Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis.

BACKGROUND & AIMS: Whether non-selective ß-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH). METHODS: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach. RESULTS: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989). CONCLUSIONS: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42019144786. LAY SUMMARY: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective ß-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective ß-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.

Findings from a large Asian chronic hepatitis C real-life study.

There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4-3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3-3.1, P = 0.002). In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype.

Role of assessment for retreatment with Transarterial chemoembolization score in decision of Retreatment with trans-arterial chemo-embolization Sessions in patients with hepatocellular carcinoma.

BACKGROUND: The objective behind this study was to determine that Assessment for Retreatment with Transarterial chemoembolization (ART) score is really applicable in patients with hepatocellular carcinoma. METHODS: A cross sectional observational study was conducted on all patients with hepatocellular carcinoma of intermediate stage and undergone ≥2 Transarterial chemoembolization. ART score was assessed before and after each session of Transarterial chemoembolization. Multi-logistic regression analysis was performed to compare the final outcome of patients with ART score of ≥2.5 into groups with two and more than two Trans-arterial chemo-embolization sessions. RESULTS: A total of 100 HCC patients were recruited for final analysis. Our study participants consisted of total 100 HCC patients. Mean Child Pugh score was 6.1±0.95. In our study, most of the study participants (n=63) had ART score of less than 1.5 as compared to ART score >2.5 (n=37). A significant proportion of patients with ART score of <1.5 prior to second Trans-arterial chemo-embolization had better median survival as compared to patients with ART score of >2.5, p-value<0.001. Patients with ART score of more than 2.5 did not show any survival benefit after having 3rd or 4th Trans-arterial chemo-embolization session, p=0.47. CONCLUSIONS: Our study findings suggest that those HCC patients who receive multiple sessions of TACE with a low ART score have more favourable outcomes with increased survival rate.

Use of medical abbreviations and acronyms: knowledge among medical students and postgraduates.

INTRODUCTION: Inappropriate use of abbreviations and acronyms in healthcare has become an international patient safety issue. The aim of this study was to assess the knowledge of medical abbreviations and acronyms among residents of the department of medicine at a tertiary-care hospital. METHODS: Internal medicine residents (IMRs), subspecialty residents (SRs) and students were asked to complete a self-administered questionnaire which comprised standard abbreviations used in medicine and its various subspecialties. Scores obtained by the residents were classified into three categories: >70% correct answers; 50-69% correct answers; <50% correct answers. RESULTS: A total of 77 IMRs, SRs and medical students participated. Overall, good responses were achieved by 53 (68.8%), 16 (20.8%) attained satisfactory responses, and eight (10.4%) had unsatisfactory scores. The majority of SRs achieved good responses (19/22 (86%)), followed by IMRs (30/40 (75%)) and students (4/15 (26.7%)). Evaluation of their knowledge taken from the list of 'do not use' abbreviations showed that 89.6% reported using 'Q.D.' instead of 'once a day', and 93% used 'IU' instead of the entire phrase 'international unit'. The top five 'not to use' abbreviations were ZnSO4, µg, MgSO4, IU and SC, with the frequency 100%, 96%, 94.8%, 93% and 90%, respectively. CONCLUSIONS: This study showed that there is a knowledge gap among trainees in medicine regarding the meaning and usage of common medical abbreviations. We therefore recommend proper education of trainees in medicine to ensure they understand the meaning of abbreviations and are aware of the list of 'do not use' abbreviations.

Guidelines on gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common acid-related disorder encountered during clinical practice in Pakistan and is associated with significant impairment of health-related quality of life. A number of guidelines and recommendations for the diagnosis and management of GERD have been published in different countries, but a Pakistani accepted directive by the standards of evidence-based medicine is still lacking. Our aim was to create an understanding of the natural history and presentations of reflux disease; evaluating possible treatment options available for the patients with complex and uncomplicated reflux ailments with the development of current and up to date evidence based endorsement, relevant to the needs of Pakistani health care providers in order to treat oesophageal manifestations of GERD. In order to make such guidelines, a comprehensive literature search was conducted with pertinent evidence reviewed, and quality of relevant data assessed. The resultant conclusions were based on the best available evidence and expert opinion of the authors of technical review panel.

Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial.

BACKGROUND & AIMS: Esophageal variceal bleed is a major problem in patients with cirrhosis. Endoscopic variceal ligation (EVL) has been shown to be equal to or better than propranolol in preventing first bleed. Carvedilol is a non-selective ß blocker with alpha-1 adrenergic blocker activity. Hemodynamic studies have shown carvedilol to be more effective than propranolol at reducing portal pressure. We compared efficacy of carvedilol with EVL for primary prophylaxis of esophageal variceal bleed. METHODS: Cirrhotic patients with esophageal varices were randomized to carvedilol 12.5mg daily or EVL at three university hospitals of Pakistan. End points were esophageal variceal bleeding, death or liver transplant. RESULTS: Two hundred and nine patients were evaluated. Eighty two and eighty six patients were randomized in carvedilol and EVL arms respectively. Mean age was 48 ± 12.2 years; 122 (72.7%) were males; 89.9% had viral cirrhosis; mean Child-Pugh score was 7.3 ± 1.6 and mean follow up was 13.3 ± 12.1 months (range 1-50 months). Both EVL and carvedilol groups had comparable variceal bleeding rates (8.5% vs. 6.9%), bleed related mortality (4.6% vs. 4.9%) and overall mortality (12.8% vs. 19.5%) respectively. Adverse events in carvedilol group were hypotension (n=2), requiring cessation of therapy, while transient nausea (n=18) and dyspnea (n=30) resolved spontaneously. In the EVL arm, post banding ulcer bleed (n=1) and chest pain (n=17), were termed as serious adverse events while transient dysphagia (n=58) resolved without treatment. CONCLUSIONS: Although our study is underpowered, the findings suggest that carvedilol is probably not superior to EVL in preventing first variceal bleed in patients with viral cirrhosis.

Subcutaneous and paraspinal tuberculous abscesses in a patient with Crohn's disease.

This case involves a man with longstanding Crohn's disease on azathioprine therapy who developed a rare manifestation of tuberculosis, presenting as a subcutaneous tuberculous abscess and tuberculous spondylitis. The patient's immunocompromised state due to azathioprine raised the risk for opportunistic infections. The unique aspects include the absence of disseminated tuberculosis and the development of tuberculous paraspinal and subcutaneous abscesses in a patient with Crohn's disease. The case underscores the importance of vigilance for rare infections in immunosuppressed individuals and highlights the need for tuberculosis screening before initiating immunosuppressive therapies. The patient was successfully treated with antituberculous medication, emphasising the importance of a tailored approach in managing such cases.

Road to recompensation: Baveno VII criteria and transjugular intrahepatic portosystemic shunt in liver cirrhosis.

Liver cirrhosis has long been considered a point of no return, with limited hope for recovery. However, recent advancements, particularly the Baveno VII criteria and the utilization of transjugular intrahepatic portosystemic shunt (TIPS), have illuminated the concept of hepatic recompensation. In this editorial we comment on the article by Gao et al published in the recent issue. This editorial provides a comprehensive overview of the evolution of understanding cirrhosis, the criteria for recompensation, and the efficacy of TIPS in achieving recompensation. We discuss key findings from recent studies, including the promising outcomes observed in patients who achieved recompensation post-TIPS insertion. While further research is needed to validate these findings and elucidate the mech-anisms underlying recompensation, the insights presented here offer renewed hope for patients with decompensated cirrhosis and highlight the potential of TIPS as a therapeutic option in their management.

Real-world comparison of terlipressin vs. octreotide as an adjuvant treatment in the management of variceal bleeding.

Variceal bleeding is a major complication and the leading cause of death in patients with cirrhosis and portal hypertension. This study aims to compare the efficacy and safety of terlipressin vs octreotide as an adjuvant to endoscopic management of patients with esophageal variceal bleeding in a real-time scenario. We reviewed the medical records of patients with esophageal variceal bleeding from January 2005 to December 2020 at our tertiary care Aga Khan University Hospital. Mortality was assessed after 6 weeks. A total of 842 patients with variceal bleed were evaluated. 624 patients (74.1%) and 218 patients (25.9%) received Terlipressin and Octreotide respectively. On multiple regression analysis, cardiac events during hospital stay (OR: 11.22), presence of Porto-systemic encephalopathy (OR: 3.79), and elevated bilirubin levels at the time of presentation were found to be independent risk factors for increased six weeks mortality. Moreover, cardiac events during hospital stay (OR: 3.26), Porto-systemic encephalopathy at presentation (OR: 3.06), and octreotide administration (OR: 1.80) were identified as independent risk factors for increased length of hospital stay. Terlipressin and Octreotide have similar outcomes in terms of control of bleeding, hospital stay, mortality, and side effects when used as adjuvant therapy for the management of variceal bleeding.

Low rate of recurrence of Helicobacter pylori infection in spite of high clarithromycin resistance in Pakistan.

BACKGROUND: The aim was to investigate the reinfection rate of H. pylori during a follow-up period of 12 months in adults who had undergone eradication therapy. METHODS: One hundred-twenty patients; 116 with gastritis, 3 with duodenal ulcer and 1 gastric ulcer, were studied. Their mean age was 41±13 years (range 18-77) and male: female ratio of 2:1. H. pylori were cultured and antibiotic sensitivity was determined by Epsilometer test (E-test) for clarithromycin (CLR) and amoxicillin (AMX). Primers of urease C gene of H. pylori and Sau-3 and Hha I restriction enzymes were used for polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). 14C urea breath test (14C-UBT) was performed 4 weeks after the eradication therapy. The successfully treated patients were observed for 12 months with 14C-UBT to assess H. pylori status. If 14C-UBT was negative, it was repeated after every 12 weeks. If 14C-UBT was positive, endoscopy was repeated with biopsies. RESULT: The eradication therapy was successful in 102(85%) patients. Out of forty-seven H. pylori isolates cultured, clarithromycin sensitivity was present in 30(64%) and amoxicillin in 45(98%), respectively. Follow-up 14C-urea breath tests of all 102 patients who eradicated H. pylori remained negative up to 9 months. However, in 6 patients, the 14C-UBT confirmed recurrence at 12 months. The recurrence rate was 6%. CONCLUSION: A low rate of recurrence of H. pylori infection was found in patients with dyspeptic symptoms. H. pylori isolates demonstrated a high invitro clarithromycin resistance.

Short course adjuvant terlipressin in acute variceal bleeding: a randomized double blind dummy controlled trial.

BACKGROUND & AIMS: Terlipressin is recommended for 3-5 days as adjuvant to endoscopic variceal band ligation (EVBL) in esophageal variceal bleeding (EVB). We assessed whether terlipressin can be administered for a shorter period of time to patients with EVB. METHODS: All eligible EVB patients received 24h of open label terlipressin at presentation. After successful EVBL, patients were randomized to receive active or dummy terlipressin for the next 48 h. We excluded patients with failure to achieve initial hemostasis, bleeding gastric varices, known hepatoma, and/or portal vein thrombosis, advanced cirrhosis (Child-Pugh score ≥12), and patients on a ventilator. The primary outcome was failure to control EVB. The secondary outcomes were 30-day mortality; re-bleeding and composite outcome of failure to control EVB. RESULTS: A total of 130 eligible patients were randomized to receive terlipressin for a total of 24 (short course or SC) or 72 h (usual course or UC). Baseline patient characteristics were comparable; the majority of patients were HCV-infected and male. There was one failure to control EVB (1.5%) in UC and none in SC terlipressin (p=0.50). The 30-day re-bleeding rate was 1.5% and 3.1% in UC, and SC terlipressin, respectively (p=0.50). The 30-day mortality was 12, 6 (9.2%) patients in each group (p=0.50). The 30-day failure to control bleeding was observed in 14 patients; seven in each group (p=0.494). CONCLUSIONS: In patients with esophageal variceal bleeding, a 24-h course of terlipressin is as effective as a 72-h course when used as an adjunctive therapy to successful EVBL.

The clinical, endoscopic and histological spectrum of the solitary rectal ulcer syndrome: a single-center experience of 116 cases.

BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is an uncommon although benign defecation disorder. The aim of this study was to evaluate the variable endoscopic manifestations of SRUS and its association with other diseases. METHODS: All the patients diagnosed with SRUS histologically from January 1990 to February 2011 at The Aga Khan University, Karachi were included in the study. The medical records were reviewed retrospectively to evaluate the clinical spectrum of the patients along with the endoscopic and histological findings. RESULTS: A total of 116 patients were evaluated. The mean age was 37.4 ± 16.6 (range: 13-80) years, 61 (53%) of the patients were male. Bleeding per rectum was present in 82%, abdominal pain in 49%, constipation in 23% and diarrhea in 22%. Endoscopically, solitary and multiple lesions were present in 79 (68%) and 33 (28%) patients respectively; ulcerative lesions in 90 (78%), polypoidal in 29 (25%), erythematous patches in 3 (2.5%) and petechial spots in one patient. Associated underlying conditions were hemorrhoids in 7 (6%), hyperplastic polyps in 4 (3.5%), adenomatous polyps in 2(2%), history of ulcerative colitis in 3 (2.5%) while adenocarcinoma of colon was observed in two patients. One patient had previous surgery for colonic carcinoma. CONCLUSION: SRUS may manifest on endoscopy as multiple ulcers, polypoidal growth and erythematous patches and has shown to share clinicopathological features with rectal prolapse, proctitis cystica profunda (PCP) and inflammatory cloacogenic polyp; therefore collectively grouped as mucosal prolapse syndrome. This may be associated with underlying conditions such as polyps, ulcerative colitis, hemorrhoids and malignancy. High index of suspicion is required to diagnose potentially serious disease by repeated endoscopies with biopsies to look for potentially serious underlying conditions associated with SRUS.

Epidemiology of functional gastrointestinal disorders using ROME III adult questionnaire, a population based cross sectional study in Karachi-Pakistan.

OBJECTIVE: Functional Gastrointestinal Disorder (FGIDs) are a heterogenous group of disorders, with Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD) being the most common disorders worldwide. The purpose of this study was to identify the spectra of FGIDs classified according to the ROME III criteria amongst an adult Pakistani population. It also aimed to correlate the psychosocial alarm symptoms with the prevalence of FGIDs and report the overlap of all FGID. DESIGN: This was a community based cross-sectional study. Multi-stage cluster sampling technique was applied, and 1062 households were initially randomly chosen using systematic sampling technique. Only one person from each household was enrolled in the study. After eligibility screening, 860 participating individuals were requested to fill out a structured ROME III interview questionnaire, administered to them by a trained interviewer. RESULTS: FGIDs were diagnosed in 468 individuals (54.4%), out of 860 participants. FD was found to be the most prevalent (70.2%), followed by Functional Heartburn (58.9%) and Functional bloating (56.6%). Amongst a total of 468 participants diagnosed with FGIDs, 347 (74.1%) had overlapping disorders. There was also a higher incidence of psychosocial alarm symptoms including higher pain severity (62.6% vs 46.4%) and being victimized at some point in their lives (26.1% vs 6.6%) amongst FGID patients. CONCLUSION: There is a high disease burden of FGIDs in this study population, with approximately half of the population suffering from at least one type of FGID. Overlapping disorders are also common in this part of the world.

Ergonomics of gastrointestinal endoscopies: Musculoskeletal injury among endoscopy physicians, nurses, and technicians.

BACKGROUND: Musculoskeletal injuries (MSI) have plagued endoscopists and ancillary staff for decades without any innovative and strong ergonomic guidelines. It has placed a physical and mental strain on our endoscopists and ancillary staff. We have very have limited data supporting this claim in our region and most data is supported by western literature. AIM: To document the prevalence of MSI, and awareness and practices of ergonomics by endoscopists and ancillary staff. METHODS: This is an observational cross-sectional study, conducted in Karachi, a city that boasts the maximum number of daily endoscopies in the country. An eleven-point self-administered questionnaire was distributed and used to evaluate MSI and ergonomic adjustments amongst three tertiary care setups in Karachi. An onsite survey via a 13-point checklist for endoscopy suite facilities was used to assess the ergonomically friendly conveniences at five tertiary care setups in Karachi. A total of 56 participants replied with a filled survey. RESULTS: There were 56 participants in total with 39 (69.6%) males. Pain and numbness were documented by 75% of the patients, with pain in the neck (41.1%), lower back (32.1%), shoulder (21.4%), thumb (12.5%), hand (23.2%), elbow (8.9%), and carpal tunnel syndrome (CTS) (7.1%). Of those, 33.3% attributed their symptoms to endoscopy, 14.2% said that symptoms were not caused by endoscopy, and 52.4% were not certain whether endoscopy had caused their symptoms. Twenty-one point four percent of patients had to take time off their work, while 33.9% took medications for pain. Ergonomic modifications to prevent musculoskeletal injury, including placement of endoscopic monitor at eye level and the cardiac monitor in front, stopping the procedure to move patients, sitting while performing colonoscopy, and navigating height-adjustable bed were used by 21.4%. Nine out of 13 ergonomic facilities were not present in all five tertiary care hospitals. Conveniences, such as anti-fatigue mats, height-adjustable computer stations, and time out between patients were not present. CONCLUSION: Three-fourth of our endoscopists reported MSI, of which more than half were not sure or attributed this problem to endoscopy. The prevalence of MSI warrants urgent attention.

Impact of coronavirus disease 2019 on prevention and elimination strategies for hepatitis B and hepatitis C.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality since its first case was discovered in December 2019. Since then, multiple countries have witnessed a healthcare system collapse due to the overwhelming demand for COVID-19 care. Drastic measures have been taken globally in order to curb the spread of the virus. However, those measures have led to the disruption of other aspects of healthcare, increasing the burden due to other medical conditions. We have also stepped back in achieving the ambitious goal set in place by World Health Organization to eliminate viral hepatitis as a public threat by 2030. Hepatitis B and C are chronic conditions with a significant worldwide burden, and COVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. In this review, we elucidate the impact of the ongoing COVID-19 pandemic on the interventions targeted towards the elimination of hepatitis B virus and hepatitis C virus. Some of the salient features that we have covered in this review include hindrance to screening and diagnostic tests, neonatal vaccinations, the transmission dynamics affecting hepatitis B virus and hepatitis C virus, role of limited awareness, restrictions to treatment accessibility, and disparity in healthcare services. We have highlighted the major issues and provided recommendations in order to tackle those challenges.

Impact of Gastrointestinal Diseases on Health-Related Quality of Life of Patients in Pakistan.

Objective This study aimed to evaluate the impact of gastrointestinal (GI) diseases on health-related quality of life (HRQoL) in Pakistani patients. Methods A cross-sectional study was conducted from 1st January 2019 to 15th February 2019 at a tertiary care hospital in Pakistan by employing a self-administered questionnaire called Gastrointestinal Quality of Life Index (GIQLI). Questionnaires were distributed among the patients presenting to outpatient gastroenterology clinics to evaluate their HRQoL. Results A total of 199 patients were included in this study, and their mean GIQLI score was 87.8 ± 17.8. Results showed that more severe core symptoms can lead to a poorer QoL. Overall GIQLI scores and most of its domain scores were lower in females as compared to males (p-value: 0.02). Obese patients had an overall lower mean GIQLI score including in the GI, psychological, and social domains while advanced age was associated with a higher disease-specific GIQLI score. Conclusion Based on our findings, GI diseases negatively impact the HRQoL in patients. Physicians need to consider the different domains of QoL as part of a holistic approach to treating these patients.