increase in the platelets count was detected at the end of treatment in comparison to the pretreatment levels (P<0.001), and after achieving SVR (P <0.001) when compared to the pretreatment values. CONCLUSION: Improvement of platelets count occurs after HCV therapy with DAAS in patients with liver cirrhosis. These results suggested that HCV eradication may have a role in the improvement of platelet count.

Covid-19: Urgent Call to Action.

Novel Corona Virus 2019 (COVID-19) is a new virus spread rapidly all over the world. It has specific respiratory or gastrointestinal tract symptoms. Its reported complications include respiratory distress, systemic inflammatory response syndrome, and septic shock. Due to heavy cytokines released by the virus; corticosteroids (40-120 mg / day) were given to severe cases to reduce pneumonia. It's a difficult task to control the spread of SARS-CoV-2, and to invent proper vaccines and treatments. In this review, the existing understanding of fatal, pandemic human coronavirus SARS-Cov2 (COVID-19), with special reference to its diagnosis, origin, transmission, and different approaches to develop its therapeutics, will be discussed.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir/ribavirin in management of Egyptian chronic hepatitis C virus patients with chronic kidney disease: A real-life experience.

Treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease was difficult in the past because of the use of interferon (IFN). It was associated with high risk IFN-related adverse reactions due to reduced renal clearance of IFN. This study aimed to evaluate the antiviral efficacy, safety, and tolerability of ombitasvir/paritaprevir/ritonavir/ribavirin in chronic kidney disease patients infected with chronic HCV.This observational, open-label prospective study was carried out on 103 patients infected chronic HCV with different grades of renal impairment. Paritaprevir/ritonavir and ombitasvir (75/50/12.5 mg) twice daily plus ribavirin were given to the patients for 12 weeks. Dose adjustment of ribavirin was done according to degree of renal impairment.Sustained virological response (12 weeks after the end of treatment) occurred in 101 patients (98.1%). Anemia occurred in 48 patients. No serious adverse events were observed in any patient.Paritaprevir/ritonavir and ombitasvir plus ribavirin for 12 weeks was considered to be safe and effective in the treatment of chronic HCV infected patients with varying degrees of renal impairment.

Outcomes of Treatment and Predictors of Response to Sofosbuvir Plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection.

BACKGROUND & AIMS: Treatment plan of chronic HCV infection has dramatically improved after the introduction of different groups of Direct-Acting Antiviral (DAA) drugs. These drugs have been found to be safe and effective. Sofosbuvir (SOF) plus simeprevir (SMV) regimen has been shown to be tolerable and effective in treatment of patients with HCV genotype 1. The aim of the study was to evaluate the safety and the efficacy of combined sofosbuvir plus simeprevir treatment in genotype 4 chronic HCV patients. METHODS: This open-label multicenter prospective study was carried out on 381 Egyptian patients with chronic hepatitis C virus- infection. Treatment experienced and treatment-naive patients were included. Subjects administrated a regimen of sofosbuvir (400 mg/ day) plus semiprevir (150 mg /day) for twelve weeks. Sustained Virological Response (SVR) was confirmed by undetectable HCV RNA by quantitative PCR 3 months after the end of the treatment. RESULTS: 97.6% (372 /381) of patients had SVR. None of the studied clinical and demographic characteristics were associated with the SVR status. However, patients who failed to achieve SVR showed low albumin level and high total leucocyte. The most common side effects of the studied regimen were headache, fatigue, itching, photosensitivity, and cough. CONCLUSIONS: Twelve weeks' regimen of sofosbuvir plus simeprevir was considered to be safe and tolerable in the treatment of HCV genotype 4; also it was associated with high SVR (97.6%).

Amyloid A in Serum and Ascitic Fluid as a Novel Diagnostic Marker of Spontaneous Bacterial Peritonitis.

BACKGROUND: Diagnosis of Spontaneous Bacterial Peritonitis (SBP) depends mainly on ascetic fluid culture which may be negative in spite of the clinical suggestion of SBP and high ascetic fluid neutrophilic count. AIMS: This study aimed to evaluate the biological importance of amyloid A biomarker in both serum and ascetic fluid to diagnose SBP as early as possible and to compare it to other markers (C-reactive protein (CRP), and the neutrophil-to-lymphocyte ratio (NLR)). METHODS: This study included 37 patients with hepatic ascites; twenty-two of them had SBP, and 15 patients did not have SBP. Serum and ascetic fluid amyloid A, ascetic fluid neutrophil, C-reactive protein, and neutrophil-to-lymphocyte ratio were measured in all subjects before the start of antimicrobial chemotherapy to the infected ones. RESULTS: Both the serum and ascetic fluid amyloid and also, CRP were significantly higher in patients infected with ascetic fluid than others. The cut-off point of serum amyloid A for early detection of SBP was 9.25ug/ml with the high sensitivity and specificity. For ascetic amyloid A, the sensitivity and specificity were 90.09% and 60% at cut-off point 2.85ug/ml, respectively. CONCLUSION: Amyloid A in serum and ascitic fluid can be considered as a good biomarker for early diagnosis of SBP.

Hepatitis C Virus: Efficacy of New DAAs Regimens.

BACKGROUND: HCV treatment showed dramatical change due to the introduction of potent, strong, direct antiviral drugs. Before the appearance of Direct-acting antivirals, multiple therapeutic interventions were used for hepatitis C, but none of these interventions were effective on patient-centered outcomes. Direct-acting antivirals cause disruption of viral replication because they target specific nonstructural viral proteins. AIM: To review the advantages of efficient HCV therapy and its long term drawbacks. METHODS: A search of the literature published in indexed databases (PubMed, Medline In-Process, and Embase) within the last 5 years was conducted. Any duplicated citations were excluded before first-pass screening. Citations (titles and abstracts) were screened for eligibility by a single reviewer. Full texts (including congress abstracts, posters and other congress communications) of citations deemed relevant during title and abstract screening were retrieved for second-pass review. RESULTS: Studies on the clinical effects of DAAs for hepatitis C show better tolerance, improved survival and fewer complications when compared to previous interferon therapy. CONCLUSION: HCV treatment has improved dramatically. Since that time, there are multiple approved oral therapies all with high efficacy. The most important factor which should be considered during choosing appropriate therapy is to ensure that it covers the viral genotype of the infected patients.

Role of Both Protein C and Antithrombin III as Predictors of Stage of Liver Disease in Chronic Viral Hepatitis B or C Infected Patients.

BACKGROUND & AIMS: Chronic liver disease is characterized by complex hemostatic disorders because the liver is the site where most of the coagulation factors and their inhibitors are synthesized. The aim of this study was the evaluation of protein C and antithrombin III in different stages of chronic hepatitis B and C and to determine their possible role as markers of liver cell damage in different clinical stages. METHODS: The study included 60 subjects who were subdivided into 4 groups: (Group I): 15 patients diagnosed as chronic viral hepatitis B or C, (Group II): 15 patients with compensated liver cirrhosis, (Group III): 15 patients with decompensated liver cirrhosis, and (Group IV) (control group): 15 healthy individuals. History taking, clinical examination and abdominal ultrasonography were made for all subjects. Investigations were done in the form of liver function tests (ALT, AST, ALP, serum bilirubin, and serum albumin), PT, PTT, CBC. Plasma levels of Antithrombin III & protein C were estimated by automated Stago compact coagulation analyzer. RESULTS: In all patient groups, the mean value of Protein C showed significant decrease when compared to control group, mean value of antithrombin III showed a significant decrease in compensated and decompensated subjects when compared to chronic hepatitis and control groups. Antithrombin III and protein C showed a significant negative correlation with (ALT, AST, PT, PTT, INR). However, this correlation was positive with Albumin. CONCLUSION: Antithrombin III and protein C are natural anticoagulants and can be considered as markers of different stages of chronic liver disease. This is supported further by the comparison between the levels of these parameters and clinical stages of liver disease. Protein C is more sensitive than ATIII as a marker of hepatocellular damage.

Orphenadrine in treatment of muscle cramps in cirrhotic patients: a randomized study.

OBJECTIVE: Many patients of liver cirrhosis are complaining of muscle cramps, which are annoying to them. There is no effective treatment for muscle cramps in cirrhotic patients till now. This study purposed to evaluate efficacy and safety of orphenadrine in the treatment of muscle cramps in cirrhotic patients. METHODS: One hundred and twenty four patients who had muscle cramps three or more times weekly were included. They were divided into two arms: 62 patients administrated orphenadrine and 62 administrated placebo. They were followed up till 2 weeks after the end of therapy. Muscle cramps were evaluated using questionnaire as regards severity, duration, and frequency. Also, side effects of orphenadrine were recorded. RESULTS: Frequency, duration of muscle cramps, and pain score improved significantly after 1 month of orphenadrine therapy in comparison to placebo. Few side effects were recorded in the form of dry mouth, drowsiness, and nausea. CONCLUSION: Orphenadrine is considered as promising safe drug for treatment of muscle cramps associated with liver cirrhosis.

Serum Vitamin D Levels in Chronic Hepatitis B Patients Before and During Treatment.

BACKGROUND & AIMS: Hepatitis B is a potentially life-threatening liver infection and it is a major global health problem. Over the past decade, numerous studies have reported that patients with CLD, especially HCV-positive and HBV-positive patients, have decreased 25(OH) D levels. The current study was designed to assess the serum levels of vitamin D [25(OH) D3] in chronic hepatitis B patients, before and during treatment with antiviral therapy. METHODS: It was a prospective study in which 80 subjects were enrolled between December 2017 and June 2018. A total of 50 treatment-naïve chronic HBV patients and 30 healthy subjects were recruited. The studied cases received treatment in the form of Lamivudine 100 mg tablet, once daily. Full routine laboratory investigations, HBV DNA measurement by real-time PCR were conducted once before initiation of antiviral treatment and again at least 6 months later. Serum vitamin D level [25(OH)D3 was assessed twice, once before initiation of antiviral treatment and again at least 6 months later. This was done for all the patients enrolled in the study. RESULTS: The studied cases showed a significantly low mean serum Vitamin D level when assessed before treatment (21.6 ± 5.8 ng/ml), compared to the level after 6 ms of treatment (31.1 ± 7.3 ng/ml) which was comparable to that of the control group (33.4 ± 5 ng/ml). CONCLUSION: The present study highlights the impact of antiviral therapy on vitamin D deficiency in CHB patients, where effective therapy improves vitamin D levels. Meanwhile, it is recommended to study the impact of vitamin D replacement and correction on the disease progression or regression.

The Effect of Stem Cell Transplantation Therapy for Post Viral Chronic Liver Cell Failure on Associated Type II Diabetes Mellitus: A Pilot Study.

BACKGROUND: It was observed that type II diabetes mellitus associated with chronic liver failure improved after stem cell transplantation. However, there were no adequate studies regarding this issue. The aim of this study was to evaluate the effect of stem cell transplantation on associated type II diabetes mellitus and on the liver function tests. METHODS: This pilot study included 30 patients of post-hepatitis chronic liver failure who were classified into two groups: Group I included patients with chronic liver cell failure associated with type 2 diabetes. Group II included patients without type II diabetes. Autologous CD34+ and CD133+ stem cells were percutaneously infused into the portal vein. Responders (regarding the improvement of diabetes as well as improvement of liver condition) and non-responders were determined. Patients were followed up for one, three and six months after the intervention evaluating their three-hour glucose tolerance test, C- peptide (Fasting and postprandial), Child-Pugh score and performance score one month, three months, and six months after stem cell therapy. RESULTS: Both synthetic and excretory functions of the liver were improved in 10 patients (66.66 %) of group I and in 12 patients (80 %) of group II. Significant improvement in the Oral Glucose Tolerance Test in the responders of both the groups was well defined from the 3rd month and this was comparable to changes in liver function tests and Child-Pugh score. CONCLUSION: Successful stem cell therapy in chronic liver cell failure patients can improve but not cure the associating type 2 diabetes by improving insulin resistance.

Study of Serum Soluble Programmed Death Ligand 1 as a Prognostic Factor in Hepatocellular Carcinoma in Egyptian Patients.

BACKGROUND: The expression of programmed cell death ligands on tumor cells has a role in the suppression of antitumor immunity, resulting in tumor immune evasion. OBJECTIVE: In this study, we evaluated the prognostic value of the soluble form of programmed death-ligand1 (sPD-L1) in Egyptian hepatocellular carcinoma (HCC) patients. METHODS: This prospective cohort study was performed between November 2016 to November 2018 on 85 individuals (25 HCC patients, 25 HCC with vascular invasion and/or extrahepatic metastasis, 25 patients with liver cirrhosis, 10 healthy controls). The levels of sPD-L1 were determined in all subjects and compared in different groups and stages of cirrhosis and HCC. The association between sPD-L1 levels and overall survival (OS) was assessed. RESULTS: Significant statistical difference in sPD-L1 was detected between different study groups. The cut-off value for normal sPD-L1 was defined by high sPD-L1 levels determined in a healthy control cohort. It was 2.522 ng/ml. In HCC patients, cut-off value was 7.42 ng/ml (sensitivity 88%, specificity 100%). In HCC with vascular invasion or metastasis, cut-off value was 9.62 ng/ml (sensitivity 88%, specificity 88%). Patients with high serum sPD-L1 or serum bilirubin concentrations had an increased risk of mortality. CONCLUSION: High sPD-L1 level could be a possible prognostic indicator for a poor outcome in liver cirrhosis and HCC patients. The predictive value of sPD-L1 levels for a successful anti- PD1/PD-L1 therapy should be investigated in the future.

Randomized-controlled trial of methocarbamol as a novel treatment for muscle cramps in cirrhotic patients.

BACKGROUND: Muscle cramps occur in 29-88% of patients with liver cirrhosis. They adversely affect quality of life. This study aimed to evaluate the efficacy and safety of methocarbamol as a novel therapy in controlling muscle cramps in cirrhotic patients. PATIENTS AND METHODS: This study was carried on 100 patients with liver cirrhosis in addition to chronic hepatitis C who presented with frequent muscle cramps (≥three cramps per week). Half of these patients received methocarbamol and the other half received placebo. This was done through equal randomization. Questionnaires on muscle cramp were answered. Patients were evaluated before, after 1 month of treatment, and 2 weeks after washout of treatment in terms of severity, duration, and frequency of cramps. Liver, renal functions, and electrolytes were analyzed. Also, any side effect was detected. RESULTS: Patients who were treated with methocarbamol showed a significant decrease in the frequency and duration of cramps. Also, the pain score improved significantly. However, no significant changes were observed in the placebo group. Few side effects of methocarbamol were recorded, including dry mouth and drowsiness. CONCLUSION: Methocarbamol seems to be a promising safe and well-tolerated medication, and plays a role in the treatment of muscle cramps in patients with liver cirrhosis.

IL-1α correlates with severity of hepatitis C virus-related liver diseases.

BACKGROUND AND AIMS: Immunoregulatory cytokines influence the persistence of hepatitis C virus (HCV) chronic infection and the extent of liver damage. Interleukin-1 (IL-1) plays an important role in the inflammatory process. Some studies have demonstrated that IL-1α production was impaired in patients with chronic infections of HCV, implying that IL-1α may play a role in viral clearance. The aim of this study was to evaluate the serum level of proinflammatory cytokine IL-1α in patients with chronic hepatitis C (CHC). METHODS: This study was performed on 20 CHC patients with cirrhosis in (Group I), 20 CHC patients without cirrhosis in (Group II), 20 hepatocellular carcinoma (HCC) patients with positive anti-HCV in (Group III), and 10 healthy subjects as a control group. Serum levels of IL-1α were measured by enzyme-linked immunoassay technique. RESULTS: IL-1α had the highest mean concentration in the HCC group and then in the group of CHC with cirrhosis compared to the group of CHC without cirrhosis. Also, it was higher in all studied groups than in the control group (P<0.001). Statistical analysis showed that IL-1α was positively correlated with bilirubin (P≤0.001), alanine aminotransferase (P=0.006), aspartate aminotransferase (P=0.001), and viral load (P=0.001) but it was negatively correlated with albumin (P≤0.001) and Hb (P≤0.001), and was not significantly correlated with other parameters (age, international normalized ratio, urea, creatinine, white blood cells, and platelet count). CONCLUSION: Serum level of IL-1α was elevated in patients with CHC and its related liver diseases (liver cirrhosis and HCC) and can be used as an important parameter of inflammatory activity and for fibrosis evaluation in patients with chronic liver disease.