Predictors of Minimal Hepatic Encephalopathy in Patients with Cirrhosis

Background/Aim:

Minimal hepatic encephalopathy (MHE) impairs patient’s daily functioning of life. Predictors of MHE in cirrhotic patients have not been evaluated.

Patients and Methods:

A total of 200 cirrhotic patients (Child A, 74 [37%]; Child B, 72 [36%]; Child C, 54 [27%]) were evaluated by psychometry, P300 auditory event-related potential (P300ERP) and critical flicker frequency (CFF). MHE was diagnosed by abnormal psychometry (>2 S.D.) and P300ERP (>2.5 S.D.). Univariate and multivariate logistic regression analyses were performed to determine the predictors of MHE.

Results:

Eighty-two (41%) patients were diagnosed to have MHE – 26/74 (35%) in Child A, 26/72 (36%) in Child B and 30/54 (56%) in Child C. Ninety-seven (48.5%) patients had abnormal psychometric tests, and 96 (48%) had prolonged P300ERP (>358 ms). Sixteen (16.5%) patients with abnormal psychometry had P300ERP < 358 ms, and 15 (14.5%) patients with normal psychometry results had P300ERP > 358 ms. One hundred and three patients had CFF value < 39 Hz with specificity of 86.6% and sensitivity of 72.9% for MHE. Model for end-stage liver disease (MELD) (17.9 ± 5.7 vs. 13.4 ± 4.2, P = 0.005), Child-Turcotte-Pugh (CTP) score (8.4 ± 2.5 vs. 7.7 ± 2.2, P = 0.02), ammonia (104.8 ± 37.9 vs. 72.5 ± 45.2 µmol/L, P = 0.001) and CFF (37.0 ± 2.8 vs. 41.0 ± 3.4 Hz, P = 0.001) were significantly higher in MHE as compared to non-MHE patients. Ninety-one (45.5%) patients had MELD > 15.5, 115 (57.5%) had CTP score > 7.5, while 93 (46.5%) had venous ammonia > 84.5 µmol/L. On univariate analysis, MELD (8.52 [95% CI, 4.46-16.26; P = 0.001]), CFF (17.34 [95% CI, 8.16-36.85; P = 0.001]) and venous ammonia (7.80 [95% CI, 4.11-14.81; P = 0.003]) were associated with MHE; while CTP score (1.51 [95% CI, 0.85-2.69; P = 0.30]) was not significant. On multivariate analysis, MELD, CFF and venous ammonia were predictive of MHE.

Conclusion:

Prevalence of MHE in this study was 41%; and MELD > 15.5, CFF < 39 Hz and venous ammonia > 84.5 µmol/L were predictive of MHE.     

Inhibitory Control Test,Critical Flicker Frequency,and Psychometric Tests in the Diagnosis of Minimal Hepatic Encephalopathy in Cirrhosis

Background/Aim:

Minimal hepatic encephalopathy (MHE) impairs health-related quality of life and driving ability of the patient.

Objective:

We assessed the utility of the inhibitory control test (ICT), critical flicker frequency (CFF), and psychometry in the diagnosis of MHE.

Patients and Methods:

Consecutive patients with cirrhosis underwent number connection tests A and B (NCT-A, B), digit symbol test (DST), line tracing test (LTT), serial dot test (SDT), CFF, and ICT at baseline and after four hours. Fifty healthy subjects served as controls for the ICT test.

Results:

Fifty patients with cirrhosis (43.4 ± 10.2 yrs, M: F 42:8) underwent psychometric tests [NCT-A (48.3 ± 17.7 vs. 42.6 ± 17.3 sec, P = 0.001), NCT-B (85.7 ± 40.1 vs. 90.2 ± 37.0 sec, P = 0.18), DST (23.5 ± 9.3 vs. 23.0 ± 8.7, P = 0.45), LTT (96.6 ± 48.2 vs. 96.8 ± 46.8 sec, P = 0.92), SDT (88.0 ± 39.5 vs. 83.4 ± 37.2 sec, P = 0.02)] at baseline and after four hours. Target accuracy of ICT was lower in patients with cirrhosis compared with controls (88.4 ± 5.6 vs. 95.6 ± 2.1, P = 0.01), whereas ICT lures were higher (18.3 ± 4.2 vs 10.2 ± 2.8, P = 0.01). Patients with cirrhosis showed a reduction in lures in the second evaluation compared with the first (18.3 ± 4.2 vs. 17.1 ± 4.3, P = 0.003) but no change in target accuracy (88.4 ± 5.6 vs. 88.4 ± 5.3, P = 0.97). Control subjects did not show any change either in lures (10.2 ± 2.8 vs. 10.3 ± 2.1, P = 0.65) or target accuracy (95.6 ± 2.1 vs. 95.5 ± 2.2, P = 0.82). The sensitivity and specificity of ICT test for the diagnosis of MHE at lure rate >16.5 was 88.5 and 56%, respectively. CFF in patients with MHE (38.4 ± 1.8 vs. 38.6 ± 1.5, P = 0.3) and non MHE (40.6 ± 2.2 vs. 40.8 ± 2.2, P = 0.6) did not show any difference after four hours as in controls (41.9 ± 2.4 vs. 42.1 ± 2.0, P = 0.3). Thirty one (31%) patients preferred psychometric tests, 57 (57%) preferred CFF and only 12 (12%) preferred ICT (P = 0.001).

Conclusions:

ICT, CFF, and psychometric tests are useful tools to assess MHE, and CFF was preferred by this study cohort.     

Lactulose for Minimal Hepatic Encephalopathy in Patients with Extrahepatic Portal Vein Obstruction

Background/Aims:

Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO.

Patients and Methods:

Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months.

Results:

Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 μmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation.

Conclusions:

Lactulose is effective in the treatment of MHE in patients with EHPVO.     

Effect of Rifaximin,Probiotics, and l-Ornithine l-Aspartate on Minimal Hepatic Encephalopathy: A Randomized Controlled Trial

Background/Aims:

Minimal hepatic encephalopathy (MHE) implies subtle impairment of cognitive functions in the absence of features of overt encephalopathy. We aimed to determine the prevalence of MHE in patients with liver cirrhosis and to find out the effect of rifaximin, probiotics, and l-ornithine l-aspartate (LOLA) individually in reversal of MHE by comparing it with placebo group.

Patients and Methods:

This study was carried out in two phases. Phase I included the recruitment of 250 apparently healthy controls and extraction of normative data utilizing three neuropsychometric tests (NPTs) and critical flicker frequency (CFF) test. Phase II consisted of screening and recruitment of patients of MHE followed by drugs trial. A total of 317 cirrhotics were screened; 111 were excluded and the remaining 206 cirrhotics were screened for MHE using NPTs and/or CFF test. Of these, 124 patients with MHE were randomized to receive LOLA (n = 31), rifaximin (n = 31), probiotics (n = 32), for 2 months and were compared with patients who were given placebo (n = 30).

Results:

Out of 206 cirrhotics, 124 (60.19%) had MHE. Among these 124 MHE patients, 87 (70.16%) patients had CFF <39Hz, 112 (90.32%) patients with MHE had two or more abnormal NPTs, and 75 (60.48%) patients had abnormality on both the CFF values and more than two abnormal NPTs. Intention-to-treat analysis showed the number of patients who improved after giving treatment were 67.7% (21/31), 70.9% (22/31), 50% (16/32), and 30% (9/30) for LOLA, rifaximin, probiotics, and placebo, respectively. CFF scores and improvement in psychometric tests after treatment were significantly higher (P < 0.05) for LOLA, rifaximin, and probiotics as compared with placebo group.

Conclusions:

Prevalence of MHE is high in patients with cirrhosis of liver. Rifaximin, LOLA, and probiotics are better than giving placebo in patients with MHE.     

Correlation of HVPG Level with CTP Score,MELD Score,Ascites, Size of Varices,and Etiology in Cirrhotic Patients

Background/Aim:

This study intends to determine the correlation of a patient''s hepatic venous pressure gradient (HVPG) measurement with six factors: Child–Turcotte–Pugh (CTP) score, model for end-stage liver disease (MELD) score, presence of ascites, size of varices, presence of variceal bleeding, and an etiology of cirrhosis. The study also aims to identify the predictors of higher HVPG measurements that can indirectly affect the prognosis of cirrhotic patients.

Patients and Methods:

Thirty patients diagnosed with cirrhosis were enrolled prospectively and each patient''s HVPG level was measured by the transjugular catheterization of the right or middle hepatic vein. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were measured using a 7F balloon catheter. The HVPG level was calculated as the difference between the WHVP and FHVP measurements.

Results:

The mean HVPG level was higher in alcoholic than in nonalcoholic cirrhosis (19.5 ± 7.3 vs 15.2 ± 4.5 mm Hg, P = 0.13). The mean HVPG was also higher in bleeders compared with nonbleeders (18.5 ± 5.3 vs 10.7 ± 3.1 mmHg, P = 0.001). Patients with varices had a higher mean HVPG level than those without varices (17.4 ± 5.8 vs 11.7 ± 3.9 mmHg, P = 0.04). The difference among the three categories of varices (small, large, and no varices) was statistically significant (P = 0.03). In addition, the mean HVPG level was higher in patients with ascites than in those without ascites (18.7 ± 4.7 vs 11 ± 5.3 mmHg, P = 0.002), and it was significantly higher in patients in CTP class C (21.8 ± 5.5 mmHg) as compared with those in CTP class B (16.9 ± 2.9 mmHg) and CTP class A (10.5 ± 4.1 mmHg; P ≤ 0.001).

Conclusion:

HVPG levels were significantly higher in patients in CTP class C as compared with those in CTP classes A and B, thereby indicating that an HVPG measurement correlates with severity of liver disease. A high HVPG level signifies more severe liver disease and can predict the major complications of cirrhosis.     

Profile of Hepatic Encephalopathy in Children with Cirrhosis and Response to Lactulose

Background/Aim:

Hepatic encephalopathy (HE) is associated with a poor prognosis. There is paucity of data on the treatment of HE with lactulose in children with cirrhosis.

Patients and Methods:

Retrospective analysis of consecutive cirrhotic patients (<18 years) with HE was done. HE was defined according to West-Haven criteria. Response was defined as complete if patients recovered completely from HE, partial response was defined as improvement of encephalopathy by one or more grades from admission but not complete recovery, and defined as non response if patient did not show any improvement or deteriorated further even after 10 days of lactulose therapy.

Results:

A total of 300 patients were admitted with cirrhosis and HE (278 adults and 22 children). Of 22 patients, 16 (73%) patients had complete response to lactulose and six (27%) patients did not [three (13.5%) patients worsened (non response) and three (13.5%) did not recover fully even after 10 days of treatment (partial response)]. Comparing baseline characteristics of patients who had complete response (n=16) versus partial (n=3) and non response (n=3), there was significant difference in mean arterial pressure (78.1±10.7 vs 62.6±5.0 mmHg, P=0.003), serum sodium (131.3±3.2 vs 126.5±5.2, P=0.01) and serum creatinine (0.78±0.3 vs 1.1±0.3 mg/dl, P=0.02). We did not find any difference in baseline characteristics of these patients regarding CTP score (9.6±1.2 vs 10.6±1.2), MELD score (17.6±2.9 vs 17.1±3.4), severity of HE (2.5±0.6 vs 2.6±0.5) and etiology of precipitating factors (P=0.78).

Conclusions:

Lactulose therapy causes complete recovery from hepatic encephalopathy in 73% of pediatrics patients with cirrhosis.     

A Survey of Patterns of Practice and Perception of Minimal Hepatic Encephalopathy: A Nationwide Survey in India

Background/Aim:

Minimal hepatic encephalopathy (MHE) leads to overt hepatic encephalopathy (HE) and impairs quality of life in patients with cirrhosis. Awareness of MHE and its management among physicians is not known.

Patients and Methods:

We conducted a survey among 673 physicians in India from academic and nonacademic institutes to understand the clinical burden, perceived severity, management patterns, and the barriers to providing care for this condition.

Results:

Overall awareness of MHE in this survey was 75% (n = 504). Awareness of MHE was significantly higher in physicians working in teaching hospitals compared with those in nonteaching hospitals (79% vs 71%, P = 0.02). Similarly, gastroenterologists were more aware of MHE compared with nongastroenterologists (91% vs 66%, P = 0.001). Only 6.3% physicians screened all of their patients for MHE, whereas frequency of testing for MHE, either being nil or less than 10% of their patients was 64.7%. The most common test was paper and pencil test (86%) and the reason for nonscreening was nonavailability of time to test and also equipment or method (81%). A majority of physicians (88%) think that MHE affects quality of life. Physicians (61%) had an opinion that there should be some registry of MHE regardless of the cost and effort involved. Lactulose was used in 93% of cases, followed by rifaximin (82%) in the management of MHE.

Conclusion:

The overall awareness of MHE was 75% and it was significantly more in physicians of academic institutes. Despite awareness of its effect on quality of life, a majority of physicians did not test for MHE in their day-to-day practice.     

Neuropsychological impairment in severe acute viral hepatitis is due to minimal hepatic encephalopathy

Background and Aims: Minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis may have prognostic significance with regard to the development of clinical hepatic encephalopathy (HE) and deterioration in patient quality of life. Its prevalence in acute viral hepatitis (AVH) is not known. Patients and Methods: Consecutive 20 AVH patients (age, 29.9±7.9 years; M:F 18:2, hepatitis A:B:E: 2:16:2) without overt encephalopathy were evaluated for MHE and followed up. All patients underwent number connection tests – A and B, figure connection tests – A and B, digit symbol test and object assembly test and critical flicker frequency (CFF) at baseline and after the resolution of icterus. MHE was diagnosed if two or more psychometric tests were abnormal. Results: Prevalence of MHE (n=5) was 25%, which resolved on follow‐up during the anicteric resolution phase. Five (25%) patients had greater than two abnormal psychometry tests and four (20%) had CFF <38 Hz. CFF alone had sensitivity and specificity of 80 and 100%, respectively, in the diagnosis of MHE. There was significant difference in the performance of CFF during the icteric and resolution phase of AVH (40.6±3.4 vs 41.8±2.1 Hz, P=0.04). Arterial ammonia level were higher in patients with MHE compared with patients without MHE (88.2±23.5 vs 53.8±10.9 μmol/L, P=0.001). On univariate analysis fasting ammonia level at baseline was significantly associated with all the psychometric tests (P=0.001). None of the patients developed HE either in MHE group or in those who did not had MHE at baseline. Conclusions: MHE occurs in 25% of patients with AVH and resolves on follow up with recovery of AVH. Raised arterial ammonia during the icteric phase is associated with development of MHE.     

Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis: an open labeled randomized controlled trial of lactulose versus no lactulose

Background and Aim: Development of overt hepatic encephalopathy (HE) is associated with poor prognosis in patients with cirrhosis. Lactulose is used for the treatment of HE. There is no study on the prevention of overt HE using lactulose in patients who never had HE earlier. Methods: Consecutive cirrhotic patients who never had an episode of overt HE were randomized to receive lactulose (Gp‐L) or no lactulose (Gp‐NL). All patients were assessed by psychometry (number connection test [NCT‐A and B], figure connection test if illiterate [FCT‐A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency test (CFF) at inclusion and after 3 months. These patients were followed every month for 12 months for development of overt HE. Results: Of 250 patients screened, 120 (48%) meeting the inclusion criteria were randomized to Gp‐L (n = 60) and Gp‐NL (n = 60). Twenty (19%) of 105 patients followed for 12 months developed an episode of overt HE. Six (11%) of 55 in the lactulose (Gp‐L) group and 14 (28%) of 50 in the Gp‐NL (P = 0.02) developed overt HE. Ten (20%) of 50 patients in Gp‐NL and five (9%) of 55 patients in the Gp‐L group died, P = 0.16. Number of patients with minimal hepatic encephalopathy (MHE) were comparable in two groups at baseline (Gp‐L vs Gp‐NL, 32:36, P = 0.29). Lactulose improved MHE in 66% of patients in Gp‐L. Taking a cutoff < 38 Hz sensitivity and specificity of CFF in predicting HE were 52% and 77% at baseline and 52% and 82% at 3 months of treatment. On multivariate analysis, Child's score and presence of MHE at baseline were significantly associated with development of overt HE. Conclusions: Lactulose is effective for primary prevention of overt hepatic encephalopathy in patients with cirrhosis.     

Predictors of nonresponse to lactulose for minimal hepatic encephalopathy in patients with cirrhosis

Background/Aims: Minimal hepatic encephalopathy (MHE) impairs health‐related quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients. Lactulose is effective in the treatment of MHE. However, not all patients respond to lactulose. We evaluated predictors of nonresponse to lactulose. Patients and methods: Consecutive 110 cirrhotic patients without HE were evaluated for MHE by psychometry, P300 auditory event‐related potential (P300ERP), venous ammonia and critical flicker frequency (CFF). MHE was diagnosed by abnormal psychometry and P300ERP (>2 SD). MHE patients were treated with lactulose for 1 month. Response was defined by normalization of the abnormal test parameters (both psychometric tests and P300ERP). Results: Sixty patients (54.5%) were diagnosed as having MHE: 17/39 (44%) in Child's A, 21/42 (50%) Child's B and 22/29 (76%) in Child's C. There was a significant difference between Child's C's vs Child's A's and B's (P<0.05). Abnormal psychometric tests and abnormal P300ERP were seen in 74 (67%) and 74 (67%) patients respectively. Of 60 patients with MHE, after treatment, psychometry remained abnormal in 22 (36.6%) and P300ERP in 21 (35%) patients. CFF was<38 Hz in 34 (57%) and 11 (18%) patients, respectively, before and after treatment in MHE patients. There was a significant difference between the baseline serum sodium level (134.7±2.6 vs 131.1±2.2 mmol/L, P=0.001) and the venous ammonia level (76.6±20.7 vs 113.4±22.8 μmol/L, P=0.001) between responders vs nonresponders. Receiver operating characteristic analysis was performed to identify the cutoff for venous ammonia [cutoff 93.5 mmol/L, area under the curve (AUC) 0.892 (0.814–0.970)] and for the serum sodium level [cutoff 132.5 mmol/L, AUC 0.874 (0.779–0.998)]. Taking a cutoff of 93.5 mmol/L for ammonia patient had a sensitivity of 88.5% and a specificity of 79.4%, respectively, and a cutoff of 132.5 mmol/L for serum sodium patient had a sensitivity of 76.5% and a specificity of 88.5% for nonresponse to lactulose. On univariate analysis and multivariate analysis, serum sodium and venous ammonia were the only two parameters associated with nonresponse to lactulose. Conclusion: The prevalence of MHE was 55% and MHE improved in 57% patients with lactulose. Baseline low serum sodium and high venous ammonia were highly predictive of nonresponse to lactulose therapy.     

Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis

BACKGROUND:Minimal hepatic encephalopathy (MHE) impairs quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients.Diagnosis of MHE requires cumbersome tests.Lactulose is effective in the treatment of MHE.This study aimed to evaluate the use of critical flicker frequency (CFF) for the diagnosis of MHE in cirrhotic patients after treatment.METHODS:One hundred and ten patients were evaluated by psychometry (number connection tests A,B or figure connection tests A,B),P300 auditory eve...     

Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol-related cirrhosis

Background & Aims

Removing the primary aetiological factor in decompensated cirrhosis may lead to a restoration of hepatic function. In this study, we investigated the clinical implications of recompensation and the subsequent survival in patients with decompensated alcohol-related cirrhosis.

Methods

The rate of recompensation was evaluated in patients with decompensated alcohol-related cirrhosis and persistent alcohol abstinence undergoing a hepatic venous pressure gradient (HVPG) measurement. Recompensation was defined according to Baveno VII criteria as resolution of ascites and hepatic encephalopathy, absence of variceal bleeding and improvement in liver function.

Results

Two hundred and four abstinent patients with decompensated alcohol-related cirrhosis (age: 57.2 [IQR:50.1–63.7] years; 75.0% male; median MELD: 15 [IQR:11–19]) and a median HVPG of 20 (IQR:18–24) mmHg were included. During a median follow-up of 24.4 (IQR:10.9–50.4) months, 37 patients (18.1%) achieved abstinence-induced recompensation. Lower baseline HVPG, lower Child-Pugh score, lower BMI, higher albumin and higher mean arterial pressure were linked to a higher probability of recompensation. After adjusting for age, disease severity, portal hypertension and systemic inflammation, achieving recompensation resulted in a significant and considerable reduction in liver-related mortality (adjusted HR: 0.091 [95% CI: 0.012–0.677]; p = .019). Only 13 patients (6.4%) developed hepatocellular carcinoma, with a tendency towards a lower risk upon recompensation (HR: 0.398 [95% CI: 0.084–1.878]; p = .245), yet this finding did not reach statistical significance and requires further investigation.

Conclusions

Alcohol abstinence led to recompensation in 18.1% of our cohort of HVPG-characterised patients with decompensated alcohol-related cirrhosis. Achieving hepatic recompensation resulted in a >90% risk reduction in liver-related mortality.     

Hepatocellular carcinoma in Budd-Chiari syndrome: a single center experience with long-term follow-up in South Korea

AIM:To evaluate long-term clinical course of BuddChiari syndrome(BCS) and predictive factors associated with the development of hepatocellular carcinoma(HCC) and survival.METHODS:We analyzed 67 patients with BCS between June 1988 and May 2008.The diagnosis of BCS was confirmed by hepatic venous outflow obstruction shown on abdominal ultrasound sonography,computed tomography,magnetic resonance imaging,or venography.The median follow-up period was 103 ± 156 [interquartile range(IQR)] mo.RESULTS:The median age of the patients was 47 ± 16(IQR) years.At diagnosis,54 patients had cirrhosis,25(37.3%) Child-Pugh class A,23(34.3%) Child-Pugh class B,and six(9.0%) patients Child-Pugh class C.During the follow-up period,HCC was developed in 17 patients,and the annual incidence of HCC in patients with BCS was 2.8%.Patients in HCC group(n = 17) had higher hepatic venous pressure gradient(HVPG) than those in non-HCC group(n = 50)(21 ± 12 mmHg vs 14 ± 7 mmHg,P = 0.019).The survival rate of BCS patients was 86.2% for 5 years,73.8% for 10 years,and 61.2% for 15 years.In patients with BCS and HCC,survival was 79% for 5 years,43.1% for 10 years,and 21.5% for 15 years.CONCLUSION:The incidence of HCC in patients with BCS was similar to that in patients with other etiologic cirrhosis in South Korea.The HVPG is expected to provide additional information for predicting HCC development in BCS patients.     

Laparoscopic Versus Open Appendectomy: A Comparison of Primary Outcome Measures

Background/Aim:

The aim of the study was to compare laparoscopic and open appendectomy (OA) in terms of primary outcome measures. Study design: A randomized controlled trial. Place and duration of the study: Khyber Teaching Hospital, Peshawar, Pakistan, February 2008 to December 2009.

Patients and Methods:

A total of 160 patients were divided into two groups, A and B. Group A patients were subjected to laparoscopic appendectomy (LA), whereas Group B patients were subjected to OA. Data regarding age, gender, and primary outcome measures, such as hospital stay, operative duration, and postoperative complication, were recorded and analyzed. Percentages were calculated for categorical data, whereas numerical data were represented as mean ± SD. Chi-square test and t test were used to compare categorical and numerical variables, respectively. Probability ≤ 0.05 (P ≤ 0.05) was considered significant.

Results:

After randomization, 72 patients in group A and 75 patients in group B were analyzed. The mean age of patients in groups A and B was 23.09 ± 8.51 and 23.12 ± 10.42 years, respectively, (P = 0.981). The mean hospital stay was 1.52 ± 0.76 days in group A and 1.70 ± 1.06 days in group B (P = 0.294). The mean operative duration in group A and B were 47.54 ± 12.82 min and 31.36 ± 11.43 min, respectively (P < 0.001). Pain (overall level) was significantly less in group A compared with group B (P = 0.004). The two groups were comparable in terms of other postoperative complications, such as hematoma (P = 0.87), paralytic ileus (P = 0.086), urinary retention (P = 0.504), and wound infection (P = 0.134).

Conclusion:

LA is an equivalent procedure and not superior to OA in terms of primary outcome measures.     

Non-selective β-blockers improve the correlation of liver stiffness and portal pressure in advanced cirrhosis

Background

Liver stiffness (LS) correlates with portal pressure (hepatic venous pressure gradient, HVPG). However, the dynamic components of portal hypertension (PHT) in advanced cirrhosis may not be adequately assessed by TE. The influence of treatment with non-selective β-blockers (NSBB) on the correlation of HVPG and LS has not been investigated.

Methods

One hundred and twenty-two patients with esophageal varices were included. LS, hemodynamic parameters, and HVPG were recorded at baseline (BL) and after 6?weeks of treatment with NSBB (FU). The correlation of LS and HVPG was compared to control patients with HVPG?≤?12?mmHg.

Results

Patients with higher Child-Pugh stages (A:88/B:25/C:9) had higher levels of liver stiffness (47.4?±?16.5 vs. 70.3?±?7.9 vs. 73.7 ± 2.1 kPa) and HVPG (21?±?5 vs. 26?±?5 vs. 26?±?4?mmHg). The correlation of LS and HVPG was stronger in controls with HVPG?≤?12?mmHg (R?=?0.951; P??12?mmHg (R?=?0.538; P?=?0.0004). The association of HVPG with LS became stronger under treatment with NSBB, which finally restored the linear correlation of HVPG and LS (R?=?0.930; P?R?=?0.864), but not in nonresponders (R?=?0.535), whereas changes in LS, heart rate, and MAP were similar in responders and nonresponders.

Conclusions

Targeting the hyperdynamic circulation and the increased splanchnic blood inflow by treatment with NSBB unmasks the linear (mechanical) correlation of HVPG and LS in patients with HVPG?>?12?mmHg. Measurement of LS by TE is not a feasible method to assess the dynamic components of PHT.     

Correlation between changes of blood pressure with insulin resistance in type 2 diabetes mellitus with 4 weeks of pioglitazone therapy

OBJECTIVE:

To examine effects of pioglitazone (PIO) on systolic, diastolic, pulse and mean blood pressures (SBP, DBP, PP and MP, respectively) in type 2 diabetes mellitus (T2DM).

MATERIALS AND METHODS:

One hundred and six normotensive patients with T2DM with mean fasting blood glucose (FBS; 183 ± 6 mg/dl) were randomly divided into two groups. Test group was treated with 15 mg of PIO in addition to metformin 500 mg three times per day in both groups. SBP, DBP, PP and MP and fasting insulin, FBS and lipid profiles were measured before and after PIO therapy.

RESULTS:

There was a significant reduction in SBP (123 ± 2 vs. 118 ± 2 mmHg, P < 0.05), PP (41 ± 1 vs. 37 ± 1 mmHg, P < 0.05), and MP (95 ± 1 vs. 91 ± 1, P < 0.05). Clinical reduction in DBP was observed but not significant (82 ± 2 vs. 81 ± 1 mmHg, P > 0.05). There was a significant correlation between decline in SBP and DBP with respective baseline values (r = 0.76, P < 0.001 and r = 0.62, P < 0.001, respectively). Changes in PP and MP strongly correlated with baseline values (r = 0.51, P < 0.05 and r = 0.56, P < 0.05, respectively). There was a parallel reduction of FBS (183 ± 2 vs. 121 ± 3, P < 0.001) but reduction in IR or lipid profiles was not significant in test group. Changes in BP were not significant in control group ( P > 0.05).

CONCLUSION:

PIO treatment of T2DM showed early reduction of SBP and MP within first 4 weeks. Results suggest that pharmacodynamic effects of PIO mainly affect the systolic component. We hereby suggest that reduction of BP by PIO is independent from mechanisms of changes in IR and dyslipidaemia in normotensive diabetic patients.     

Role of Proteases and Antiprotease in the Etiology of Chronic Pancreatitis

Background/Aim:

Chronic pancreatitis (CP) is the progressive and irreversible destruction of the pancreas characterized by the permanent loss of endocrine and exocrine function. Trypsin, the most important digestive enzyme plays a central role in the regulation of all other digestive enzymes. Chymotrypsin, an endopeptidase hydrolyzes peptides at amino acids with aromatic side chains. Alpha-1-antitrypsin is a principal antiprotease which protects the mucosal tissue from the proteolytic effects of trypsin and chymotrypsin by the formation of molar complexes. The present study is aimed at examining the role of proteases (trypsin and chymotrypsin) and anti-protease (α1-anti-trypsin) in the etiopathogenesis of chronic pancreatitis.

Patients and Methods:

A total of 90 CP patients and 110 age and sex matched controls were considered for the study. Serum trypsin, chymotrypsin and α1-anti-trypsin levels were determined prospectively in CP patients and compared to healthy controls as described previously.

Results:

The mean activity of trypsin were found to be increased in CP patients (X ± SD = 0.82 ± 0.838) in comparison to normal control group (X ± SD = 0.55 ± 0.328), (P = 0.001). Chymotrypsin activity were also found to be elevated in CP patients (X ± SD = 0.63 ± 0.278) in comparison to control group (X ± SD = 0.39 ± 0.295), (P = 0.0001). The mean α-1-anti-trypsin activity were found to be lowered in CP patients (X ± SD = 0.42 ± 0.494) in comparison to control group (X ± SD = 0.67 ± 0.465), with the variation being significant (P = 0.0003).

Conclusion:

The findings suggest an imbalance in the synthesis and degradation of proteolytic enzymes and antiprotease indicating an altered aggressive and defensive role in the pathogenesis of chronic pancreatitis.     

Critical flicker frequency: diagnostic tool for minimal hepatic encephalopathy

BACKGROUND/AIMS: Minimal hepatic encephalopathy (MHE) is associated with poorer quality of life and increased work disability. Diagnosis requires cumbersome psychometric and neurophysiological tests. We evaluated critical flicker frequency (CFF) to diagnose MHE. METHODS: 156 cirrhotic patients (age 41+/-12.5 yr) without overt encephalopathy (Child A 63, Child B 56, Child C 37) were evaluated by psychometric (number connection tests A, B or figure connection tests A, B), P300 auditory event related potential (ERP) and CFF. MHE was diagnosed by abnormal psychometric and/or P300 auditory event related potential. RESULTS: Prevalence of MHE was 53% with 27 (43%) in Child's A, 33 (59%) in Child's B and 23 (62%) in Child's C cirrhosis (p=NS). Of 83 patients, 72 (87%) had abnormal psychometry, 64 (77%) had abnormal P300 auditory event related potential (ERP) (380.6+/-28.8 ms) and in 66 (80%) CFF was below 39 Hz. 60 (83%) patients with abnormal psychometry and 51 (80%) with abnormal P300 auditory event related potential had CFF below 39 Hz. CFF sensitivity (96%), specificity (77%) and positive predictive value (68%), negative predictive value (98%) and diagnosis accuracy was 83.3% when compared to patients with both abnormal psychometry and P300ERP. CONCLUSIONS: Critical flicker frequency is a simple, reliable and accurate test without any age or literacy dependence for the diagnosis of MHE.     

Transient Elastography to Assess Hepatic Fibrosis in Hemodialysis Chronic Hepatitis C Patients

Summary

Background and objectives

Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan^®) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients.

Design, setting, participants, & measurements

A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard.

Results

The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P < 0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P = 0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P = 0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93–100%) and specificity (88–99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively.

Conclusions

TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.     

Characteristics of Treatment Na?ve Chronic Hepatitis B in Bangladesh: Younger Populations are More Affected; HBeAg-negatives are More Advanced

Background/Aim:

Bangladesh is a densely populated country with intermediate endemicity for chronic hepatitis B (CHB). The aim of the present study was to evaluate the biochemical, virological and histological character of CHB patients and to examine the relationship between these indices.

Materials and Methods:

One thousand and twenty-two patients of CHB fulfilled our inclusion criteria. Inclusion criteria were (1) HBsAg positive for at least 6 months, (2) HBeAg-positive or negative and (3) hepatitis B virus (HBV) DNA positive. Patients with detectable antibodies to human immunodeficiency virus (HIV), hepatitis Delta virus (HDV) or hepatitis C virus (HCV), with previous antiviral treatment, overt cirrhosis and hepatocellular carcinoma, were excluded. Of these, 191 patients were randomly selected for liver biopsy and were evaluated for analysis.

Results:

In the 191 patients, male to female ratio was 4.6:1; age distribution was 26.5 ± 8.5 (mean ± standard deviation) years. One hundred and seventy-eight (93.2%) patients were under 40 years. Sixty-eight (35.6%) patients were HBeAg-negative, had less DNA load, and were significantly older, more fibrotic and cirrhotic (P < 0.001). Correlation was not found between DNA level and histological activity. Histological activity was not correlated with ALT level in HBeAg-positive patients (P < 0.001).

Conclusion:

CHB affects the younger population in Bangladesh. HBeAg-positive CHB was associated with more fibrosis and cirrhosis. Serum HBV DNA levels do not correlate with the severity of histological lesions in all patients. Evaluation by liver biopsy remains gold standard for taking decision of treatment.