Abdulrahman Aljumah

Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial

Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock. Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality. Results The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98–2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92–1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04–6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08–8.36, p = 0.02). Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.)

Outcome predictors of cirrhosis patients admitted to the intensive care unit

Objective To evaluate outcome predictors of patients with cirrhosis admitted to an intensive care unit (ICU). Methods One hundred and twenty-nine consecutive patients with cirrhosis admitted to the ICU at a tertiary care transplant centre in Saudi Arabia between March 1999 and December 2000 were entered prospectively in an ICU database. Liver transplantation patients and readmissions to the ICU were excluded. The following data were documented: demographic features, severity of illness measures, parameters of organ failure, presence of gastrointestinal bleeding, and sepsis. The need for mechanical ventilation, renal replacement therapy and pulmonary artery catheter placement was recorded. The primary endpoint was hospital outcome. Results Cirrhotic patients admitted to the ICU had high hospital mortality (73.6%). However, the actual mortality was not significantly different from the predicted mortality using prediction systems. There was an association between the number of organs failing and mortality. Coma and acute renal failure emerged as independent predictors of mortality. All patients who were monitored with pulmonary artery catheterisation in this study died. Patients requiring mechanical ventilation and renal replacement therapy had very high mortalities (84% and 89%, respectively). All 13 cirrhotic patients admitted to ICU immediately post-cardiac arrest in this study died. Conclusions Cirrhotic patients admitted to ICU have a poor prognosis, especially when admitted with coma, acute renal failure or post-cardiac arrest. The consistently poor prognosis associated with certain ICU interventions should raise new awareness regarding limitations of medical therapy. These mortality statistics compel a critical re-examination of uniformly aggressive life support for the critically ill cirrhotic patient, a percentage of whom will not benefit from invasive measures.

Effect of erythromycin before endoscopy in patients presenting with variceal bleeding: a prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND Blood in the stomach and esophagus in patients with variceal bleeding often obscures the endoscopic view and makes endoscopic intervention difficult to perform. Erythromycin, a motilin agonist, induces gastric emptying. OBJECTIVE To assess the effect of erythromycin on endoscopic visibility and its outcome in patients with variceal bleeding. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Tertiary care hospital. PATIENTS Adult patients with liver cirrhosis presenting with hematemesis within the previous 12 hours. INTERVENTION Either 125 mg erythromycin or placebo administered intravenously 30 minutes before endoscopy. MAIN OUTCOME MEASUREMENTS Endoscopic visibility during index endoscopy and mean duration of procedure. SECONDARY OUTCOME MEASUREMENTS: Need for repeat endoscopy and blood transfusions within 24 hours, endoscopy-related complications, and length of hospital stay. RESULTS A total of 102 patients received either erythromycin or placebo (53 erythromycin and 49 placebo). Forty-seven patients in the erythromycin group and 43 in the placebo group had variceal bleeding and were considered for final analysis. A completely empty stomach was seen in 48.9% of the erythromycin group versus 23.3% of the placebo group (P<.01). Mean endoscopy duration was significantly shorter in the erythromycin group than in the placebo group (19.0 minutes vs 26.0 minutes, respectively; P<.005). Length of hospital stay was significantly shorter in the erythromycin group than in the placebo group (3.4 days vs 5.1 days, respectively; P<.002). The need for repeat endoscopy and the mean number of units of blood transfused did not differ significantly in the 2 groups. No adverse events were observed with erythromycin. LIMITATIONS Sample size not sufficient to measure the need for repeat endoscopy and survival benefit. CONCLUSIONS Erythromycin infusion before endoscopy in patients with variceal bleeding significantly improves endoscopic visibility and shortens the duration of the index endoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01060267.).

Efficacy and safety of treatment of hepatitis C virus infection in renal transplant recipients

AIM To assess the efficacy and safety of combined pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) infection in renal transplant recipients. METHODS This is a retrospective chart review of post renal transplant patients who were positive for anti-HCV and HCV-RNA, and who have received treatment with combination of pegylated interferon and ribavirin between October 2003 and December 2008. Only patients with stable graft function and absence of evidence of cirrhosis and who received the therapy for continuous 48 wk were included. Nineteen patients (13 male and 6 female) were identified and included. The patients complete blood count, liver and kidney profile, and calculated glomerular filtration rate (GFR) were monitored every 6-8 wk while on treatment. HCV-RNA was tested at 12 wk for early virological response, at 48 wk for end of treatment response (ETR), and then retested at 24, and 48 wk after completion of therapy for sustained virological response (SVR). Liver biopsies were obtained before treatment from all patients and graft kidney biopsies were performed as required. RESULTS Of the entire cohort, 9 patients (47.4%) showed an ETR and 8 had SVR (42.1%). Of the 8 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 78.9% had their ALT normalized (including the virological non responders). ALT was normal in all responders at the end of therapy and at 24 wk post therapy (100%). Only one patient (5.3%) developed an increase in creatinine and decline in GFR from baseline towards the end of treatment. This patients kidney biopsy revealed borderline rejection. There was no impact on response by HCV-genotype, initial HCV RNA load, age or sex of the patient or duration post transplant before commencement of therapy. All patients tolerated treatment in the same way as non-transplant with no unusual or increased occurrence of side effects. CONCLUSION The combination of pegylated interferon and ribavirin is effective in suppressing HCV-RNA, with a low risk of graft rejection or failure in HCV infected renal transplant recipients.

Etomidate and mortality in cirrhotic patients with septic shock.

BackgroundClinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone.MethodsThis is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome.ResultsSixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality.ConclusionsIn this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.

Intra-abdominal pressure and abdominal perfusion pressure in cirrhotic patients with septic shock

BackgroundThe importance of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in cirrhotic patients with septic shock is not well studied. We evaluated the relationship between IAP and APP and outcomes of cirrhotic septic patients, and assessed the ability of these measures compared to other common resuscitative endpoints to differentiate survivors from nonsurvivors.MethodsThis study was a post hoc analysis of a randomized double-blind placebo-controlled trial in which mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) and IAP were measured every 6 h in 61 cirrhotic septic patients admitted to the intensive care unit. APP was calculated as MAP - IAP. Intra-abdominal hypertension (IAH) was defined as mean IAP ≥ 12 mmHg, and abdominal hypoperfusion as mean APP < 60 mmHg. Measured outcomes included ICU and hospital mortality, need for renal replacement therapy (RRT) and ventilator- and vasopressor-free days.ResultsIAH prevalence on the first ICU day was 82%, and incidence in the first 7 days was 97%. Compared to patients with normal IAP, IAH patients had significantly higher ICU mortality (74.0% vs. 27.3%, p = 0.005), required more RRT (78.0% vs. 45.5%, p = 0.06) and had lower ventilator- and vasopressor-free days. On a multivariate logistic regression analysis, IAH was an independent predictor of both ICU mortality (odds ratio (OR), 12.20; 95% confidence interval (CI), 1.92 to 77.31, p = 0.008) and need for RRT (OR, 6.78; 95% CI, 1.29 to 35.70, p = 0.02). Using receiver operating characteristic curves, IAP (area under the curve (AUC) = 0.74, p = 0.004), APP (AUC = 0.71, p = 0.01), Acute Physiology and Chronic Health Evaluation II score (AUC = 0.71, p = 0.02), but not MAP, differentiated survivors from nonsurvivors.ConclusionsIAH is highly prevalent in cirrhotic patients with septic shock and is associated with increased ICU morbidity and mortality.

Epidemiology, disease burden, and treatment strategies of chronic hepatitis C virus infections in Saudi Arabia in the new treatment paradigm shift

Background/Aims: Around 101,000 individuals are estimated to be viremic for chronic hepatitis C virus (HCV) in the Kingdom of Saudi Arabia (KSA) in 2014; however, only about 20% have been diagnosed. We aim to assess baseline epidemiology, disease burden, and evaluate strategies to eliminate HCV in KSA. Materials and Methods: The infected population and disease progression were modeled using age- and gender-defined cohorts to track HCV incidence, prevalence, hepatic complications, and mortality. Baseline assumptions and transition probabilities were extracted from the literature. The impacts of two scenarios on HCV-related disease burden were considered through increases in treatment efficacy alone or treatment and diagnosis. Results: In 2030, it is estimated by the base scenario that viremic prevalence will increase to 103,000 cases, hepatocellular carcinoma (HCC) to 470, decompensated and compensated cirrhosis cases to 1,300 and 15,400, respectively, and liver-related mortality to 670 deaths. Using high efficacy treatment alone resulted in 2030 projection of 80,700 viremic cases, 350 HCC cases, 480 liver-related deaths, and 850 and 11,500 decompensated and compensated cirrhosis cases, respectively. With an aggressive treatment strategy, in 2030 there will be about 1,700 viremic cases, 1 HCC case, about 20 liver-related deaths, and 5 and 130 cases of decompensated and compensated cirrhosis, respectively. Delaying this strategy by one year would result in 360 additional deaths by 2030. Conclusions: HCV in KSA remains constant, and cases of advanced liver disease and mortality continue to rise. Considered increases in treatment efficacy and number treated would have a significantly greater impact than increased treatment efficacy alone. The projected impact will facilitate disease forecasting, resource planning, and strategies for HCV management. Increased screening and diagnosis would likely be required as part of a national strategy.

Pegylated versus standard interferon plus ribavirin in chronic hepatitis C genotype 4: A systematic review and meta-analysis

Treatment of hepatitis C genotype 4 (HCV‐G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta‐analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR).

Tracing the epidemic history of hepatitis C virus genotypes in Saudi Arabia

HCV genotype 4 is highly prevalent in many Middle Eastern countries, yet little is known about the genotypes epidemic history at the subtype-level in this region. To address the dearth of data from Saudi Arabia (SA) we genotyped 230 HCV isolates in the core/E- and NS5B-region and analyzed using Bayesian phylogenetic approaches. HCV genotype 4 (HCV/4) was positive in 61.7% (142/230) of isolates belonging to 7 different subtypes with the predominance of 4d (73/142; 51.4%) followed by 4a (51/142; 35.9%). Phylogenetic analysis also revealed a distinct epidemiological cluster of HCV/4d for Saudi Arabia. HCV/1 appeared as the second most prevalent genotype positive in 31.3% (72/230) of isolates with the predominance of 1b (53/72; 73.6%) followed by 1a (16/72; 22.2%), and 1g (3/72; 4.1%). A small proportion of isolates belonged to HCV/3a (12/230; 5.2%), and HCV/2a (4/230; 1.7%). We estimate that the genotype 4 common ancestor existed around 1935 (1850-1985). Genotype 4 originated plausibly in Central Africa and multiple subtypes disseminated across African borders since ~1970, including subtype 4d which dominates current HCV infections in Saudi Arabia. The Bayesian skyline plot (BSP) analysis showed that genotype 4d entered the Saudi population in 1900. The effective number of HCV infections grew gradually until the second half of the 1950s and more rapidly until the early-80s through the use of imported blood units and blood products. Subsequently, the rate of HCV infection in the Saudi Arabian population was stabilized through effective screening of blood and infection control measures.

Magnitude and causes of loss to follow-up among patients with viral hepatitis at a tertiary care hospital in Saudi Arabia.

BACKGROUND Non-adherence with recommended follow-up visits is a major barrier for completing treatment of viral hepatitis and is consequently associated with unfavorable outcomes of health services. OBJECTIVES To estimate the magnitude and identify perceived reasons and patient characteristics associated with loss to follow-up in a tertiary care setting. METHODS A two-step cross-sectional study design was used, including a chart review (2011) followed by phone survey (2012). Loss to follow-up was recorded among those who were diagnosed with hepatitis B (HBV) or C (HCV) during 2009-2010 but never returned for recommended/scheduled follow-up appointment(s). RESULTS A total of 328 patients (202 HBV and 126 HCV) were included in the current analysis. The average age was 49.6±17.9years, and 57% were males. Out of 328, 131 (40%) were not advised to do follow-up, and 98 (30%) were not doing follow-up. Perceived reasons for loss to follow-up were as follows: unaware that a follow-up appointment was scheduled (69%), never informed of need for follow-up by healthcare provider (15%), personal belief that follow-up was not necessary (9%), logistical reasons (3%) and other reasons (5%). Loss to follow-up was higher among those who had been diagnosed with HBV, referred by non-liver-related specialty, never advised to follow-up, unaware of their diagnosis, incorrectly identified their type of hepatitis, lacking hepatitis complications, having full medical coverage, pregnant, and those with low knowledge or negative attitude towards hepatitis. CONCLUSIONS Loss to follow-up is a significant problem among patients with hepatitis in a tertiary care center, with several patient and system failures being implicated.