National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Peliosis Hepatis Complicating Pregnancy: A Rare Entity.

Peliosis hepatis (PH) is a rare, benign condition of the liver characterized by the presence of blood-filled lacunar spaces in the parenchyma. It usually has a chronic presentation and is a rare cause of portal hypertension reported in adult patients. Its etiology is diverse and ranges from infectious agents to tumors to toxic substances and anabolic steroids; however, the cause remains unclear in 25-50% of patients. Similarly, the symptomatology and imaging findings are diverse. Biopsy is the definitive test to diagnose the condition. Herein, we present a case of a young female presenting in her seventh month of gestational amenorrhea with signs of portal hypertension and subsequently diagnosed to have PH. She was managed conservatively and delivered her baby normally. Later, she presented with spontaneous bacterial peritonitis and hepatic encephalopathy and developed hepatorenal syndrome. She later succumbed to her illness. The condition should be kept in the differential diagnosis of the atypical liver masses and liver diseases causing portal hypertension.

Dietary Exposure and Natural Occurrence of Total Aflatoxins in Basmati Rice of Pakistan.

This study presents the assessment of total aflatoxins (TAFs) in basmati rice (brown, 1,081; white, 1,170) collected from different areas of Punjab, Pakistan, during 2010 to 2015. Due to the carcinogenicity of TAFs, daily dietary exposure is also evaluated based on rice consumption survey data. Methodology was standardized by matrix spike recoveries at four fortification levels (0.1, 0.5, 2.5, and 12.5 ng/g) for TAFs (aflatoxins B1 [AFB1], B2 [AFB2], G1 [AFG1], and G2 [AFG2]). The present study reveals that 1,750 samples (77.74%) were tainted with AFB1, whereas TAFs were detected in 370 samples (16.43%). Of positive samples, 854 brown rice samples (79%) were positive for AFB1, and 154 samples (14.24%) were contaminated with TAFs. For white rice, 896 samples (76.58%) were contaminated with AFB1, whereas 205 samples (18.46%) were found positive for TAFs. Study findings were used to construct a frequency distribution, and AFB1 levels were also compared against permissible levels of TAFs (10 ng/g) as legislated by the European Commission. Results further revealed that daily dietary exposure of TAFs ranged from 0.51 to 10.22 ng/kg of body weight per day, which exceeds the permissible limit of 1 ng/kg of body weight per day as defined by the Joint FAO/WHO Expert Committee on Food Additives.

Ascites in Patients on Maintenance Hemodialysis: Causes, Characteristics and Predicting Factors.

OBJECTIVE: To describe the causes, characteristics and factors associated with ascites in patients on maintenance hemodialysis. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from November 2007 to November 2014. METHODOLOGY: All patients on maintenance hemodialysis and age > 16 years with ascites were included. Frequencies and percentages were computed for different categorical variables. Chi-square or Fischer exact test were used to identify factors associated with ascites like frequency of hemodialysis, serum albumin and cardiac ejection fraction (EF). Odds ratios were calculated for associated factors. RESULTS: Ninety patients were included in this study; 55.5% were males. Median age was 33 years. Cause of ascites was nephrogenic in 77.8%, cardiac failure in 16.7%, hypothyroidism in 6.67%, liver cirrhosis in 4.4%, abdominal tuberculosis in 2.2%, and peritoneal carcinomatosis in 1.1% patients. The ascites was severe in 53.3% patients and severity was associated with serum albumin < 2.8 gm/dL(p=0.007) and cardiac EF < 40% (p=0.028). The ascites was low serum ascites albumin gradient (SAAG), high protein type (LSHP) in 60% patients and associated with hemorrhage (p=0.040). High SAAG, high protein (HSHP) ascites, found in 33.3%, was associated with cardiac EF < 40% (p=0.005) and portal hypertension (p=0.048). High SAAG, low protein (HSLP) ascites, seen in 6.7%, was associated with portal hypertension (p=0.006). CONCLUSION: The commonest cause of ascites in hemodialysis dependent patients is nephrogenic followed by cardiac failure. Low serum albumin and low cardiac EF predispose to severe forms of ascites.

Prevalence and Characteristics of Duodenal Villous Atrophy in Renal Transplant Patients Presenting With Persistent Diarrhea in a Developing Country.

OBJECTIVES: Persistent diarrhea is a common complication after solid-organ transplant, including kidney transplant. Data on duodenal villous atrophy as a cause of persistent diarrhea in renal transplant recipients are scarce. MATERIALS AND METHODS: We conducted a prospective analysis of 207 patients who received renal transplants from 2009 to 2012 with persistent diarrhea and who underwent upper gastrointestinal endoscopy and duodenal biopsies. Duodenal biopsies were examined for duodenal villous atrophy. Age, sex, transplant duration, and drugs were compared between patients with and without duodenal villous atrophy. After exclusion of known causes of duodenal villous atrophy, a 3-month course of antibiotics was given and outcomes were analyzed. RESULTS: Of 207 renal transplant recipients, 104 patients (49.8%) displayed duodenal villous atrophy. Of these, 92 (88.5%) were male patients. The mean age of patients with duodenal villous atrophy was 34.9 ± 10.3 years. The mean onset of persistent diarrhea in DVA-positive patients posttransplant was 2.16 ± 0.8 years. Celiac disease serology was positive in 18 (17.3) patients. Giardiasis was demonstrated in 11 patients (10.7%), whereas immunoproliferative small intestinal disease was shown in 7 patients (6.8%). The remaining 68 patients (65.38%) received antibiotics, with 50 recipients (74.6%) showing complete response, although 13 of these patients (26%) relapsed. Among the remaining 18 patients (26.47%), 9 (50%) had other causes and 9 (50%) had no cause found. Isoniazid prophylaxis showed statistically significant negative association with duodenal villous atrophy. CONCLUSIONS: Duodenal villous atrophy is highly prevalent in renal transplant recipients irrespective of age, sex, and posttransplant duration. We found tropical sprue, giardiasis, immunoproliferative small intestinal disease, and celiac disease to be important causes of duodenal villous atrophy. Therefore, duodenal biopsy is recommended in renal transplant recipients with persistent diarrhea.

Celiac Crisis in Refractory Celiac Disease Type I with Neurological Manifestations: A Diagnostic Dilemma.

Celiac crisis is a life-threatening condition in which patients have profuse diarrhea and severe metabolic disturbances. Refractory Celiac Disease (RCD) is a rare condition defined as persistence of symptoms despite being on Gluten Free Diet (GFD) for 6 months. Neurological involvement in Celiac Disease (CD) is seen in around 8 - 10% of adult patients; however, it is rare in children. Herein we present a case of an adolescent presenting with neurological symptoms and celiac crisis and diagnosed as RCD, type 1. He was treated with high dose steroids. This case underscores the need to consider RCD in patients presenting in celiac crisis and showing no improvement on GFD.

Autoimmune pancreatitis with extraocular muscles involvement.

Autoimmune pancreatitis is characterised by diffuse enlargement of pancreas, narrowing of pancreatic duct, lymphoplasmacytic infiltrations and fibrosis. The disease is responsive to corticosteroid. We report the case of a 32-year-old male who presented with unilateral exophthalmos and obstructive jaundice secondary to pancreatic head mass and biliary tract stricture. Serum immunoglobulin G level was raised with a very high immunoglobulin G4 subclass. Ophthalmological imaging revealed unilateral thickening of extraocular muscles. The patient responded well to corticosteroid with resolution of biliary strictures, pancreatic head mass and exophthalmos.

Early, non-refractory celiac disease associated with microscopic colitis and splenomegaly.

Celiac Disease (CD), also known as non-Tropical sprue, and Celiac sprue is an immune-mediated disorder, triggered by gluten containing grains in genetically susceptible people. The disease may be diagnosed at any age and can affect many organ systems. Its diagnosis and management can often be challenging. A high index of suspicion is required to diagnose this disease at an early stage in patients presenting with atypical symptomatology and delayed onset. Although serological tests are widely used, duodenal biopsy remains the gold standard for diagnosis of CD. Even though CD affects various body systems, Microscopic Colitis (MC) and refractory sprue are among the main gastrointestinal complications of CD, which are resistant to Gluten-Free Diet (GFD). A thorough and appropriate evaluation is mandatory for an early and accurate diagnosis of these complications. Herein, we report a case of a young female with CD in early phase in concordance with MC and splenomegaly.

Clinical presentation and predictors of survival in patients with Budd Chiari syndrome: experience from a tertiary care hospital in Pakistan.

OBJECTIVE: To determine aetiology, clinical presentation and predictors of survival in Budd Chiari Syndrome patients. METHODS: The prospective observational study based on non-probability convenient sampling was conducted at the Sindh Institute of Urology and Transplantation (SIUT), Karachi, and comprised Budd Chiari Syndrome patients between January 2004 and December 2013. The patients were evaluated for onset of symptoms, causes, mode of presentation and predictors of survival. SPSS 20 was used for statistical analysis. RESULTS: Of the 25 patients, 16(64%) were males, and 16(64%) belonged to the paediatric age group. Overall age range was 2-50 years with a mean of 14.7 ± 12.41 years. Presentation was chronic in 14(56%) patients, acute in 10(40%) and acute on chronic in 1(4%). Commonest morphological abnormality involved was hepatic veins alone in 14(56%). Probable aetiologies were hypercoagulable states in 21(84%) patients, infections in 2(8%) and malignancy in 1(4%). Among hypercoagulable states, protein C deficiency was the commonest, affecting 9 (36%) patients. Seven (28%) patients died; acute 4 (16%) and chronic 3 (12%). Causes of death included sepsis 4 (16%), fulminant hepatic failure 1 (4%), gastrointestinal bleeding 1 (4%), and bleeding from liver biopsy site 1 (4%). Poor survival was associated with bilirubin > 5 mg/dl (p < 0.031), serum alanine transaminase > 40 U/L (p < 0.005), serum albumin < 2.8 g/dl (p < 0.008), Child-Turcotte-Pugh score > 10 (p < 0.001) and absence of varices (p < 0.025). Cox regression analysis failed to show any significant independent predictors of survival. CONCLUSION: Budd Chiari Syndrome affected young patients more frequently and was associated with high mortality. The commonest aetiology was hypercoagulable state. Survival was poor in patients with decompensated liver disease and those with an acute clinical presentation.

Gastritis profunda cystica presenting as gastric outlet obstruction and mimicking cancer: A case report.

Gastritis cystica profunda (GCP) is a rare, benign lesion of the stomach characterized by polypoid hyperplasia and/or ulcerated mucosal lesion and cystic dilatation of the gastric glands extending into the submucosa or muscularis propria of the stomach. Its etiology and pathogenesis are still incompletely understood. The most important factor is assumed to be a history of prior gastric surgery. We herein present a case of a young adult female with upper gastrointestinal (GI) symptoms. She underwent upper GI endoscopy twice, which revealed pyloric narrowing and intramural mass. Gastric endoscopic mucosal biopsies were performed, but no tumor was identified and her symptoms persisted. Imaging studies also revealed a mass lesion. Open laparotomy and partial gastrectomy with histopathology of the resected specimen revealed the true nature of the lesion. Surgery also improved her symptoms. GCP should be kept in the differential diagnosis of gastric mural mass lesions.

Clinical presentation of extrahepatic portal vein obstruction: 10-year experience at a tertiary care hospital in Pakistan.

OBJECTIVE: To evaluate the clinical presentation, possible etiological factors, management and outcome of patients in our hospital with extrahepatic portal vein obstruction (EHPVO). MATERIALS AND METHODS: This study included patients with EHPVO followed up in our department during last 10 years. Patients of cirrhosis with EHPVO were excluded. Patients' clinical presentation, etiology of EHPVO, management and outcome results were analyzed. RESULTS: Of 30 patients, 19 (67.9%) were males. Median age was 12 years. Of 14 patients who underwent liver biopsy 9 had histological activity index stage of 1/6. History of omphalitis and pulmonary tuberculosis was present in one case each. Of 22 patients with the available thrombophilia profile, nine patients had a deficiency of protein C, five patients had a deficiency of protein S, one each had reduced level S of anti-thrombin III and factor V mutation. The predominant presenting symptom was hematemesis (15 patients, 53.6%). Seven patients (25%) had splenomegaly. Three patients (10.7%) had no esophageal varices on endoscopy. Three patients underwent splenectomy due to severe pancytopenia. Endoscopic retrograde cholangipancreatography was performed in four patients (14.3%) due to portal biliopathy. Common bile duct stenting was performed in all four patients. Of them, one patient underwent splenorenal shunt operation for indication of hemobilia. One patient died at the age of 40 years, due to cholangitis and sepsis. CONCLUSIONS: Results from this study show that the anticoagulant deficiency is a common cause of EHPVO in our setup. Hematemesis is a common presenting symptom. Some of these patients have symptomatic portal biliopathy.

An unusual presentation of Ménétrier's Disease.

Ménétrier's Disease (MD) is a rare acquired hypertrophic gastropathy characterized by giant hypertrophic rugal folds, hypochlorhydria, and hypoproteinemia. The definitive etiology of MD is controversial, although infection with Helicobacter pylori (H. pylori) has been implicated in adults. It presents as a constellation of symptoms including epigastric pain, fatigue, vomiting, weight loss, anorexia, and edema. None of these signs and symptoms is specific for the disease. The gastrointestinal symptoms and the degree of hypoalbuminemia can be profound, the latter resulting from the leakage of protein from the gastric lining. The disease is more common in males. Herein, we report a case of a young woman presenting with the chief complaint of peripheral edema with minimal gastrointestinal symptoms, which was diagnosed as MD on endoscopic evaluation and histopathological examination of gastric biopsy. A high index of suspicion is needed to correctly diagnose this condition for its optimal management.

Prevalence of cryptosporidiosis in renal transplant recipients presenting with acute diarrhea at a single center in Pakistan.

BACKGROUND: Cryptosporidium is an intracellular protozoan organism which causes diarrhea, both in immunocompetent and immunocompromised hosts. Renal transplant recipients are prone to develop a variety of infections including protozoal infections. OBJECTIVES: The aim of this study was to determine the prevalence of cryptosporidiosis in our renal transplant recipients presenting with acute diarrhea. PATIENTS AND METHODS: During six months of the study, 644 renal transplant recipients presented with acute diarrhea. Single stool sample was obtained for detailed analysis including gross and microscopic examination for red blood cells, pus cells, ova, cysts, and protozoa. The modified Ziehl-Neelsen (ZN) staining was done to identify the oocysts of cryptosporidia. RESULTS: Out of 644 renal transplant patients, oocysts of cryptosporidia were identified in 343 patients (53%). Detailed stool analysis of these patients showed the presence of numerous pus cells in 27 (7.9%) patients, co-infection with giardia intestinalis cysts in 15 (4.3%), and entamoeba histolytica cysts in 10 (2.9%). In all, out of 343 patients, 43 (12.5%) had dual infection with bacteria and protozoa in addition to cryptosporidiosis. CONCLUSIONS: Cryptosporidium is an important pathogen causing acute diarrhea in renal transplant recipients in our set up. Stool examination is usually negative for pus cells. It is recommended that in all transplant recipients presenting with acute diarrhea modified ZN staining should be done to rule out cryptosporidiosis in highly endemic areas like Pakistan.

Whipple's disease.

Whipple's disease is a rare chronic multi-systemic infection, caused by Gram-positive bacillus Tropheryma whipplei. The infection usually involves the small bowel, but other organs may also be involved. The diagnosis is often challenging and can only be made on histopathological examination. This report describes 2 patients presenting with abdominal pain and weight loss who finally were diagnosed to have Whipple's disease. One of the patients was a renal transplant recipient. To the best of authors' knowledge, no case of Whipple's disease has yet been reported in Pakistan. The diagnosis were made on the basis of histopathological evaluation of duodenal biopsies. The cases underscore the need for diligent histopathological evaluation of the upper gastrointestinal biopsies and a high index of suspicion for an accurate diagnosis of the condition. The approach to the diagnosis and management of the condition is discussed.

Clinical Profile and HLA Typing of Autoimmune Hepatitis From Pakistan.

BACKGROUND: Human leukocyte antigen (HLA) typing in autoimmune hepatitis (AIH) has been investigated in different populations and ethnic groups, but no such data is available from Pakistan. OBJECTIVES: The aim of this study was to evaluate the clinical profile of autoimmune hepatitis (AIH), and determine the associated antigens and alleles by performing HLA typing. PATIENTS AND METHODS: A total of 58 patients, diagnosed and treated as AIH in the last 10 years were reviewed. Diagnosis was based on International AIH Group criteria. Forty one patients underwent liver biopsy. HLA typing was performed in 44 patients and 912 controls by serological method for HLA A and B, and by PCR technique using sequence specific primers for DR alleles. RESULTS: Of 58 cases, 35 were females (60.3%). The median age was 14.5 (range 4-70 years), and AIH score was 14 (10-22). Thirty-six (62.0%) patients had type 1 AIH, 10 (17.2%) type 2, and the remaining 12 were seronegative with biopsy proven AIH. Forty-nine patients (84.4%) had cirrhosis. Twenty-four (41.4%) patients had ascites at the time of presentation. Among 41 patients who underwent liver biopsy, thirty-two had advance stages III and IV disease, and twenty had severe grade of inflammation. Fifteen patients had other associated autoimmune diseases and one developed hepatocellular carcinoma. HLA A2 (P = 0.036), HLA A9 (23) (P = 0.018), HLA A10 (25) (P = 0.000), HLA A19 (33) (P = 0.000), HLA B15 (63) (P = 0.007), HLA B40 (61) ( P = 0.002), HLA DR6 (P = 0.001) with its subtypes HLA-DRB1*13 (P = 0.032) and HLA-DRB1*14 (p = 0.017) were more prevalent in AIH with statistical significance than controls. CONCLUSIONS: AIH in our region presents with advanced disease affecting predominantly children and adolescents. There is a genetic association of HLA DR6 along with other alleles and antigens in our patients with AIH.

Three years old child with juvenile hyaline fibromatosis presenting with rectal bleeding.

Juvenile hyaline fibromatosis is a rare inherited autosomal recessive disorder which is caused by mutation of CMG2 gene on chromosome 4q21. Mutation of this gene protein can disrupt the formation of basement membranes. Hyalinization of various body tissues like skin, joints, and bones leads to development of skin papules, gingival hyperplasia, osteolytic lesions in bones, and joint contractures. We had a case of a 3 years old female child with Juvenile Hyaline Fibromatosis who presented with rectal bleeding. She had a bleeding mucocutaneous lesion in anal canal along with papullonodular lesions on the face, gingival hypertrophy and flexion contractures of small joints of hands and feet. Excision of the anal lesion revealed histopathological features of Juvenile Hyaline Fibromatosis.

Adverse events following transarterial chemoembolization for hepatocellular carcinoma and factors predicting such events.

OBJECTIVE: To document the adverse events after transarterial chemoembolisation and factors predicting such events. METHODS: The prospective observational study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, from November 2009 to November 2011. All patients diagnosed as hepatocellular carcinoma were included in this study. Complications developing within the first 6 weeks of the procedure were recorded. SPSS version 16 was used for statistical analysis. RESULTS: Of the total 80 patients, 59 (73.8%) were male. The overall mean age was 52.25 +/- 9.24 (range: 28-76 years). Most common etiology was hepatitis C related cirrhosis in 55 (68.8%). Adverse events developed in 46 (57.5%) patients. Post transarterial chemoembolisation syndrome was seen in 37 (46.3%). Of those with the syndrome, 24 (64.8%) patients had no additional complications, while 3 (8%) had renal dysfunction, 2 (5%) hypertensive crisis, and 1 (2.7%) patient each had urinary tract infection, pneumonia and sepsis. Decompensation of cirrhosis occurred in 6 (7.5%) patients of whom 3 (50%) developed sepsis and died. The syndrome was associated with tumour size > 5cm (p = 0.001) and higher dose of lipoidol (p = 0.0001). Decompensation of cirrhosis was associated with low basal albumin (p = 0.002), advanced basal child turcotte pugh (p = 0.005) and model for end-stage liver disease (p = 0.006) scores. CONCLUSION: Transarterial chemoembolisation, though generally safe, may lead to serious complications in patients with advanced liver disease. Post-procedure syndrome was associated with increased tumour size and lipoidol dose.

Job's syndrome with an atypical presentation.

Hyper Immunoglobulin E syndrome also called Job's or Buckley Syndrome is a rare primary immunodeficiency disease characterized by elevated serum IgE levels (> 2000 IU/ml), recurrent infections and eosinophilia. Other features include coarse facies and non-immunologic abnormalities of the dentition, bones, vasculature and connective tissues. We are reporting a case of a twenty four years old male with coarse facies who presented with severe pallor and upper gastrointestinal bleeding. Investigations revealed markedly elevated serum IgE levels (11,800 IU/ml), severe anaemia, esophageoduodenal erosions, Helicobacter pylori (H. pylori) gastritis and oro-esophageal candidiasis.

Non-alcoholic fatty liver disease among visitors to a hepatitis awareness programme.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. The present study aimed to evaluate the prevalence of NAFLD among the visitors screened on World Hepatitis Day 2010 and 2011. METHODS: Attendees of the hepatitis awareness programme (n = 928) were offered screening to rule out liver ailments. The participants were evaluated on history, body mass index (BMI) measurement, blood tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), alanine aminotransferase (ALT) levels and abdominal ultrasound (US). RESULTS: On ultrasonography, fatty liver was present in 142 of 806 subjects who were found negative for viral serology and had no history of regular alcohol intake. This accounted for 15.3% of all the visitors. Comparing them with the rest of the serology-negative alcohol-negative subjects, there were more housewives (p = 0.005) with fatty liver. They were older with mean age 43.3 +/- 12.1 years compared to 33.1 +/- 16.1 years (p = 0.000) in patients without fatty liver and had a higher BMI 28.6 +/- 6.0 kg/m2 vs. 22.2 +/- 5.3 kg/m2 (p = 0.000). Regression analysis suggested BMI as the only significant independent risk factor (p = 0.000). However, 32 subjects with fatty liver had BMI < 25 kg/m2 and 6 of them had diabetes mellitus. Thirty-one subjects (21.8%) with fatty liver had raised ALT level (p = 0.000) and possible non-alcoholic steatohepatitis (NASH) which accounts for 3.34% (31/928) of the total visitors. CONCLUSIONS: This analysis reveals that our general population is at risk of having NAFLD and NASH and these should be looked into even in non-obese persons.