Evaluation of different diagnostic modalities of minimal hepatic encephalopathy in cirrhotic patients: case-control study.

INTRODUCTION: Minimal hepatic encephalopathy (MHE) represents one of the most overlooked complications of liver cirrhosis. AIM OF THE STUDY: To compare the utility and efficacy of different MHE diagnostic modalities. MATERIAL AND METHODS: This case-control study was conducted on hepatitis C virus (HCV)-related compensated cirrhotic patients. The Psychometric Hepatic Encephalopathy Score (PHES) was used to assign patients to MHE and controls. All patients were subjected to plasma ammonia, serum 3-nitrotyrosine (3-NT), critical flicker frequency (CFF), and the modified inhibitory control test (ICT). RESULTS: CFF was significantly lower in the control group (38.5, 40 Hz, p = 0.003). The unweighted lures on ICT were 8.7, 4.9 in MHE and controls (p < 0.001). Moreover, ammonia was higher in the MHE group (89, 61.5 µmol/l, p < 0.001). 3-NT was also higher in the MHE group (31.5, 13.7 nmol/l, p < 0.001) respectively. CFF at cutoff < 39 Hz had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 57.5%, 77.5%, 71.9% and 64.6%, respectively; in modified ICT, at cutoff > 5 unweighted lures the values were 87.5%, 80%, 81.4% and 86.5%, respectively; in ammonia, at cutoff ≥ 76.45 µmol/l the values were 65%, 72.5%, 70.3% and 67.4%, respectively; for 3-NT at cutoff ≥ 14.15 nmol/l the values were 85%, 82.5%, 82.9% and 84.6%, respectively. The accuracy for MHE diagnosis was 67.5%, 83.3%, 68.8%, 83.8% relying on CFF, 3-NT, ammonia, and ICT respectively. On multivariate analysis, CFF < 39 Hz (OR = 10.2, p = 0.04), modified ICT > 5 unweighted lures (OR = 43.2, p = 0.002), and serum 3-NT levels ≥ 14.15 nmol/l (OR = 50.4, p < 0.001) were independent predictors of MHE. CONCLUSIONS: 3-NT and ICT are advantageous to reveal MHE in compensated liver cirrhosis, while CFF can be only used as adjuncts, with humble merits of ammonia.

Hyaluronic acid as a potential marker for assessment of fibrosis regression after direct acting antiviral drugs in chronic hepatitis C patients.

INTRODUCTION: Fibrosis is an inevitable complication of chronic hepatitis C virus (HCV) infection. Direct acting antivirals (DAAs) radically treated HCV and were suggested to ameliorate fibrosis. Silymarin (a natural herbal remedy) was proposed to further decrease hepatic inflammation and fibrosis. Consequently, serial monitoring of liver fibrosis status by different biomarkers is needed. AIM OF THE STUDY: To assess hyaluronic acid (HA) as a potential marker of fibrosis regression after DAAs in chronic HCV patients; in addition, to evaluate silymarin as an agent that, beside DAAs, could further improve fibrosis. MATERIAL AND METHODS: Two groups were included (150 patients each). Group 1 received DAAs only, while group 2 received DAAs followed by silymarin. Hyaluronic acid and FIB4 score were assessed at baseline before treatment and 1 year after inclusion in the study. RESULTS: We found that DAA therapy alone or in combination with silymarin resulted in a significant reduction in serum HA level. However, the latter case showed a statistically significantly greater reduction (p = 0.034). Mean ±SD of serum HA level was 211.8 ±179.9 and 143.3 ±123.9 µg/l before and one year after inclusion respectively in group 1 (p = 0.001) and also, its level decreased significantly in group 2 from 188.3 ±211.8 µg/l before receiving DAAs to 126.4 ±136.9 µg/l at one year after inclusion (p = 0.001). There was no significant difference between the 2 studied groups as regards FIB-4 at 1 year after inclusion (p = 0.103). CONCLUSIONS: Hyaluronic acid might be a sensitive marker for monitoring fibrosis regression in treated chronic HCV patients. Adding silymarin to treatment protocols could ameliorate the fibrosis status.

Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID-19: A randomized controlled trial.

Only a few treatments are approved for coronavirus disease-2019 (COVID-19) infections, with continuous debate about their clinical impact. Repurposing antiviral treatments might prove the fastest way to identify effective therapy. This trial aimed to evaluate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or ravidasvir (RDV) added to standard care (SOC) for patients with moderate and severe COVID-19 infection. Multicentre parallel randomized controlled open-label trial. One hundred and twenty eligible patients with moderate and severe COVID-19 infection were randomized to one of the study arms. Ten days of treatment with SOF plus DCV or RDV in addition to the standard of care compared to SOC. Follow up in 7 days. Sum of the counted symptoms at 7 and 10 days, mean change in oxygen saturation level, viral negativity, and rate of intensive care unit (ICU) admission. Compared to SOC, the SOF-DCV group experienced a significantly lower sum of the counted symptoms (fever, headache, generalized aches, or respiratory distress) combined with no evidence of deterioration (ICU admission and mechanical ventilation) on Days 7 and 10 of treatment. Oxygen saturation also significantly improved among the SOF-DCV group compared to SOC starting from Day 4. The study also showed positive trends regarding the efficacy of SOF-DCV with a lower incidence of mortality. On the other hand, adding SOF-RDV to SOC did not show significant improvements in endpoints. The results support the efficacy and safety of SOF-DCV as an add-on to SOC for the treatment of moderate to severe COVID-19 infections.

Khat-induced liver injuries: A report of two cases.

Khat is consumed for recreational purposes in many countries, including Yemen, where >50% of adults chew khat leaves regularly. A wide spectrum of khat-induced liver injuries has been reported in the literature. Herein, we report two patients with khat-induced liver injury. Both patients clinically presented with acute hepatitis, one of whom showed radiological evidence of hepatic outflow obstruction. Based on the histological tests, both patients had acute hepatitis, which indicated drug-induced liver injury (DILI) on a background of chronic hepatitis and portal fibrosis; of the two, one presented with symptoms of immune-mediated liver injury.

Effect of different therapeutic modalities on systemic, renal, and hepatic hemodynamics and short-term outcomes in cirrhotic patients with spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a major risk factor for hepatorenal syndrome. Albumin infusion has been shown to prevent renal impairment and reduce mortality in SBP. The study aimed to compare the effect of different therapeutic modalities on hemodynamics and short clinical outcomes in high-risk patients with SBP. METHODS: Two hundred cirrhotic patients with SBP and bilirubin greater than 4 mg[Fraction Slash]dl or creatinine more than 1 mg[Fraction Slash]dl were enrolled. Patients were randomized to receive albumin, terlipressin, low-dose albumin plus terlipressin, or midodrine. Systemic, renal, and hepatic hemodynamics were estimated at baseline, 3, and 10 days of treatment. Renal impairment was diagnosed when the blood urea nitrogen or serum creatinine levels increased by more than 50% of the pretreatment value. RESULTS: SBP resolved in most of patients in all groups (P>0.05). Cardiac output and portal flow decreased, whereas systemic vascular resistance increased significantly in terlipressin and albumin plus terlipressin groups compared with the albumin group after 3 and 10 days. After 10 days, plasma renin activity, renal, and hepatic arteries resistive index were significantly higher in the midodrine group compared with the albumin group. The midodrine group did not show any significant changes in the heart rate, mean arterial pressure, cardiac output, and portal blood flow compared with the albumin group after 3 or 10 days. There was no significant difference in renal impairment or mortality between any of the groups. CONCLUSION: Terlipressin and low-dose albumin plus terlipressin could be used as a therapeutic alternative to standard-dose albumin in high-risk SBP patients.

Neutrophil Gelatinase-Associated Lipocalin: A New Marker of Renal Function in C-Related End Stage Liver Disease.

Background/Aims. Renal impairment is a common complication of cirrhosis. Serum creatinine is less sensitive in these patients. Measurement of the glomerular filtration rate (GFR) is the gold standard but time consuming. The aim is to validate plasma NGAL (pNGAL) and urinary NGAL (uNGAL) as markers of renal function in patients with HCV related cirrhosis. Patient and Methods. One hundred HCV related end stage liver cirrhosis patients were randomized into two groups: Group I (n = 35), patients with GFR < 60 mL/m measured by isotope scanning of the kidney (Renogram), and Group II (n = 65), patients with GFR ≥ 60 mL/m. The pNGAL and uNGAL were measured within 2 days of the Renogram. Results. Both groups were matched with age, sex, and Child Pugh score. There was statistically significant difference between both groups regarding serum creatinine (1.98 ± 1.04 versus 1.38 ± 0.88 mg/dL; p = 0.003) and pNGAL level (5.79 ± 2.06 versus 7.25 ± 3.30 ng/dL; p = 0.019). Both groups were comparable (p > 0.05) for the uNGAL (6.00 ± 0.78 versus 6.03 ± 0.96 ng/mL). Unlike uNGAL, the pNGAL positively correlated with total GFR by Renogram (r = 0.3; p = 0.001). With a cutoff ≥4 ng/mL, pNGAL had 94.3% sensitivity and 1.5% specificity and PPV = 34, NPV = 33.3, LR+ = -175.1, and LR- = -60.6. Conclusion. The pNGAL is a promising marker of the renal function in patients with cirrhosis.

The impact of paracentesis flow rate in patients with liver cirrhosis on the development of paracentesis induced circulatory dysfunction.

BACKGROUND/AIMS: Ascites is a dreadful complication of liver cirrhosis associated with short survival. Large volume paracentesis (LVP) is used to treat tense or refractory ascites. Paracentesis induced circulatory dysfunction (PICD) develops if no plasma expanders are given with ominous complications. To study the effect of ascites flow rate on PICD development. METHODS: Sixty patients with cirrhosis and tense ascites underwent LVP of 8 L were randomized into 3 equal groups of different flow rate extraction; group I (80 mL/minute), group II (180 mL/minute) and group III (270 mL/minute). Plasma renin activity (PRA) was measured baseline and on day six. PICD was defined as increase in PRA >50% of the pretreatment value. RESULTS: In group I through 3; the mean age was (52.5±9.4 vs. 56.4±8.5 vs. 55.8±7.1 years; P>0.05), mean arterial pressure (81.4±5.6 vs. 81.5±7 vs. 79.5±7.2 mmHg; P>0.05), MELD (17.6±4.1 vs. 15.8±4.1 vs. 14.7±4.5). Baseline PRA was comparable (1,366.0±1244.9 vs. 1,151.3±1,444.8 vs. 951.9±1,088 pg/mL; P>0.05). There was no statistically significant (P>0.05) flow mediated changes (Δ) of creatinine (0.23±0.27 vs. 0.38±0.33 vs. 0.26±0.18 mg/dL), MELD (1.25±5.72 vs. 1.70±2.18 vs. 1.45±2.21) or PRA (450.93±614.10 vs. 394.61±954.64 vs. 629.51±1,116.46 pg/mL). PICD was detected in a similar frequency in the three groups (P>0.05). On univariate logistic analysis only female sex was a fairly significant PICD predictor (Wald 3.85, odds ratio 3.14; P=0.05). CONCLUSIONS: The ascites flow rate does not correlate with PICD development.

Study of adiponectin in chronic liver disease and cholestasis.

PURPOSE: Adiponectin is an adipocytokine suggested to have a hepatoprotective effect. To date, little information is available in the literature regarding changes in serum adiponectin levels in cirrhosis and cholestasis and the associated metabolic disturbances. In order to elucidate the role of adiponectin in chronic liver disease our aim was to determine serum adiponectin in patients with different grades of cirrhosis and cholestasis and to correlate it with markers of liver injury, inflammation and cholestasis. We also aimed to correlate adiponectin with markers of metabolic syndrome such as body mass index and insulin resistance. METHODS: Forty patients with cirrhosis; 30 patients with cirrhosis and cholestasis; and 20 matched controls were studied. They were subjected to clinical assessment, laboratory investigations: serum bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, C-reactive protein, prothrombin activity, fasting blood sugar, insulin. HOMA index was calculated. Abdominal ultrasonography and upper GI endoscopy were performed. RESULTS: Adiponectin was elevated in patients with cirrhosis and cirrhosis/cholestasis and was significantly higher in Child A and B. Adiponectin showed correlation with liver cell injury, marker of inflammation, synthetic liver function and markers of cholestasis. Adiponectin did not correlate with complications of cirrhosis as ascites and esophageal varices nor did it correlate with BMI or HOMA. CONCLUSIONS: Adiponectin is elevated in cirrhosis and shows correlation with degree of hepatocellular injury and cholestasis. Finally, adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function.

Role of hepatitis C infection in chronic liver disease in Egypt.

Hepatitis C virus (HCV) is considered the most common etiology of chronic liver disease (CLD) in Egypt, where prevalence of antibodies to HCV (anti-HCV) is approximately 10-fold greater than in the United States and Europe. Reported are results that show the role of HCV in both overt and occult CLD, the risk factors for CLD and for HCV infection, and the relative importance of chronic HCV, hepatitis B, or both in causing hepatic morbidity. Case patients included 237 new outpatients at the National Liver Institute. Controls comprised 212 sex- and age-matched neighbors without liver disease. Case patients were more likely than controls to report a history of blood transfusions, schistosomiasis, or parenteral therapy for schistosomiasis; to have anti-HCV, HCV RNA, hepatitis B surface antigen, and serum alanine aminotransferase (ALT) elevations; and to have abdominal ultrasound findings of cirrhosis, portal hypertension, and splenomegaly. Anti-HCV-positive case patients were more likely than anti-HCV-negative patients to be male, older, and farmers: to have received a blood transfusion or parenteral therapy for schistosomiasis; to have ALT elevations; and to have ultrasound findings of cirrhosis, portal hypertension, and spleen enlargement. Anti-HCV-positive controls were more likely than anti-HCV-negative controls to have received parenteral therapy for schistosomiasis. These data support the belief that HCV is the predominant cause of CLD in Egypt and suggest there is a large underlying reservoir of HCV-caused liver disease.