Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

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.

Diagnosis, Management And Prevention Of Hepatitis C In Pakistan 2017.

AIMS AND OBJECTIVES: Since the advent of direct acting antiviral agents, there is a revolutionary change in the management of HCV infection. Newer drugs with different mechanism of action are being introduced and are expected to be available in coming few months in Pakistan as well. The main purpose of the guideline is to review and induct the latest research in field of HCV infection in Pakistani perspective so that our healthcare professionals can apply the new recommendations in timely and judicial manner. Target groups of guidelines are general physicians treating hepatitis C, hepatologists and gastroenterologists. Other beneficiaries of these guidelines are public health institutions of Pakistan, which provide free treatment to deserving patients under National Hepatitis Prevention and Control Program and Pakistan Bait-ul- Mal Program. METHODOLOGY: These guidelines are based on the review of National consensus practice guidelines: Diagnosis, Management and Prevention of Hepatitis C Pakistan 2009. Published data in National and International Journals searched with the help of Google search and pub med, and 2015-16 guidelines of HCV by AASLD, EASL, APASL and WHO. Local studies are preferably added with references to enhance the Pakistani perspective. Evidence was also taken from published studies. Recommendations have been based upon evidence from national publications on the subject and scientific presentations at national liver meeting as well from experts' personal experience and opinion.

Low dose albumin for the prevention of renal impairment following large volume paracentesis in cirrhosis.

OBJECTIVES: To evaluate the effect of low dose Albumin i.e. 4 grams per litre of ascitic fluid after large volume paracentesis (LVP) for the prevention of paracentesis induced circulatory dysfunction (PICD) related renal impairment in cirrhosis. METHODS: Case records of all patients with cirrhosis who underwent LVP from January 12(th), 2011 till December 29(th), 2013 were reviewed. Patients were excluded if they had spontaneous bacterial peritonitis, creatinine >1.5 mg/dl, hepatoma or if volume of ascitic fluid removed was <5 litres. Data including age, gender, cause of cirrhosis, CTP score and volume of ascitic fluid drained were noted. In addition serum creatinine and serum sodium at baseline and one week post paracentesis were recorded. RESULTS: Two hundred and fourteen patients with cirrhosis underwent LVP during the study period. One hundred and thirty nine patients met the inclusion criteria and were analyzed. Patients were divided into two groups based on the amount of albumin given. The amount of albumin given was 25 grams and 50 grams while the volume of ascitic fluid removed were 6.2±1 litres and 10.4±1.5 litres in groups A and B respectively. One hundred and eight patients were in group A while thirty one patients were in group B respectively. Both groups received albumin at a dose of 4 grams per litre of ascitic fluid removed. Mean age in both groups were 53 years. Hepatitis C was the commonest etiology in both the groups, followed by Hepatitis B. More than 70% patients in both the groups were in child class C. Serum creatinine at baseline and one week post LVP was 1.04±0.24 mg/dl and 1.07±0.35 mg/dl in GROUP A while 1.11±0.23 mg/dl and 1.41±0.94 mg/dl in GROUP B. (P value 0.35). Similarly, serum sodium at baseline and one week post LVP was 130 ±5.6 meq/lit and 129.6±5.9 meq/lit in GROUP A while 127.6±5.8 meq/lit and 128±6.2 meq/lit in GROUP B respectively. (P value 0.14). CONCLUSION: This study suggests that 4 grams of albumin per litre of ascitic fluid drained is effective in preventing the PICD related renal impairment following large volume paracentesis in cirrhosis.

Value of Adjusted Blood Requirement Index in determining failure to control bleed in patients with variceal bleeding.

INTRODUCTION: Variceal bleeding is a serious complication in patients with cirrhosis. Among the criteria that were proposed in Baveno conferences, the Adjusted Blood Requirement Index (ABRI) has not been validated prospectively in clinical practice. We therefore aim to evaluate the measurement of ABRI as a marker of failure to control bleeding and to evaluate the consistency of ABRI in relation to other criteria of failure to control variceal bleeding. PATIENTS AND METHODS: All patients with variceal bleeding who presented to Aga Khan University Hospital from January 2010 to December 2012 who were administered transfusion of packed red blood cells were included after obtaining informed consent. All patients were managed as per the standard protocol with intravenous terlipressin along with band ligation and injection of cyanoacrylate in cases of esophageal and fundal varices, respectively. Hemoglobin and hematocrit were measured every 6 h for 48 h and then every 12 h until 5 days of index bleed in each patient. Packed cells were transfused if hemoglobin decreased below 8 g/dl. The number of blood units transfused, change in hemoglobin values, and ABRI were calculated after each unit of blood transfusion till 120 h. In patients in whom bleed could not be controlled, an ABRI value of 0.75 or more was compared with other Baveno IV-based parameters that define failure to control variceal bleeding. RESULTS: During the study period, 137 eligible patients with variceal bleed were admitted. The mean age of the patients was 52±12 years. The majority of patients (50.4%) were in Child-Pugh class B, followed by 38% in Child-Pugh class C. According to the Baveno IV criteria, overall failure to control acute variceal bleeding occurred in 52 (37.9%) patients. Excluding ABRI, failure to control bleeding was found in 22/137 (16%) patients, whereas ABRI-based criteria showed that in 34/137 (24.8%) patients, bleeding could not be controlled. There were only four (2.9%) patients with variceal bleeding in whom ABRI and other additional Baveno IV-based criteria for failure to control bleeding were present. When ABRI was compared with other criteria for failure to control bleeding, it showed a sensitivity and specificity of 19 and 25%, respectively. CONCLUSION: This study showed that ABRI is not a useful additional tool to define failure to control bleeding after variceal hemorrhage in cirrhotic patients.

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.

Varied presentation of celiac disease in Pakistani adults.

The objective of this retrospective study was to evaluate presentation of celiac disease in adults. It included 77 patients, 41 (53.2%) males with median age 26 years and median body mass index of 18 (16 - 22) kg/m². Typical presentation with gastrointestinal symptoms was seen in 76.6%. Atypical presentation with extra intestinal complaints in 7.8% and silent presentation in 15.6%. Major symptoms were diarrhea in 64.9%, weight loss 36.4%, abdominal pain 35.1%, vomiting 32.5%, pallor 24.7%, and weakness 13%. Iron deficiency was documented in 20.8%, B12 deficiency in 9.1%, folic acid deficiency in 6.5% and vitamin D deficiency in 10.4%. Half of the patients had haemoglobin less than 11 g/dl. Osteoporosis and osteomalacia, hypothyroidism, diabetes and atrophic gastritis were seen in 2.6% each. Raised alanine aminotransferase was documented in 23.4%. Duodenal biopsy, done in 39 patients, revealed increased intraepithelial lymphocytes in 11, along with crypt hyperplasia in 3, partial villous atrophy in 15 and sub-total villous atrophy in 10. In conclusion, celiac disease in adults should be looked for in patients with chronic diarrhea or irritable bowel syndrome like symptoms, underweight, anaemic, or having nutritional deficiencies.

Perception and knowledge about dietary intake in patients with liver cirrhosis and its relationship with the level of education.

OBJECTIVE: To determine patients perception and knowledge regarding diet in cirrhosis and its relationship with the level of patients education. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: This study was conducted at Gastroenterology Outpatient Clinics at the Aga Khan University Hospital, Karachi, the Aga Khan Health Services, Malir, Karachi and Hamdard University, Karachi, from January to December 2010. METHODOLOGY: Consecutive adult patients with compensated cirrhosis were enrolled. Demographic data, level of education, type and reason of food restriction as well as the source of dietary information was asked. Baseline laboratory test were performed, and nutritional status was assessed by BMI normogram. RESULTS: Ninety patients, 58% male were enrolled. Mean age of the patient was 49 ± 11 years. Overall 73% of the patients were restricting fat, meat, fish and eggs in their diet; 53% were in uneducated group and 47% were in educated group (CI, 0.24-1.62, p-0.34). Twenty two patients (62.8%) in uneducated and 21 in educated group (68%) were restricting diet on the advice of their doctors, whereas 13 in uneducated group (37%) and 11 in educated group (32%) believed these dietary components to be harmful for the liver. Thirty two of uneducated patient (71.1%) and 28 of educated patients (62.2%) believed that vegetables, fruits and sugarcane had a beneficial effect on the liver. Main source of dietary information to the patients was the doctor. On sub-group analysis those who restricted diet irrespective of their educational level, had more patients with BMI less than 18.5 kg/m2, (CI 0.01-0.94, p-0.001), haemoglobin less than 12 g/dl (CI 0- 0.03, p-0.001) and serum albumin less than 3 g/dl (CI 0.1- 03, p-0.001). CONCLUSION: Both educated and uneducated classes of the patients have improper knowledge and perception of diet in cirrhosis. Patients with cirrhosis who restricted diet, had relatively low BMI, haemoglobin and albumin as compared to those who did not restrict. Main source of dietary information to cirrhotic patients were health care personnels.

Nutritional status in patients with hepatitis C.

OBJECTIVE: To assess the nutritional status via the SGA (subjective global assessment) screening tool of patients at all stages of hepatitis C virus (HCV) liver disease. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Out-patient Clinics of the Aga Khan University Hospital, Karachi, conducted from October 2009 to January 2011. METHODOLOGY: Patients with hepatitis C virus infection and their HCV-negative attendants were enrolled from the outpatient clinics, and categorized into 4 groups of 100 patients each: healthy controls (HC), those with chronic hepatitis C infection (CHC), compensated cirrhotics (CC) and decompensated cirrhotics (DC). The validated subjective global assessment (SGA) tool was used to assess nutritional status. RESULTS: A total of 400 patients were enrolled. Most of the patients in the HC group were class 'A' (best nutritional status). In contrast, the majority (64%) in the DC group were in the class 'C' (worst status). The compensated cirrhosis (CC) group showed that 90% of patients were malnourished, while 98% of all patients were malnourished in the DC group, predominantly class 'C'. Most importantly, 14% of patients with chronic hepatitis C (CHC) also scored a 'B' on the SGA; which when compared to HC was statistically significant (p=0.005). As the groups progressed in their disease from CHC to DC, the transition in nutritional status from 'A' to 'C' between groups was statistically significant. CONCLUSION: Malnutrition occurs early in the course of HCV, and progresses relentlessly throughout the spectrum of HCVdisease.

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.

Haemobilia: a rare cause of gastrointestinal bleeding.

Iatrogenic injury to hepatic duct leading to pseudoaneurysm and haemobilia can occur following laparoscopic cholecystectomy. We report a case of a 60 years old man presenting with haematemesis found to have pseudoaneurysm of accessory hepatic artery 4 months after laparoscopic cholecystectomy. Diagnosis was made by computed tomography (CT) scan followed by celiac and mesenteric artery angiogram. The bleeding was successfully treated with coil embolization.

Regular post dinner walk; can be a useful lifestyle modification for gastroesophageal reflux.

OBJECTIVES: To evaluate the correlation of gastroesophageal reflux disease (GERD) symptoms with routine post dinner physical activity and time interval before going to bed, in multiethnic South Asian population. METHODS: Prospective, cross sectional analytical, multicenter study was conducted from February 2009 to March 2010. Patient's relative sitting in outpatient clinics with no comorbids, nonsmoker and non alcoholic were included. They were asked to fill a validated GERD questionnaire and were also inquired about routine post dinner physical activity (lying, sitting, walking) and dinner-bed time interval. Odds Ratios (OR) and their 95% Confidence Intervals (CI) were estimated using Logistic Regression, with gastroesophageal reflux (GER) symptoms as an outcome. RESULTS: Subjects analyzed were 1875. Mean age was 35.37 +/- 12.69 years of which 689 (36.74%) had GERD symptoms. GERD symptoms were 42.08% in routine post dinner recumbency position. While 35.17% and 30.52% had the symptoms in post dinner sitting and walking before going to bed [OR for walking 0.66 (95% CI 0.5-0.88) when compared with lying posture]. GERD symptoms were 45.86% among those with dinner-bed time of one hour, progressively decreasing to 41.68%, 31.45% and 29.88% in the second, third and forth hour respectively. Odds ratio was significant only at 3rd [0.55 (0.41-0.74)] and > or = 4th hr [0.51 (0.37-0.71)] when compared with first hour. CONCLUSION: Regular post dinner walk and > 3 hour dinner-bed time interval were less associated with GERD symptoms.

Efficacy of L-ornithine-L-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy.

OBJECTIVE: To evaluate the efficacy of L-ornithine-L-aspartate (LOLA) as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy (HE). STUDY DESIGN: Randomized placebo controlled study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi in the year 2003-2004. METHODOLOGY: Patients with HE were randomized to receive LOLA or placebo medicine as an adjuvant to treatment of HE. Number connection test-A (NCT-A), ammonia level, clinical grade of HE and duration of hospitalization were assessed. RESULTS: Out of 120 patients, there were 62 males with mean age of 57 ± 11 years. Improvement in HE was higher (n=40, 66.7%) in LOLA group as compared to the placebo group (n=28, 46.7%, p=0.027). In patients with grade I or less encephalopathy, improvement was seen in 6 (35.3%) and 3 (20%) patients in LOLA and placebo groups respectively (p=0.667). Patients with HE grade II and above showed improvement in 34 (79.1%) and 25 (55.6%) cases in LOLA and placebo group respectively (p=0.019). On multivariate analysis patients with HE of grade II and above showed prothrombin time, creatinine level and use of LOLA influencing the outcome. Duration of hospitalization was 93.6 ± 25.7 hours and 135.2 ± 103.5 hours in LOLA and placebo groups respectively (p=0.025). No side effects were observed in either groups. CONCLUSION: In cirrhotic patients with advanced hepatic encephalopathy treatment with LOLA was safe and associated with relatively rapid improvement and shorter hospital stay.

Impact of a bleeding care pathway in the management of acute upper gastrointestinal bleeding.

OBJECTIVES: Upper gastrointestinal (UGI) bleeding carries high morbidity and mortality. The use of a bleeding care pathway (BCP) may improve outcomes, but the results are inconsistent in various studies. METHODS: A BCP for patients with UGI bleed with admission in a bleeding care unit (BCU) has been in use at our hospital since 2005. Prior to this, a high dependency unit was used for management of all emergencies including UGI bleeding. We compared the length of stay in the bleeding care/high dependency unit, total hospital stay, time to UGI endoscopy after admission, and survival between pre-2005 and post-2005 patients. RESULTS: Five hundred and fifty-one patients were admitted with acute UGI bleed in the last 5 years; 121 belonged to pre-BCP (2004) period and 430 after implementation of the pathway (2005-2008). The mean (SD) time to UGI endoscopy improved from 21.3 (7.4) hours in the pre-BCU era to 9.4 (9.9) hours in BCU, p < 0.001. BCU stay was shorter from 2.41 (1.4) days pre-BCP to 1.93 (1.32) days post-BCP, (p < 0.001). The total hospital stay in pre-BCU (4.0 [2.08] days) as compared to BCU (4.13 [2.62] days; p = 0.58) was similar; there was no impact of BCU on survival. CONCLUSION: A BCU implementation showed improvement in time to UGI endoscopy, and did not reduce BCU stay or impact survival.

Frequency and characteristic features of portal hypertensive gastropathy in patients with viral cirrhosis.

OBJECTIVE: To determine the frequency and specific characteristic features of portal hypertensive gastropathy (PHG) in cirrhosis due to viral etiology. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from June 2006 till June 2008. METHODOLOGY: Patients with hepatitis B and C cirrhosis were included who underwent screening esophago-gastroduodenoscopy (EGD) for varices. Baveno III consensus statement was used for diagnosing PHG on endoscopy and divided them into two subgroups i.e. mild and severe. Data related to platelet/spleen ratio, MELD score and Child Turcotte Pugh (CTP) score indicating severity of cirrhosis were recorded in all patients. Findings were compared by using independent sample t-test. RESULTS: Out of 360 patients who underwent screening EGD, 226 (62.8%) were males. Two hundred and eighty one (78%) had hepatitis C while 79 (22%) suffered from hepatitis B related cirrhosis. Three hundred patients (83.3%) had PHG while 71 (24%) had severe PHG. Higher proportion of esophageal varices (89.7%) was present among those who had PHG (p < 0.001). On univariate analysis lower platelet counts (117±55 vs. 167±90; p < 0.001), increased spleen size (14.1±2.9 cm vs. 12±2.4cm; p < 0.001) were found in PHG patients as compared to those without it. Similarly, lower platelet/spleen ratio was noted in patients with severe PHG (916±400 vs. 1477±899; p < 0.001). Furthermore, on multivariate analysis CTP score > 8 MELD score > 12 and platelets/spleen ratio < 900 were significantly associated factors with severe PHG. CONCLUSION: Frequency of PHG was 83% while severe PHG was seen in 24% cases of viral hepatic cirrhosis. MELD score > 12, CTP score ³ 8 and platelets/spleen ratio < 900 were significant factors of severe PHG.

Model for end-stage liver disease (MELD) score as a useful prognostic marker in cirrhotic patients with infection.

OBJECTIVE: To determine the association of Model for End stage liver disease (MELD) score to the outcome of cirrhotic patients with bacterial infection and to compare it with Child-Turcott-Pugh (CTP) score. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 2005 to December 2007. METHODOLOGY: Patients with diagnosis of liver cirrhosis and bacterial infection were included. Demographic features, laboratory data and type of infection were recorded. Multiple logistic regression assays were applied to determine the factors associated with poor outcome in cirrhotics with infection. Receiver-Operating Characteristics (ROC) were used to determine the cut-off values of CTP score and MELD score with the best sensitivity and specificity. RESULTS: A total of 530 patients, 313 male (59%) with a mean age of 53 +/- 13 years were analyzed. Spontaneous bacterial peritonitis was the predominant infection seen in 369 (69%) patients. One hundred and eighty six (35%) patients died. Factors associated with poor outcome were a CTP score of more than 11 (p=0.001), raised blood urea nitrogen (p=0.020), raised creatinine (p=0.004), shock (p=0.002), and MELD score > 22 (p=0.03). An eight percent increase in mortality rate was noticed with every one point rise in MELD score above 22. ROC curve showed that the specificity of CTP and MELD score to predict poor outcome in these patients was 36% and 59% respectively. CONCLUSION: Child-Turcott-Pugh score more than 11, raised BUN and creatinine, shock and high MELD score were poor prognostic markers in cirrhotic patients with infection. MELD score had better specificity than CTP score in determining outcome.

Factors determining the clinical outcome of acute variceal bleed in cirrhotic patients.

Variceal bleed is a severe complication of portal hypertension. We studied the predictors of failure to control variceal bleed and re-bleed in patients with cirrhosis. We reviewed the case records of 382 consecutive patients admitted with variceal bleed from January 2001 to December 2005. Diagnosis of cirrhosis was made on clinical, laboratory, and radiological parameters. Acute variceal bleeding, failure to control bleed, and re-bleeding were defined according to Baveno III consensus report. Failure to control bleed was observed in 39 (10.2%) patients while in hospital re-bleed occurred in 49 (12.8%) patients. Thirty-four patients died. Diabetes was present in 148 (39%) patients. On multivariate logistic regression analysis, predictors of failure to control bleed were presence of diabetes mellitus and active bleeding at the time of endoscopy; predictors of in-hospital re-bleed were diabetes mellitus and serum bilirubin >3 mg/dL. Diabetes mellitus, active bleeding at endoscopy and bilirubin >3 mg/dL are bad prognostic factors for initial control of variceal bleed, and recurrent bleed in patients with cirrhosis.

Role of N-acetylcysteine in adults with non-acetaminophen-induced acute liver failure in a center without the facility of liver transplantation.

PURPOSE: We aimed to study the role of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). METHODS: A total of 47 adult patients were prospectively enrolled with NAI-ALF (group 1 or NAC group) and oral NAC was given. The primary outcome was reduction in mortality with the use of NAC in NAI-ALF. The secondary outcomes were to evaluate safety of NAC and to assess factors predicting mortality. We compared these results with records of NAI-ALF patients admitted in our hospital from 2000 to 2003 (n = 44) who were not given NAC (group 2 or historical controls). RESULTS: The two groups were comparable for the etiology of ALF, prothrombin time (PT), alanine aminotransferase, creatinine, albumin, etc. The mean age in group 1 was 27.7 ± 11.8 years and in group 2 37.5 ± 18.8 years (P = 0.004). Bilirubin was 20.63 ± 11.03 and 14.36 ± 8.90 mg/dl in groups 1 and 2, respectively (P = 0.004). There were 8 (17%) and 1 (2.3%) pregnant ALF women with acute hepatitis E virus (HEV) infection in groups 1 and 2, respectively (P = 0.031). All patients were given supportive care, including mechanical ventilation. A total of 34 (37.36%) patients survived; 22 (47%) in group 1 (NAC group) and 12 (27%) in group 2 (controls) (P = 0.05). On multivariable regression analysis, patients not given NAC (odds ratio [OR] = 10.3, 95% confidence interval [CI] = 1.6-65.7), along with age older than 40 years (OR = 10.3, 95% CI = 2.0-52.5), PT more than 50 s (OR = 15.4, 95% CI = 3.8-62.2), patients requiring mechanical ventilation (OR = 20.1, 95% CI = 3.1-130.2), and interval between jaundice and hepatic encephalopathy (OR = 5.0, 95% CI = 1.3-19.1) were independent predictors of mortality. CONCLUSIONS: The use of NAC causes reduction in NAI-ALF mortality and its use was safe.

Helicobacter pylori infection: approach of primary care physicians in a developing country.

BACKGROUND: The aim of the study was to assess the knowledge and practices of primary care physicians in diagnosis and management of Helicobacter pylori (H. pylori) infection in developing country. METHODS: This convenient sample based, cross sectional study was conducted in primary care physicians of Karachi, Pakistan from March 2008 to August 2008 through a pretested self-designed questionnaire, which contained 11 items pertaining to H. pylori route of transmission, diagnosis, indication for testing, treatment options, follow up and source of information. RESULTS: Out of 509 primary care physicians, 451 consented to participate with the response rate of 88.6%. Responses of 426 primary care physicians were analyzed after excluding 19 physicians. 78% of the physicians thought that contaminated water was the source of spread of infection, dyspepsia was the most frequent indication for investigating H. pylori infection (67% of the physicians), while 43% physicians were of the view that serology was the most appropriate test to diagnose active H. pylori infection. 77% of physicians thought that gastric ulcer was the most compelling indication for treatment, 61% physicians preferred Clarithromycin based triple therapy for 7-14 days. 57% of the physicians would confirm H. pylori eradication after treatment in selected patients and 47% physicians preferred serological testing for follow-up. In case of treatment failure, only 36% of the physicians were in favor of gastroenterologist referral. CONCLUSION: The primary care physicians in this study lacked in knowledge regarding management of H. pylori infection. Internationally published guidelines and World gastroenterology organization (WGO) practice guideline on H. pylori for developing countries have little impact on current practices of primary care physicians. We recommend more teaching programs, continuous medical education activities regarding H. pylori infection.