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

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

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

An incidentally discovered asymptomatic para-aortic paraganglioma with Peutz-Jeghers syndrome

Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder characterized by mucocutaneous melanin pigmentation and gastrointestinal (GI) tract hamartomatous polyps and an increased risk of malignancy. In addition to polyposis, previous studies have reported increased risk of GI and extraGI malignancies in PJS patients, compared with that of the general population. The most common extraintestinal malignancies reported in previous studies are pancreatic, breast, ovarian and testicular cancers.We report the case of a 17-year-old boy who presented with generalized weakness, recurrent sharp abdominal pain and melena, had exploratory laparotomy and ileal resection for ileo-ileal intussusception. Pigmentation of the buccal mucosa was noted. An abdominal computed tomography scan (CT) revealed multiple polyps in small bowel loops. Gastroscopy revealed multiple dimunitive polyps in stomach and pedunculated polyp in duodenum. Colonoscopy revealed multiple colonic polyps. Pathological examination of the polyps confirmed hamartomas with smooth muscle arborization, compatible with Peutz-Jeghers polyps. CT scan guided left para-aortic lymph node biopsy revealed the characteristic features of extra-adrenal para-aortic paraganglioma. Although cases of various GI and extra GI malignancies in PJS patients has been reported, the present case appears to be the first in literature in which the PJS syndrome was associated with asymptomatic extraadrenal para-aortic paraganglioma. Patients with PJS should be treated by endoscopic or surgical resection and need whole-body screening

Irritable bowel syndrome in health care professionals in Pakistan

Objective: To evaluate the symptomatology of irritable bowel syndrome (IBS) among health care professionals attending an IBS symposium in a tertiary care university hospital. Method: A questionnaire designed to incorporate Manning and Rome II criteria was distributed among participants of an IBS symposium, most of them were health care professionals. A total of 100 questionnaires were distributed, 41 had symptoms fulfilling criteria of IBS. In these patients male: female ratio was 28:13 with age range 18-68. Results: The predominant symptom was abdominal pain 87.8 % (36/41) which was aggravated post-prandially 72.2% (29/41), relieved following defecation in 87 % (35/41) with a sense of incomplete evacuation 85.3% (35/41) and distention after defecation in 80.4 % (33/41). Anxiety and depression was present in 80% (33/41) as an extra intestinal symptom. Conclusion: Irritable bowel syndrome is common in health care workers with intestinal and extraintestinal manifestations being equally common (JPMA 53:405;2003

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

To determine the frequency and specific characteristic features of portal hypertensive gastropathy (PHG) in cirrhosis due to viral etiology. Cross-sectional descriptive study. The Aga Khan University Hospital, Karachi, from June 2006 till June 2008. 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. 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 \u3c 0.001). On univariate analysis lower platelet counts (11755 vs. 16790; p \u3c 0.001), increased spleen size (14.12.9 cm vs. 122.4cm; p \u3c 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 (916400 vs. 1477899; p \u3c 0.001). Furthermore, on multivariate analysis CTP score \u3e 8 MELD score \u3e 12 and platelets/spleen ratio \u3c 900 were significantly associated factors with severe PHG. Frequency of PHG was 83% while severe PHG was seen in 24% cases of viral hepatic cirrhosis. MELD score \u3e 12, CTP score 8 and platelets/spleen ratio \u3c 900 were significant factors of severe PHG

Candida esophagitis: Risk factors in non-HIV population in Pakistan

AIM: Candida esophagitis is a frequent infection in immunocompromised patients. This study was designed to determine its characteristics in non- human immune deficiency virus (HIV) infected patients attending a teaching hospital. METHODS: Clinical records of all patients coded by international classification of diseases 9th revision with clinical modifications\u27 (ICD-9-CM), with candida esophagitis diagnosed by esophagogastroduodenoscopy (EGD) and histopathology over a period of 5 years were studied. RESULTS: Fifty-one patients (27 males, 24 females, range 21-77 years old and mean age 52.9 years) fulfilled the criteria (0.34% of the EGD). The common predisposing factors were carcinoma (OR 3.87, CI 1.00-14.99) and diabetes mellitus (OR 4.39, CI 1.34-14.42). The frequent clinical symptoms were retrosternal discomfort, dysphagia and epigastric abdominal pain with endoscopic appearance of scattered mucosal plaques. Another endoscopic lesion was associated with candida esophagitis in 15% patients. CONCLUSION: Carcinomas, diabetes mellitus, corticosteroid and antibiotic therapy are major risk factors for candida esophagitis in Pakistan. It is an easily managed complication that responds to treatment with nystatin

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 \u27A\u27 (best nutritional status). In contrast, the majority (64%) in the DC group were in the class \u27C\u27 (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 \u27C\u27. Most importantly, 14% of patients with chronic hepatitis C (CHC) also scored a \u27B\u27 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 \u27A\u27 to \u27C\u27 between groups was statistically significant. CONCLUSION: Malnutrition occurs early in the course of HCV, and progresses relentlessly throughout the spectrum of HCVdisease