Studies related to portal hypertension

Cirrhosis of the liver is a chronic disorder resulting from a variety of known and unknown aetiological factors, which lead to hepatocyte damage and death, regeneration of remaining hepatocytes and progressive fibrosis in a sequential manner. This ultimately leads to distortion of the architecture of the liver lobules. The net result is liver cell dysfunction and an increase in the intrahepatic resistance to blood flow. The latter, combined with alteration of portal blood flow and of extrahepatic splanchnic vascular responsiveness characterizes portal hypertension.Systemic and splanchnic vasodilatation seem to be prominent features of decompensated hepatic cirrhosis and lead to a fall in the effective circulating blood volume. This results in the activation of a cascade of compensatory events, which include the RAS, release of AVP and heightened sympathetic nervous system activity. Neuronal and humoral mechanisms, therefore, seem to be central to the sodium and water retention, which occurs in cirrhosis of the liver. These pathophysiological changes contribute to fluid retention and ascites.The regulation of arterial tone in cirrhosis of the liver is complex and a multitude of factors seem to be playing a part. The areas which have been explored in the past include the role of endothelial-derived vasodilator agents, circulating vasodilator agents which act on the vascular smooth muscle, and lack of response of the vascular smooth muscle to vasoconstrictor agents.The last could in fact be a result of the first two factors. There is a paucity of data on human tissues in the literature because of difficulty in acquiring larger distributory arteries from cirrhotic patients for experimentation. Blood vessels acquired at OLT offer the opportunity to study donor (normal) and recipient (cirrhotic) blood vessels invitro under controlled standardized conditions (organ bath experiments).The development of portal hypertension itself is followed by clinically important sequelae. Enlargement of the spleen is an early and cardinal sign of portal hypertension and it is difficult to make a diagnosis of portal hypertension without the demonstration of splenomegaly. Factors which participate in the development of splenomegaly include increase in portal pressure and splanchnic blood flow, and RE cell hyperplasia. However, the correlation of spleen size to these factors is not entirely clear. The difficulty in interpreting the results of different studies in this area of medicine is partly due to the lack of information about the accuracy of methods used for determining spleen size and partly due to the paucity of data comparing the different methods of measuring spleen size including ultrasonography, CT scanning, MRI and radionuclide studies. Radionuclides have also been used to quantify splanchnic blood flows as well as liver function in the normal and patients with chronic liver disease but there is again a scarcity of data in this regardThe development of portal hypertension is associated with the opening up of portasystemic collateral shunts at different sites in order to decompress the portal circulation. Clinically important shunt vessels develop in the oesophagus, stomach and the duodenum. These assume varicose proportions and can rupture when the intravascular pressures rise above a threshold value. This can lead to potentially life threatening haemorrhage. Shunting of blood to the systemic circulation is also a contributory factor in hepatic encephalopathyImpairment of glucose tolerance and even the development of diabetes mellitus are also consequences of cirrhosis and portal hypertension occurring in 10-40% of patients. The prevalence of these abnormalities of glycaemic control increases as the duration and severity of liver disease increases. Although, it is generally believed to be a result of insulin resistance at the peripheral receptor sites, the pattern of insulin secretion from the P cells of the pancreas is also believed to be altered in this form of diabetes, particularly in the later stages. However, there are obvious problems in quantifying insulin secretion from the endocrine pancreas as it undergoes significant extraction during first pass through the normal liver and the pulse mass is lost to a large extent. Measurements done at the peripheral vein site are therefore not an accurate reflection of the quantum of insulin secretion over a period of time. TIPSS used to treat complications of portal hypertension are reviewed at portographic examinations and can be used to study the pattern of insulin secretion directly from the portal vein. Although this complex investigation could only be done in a few patients with relatively stable liver function, this human model can be used to study the pattern of insulin secretion in the patients with different grades of severity of liver disease and normal as well as abnormal glucose tolerance in hepatic cirrhosisA number of treatment strategies have been devised for prevention of bleeding and control active bleeding from varices in the gastro-intestinal tract. These include endoscopic sclerotherapy, endoscopic variceal ligation, pharmacological measures including ß adrenoreceptor blocking agents and nitrates, surgical decompressive shunts and TIPSS.TIPSS is the most recent addition to the armamentarium of treatment modalities. Although it is a highly effective of treatment, there are obvious problems in that procedure related and short and long-term complications limit its acceptability. Procedure related complications include intraperitoneal bleeding and subcapsular haematoma in the liver. The main longer-term problems relate to sepsis, precipitation of hepatic encephalopathy and SI and occlusion. A number of shunt and patient related factors have been assessed as predictors of SI and these include, age and sex of patients, the liver functions, pre- and post-stent insertion portal pressures and the diameter of the stent. The role of diabetes mellitus, which has been shown to encourage stenosis in vascular stents placed elsewhere in the body, has not been assessed in TIPSS.Accordingly, the aim of this thesis was to explore the following aspects of hepatic cirrhosis and portal hypertension.1.1 TO STUDY THE PATHOPHYSIOLOGIC MECHANISM OF VASCULAR HYPORESPONSIVENESS IN HEPATIC CIRRHOSIS. • The aim in these experiments was to investigate the role of NO release in modulating a-adrenoceptor mediated contraction in hepatic cirrhosis.1.2 TO STUDY CLINICAL SEQUELAE OF PORTAL HYPERTENSION DUE TO HEPATIC CIRRHOSIS. These were the areas of study in relation to clinical sequelae: • The clinical aspects of splenomegaly and its relation to portal haemodynamic factors in portal hypertension due to hepatic cirrhosis. • The role of radionuclides in measuring spleen size and assessing liver function in hepatic cirrosis and portal hypertension.1.3 TO STUDY THE PATTERN OF INSULIN SECRETION IN CIRRHOTIC PATIENTS WITH TIPSS AND THE IMPACT OF DIABETES MELLITUS ON TIPSS FUNCTION. • The pattern of pulsatile insulin secretion in portal vein in patients suffering from hepatic cirrhosis using a TIPSS inserted model was studied. This model should help study pattern of insulin secretion in different stages of hepatogenous diabetes mellitus, ie., impaired glucose tolerance and frank diabetes mellitus. • The effect of diabetes mellitus on the efficacy of TIPSS in the treatment of patients suffering from portal hypertension has been studie

An open study to assess the safety and efficacy of Heprovac-B vaccine 10 mcg-dose for adults

Heprovac B is a novel recombinant vaccine. There are many vaccines available in Pakistani market but Heprovac B claims to be immunogenic even at 10 meg dose. Aim of the study is to determine whether using 10 meg of Heprovac B vaccine is safe and effective in producing sufficient immunity in Pakistani population. One hundred and twenty five subjects, who fulfilled the Inclusion criteria, were enrolled for the study. Heprovac B was administered in a three-dose regimen given at 0, 1 and 6 months and adverse events were recorded. Immunogenicity was tested by measuring hepatitis B surface antibody one month after each dose received. One month after the 3rd dose 98.7% of the subjects were found to be seroprotected with geometric mean titer of 488.83 mIU/1 after the third dose. Heprovac B, vaccine was well tolerated with minimal reported adverse events. It is safe and 10 mcg is immunogenic in producing antibodies in Pakistani population against Hepatitis B virus

A Critical Discourse Analysis of News in Media about Rape Victims in Pakistan

This study aims to investigate the discourse in news coverage, specifically focusing on the reporting of rape cases, with a particular focus on victim blaming and fact-hiding in the Pakistani media discourse. Drawing on the Van Dijk model of Critical Discourse Analysis (CDA), the study intends to unveil biases or power inequalities deep rooted in the structure and management of news reporting discourse. The research seeks to ascertain whether media outlets employ deceptive language to conceal the reality in reporting on rape cases, the influence of victim blaming on readers’ perception, and how the news media copes with the reporting of rape incidents. Data collection involves analysis of news articles from five well-known Pakistani publications: The Dawn News, ARY News, Dunya News, Geo News, and the Express Tribune particularly focusing on the "Zainab\u27s Murder and Rape Case." The analysis highlights instances of deletion, word choice, hiding identity, and lack of mention of police action, which contribute to the manipulation of information in news reports. The results of the study shed light on the biased description of rape incidents in the Pakistani media, fanning victim blame and rape lores. The study stresses the need for unbiased and truthful reporting of sexual assault incidents, ensuring that the experiences of victims are accurately portrayed. By uncovering the manipulation and biases in the Pakistani news media, this research contributes to a better understanding of the discourse patterns surrounding rape cases and the potential impact on public attitudes towards victims. &nbsp

Endoscopic management of biliary leaks after open and laparoscopic cholecystectomy

Objective: To evaluate the diagnostic and therapeutic efficacy of ERCP in the management of biliary leaks.Methods: The study recruited 35 out of total 436 ERCP patients with post surgical biliary leaks, who presented to our department between January 1, 2001 and September 30, 2004. Unsuccessful ERCP and/or completely transected CBD injuries were handed over to surgery.Results: ERCP was successful in 33 (94%) patients. Of these 25 (75%) had cystic stump leaks, 3 (9%) had transected CBD, 2 (6%) had leakage from gall bladder (GB) bed, 2 (6%) had persistently draining T-tube with retained CBD stones and one (3%) patient had a leak from the right hepatic duct. CBD stenting was done successfully in 23 (92%) patients with a cystic stump leak. The other 3 patients with leakage from GB bed and right hepatic duct injury were successfully dealt with CBD stenting. The retained CBD stones were endoscopically removed. The overall therapeutic success was 93% and stents were removed after 6-8 weeks without further complications. Three patients with transected CBD were treated surgically.CONCLUSION: latrogenic Biliary system Injuries can be diagnosed and managed efficiently through Endoscopic Retrograde Cholangiopancreatography (ERCP)

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

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 \u3e 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

Accessibility of antenatal services at primary healthcare facilities in Punjab, Pakistan

Introduction: Almost one-fifth of the world\\u27s population constitutes women of reproductive age who are repeatedly exposed to pregnancy and childbearing. Many are often at high risk of illness and mortality during pregnancy and require maternal healthcare services for early detection of complications. More than 0.5 million women die every year worldwide due to pregnancy-related complications. Almost 0.03 million of them are in Pakistan. Maternal healthcare in Pakistan is poor and results in high rates of morbidity and mortality. This paper evaluates the accessibility of antenatal care (ANC) services in primary healthcare settings in the Punjab province of Pakistan during the period June 2010-August 2011. Methods: The paper uses a cross-sectional study including mix methods (qualitative and quantitative).Nine districts were included in the project; one from each administrative tier or division. Nineteen health facilities, including two rural health centres (RHCs) and 17 basic health units (BHUs) were randomly selected from each district. The total sample was 171 health facilities. The qualitative assessment was carried out through focus-group discussions (FGDs) and in-depth interviews with clients, providers, and health managers. Results: The reasons for the gaps in service accessibility were the distant location of facilities, a lack of transport, and inconvenient facility working hours. The issues of service accessibility were further exacerbated by socio-cultural factors such as low levels of client awareness, a lack of decision-making by clients, and the influence of spiritual healers and quacks. Health managers further pointed out weak co-ordination between vertical programmes and routine integrated health services, and a lack of human resources in distantly located facilities.Conclusion: In order to increase the accessibility of ANC services, facility working hours must be extended and adjusted according to the convenience of clients in primary healthcare (PHC) facilities. The utilisation of ANC services can also be increased through client awareness and gender empowerment for ANC decision-making

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