Faisal Kamal

Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis

Objectives:Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD.Methods:We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies.Results:We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39–0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51–0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29–0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37–0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46–0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46–0.98); in the randomized controlled trial, HR was 0.39 (0.15–0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding.Conclusions:Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.

Does Urgent Colonoscopy Improve Outcomes in the Management of Lower Gastrointestinal Bleeding

ABSTRACT Colonoscopy continues to be an essential diagnostic and therapeutic tool in the management of lower gastrointestinal bleeding (LGIB). Studies that have evaluated the role of urgent colonoscopy for treating LGIB have reached conflicting conclusions. We conducted a systematic review and meta‐analysis to evaluate the role of urgent colonoscopy in several outcomes in patients with LGIB. We searched Medline, Embase, Scopus and Cochrane databases from inception to July 10, 2016 for comparative studies evaluating the role of urgent versus elective colonoscopy in the management of LGIB. We evaluated mortality, rate of rebleeding, length of stay in hospital, identification of bleeding source, stigmata of recent hemorrhage and need for surgery. Pooled odds ratios (OR) were calculated for dichotomous variables whereas standard mean differences were calculated for continuous variables. We assessed quality using the Cochrane tool and Newcastle Ottawa Scale for randomized controlled trials and observational studies, respectively. We used the GRADE framework to interpret our findings. A total of 6 studies (2 randomized controlled trials and 4 observational studies) with 23,419 patients (9,498 urgent colonoscopy and 13,921 elective colonoscopy) were included in this meta‐analysis. Pooled ORs with 95% CI for mortality, rebleeding and identification of bleeding source were 0.84 (0.46‐1.53), 1.18 (0.64‐2.16) and 1.49 (0.86‐2.59), respectively. Stigmata of recent hemorrhage were more readily identified with urgent colonoscopy OR 2.85 (1.90‐4.28). There were no differences in requirement for surgery, length of hospital stay or rate of endoscopic intervention. However, these effect sizes were limited by considerable heterogeneity, which was probably due to studies being conducted in different countries having different criteria for discharge and on variations in the type of endoscopic therapy for stigmata of recent hemorrhage. In conclusion, among patients with acute LGIB, there is no evidence that urgent colonoscopy reduces mortality, rebleeding or requirement for surgery or that it improves the rate of identification of the bleeding source. However, urgent colonoscopy does increase the rate of detection of stigmata of recent hemorrhage.

Efficacy of self-expandable metal stents in management of benign biliary strictures and comparison with multiple plastic stents: a meta-analysis

Background and study aims There is burgeoning interest in the utilization of covered self-expandable metal stents (CSEMSs) for managing benign biliary stricture (BBS). This systematic review and meta-analysis evaluated cumulative stricture resolution and recurrence rates using CSEMSs and compared performance of CSEMSs and multiple plastic stents (MPS) in BBS management. Method Searches in several databases identified studies including ≥ 10 patients that utilized CSEMSs for BBS treatment. Weighted pooled rates were calculated for stricture resolution and recurrence. Pooled risk ratios (RRs) comparing CSEMSs with MPS were calculated for stricture resolution, stricture recurrence, and adverse events. Pooled difference in means was calculated to compare number of endoscopic retrograde cholangiopancreatographies (ERCPs) in each group.  Results The meta-analysis included 22 studies with 1298 patients. Weighted pooled rate for BBS resolution with CSEMS was 83 % (95 % confidence limits [95 %CLs] 78 %, 87 %; I2 = 72 %). On meta-regression analysis, resolution in chronic pancreatitis patients and post-orthotopic liver transplant patients were significant predictors of heterogeneity. Weighted pooled rate for stricture recurrence with CSEMSs was 16 % (11 %, 22 %). Overall rate of adverse events requiring intervention and/or hospitalization was 15 %. Four randomized controlled trials with 213 patients compared CSEMSs with MPS: the pooled RRs for stricture resolution, recurrence, and adverse events were 1.07 (0.97, 1.18), 0.88 (0.48, 1.63), and 1.16 (0.71, 1.88), respectively with no heterogeneity. Pooled difference in means for number of ERCPs was - 1.71 ( - 2.33, - 1.09) in favor of CSEMS. Conclusions CSEMSs appear to have excellent efficacy in BBS management. They are as effective as MPS but require fewer ERCPs to achieve clinical success.

Outcomes of Liver Transplant Recipients With Autoimmune Liver Disease Using Long-Term Dual Immunosuppression Regimen Without Corticosteroid

Background Liver transplant (LT) recipients with autoimmune liver disease (primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis) are at increased risk of developing acute cellular rejection (ACR), and in many cases graft failure due to recurrent disease. We describe our experience with dual immunosuppression without steroid maintenance and analyze its effect on disease recurrence; ACR; patient and graft survivals; and complications, such as sepsis and de novo malignancy. Methods We included 74 consecutive LT recipients (April 2006 to April 2013) with autoimmune liver disease (primary sclerosing cholangitis, 20; primary biliary cholangitis, 23; autoimmune hepatitis, 31) from a single transplant center. Immunosuppression protocol included rabbit antithymocyte globulin for induction and mycophenolate mofetil with tacrolimus or sirolimus/everolimus indefinitely for maintenance. Results Overall 1-, 3-, 5-, and 7-year patient survival was 95.9%, 90.4%, 82,2% and 74.9%, re–graft-free survival was 93.2%, 86.3%, 79.9%, and 72.8%, respectively (median follow-up, 5.5 years). In a multivariate Cox regression analysis, sepsis during post-LT period (P = 0.040; hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.04-6.11), steroid use for ACR (P = 0.037; HR, 2.60; 95% CI, 1.06-6.34), and younger age (<40 years) at LT (P = 0.038; HR, 2.53; 95% CI, 1.05-6.10) predicted graft survival, whereas steroid use for ACR was the only variable that was predictive of overall patient survival (P = 0.004; HR, 4.10; 95% CI, 1.59-10.52). Overall, 34 biopsy-proven ACR was noted in 22 LT recipients (30%), 13 (17.5%) had disease recurrence, and 34 episodes of sepsis occurred in 19 patients. Conclusions Dual immunosuppression protocol in LT recipients with autoimmune liver disease without corticosteroid maintenance had acceptable rates of survival and ACR without predisposing patients to the adverse effects of long-term steroid therapy.

Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis: A systematic review and meta-analysis

Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22–0.73) (I2=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20–0.44) (I2=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14–1.25) (I2=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18–0.86) (I2=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17–0.63) (I2=0%) and 0.28 (95% CI: 0.17–0.45) (I2=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22–0.75) (I2=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13–0.50) (I2=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

Klebsiella Pneumoniae Liver Abscess: a Case Report and Review of Literature

Klebsiella pneumoniae (K.pneumoniae) is a known cause of pyogenic liver abscess (PLA) in the absence of hepatobiliary disease. In settings of hepatic infection, it has also been known to cause disseminated infections including meningitis and endopthalmitis. Several groups of patients are particularly susceptible to infection, including patients with diabetes mellitus, those from Southeast Asia and those with the preexisting hepatobiliary disease. We present a case of K.pneumoniae PLA with bacteremia. A 39-year-old Vietnamese male with no previous medical history who presented with complaints of abdominal pain, nausea, vomiting, diarrhea and fever. A computed tomography (CT) of the abdomen showed a large complex mass in the right lobe of the liver with multiple septations. Over course of hospitalization, the patient developed acute respiratory failure and was monitored in medical intensive care unit (MICU). Blood cultures grew K. pneumonia. The patient was treated with intravenous ceftriaxone and the abscess was drained by interventional radiology. After appropriate management, he progressed well during his hospital course and was eventually discharged from the hospital. K. pneumonia PLA had previously been an endemic disease in Southeast Asia, however, with a highly mobile patient population, it is now seen throughout the world and should be in the differential of patients who present with solitary liver mass in the setting of sepsis.

Rhabdomyolysis-Associated acute Kidney Injury with Normal Creatine Phosphokinase ☆ ☆☆

ABSTRACT Rhabdomyolysis is a syndrome characterized by the breakdown of skeletal muscle and leakage of intracellular myocyte contents, such as creatine phosphokinase (CPK) and myoglobin, into the interstitial space and plasma resulting in acute kidney injury (AKI). Elevated CPK of at least 5 times the upper limit of normal is an important diagnostic marker of Rhabdomyolysis. We present a case of rhabdomyolysis with severe AKI with a normal CPK at presentation. A 32‐year‐old man presented with acute respiratory failure and AKI after an overdose of recreational drugs. Urinalysis at presentation showed trace amounts of blood, identified as rare red blood cells under microscopy. CPK was 156 U/L at presentation. Workup for glomerulonephritis and vasculitis was negative. He was initiated on renal replacement therapy, and a kidney biopsy showed severe acute tubular injury with positive myoglobin casts. Supportive management and renal replacement therapy was provided, and renal function spontaneously improved after a few weeks. This is an uncommon clinical presentation of severe rhabdomyolysis complicated by AKI. This suggests that CPK alone may not be a sensitive marker for rhabdomyolysis‐induced AKI in some cases.

On-Demand Therapy with Proton Pump Inhibitors for Maintenance Treatment of Nonerosive Reflux Disease or Mild Erosive Esophagitis: A Systematic Review and Meta-Analysis

Background Proton pump inhibitors (PPIs) are widely used for the long-term management of gastroesophageal reflux disease (GERD). However, concerns about the cost and/or inconvenience of continuous maintenance PPI treatment have led to the evaluation of various alternative approaches. Aim To assess the effectiveness of on-demand PPI therapy in the maintenance treatment of nonerosive reflux disease (NERD) or mild erosive esophagitis (EE). Methods We searched MEDLINE, EMBASE, Web of Science, and Cochrane Library from inception until October 2, 2017, for randomized controlled trials (RCTs) comparing on-demand PPI versus placebo or daily PPI in the management of NERD or mild EE (Savary-Miller grade 1). Discontinuation of therapy during the trial was used as a surrogate for patient dissatisfaction and failure of symptomatic control. We calculated pooled odds ratios (OR) to evaluate the efficacy of on-demand PPI treatment. Separate analyses were conducted for studies comparing on-demand PPI with daily PPI and with placebo. Subgroup analysis was done based on NERD studies alone and on studies of both NERD and mild EE. These were analyzed using a random effects model. Results We included 10 RCTs with 4574 patients. On-demand PPI was superior to daily PPI (pooled OR = 0.50; 95% confidence interval (CI) = 0.35, 0.72). On subgroup analysis in NERD patients only, pooled OR was 0.44 (0.29, 0.66). In studies including patients with NERD and mild EE, pooled OR was 0.76 (0.36, 1.60). For studies comparing on-demand PPI with placebo, pooled OR was 0.21 (0.15, 0.29); subgroup analyses of studies evaluating NERD only and studies conducted in NERD and mild EE showed similar results (pooled OR was 0.22 (0.13, 0.36) and 0.18 (0.11, 0.31), resp.). Conclusions On-demand PPI treatment is effective for many patients with NERD or mild EE. Although not FDA-approved, it may be adequate for those patients whose symptoms are controlled to their satisfaction.